Dr. Jill Young-Endorsement for Total Joint Complex™

Dear Michelle and Greg,

I wanted to thank you for continuing to provide Total Joint Complex™ to those interested in optimal joint health.

I have used this product personally and professionally since 1994.

My first exposure to your Total Joint Complex™  product was actually through the mother of a massage therapist who worked in my office.  She reported her mother had suffered for years with a damaged knee and had been told repeatedly that replacement surgery was necessary for any quality of life.  While she was desperate enough to finally consider surgery, she first wanted to try one last natural option.  That option was Total Joint Complex™.

After only a few short months of use as recommended, this woman was functioning without pain with increased mobility.  That is when I decided the product deserved a personal look.

I have used Total Joint Complex™ for years and my knees thank me.  Anyone who has experienced either knee or shoulder pain knows these two pains are extremely intense.  The times I have slacked on my personal supplement regimen I always jump right back on as my knees feel years older without Total Joint Complex™.

Everyone I have on Total Joint Complex™ reports not being able to imagine managing the nature effects of aging or the consequences of prior sports injuries or the residual damage from auto accidents without the help of Total Joint Complex™.

For the scientist in all of us, if you haven’t tried this product, why not experiment to see what benefits you may enjoy?

Life Priority, thank you for making this high quality product Total joint Complex. I appreciate your dedication to excellence.

Jill Young, D.C. Winfield, KS

 

Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities.

*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.

*Any testimonials on this web site are based on individual results and do not constitute a guarantee that you will achieve the same results.

With these BRAIN DRINKS as your daily allies, you can take charge of your life. So have a glass . . . Your mind is in your hands.;Neurotransmitters;choline; Durk Pearson; Sandy Shaw;brain

Your Mind is in your Hands

Your Mind Is in Your Hands

Set the stage for pursuing your personal happiness. Each new day presents challenges that, if not met and overcome, may leave you less mentally fit to control your life.

Now there’s a way to insure against the consequences of falling short of your goals and to offer you more control over your life.

By starting each day with a cool, refreshing glass of delicious LIFT™(or LIFT CAPS™), or Mind™, you can embrace a Mental Fitness™ program that can blow away your neural cobwebs and lift away the stressful storm clouds that may hold you back.*

Life extension scientists Durk Pearson & Sandy Shaw® have developed a family of products for their own personal use based on the idea of providing our brains with nutrient raw materials to manufacture neurotransmitters such as noradrenaline, which provides an adrenaline-like charge to neural circuits.* These BRAIN DRINKS are the core of Durk & Sandy’s personal Mental Fitness program. Each formulation contains the essential amino acid phenylalanine and the necessary enzyme cofactors vitamin B6, vitamin C, copper, and folic acid, along with natural flavors. With these BRAIN DRINKS as your daily allies, you can take charge of your life. So have a glass . . . Your mind is in your hands.

LIFT CAPS™ is the convenient, capsulated form of LIFT™.
Rita C. 2/5/2015- I’m taking the Lift Caps and – they’re amazing! It gives me so much energy, and I am on my feet, working and talking 9 hours a day. With the Lift Caps – what a difference people see! I’m just so happy to have my brain, body and mind back!

Matt 11/07/2015- LIFT is wonderful…without a doubt! It’s a regular part of my day and my performances.

Cindy  4/03/2014- I have been taking Lift Caps for over 10 years! They give me lots of energy and stop my craving for coffee, soft drinks and chocolate too! I LOVE THEM!

Ruth 9/23/2014- I like the LIFT because I think it gives me just what I need. I work 8 hours a day, sometimes more, with kids at school, and I just have to have the Lift in the morning. I don’t get as tired during the day when I drink it – it just works for me. I think I’m getting everything from it!

Tony 5/6/2015- LIFT helps me in the morning. I used to drink energy drinks, but this is healthier and does the same job.

Char 05/23/2014- I’ve been using Lift and Lift Caps for over 21  years and I find Lift  is the only thing that will give me the energy to go on when I feel like dropping. Love You Durk and Sandy! Thanks for your research! Please write another book!

 

Terms of Use

The information provided on this site is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional or any information contained on or in any product label or packaging. You should not use the information on this site for diagnosis or treatment of any health problem or for prescription of any medication or other treatment.

You should consult with a healthcare professional before starting any diet, exercise or supplementation program, before taking any medication, or if you have or suspect you might have a health problem. You should not stop taking any medication without first consulting your physician.

 

July 2016 Blog with Durk and Sandy

APPETIZERS

A passage from George Orwell’s iconic novel 1984 reads: “Who controls the past…controls the future; who controls the present controls the past.” And yet the past, though of its nature alterable, never had been altered. Whatever was true now was true from everlasting to everlasting. It was quite simple. All that was needed was an unending series of victories over your own memory. “Reality control,” they called it: in Newspeak, “doublethink.”

“Doublethink is essentially a form of cognitive dissonance in which one holds contradictory ideas in their mind, and accepts both as reality. Doublethink is everywhere. Every human being compartmentalizes to some extent.”

— Rob Knowles
http://constitution.com/author/rob-knowles
(downloaded 5-16-16)

People in volatile economies do not invest, because it is better to spend now than have their earnings lose value tomorrow.

The development of a future orientation requires stability and consistency in the present, or people cannot make reasonable estimates of the future consequences of their actions.

THE LESS PEOPLE CAN RELY ON THE PROMISES OF GOVERNMENT, INSTITUTIONS, AND FAMILIES, THE MORE THEY ESCHEW THE FUTURE AND FOCUS ON THE PRESENT, CREATING A WORLD OF YES AND NO, BLACK AND WHITE, IS AND IS NOT, RATHER THAN ONE FILLED WITH MAYBES, CONTINGENCIES, AND PROBABILITIES. (Emphasis added.)

— Philip Zimbardo and John Boyd, The Time Paradox, Free Press, 2008

THE MOST APPETIZING APPETIZER IN THIS ISSUE:

WONDERFUEL® C-8 MCT OIL IN AN EASY HOMEMADE MAYONNAISE

Most commercial mayonnaise contains oils composed largely of long chain omega-6 polyunsaturated fats, such as soybean oil, though there are now some brands of mayonnaise available that contain monounsaturates, such as canola oil or, at a premium price, olive oil. You might prefer a mayonnaise that contains medium chain saturated fats (MCTs), but you won’t find it at your local supermarket or even at a specialty food store. We made up our own from our WonderFuel C-8 MCT OIL (comprised of about 90% C-8 MCTs (an 8 carbon fatty acid called caprylic acid)) and it turned out great. It was very easy using a hand blender, the immersion type. Here’s the recipe we used (but of course there are many recipes available and you can add anything you like to suit your taste). In upcoming issues of this newsletter, we’ll be including more recipes that we found particularly enjoyable and fun.

For one cup of mayonnaise, you’ll need:

An immersion blender

INGREDIENTS

1 large egg yolk

1 tablespoon water

1 tablespoon lemon juice (from 1⁄2 a lemon)

3 teaspoons Dijon mustard

1 cup WonderFuel C-8 MCT OIL

INSTRUCTIONS

Place egg yolk, water, lemon juice, and mustard in the bottom of a small bowl that can easily hold your immersion blender. Pour oil on top and allow to settle for 15 seconds. Place head of immersion blender at bottom of bowl and switch it on. As mayonnaise thickens, slowly lift the head of the immersion blender up and down until all the oil is emulsified. Takes about a minute. Season mayonnaise to taste with salt, if desired. Store in a sealed container in the refrigerator for up to two weeks.

ENJOY!

SOCIAL BEHAVIOR: AGGRESSIVE OR PLAYFUL GRAY MATTER MAY MAKE A DIFFERENCE

Aggression is a character trait that is more commonly expressed by males. Not surprisingly, then, it is males that have always been the instigators and perpetrators of war. Sex, on the other hand, can also involve aggression (the extreme end of it being rape, which is also nearly exclusively carried out by men).

Sex, however, can take the place of violent combat by hijacking the aggressive behavior, a form of displacement activity. This is seen when you compare the sexual behavior in bonobos and chimpanzees. A recent paper (Rilling, 2012) studied the differences in the neural systems of bonobos and chimpanzees, trying to find what sophisticated brain imaging could reveal about why bonobos showed little aggressive behavior between males and females (who engaged in sex instead—the same is true for female-female interactions as well), while chimpanzees were inclined to engage in violent interactions, even including the killing of members of other chimp groups.

This is a very desirable type of research. We need to know how the energy of aggressive behavior can be used for peaceful activity, such as sex, and diverted from destructive ends. In the chimp-bonobo study, the results showed that “bonobos have more gray matter in brain regions involved in perceiving distress in both oneself and others, including the right dorsal amygdala and right anterior insula. Bonobos also have a larger pathway linking the amygdala with the ventral anterior cingulate cortex, a pathway implicated in both top-down control of aggressive impulses as well as bottom-up biases against harming others.” (Rilling, 2012) The authors suggest that this can help explain the relative non-violence of bonobos compared to chimpanzees, but “also behaviors like sex and play that serve to dissipate tension, thereby limiting distress and anxiety to levels conducive with prosocial behavior.”

The involvement of the amygdala, a brain area intimately involved in the sensing and regulation of fear and aggression, suggests that the switch to sexual behavior takes place in the case of bonobos with the active participation of this brain area. It would be very useful indeed to find out more about this “switch.”

THE SWITCH

The switch from aggressive behavior to sexual playfulness may be related to the following phenomenon. In studies of animals, such as rodents and non-human primates, the response to a threat involves a release of dopamine. You may be surprised at this, as dopamine is usually thought of as a response to a reward or the expectation of a reward. However, there is a subset of dopamine neurons that specifically respond to stress perceived as a threat. When an animal is exposed to a threat, its brain releases reduced amounts of dopamine in the nucleus accumbens in response to danger, but when the animal perceives that the danger is CONTROLLABLE, more dopamine (rather than less) is released in that area. “…whether an increase or decrease in [nucleus] accumbens dopamine levels is observed in response to stress depends on whether the stressor is appraised as controllable (increase) or not (decrease).” (Lloyd, 2016)

One hypothesis is that when a threat is perceived as controllable, it switches from representing a danger to a signal for possible safety and this makes all the difference to the dopamine releasing neurons in the nucleus accumbens. “Thus, provided the animal has the expectation that the situation is controllable, observation of the aversive stimulus should predict this future appetitive [rewarding] outcome…” (Lloyd, 2016)

References

Rilling et al. Differences between chimpanzees and bonobos in neural systems supporting social cognition. Soc Cogn Affect Neurosci. 7:369-79 (2012).

Lloyd and Dayan. Safety out of control: dopamine and defence. Behav Brain Funct.12(1):15. doi: 10.1186/s12993-016-0099-7. (2016).

 

WORDS OF WISDOM FROM A GHOST ON WAR AND PEACE

The following is from a satirical comic fantasy entitled “Conjuring the Ghost of Richelieu” written by David Goldman and published in his Affluent Investor on May 26, 2016 (affluentinvestor.com) with the main character being the ghost of Cardinal Richelieu (Armand Jean du Plesses, Cardinal-Duc de Richelieu):

“Do you know,” the ghastly Cardinal continued, “why really interesting wars last for 30 years? That has been true from the Peloponnesian War to my own century. First you kill the fathers, then you kill their sons. There aren’t usually enough men left for a third iteration.”

Later in the same fantasy, the Cardinal explains the problem with majority rule: “It is a matter of calculation—what today you would call game theory. If you compose a state from antagonistic elements to begin with, the rulers must come from one of the minorities. All the minorities will then feel safe, and the majority knows that there is a limit to how badly a minority can oppress a majority…” “The moment you introduce majority rule in the tribal world,” the Cardinal replied, “you destroy the natural equilibrium of oppression.”

THE MISSING MAJORITY

Thus the rise of diversity means that, although our political systems are theoretically founded on majority rule, it may be impossible to form a majority even on issues crucial to survival. In turn, this collapse of consensus means that more and more governments are MINORITY governments, based on shifting and uncertain coalitions.” “The missing majority makes a mockery of standard democratic rhetoric. It forces us to question whether, under the convergence of speed and diversity, any constituency can ever be “represented.”

—Alvin Toffler, The Third Wave
William Morrow & Co., 1980, pg. 426

 

COULD YOU BE ADDICTED TO SUGAR? 
YOU COULD BE—AND HERE’S WHY

An exceptionally informative paper (Avena, 2008) describes the authors’ experiments in rats as well as reviews papers providing a convincing body of evidence that sugar can produce neurochemical effects in the brain that mimic those of addiction to drugs such as cocaine and heroin. In its detailed overview of these effects, the paper provides a description of how sugar can be addicting, using a model developed using rats that depicted the four stages of the addictive process as (1) binging, (2) withdrawal, (3) craving, and (4) sensitization. In addition, the paper elaborates the sequential alterations in brain neurochemistry that take place during each of these stages, offering very useful guidance to many places where intervention may be helpful. “Neural adaptations include changes in dopamine and opioid receptor binding, enkephalin [part of the opioid system] mRNA expression and dopamine and acetylcholine release in the nucleus accumbens.” (Avena, 2008) (The usual limitation applies—that the evidence presented was what was known as of the date of publication, but to our knowledge, their understanding is still the accepted view of addiction.)

Many people feel compelled to eat sweet foods. These feelings are beyond their usual self-control, and are often likened to an “addiction.” But, as the evidence shows, sugar craving is not a metaphor for an addiction, but is a true addiction. The paper presents the authors’ hypothesis that “intermittent, excessive intake of sugar can have dopaminergic, cholinergic and opioid effects that are similar to psychostimulants and opiates, albeit smaller in magnitude.” (Avena, 2008)

Another paper (Morris, 2010) explains that glucose is released from the liver in response to circulating adrenaline (aka epinephrine), a neurotransmitter of the adrenergic nervous system, which is involved in feeding and glucose regulation, as discussed below.

References

Avena et al. Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev. 32(1):20-39 (2008)

Morris et al. Age-related memory impairments due to reduced blood glucose responses to epinephrine. Neurobiol Aging. 31:2136-45 (2010). (In this paper, the authors found that in a study of rats, adrenaline and glucose were about equally effective in improving memory in young rats, but that in old rats, glucose was more effective in doing so.)

 

COULD YOU BE ADDICTED TO SUGAR? 
YOU COULD BE—AND HERE’S WHY

An exceptionally informative paper (Avena, 2008) describes the authors’ experiments in rats as well as reviews papers providing a convincing body of evidence that sugar can produce neurochemical effects in the brain that mimic those of addiction to drugs such as cocaine and heroin. In its detailed overview of these effects, the paper provides a description of how sugar can be addicting, using a model developed using rats that depicted the four stages of the addictive process as (1) binging, (2) withdrawal, (3) craving, and (4) sensitization. In addition, the paper elaborates the sequential alterations in brain neurochemistry that take place during each of these stages, offering very useful guidance to many places where intervention may be helpful. “Neural adaptations include changes in dopamine and opioid receptor binding, enkephalin [part of the opioid system] mRNA expression and dopamine and acetylcholine release in the nucleus accumbens.” (Avena, 2008) (The usual limitation applies—that the evidence presented was what was known as of the date of publication, but to our knowledge, their understanding is still the accepted view of addiction.)

Many people feel compelled to eat sweet foods. These feelings are beyond their usual self-control, and are often likened to an “addiction.” But, as the evidence shows, sugar craving is not a metaphor for an addiction, but is a true addiction. The paper presents the authors’ hypothesis that “intermittent, excessive intake of sugar can have dopaminergic, cholinergic and opioid effects that are similar to psychostimulants and opiates, albeit smaller in magnitude.” (Avena, 2008)

Another paper (Morris, 2010) explains that glucose is released from the liver in response to circulating adrenaline (aka epinephrine), a neurotransmitter of the adrenergic nervous system, which is involved in feeding and glucose regulation, as discussed below.

References

Avena et al. Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev. 32(1):20-39 (2008)

Morris et al. Age-related memory impairments due to reduced blood glucose responses to epinephrine. Neurobiol Aging. 31:2136-45 (2010). (In this paper, the authors found that in a study of rats, adrenaline and glucose were about equally effective in improving memory in young rats, but that in old rats, glucose was more effective in doing so.)

 

WHEN DOPAMINE IS RELEASED IN RESPONSE TO AN AVERSIVE STIMULUS, RATHER THAN A REWARDING ONE

While dopamine is known as a signal for reward (or the anticipation of a reward), some neurons that express dopamine release dopamine in response to an AVERSIVE stimulus. The authors of a very recent paper (Lloyd, 2016) pointed out that an aversive stimulus could, if there is a way to escape it, actually be a rewarding stimulus because safety can be a reward. As they point out, “…relative to this new state of danger, the possible prospect of future safety—a positive outcome—comes into play.” “Thus, provided the animal has the expectation that it will ultimately be able to achieve safety, i.e., that the situation is controllable, observation of the aversive stimulus should predict this future appetitive [rewarding] outcome…” Another paper expressed it this way: “Neural activity in a region previously implicated in encoding stimulus reward value, the medial orbitofrontal cortex, was found to increase, not only following receipt of reward, but also following successful avoidance of an aversive outcome. This neural signal may itself act as an intrinsic reward, thereby serving to reinforce actions during instrumental avoidance.” (Kim, 2006)

This leads to the interesting economic concept of “opportunity costs,” where there is a cost to NOT doing a thing that might have a large payoff. “… if the subject fails to explore, for instance because it believes the aversive stimulus to be insufficiently controllable, then it would never discover that it actually might be removed.” The researchers then go on to explain that an inadequate response by the dopamine (D2) receptor could lead to a failure to consider the possibility of achieving safety.

References

Lloyd and Dayan. Safety out of control: dopamine and defence. Behav Brain Funct.12:15 (2016).

Kim et al. Is avoiding an aversive outcome rewarding? Neural substrates of avoidance learning in the human brain. PLoS Biol. 4(8):e233 (2006).

 

FOOD ADDICTION, A TRUE ADDICTION

The basis for addiction is REWARD. All addictive substances are rewarding. The frantic bar pressing of a rat is a good example of how important reward can be in focusing the attention of an animal. In the case of food, unlike addictive drugs, the pleasure of its consumption is important for survival. From an evolutionary perspective, it would have been highly adaptive for the consumption of food to be rewarding, especially in the case of foods rich in fat and sugar, since they can be rapidly converted into energy.

Interestingly, in the case of cocaine addiction, a decreased number of D2 receptors are available to provide the motivation to obtain and use cocaine. The form of the D2 receptor known as the TaqA1 variant that is associated with a lower release of dopamine in humans is a fairly common version of the D2 receptor in Caucasians. (Reuter, 2013) Possessing it causes individuals to be susceptible to risky behavior, including the use of addictive drugs, but also for less extreme sorts of risky activity, such as auto racing, skydiving, mountain climbing, gambling, promiscuous sexuality, and even risky trading at the stock market. Activating the D2 receptors at medium spiny neurons that express the dopamine D2 receptors has been shown in mice to suppress cocaine self-administration. (Bock, 2013) The way this works is that the D2 receptor signals reward (or the prediction of reward) and when the numbers of these receptors are reduced, dopamine release is lower, and this induces behavior to increase dopaminergic release. One way people do this is by engaging in “thrill-seeking.”

References

Reuter et al. The influence of dopaminergic gene variants on decision making in the ultimatum game. Front Hum Neurosci. 4;7:242. doi: 10.3389/fnhum.2013.00242. (June 2013).

Bock, Shin, et al. Strengthening the accumbal indirect pathway promotes resilience to compulsive cocaine use. Nat Neurosci. 16(5):632-8 (2013).

 

HOW IS FOOD INTAKE REGULATED?

A host of molecules are involved in the process of addiction. It is because an overpowering desire to consume opiates and an obvious withdrawal syndrome is easier to distinguish than an overpowering desire to eat certain kinds of food followed by its own form of the withdrawal syndrome that the label “addiction” is easy to apply to opiate addiction but is less readily recognized in the eating of food. The molecules regulating the processes tell the story.

A mechanism has been identified to explain in part how these molecules foster addiction: they activate the vitally important reward system in which the cholinergic and dopaminergic nervous systems interact. In fact, a study (Joshua, 2008) reports that midbrain dopaminergic neurons and striatal cholinergic interneurons distinguish between rewarding and aversive stimuli. Importantly, the interaction between the dopaminergic and cholinergic nervous systems links these neurotransmitters to experimental findings that show that eating is initiated by a cholinergic signal and is terminated by a dopaminergic signal. (Rada, 2000) (Other studies have reported initiation by a dopaminergic signal and termination by a cholinergic signal; thus, the evidence is inconsistent.) This hub in which the neurotransmitter systems interact is a target for the complex process of food and perhaps other addictions.

References

Joshua et al. Midbrain dopaminergic neurons and striated cholinergic interneurons encode the difference between reward and aversive events at different epochs of probabilistic classical conditioning trials. J Neurosci. 28(45):11673-84 (2008).

Rada et al. Acetylcholine release in ventral tegmental area by hypothalamic self-stimulation, eating, and drinking. Pharmacol Biochem Behav. 65(3):375-39 (2000).

 

DOPAMINE IS RELEASED IN RESPONSE TO HIGHLY PALATABLE FOOD 
WHY IS THIS RELEASE ATTENUATED FOLLOWING REPEATED SERVINGS?

Many papers (see, for example, Avena, 2011) report that the release of dopamine that normally accompanies the consumption of a tasty meal becomes attenuated as the meal progresses, suggesting (according to some papers) that this is due to a loss of “novelty” of the food. We wonder whether this is the reason for decreasing pleasure in a meal and suggest that it might be due, instead, to a downregulation of the dopaminergic receptors or transient exhaustion of the dopamine supply.

Reference

Avena et al. Overlaps in the nosology of substance abuse and overeating: the translational implications of ‘food addiction’. CURRENT DRUG ABUSE REVIEWS 4:133-139 (2011)

 

SHORT CHAIN FATTY ACIDS AND KETONES DIRECTLY REGULATE THE SYMPATHETIC (ADRENERGIC) NERVOUS SYSTEM

Another neurotransmitter system importantly involved in eating and glucose regulation is the sympathetic (adrenergic) nervous system, in which adrenaline (also called epinephrine) and noradrenaline (also called norepinephrine) are the neurotransmitters.

“To balance energy intake, dietary excess and fasting triggers an increase or a decrease in energy expenditure, respectively, by regulating activity of the sympathetic nervous system, and its dysregulation leads to metabolic disorders such as obesity and diabetes. In feeding, excessive energy is consumed by the enhancement of sympathetic function, resulting in increases in heart rate and diet-induced thermogenesis, whereas in fasting, energy use is saved by the suppression of the sympathetic function as a survival mechanism, resulting in the reduction in heart rate and activity.” “In the present study, we show that SCFAs [short chain fatty acids] and ketone bodies, major energy sources in the body, directly regulate sympathetic activity via GPR41 [an SCFA receptor].” (Kimura, 2011) Perhaps the enhancement of sympathetic function resulting from eating a fatty meal at bedtime can cause insomnia.

Reference

Kimura et al. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci U S A.108(19):8030-5 (2011).

 

THE BRAIN REQUIRES GLUCOSE FOR SELF-CONTROL

A 2007 paper reports on the advantages that having good self-control gives a person. As the paper (Gailliot, 2007) explains, prior evidence has amply shown that good self-control leads to such desirable outcomes as “healthier interpersonal relationships, greater popularity, better mental health, more effective coping skills, reduced aggression, and superior academic performance…” Other benefits they mention include reduced susceptibility to addictive drugs and to eating disorders.

The authors explained that in order for the brain to exert self-control, it requires the expenditure of energy, a lot of energy, in the form of glucose (the brain’s major source of energy). In fact, they report that a SINGLE act of self-control reduces the ability of an individual to perform a subsequent act of self-control. They describe a study in which participants had to resist eating freshly baked cookies and later, it found, those subjects who did resist were less able to persist in a task which also required self-control. The paper (Gailliot, 2007) also provided references to several other studies of limits to self-control after another act of self-control, that included control of prejudicial behavior, coping with fears of death, controlling spending, controlling one’s temper, and limiting alcohol intake.

The researchers (Gailliot, 2007) then showed that a deficiency of glucose was the cause of the reduced self-control that followed a prior act of self-control by treating some of the participants with a glucose drink after their initial task of self-control. “Even though nearly all of the brain’s activities consume some glucose, most cognitive processes are relatively unaffected by subtle or minor fluctuations in glucose levels within the normal or healthy range. Controlled, effortful processes that rely on executive function, however, are unlike most other cognitive processes in that they seem highly susceptible to normal fluctuations in glucose.” An example of such an effortful process relying on higher cognitive areas that use a lot of energy is the struggle for self-control that addicts engage in when they try to resist the urge to take drugs. It is interesting to note that a dose of sugar can temporarily overcome that urge. It is, in fact, a common anecdotal suggestion for those trying to “kick the habit” (whether for cigarettes or something else) to consume sugar for temporary relief.

In conclusion, the authors note that “…despite our manipulations, we do not intend to advocate consuming large quantities of sugar as an ideal strategy for improving self-control.” We wouldn’t either, but see next paragraph for a different approach.

We wonder how these experiments would have worked out if the subjects had been given C-8 MCT OIL as an alternative energy source, rather than glucose. It seems to us that this would make a meaningful experiment and we do think that prior evidence supports the idea that the C-8 MCT OIL could similarly support the energy requirements for self-control without promoting an insulin surge that would lower subsequent blood glucose levels.

Reference

Gailliot, Baumeister, et al. Self-control relies on glucose as a limited energy source: Willpower is more than a metaphor. J Pers Soc Psychol. 92(2):325-36 (2007).

 

LACK OF SELF-CONTROL (IMPULSIVITY) PREDICTS LIKELIHOOD OF CRIMINAL ACTIVITY

A very recent paper (Akerlund, 2016) followed 13,606 children for 18 years in a study of time discounting, that is, how much the children valued a sum of money now (about $140 in U.S. dollars) as compared to a larger sum of money (about $1,400 in U.S. dollars) 5 years later.

“Our results show that individuals with short time horizons have a significantly higher risk of criminal involvement later in life.” (Akerlund, 2016) They suggest as the reason that individuals may perceive that the relative costs and benefits of criminal activity involve rewards that “are savored immediately and its potential costs in terms of apprehension and punishment [ ] are borne in the future.”

The study’s authors use the expression “self-control” to describe an individual’s ability to resist impulsively choosing an immediate reward as compared to waiting for a later, larger reward. “… the ability to exercise self-control in the face of opportunity is hypothesized to explain a large portion of criminal behavior.” The researchers found that there is an association between intelligence and crime (being more prevalent in those with low intelligence and especially strongly associated with men of low intelligence) and that “patience [that is, non-impulsivity] among adults is significantly associated with higher cognitive ability.”

They further refer to the famous “marshmallow” experiments where 4-year old children were offered an extra marshmallow if they could delay for fifteen minutes the gratification of immediately eating a marshmallow. Those who waited were later found to have better outcomes in many aspects of their young adult lives, including SAT scores, educational achievement, income, less likelihood of using addictive drugs, and other things. The authors note that similar experiments in adults have found that time preferences (immediate vs. delayed gratification) “are significantly correlated with field outcomes such as occupational choice, credit card borrowing, and smoking.” (Akerlund, 2016)

The experimenters did not report in their paper a link (should there be one) between glucose and engagement in criminal activity and, again, we believe that this would have added to their results by providing a physiological reason for the differences between the impulsive and non-impulsive children. Because the brain requires glucose for self-control (see above), it is plausible that a relative glucose insufficiency in the brain may be a causative factor in the tendency to engage in criminal activity. (A “relative glucose insufficiency” does not necessarily mean that an individual does not consume enough glucose, but that he or she uses glucose inefficiently, as would be the case for insulin resistance.)

Reference

Akerlund, Golsteyn, et al. Time discounting and criminal behavior. Proc Natl Acad Sci U S A. Early edition. 13(22):6160-5. doi: 10.1073/pnas.1522445113. (2016).

 

THE ADRENERGIC NERVOUS SYSTEM AND PREJUDICE

A recent paper (Terbeck, 2012) showed that, in a randomized, double-blind, placebo controlled study of 36 white university students (a typical source for participants in these sorts of studies!) were given a single dose of 40 mg. of propranolol, a beta-adrenoceptor antagonist (beta blocker) and their racial bias determined by the IAT (implicit association task). The IAT assesses implicit racial prejudice (the physical expression of prejudice) by an “item sorting task” to distinguish that from explicit racial prejudice, which is limited to what the subject thinks. Explicit racial prejudice was assessed by subjects indicating how “warm” they felt toward various racial groups.

Propranolol is a widely used medication in hypertension and other conditions in which an overactive sympathetic (adrenergic) nervous system is involved.

The results showed that, compared to placebo, “propranolol significantly lowered heart rate and abolished implicit racial bias, without affecting the measure of explicit racial prejudice.” (Terbeck, 2012)

In another fairly recent paper (Kimura, 2011), scientists generated mice without a GPR41 receptor that regulates sympathetic (adrenergic) nervous system activity via the interaction of short chain fatty acids and ketone bodies with the receptor. “…a ketone body, beta-hydroxybutyrate, produced during starvation or diabetes, suppressed SNS [sympathetic nervous system] activity by antagonizing GPR41.”

References

Kimura et al. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci U S A.108(19):8030-5 (2011).

Terbeck et al. Propranolol reduces implicit negative racial bias. Psychopharmacology (Berl). Aug;222(3):419-24 (2012).

 

KETONES ARE FUEL FOR THE EYE’S PHOTORECEPTORS

POSSIBLY PROTECTIVE AGAINST MACULAR DEGENERATION

Other tissues, besides those of the brain, use ketones as a source of energy when glucose is in short supply. The retina, for example, is highly energetic, requires (like the rest of the brain) a continuously available energy source and can also use ketones as a replacement when there is an inadequate supply of glucose. “… the retina uses not only glucose, but also fatty acids, as an energy source, and [ ] the beta-oxidation of fatty acids has an important role in meeting the demands of photoreceptors. Thus defective fatty acid metabolism could contribute to the development of AMD [age-related macular degeneration].” (Rajala, 2016)

References

Rajala and Gardner. Burning fat fuels photoreceptors. Nat Med. 6;22(4):342-3. doi: 10.1038/nm.4080. (2015); Joyal et al. Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar 1. Nat Med. 22(4):439-45 (2016).

 

THE SPEED OF THOUGHT

Speeding through the universe,
Thinking is the best way to travel.

—from The Best Way To Travel by The Moody Blues

A paper has reported an attempt to compare the “speed of thought” for brains to that of digital computers. (Nagarajan, 2008) The comparative data are as of 2008, so may be considerably different now. Computers are certainly much faster and even some brains may be faster, depending upon such things as increasing the brain’s myelin content, which speeds the transmission of information in the brain (for more on this, see next section below).

While the brain’s basic unit is the neuron, that of the computer is the transistor. At the time this paper was published, “modern very large scale integrated (VLSI) microprocessor circuits” were said to “have about a million transistors per square millimeter of chip area.” In the brain, on the other hand, the smallest computing element that processes information is the neuronal synapse. The “grey matter of most brain regions contains about 10 to the fifth synapses per microliter, a value not so different from the volume density of transistors.” (Nagarajan, 2008)

After supposing that “each neuron carries out an instruction each time it produces a nerve impulse” and that the neocortex contains about 10 to the tenth neurons, the resulting calculation indicates that the modern microprocessor would provide 100 fold less instructions per second than the brain. So, the computer (at that time) was calculated to be 100 times slower than the brain, even though it had a much faster processor speed because the brain contains so many synapses.

Reference

Nagarajan and Stevens. How does the speed of thought compare for brains and digital computers? Curr Biol. 18(17):R756-8 (2008).

 

THE BRAIN’S PROCESSING SPEED DEPENDS UPON MYELIN

The myelin coat that sheaths neuronal tracts in the brain (white matter or gray matter) is what enables the brain to transmit information rapidly from one area to another. As we have written before, myelin is used by the brain as a source of fats for conversion to ketones when the brain’s supply of glucose—its primary fuel for energy—is depleted. This occurs in many circumstances, including fasting, ischemia, aging, stroke, and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, to name just a few. That is why we have written so extensively about C-8 MCT OIL, which the brain can use as a source of fat for conversion to ketones, an alternative to glucose for fuel, thus sparing its valuable and limited supply of myelin.

 

THINKING ABOUT THE FUTURE

Mental Time Travel

One of Sandy’s books on memory (The Memory Process, MIT Press, 2011) covers a lot more than just memory. It roams far and wide, with fascinating material on such things as imagination, the language of music, consciousness, romantic fiction, dreams, and a lot of other stuff, just what you might expect from a well-done book coming out of the Massachusetts Institute of Technology (note: MIT’s publications on politically “sensitive” subjects are not necessarily so well done).

In this heavily referenced book, there is a discussion on how thinking about the future uses virtually the same neural pathways as does remembering the past, being appropriately called “Mental Time Travel.” It is also called “episodic future thinking” by Alan Richardson, author of Ch. 13 of The Memory Process, pg. 280, who concludes that thinking of the future and past share common neurological mechanisms.

A very informative description of how memory works is given on pg. 290: “Episodic memories … tend to reflect personal experience rather than general knowledge or implicit skills…” These memories are depicted as being “fragmentary and fragile” and are used to “reconstruct” memories from bits and pieces put together in a creative process rather than storing “exact replicas of past experience.” The beauty of this system is that it enables the bits and pieces to be reused in new, original combinations, both for recreating the past and for imagining the future.

A 2007 published study is described in the book (pg. 279) in which researchers found that amnesic patients with damage to the hippocampus had a diminished capacity to imagine hypothetical future scenarios, something that is also seen in normal aging. It is easy to see how an inability to see what might lie ahead, particularly if it involves any rewarding events, could lead to apathy concerning whether you live or die. The “will to live” is a vital factor in remaining alive and has been shown to be important in the length of time patients with terminal diseases survive.

 

PERSONALITY AND THE COMT GENE

Personality generally “refers to the ‘characteristic patterns of behavior, thoughts and feelings’ of a person over time.” (Montag, 2015)

One cannot really understand human personalities without knowledge of dopamine and COMT (catechol-O-methyltransferase), the latter being one of the enzymes that catabolizes and inactivates dopamine. Dopamine is a neurotransmitter importantly involved in the brain’s reward circuitry. Its regulation is responsible for much of the personality differences exhibited by individuals. People who have certain variants of specific dopamine receptors show very different patterns of behavior. The DRD2 and DRD4 dopamine receptor genes are associated with, for instance, impulsivity, novelty-seeking, and risk-seeking (tending to engage in more risky types of behavior) and linked to lower levels of dopamine release.

The COMT Val158Met polymorphism (version) of the COMT gene is a high activity version of COMT, that is, it breaks down more dopamine than the Met/Met COMT polymorphism. “Carriers of the Met/Met variant [of COMT] catabolize three to four times less dopamine than carriers of the homozygous Val/Val variant.” (Montag, 2015) By catabolizing less dopamine, this means that there is more dopamine available to activate dopamine receptors. COMT Val158Met, on the other hand, causes there to be LESS dopamine available to activate dopamine receptors.

Met stands for methionine, Val for valine; the gene can either specify a valine (Val) or a methionine (Met) at position 158 and this importantly defines how strongly the COMT enzyme degrades dopamine. The variant most commonly found has a Met and a Val at that position and is called the Val158Met polymorphism. That variant is associated with a very interesting personality type that in its most productive form is found in people such as entrepreneurs, inventors, and similar types who also share personality characteristics such as being risk takers and novelty seekers. At the extreme end of the spectrum of those who have this variant may be found people who have a tendency to engage in impulsively reckless activity or thrill-seeking, and may even, in some cases, use addictive drugs.

The authors of Montag, 2015 explained that they searched the PubMed.gov literature for papers on COMT Val158Met and found that, at the time, there were nearly 400 papers on the subject. They then narrowed the search by using the keywords “COMT Val158Met” and “personality” as search terms and received back 56 papers. (They also searched “Google Scholar” using these keywords.) Ultimately, they focused on papers dealing with “COMT in the context of [ ] [certain] biologically oriented personality theories…” The literature on COMT continues to rapidly increase.

INHIBITING COMT TO DECREASE DOPAMINE

DEGRADATION IN THE BRAIN GREATER REWARDS™

We developed a formulation called GREATER REWARDS that we take regularly to inhibit COMT to reduce the degradation of dopamine, thereby increasing the reward signaling of dopamine. One of its ingredients is EGCG, epigallocatechin-3-O-gallate, the major catechin found in green or white tea. EGCG is a high-potency inhibitor of COMT (catechol-O-methyltransferase). (Zhu, 2008)

Another ingredient in our GREATER REWARDS is taurine. Taurine increases dopamine levels in the dopamine reward system. The rat dopamine reward system is organized like that of humans, with the mesolimbic dopamine neurons projecting from the ventral tegmental area to the nucleus accumbens. Researchers looking for receptors involved in the regulation of dopamine in this pathway reported that local perfusion of taurine (by microdialysis) increased dopamine levels in the nucleus accumbens reward center and that this involved taurine acting as an agonist at (activating) glycine receptors. (Ericson, 2006)

Another constituent of GREATER REWARDS is quercetin, a flavonoid found in many plants. It has been shown to possibly inhibit COMT. (Singh, 2003; Nagai, 2004)

We’ve also added lithium. In the low concentrations found in drinking water and in some mineral waters, lithium has a protective effect against suicide and reduces the number of arrests for robbery, burglary, and theft, suggesting that it can help decrease impulsivity. “…the antisuicidal effects of lithium may work at lower levels than so-called therapeutic levels and not only in patients with mood disorders but also in the general population.” (Schrauzer, 1990; Terao, 2009)

We’ve also added hesperidin, a flavonoid widely found in fruits and vegetables for its ability to promote neurogenesis by enhancing the survival of neural progenitors that are developing into mature neurons. (Nones, 2012)

References

Montag et al. The role of the catechol-O-methyltransferase (COMT) gene in personality and related psychopathological disorders. CNS Neurol Disord Drug Targets. 11(3):236-50 (2012).

Zhu et al. Molecular modelling study of the mechanism of high-potency inhibition of human catechol-O-methyltransferase by (-)-epigallocatechin-3-O-gallate. Xenobiotica.38(2):130-46 (2008).

Ericson et al. Taurine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine. Eur J Neurosci. 23:3225-9 (2006).

Singh et al. Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition. Pharmacology. 68:81-8 (2003).

Nagai et al. Strong inhibitory effects of common tea catechins and bioflavonoids on the O-methylation of catechol estrogens catalyzed by human liver cytosolic catechol-O-methyltransferase. Drug Metab Dispos. 32(5):497-504 (2004).

Nones et al. Effect of the flavonoid hesperidin in cerebral cortical progenitors in vitro: indirect action through astrocytes. Int J Dev Neurosci. 30:303-13 (2012).

Schrauzer and Shrestha. Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions. Biol Trace Elem Res. 25:105-113 (1990).

Terao et al. Even very low but sustained lithium intake can prevent suicide in the general population? Med Hypotheses. 73:811-2 (2009).

 

PERSONALITY AND THE 2 GENE 
“REWARD DEFICIENCY SYNDROME”

by Sandy Shaw

Reward deficiency syndrome is the actual name of a psychiatric disorder, in which people do not have as much dopaminergic activity in the brain’s reward circuitry as most other people do. A reduced number of DRD2 dopamine receptors is a way that this can happen.

Some of those who appear to suffer from “reward deficiency syndrome” could be classed as “losers.” Yet, some “losers” are in fact quite successful in material terms, but are simply unable to FEEL good about their material or other successes. A good example could be Ray Charles, who surely must have earned an immense amount of money in his life, yet sung (and possibly wrote) many songs with the theme of being a loser; his “BORN TO LOSE” is a particularly apt example.

The reward deficiency syndrome is characterized by behavior that you can see in many people around you and which now seems to have spread throughout the population of young adults, particularly among men. The most notable features of reward deficiency syndrome can include risk-seeking, novelty seeking, a high risk for addictive, impulsive, and compulsive behavioral propensities such as compulsive shopping, pathological gambling, sexual infidelity and promiscuity, as well as drug addiction, smoking, and often suffering from attention-deficit hyperactivity disorder. (See, for example, Blum, 2008)

The key mechanism behind the reward deficiency syndrome is explained: In individuals possessing an abnormality in the DRD2 dopamine receptor gene, the brain lacks sufficient numbers of dopamine receptor sites to use the normal amount of dopamine in reward centers. (Blum, 2008) What this means is that individuals with this form of the DRD2 gene (and it is far from uncommon, judging from the features of the reward deficiency syndrome as noted in the paragraph above) are driven to “engage in activities that will increase brain dopamine function…” because it is “…the DRD2 gene that makes it difficult for neurons to respond to dopamine, the neurotransmitter that is involved in feelings of pleasure and the regulation of attention.” (Blum, 2008)

Obese individuals have fewer D2 dopamine receptors than lean individuals do. Eating causes a release of dopamine in the dorsal striatum and the amount of dopamine released is correlated with the pleasure of eating. “It has therefore been postulated that obese individuals have hypofunctioning reward circuitry, which leads them to overeat to compensate for a hypofunctioning dopamine reward system.” (Stice, 2008) In order to study striatal dopamine activity, the authors (Stice, 2008) used blood oxygen level-dependent (BOLD) fMRI to identify the areas of the brain activated when the subjects ate either a chocolate milk shake or a “tasteless solution” placebo (water). The results were consistent with the hypothesis that “the dorsal striatum is less responsive to food reward in obese, relative to lean, individuals, potentially because the former have reduced D2 receptor density and compromised dopamine signaling, which may prompt them to overeat in an effort to compensate for this reward deficit.” (Stice, 2008)

References

Stice et al. Relation between obesity and blunted striatal response to food is moderated by Taq1A allele. Science. 322:449-52 (2008).

Blum et al. Attention-deficit-hyperactivity disorder and reward deficiency syndrome. Neuropsychiatr Dis Treat. 4(5):893-917 (2008).

 

REWARD DEFICIENCY SYNDROME AND MULTIPLE ADDICTIONS

A recent paper (Blum, 2011) provides a very extensive overview of the “Reward Deficiency Syndrome” as well as describing the results of a study of the incidence of dopaminergic genes in two families with multiple addictions. A certain variation of the DRD2 gene (Taq1, also called TaqA1) was found in these families, an incidence of 100% in “Family A” (with N=32) and 47.8% in “Family B” (with N=23). As the authors explain, “[t]he DRD2 gene, and especially the Taq1 allele, has been associated with neuropsychiatric disorders in general, including alcoholism, other addictions (e.g. carbohydrate), and it also may be involved in co-morbid antisocial personality disorder symptoms…” and other conditions such as “attention deficit hyperactivity disorder (ADHD) or Tourette Syndrome and high novelty-seeking behavior.”

“Utilizing a Bayesian mathematical model, we have found that at least for carriers of the DRD2 A1 allele, the estimated predictive value [of having the reward deficiency syndrome as a result of having the gene] is 74%.” Meanwhile, Table 3 in the study (pg. 4437) shows the correlation of the reward deficiency syndrome and psychiatric disorders with DRD2, disorders* which include novelty or sensation seeking, pathological gambling, post-traumatic stress disorder excessive eating, extraversion and creativity, hypersexuality, and many others. The authors note that there is a “significantly higher frequency for the DRD2 Taq1A polymorphism among addicts (69.9%) compared to control subjects (42.6%)…”

* Though these conditions are called “disorders,” by the authors, some, such as creativity, may be beneficial when they are not associated with pathology.

Reference

Blum et al. Generational association studies of dopaminergic genes in reward deficiency syndrome (RDS) subjects: selecting appropriate phenotypes for reward dependence behaviors. Int J Environ Res Public Health. 8:4425-59 (2011)

 

THE DRD2 GENE UNEQUIVOCALLY IDENTIFIED AS REGULATING RISKY BEHAVIOR IN RATS

A study of rats published in NATURE (Zalocasky, 2016) provides strong support for the view that DRD2 gene expression in the nucleus accumbens (NAc) is importantly involved in risky behavior such as gambling.

The experiments presented rats with an opportunity to get a sure reward of sugary treats every time or a much larger reward of the same treats (but only 25% of the time) when they pressed a lever. Some of the rats were considered “daredevils” as they kept on going for the big reward even after getting nothing time and time again. Others were cautious and went for the sure reward. Rats with the MOST DRD2 activity were the ones that became very cautious (“chicken”) after a loss (receiving nothing). The daredevil rats had low levels of DRD2 activity and kept on going for the big one.

THRILL SEEKING

People with the syndrome are prone to activities that supply extra stimulation to cause enough dopamine release to provide pleasure, hence, thrill-seeking, the desire to engage in risky, often dangerous activities, such as (for example) skydiving, gambling, using potentially dangerous drugs, and promiscuous unprotected sex. The DRD2 genetic variant has also been associated with aggressive behavior, “which also stimulates the brain’s use of dopamine.” (Blum, 2008)

References

Zalocusky et al. Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making. Nature. 31;531(7596):642-6. doi: 10.1038/nature17400 (2016 Mar).

Blum et al. Attention-deficit-hyperactivity disorder and reward deficiency syndrome. Neuropsychiatr Dis Treat. 4(5):893-917 (2008).

Durk Pearson & Sandy Shaw, sued the FDA in the 1990s for refusing their request to authorize specific health claims for dietary supplements.

FDA regulates both finished dietary supplement products and dietary ingredients

FDA regulates both finished dietary supplement products and dietary ingredients. FDA regulates dietary supplements under a different set of regulations than those covering “conventional” foods and drug products. Under the Dietary Supplement Health and Education Act of 1994 (DSHEA):

  • Manufacturers and distributors of dietary supplements and dietary ingredients are prohibited from marketing products that are adulterated or misbranded.  That means that these firms are responsible for evaluating the safety and labeling of their products before marketing to ensure that they meet all the requirements of DSHEA and FDA regulations.
  • FDA is responsible for taking action against any adulterated or misbranded dietary supplement product after it reaches the market.

This section provides detailed information about:http://www.fda.gov/Food/DietarySupplements/

June 2016 Blog with Durk and Sandy

APPETIZERS

In geological terms, [ ] it is fair to say that the next earthquake in Los Angeles has already started. Prediction moves from a science to an art when you realize that pre-incident indicators are actually part of the incident. 
— Gavin de Becker (from his book Gift Of Fear, Dell Trade Paperback, 1997, pp. 104-105

[D&S comment: True, but it offers no comfort to know that the BIG ONE is already started…]

Never attribute to malice that which can be adequately explained by stupidity, but don’t rule out malice.
— Robert A. Heinlein

DO WHAT YOU TELL YOURSELF TO DO AND DON’T TAKE NO FOR AN ANSWER. 
— Stephen F. Kaufman, author

The Way of The Modern Warrior, title of chapter 43 … “Tu ne cede malis, sed contra audentieor ito.” (TRANSLATION FROM THE LATIN: Do not give in to evil but proceed ever more boldly against it.)
— motto of the Ludwig von Mises Institute

I consider that the brain has the most power for man… The eyes and ears and tongue and hands and feet do whatsoever the brain determines … it is the brain that is the messenger to the understanding [and] the brain that interprets the understanding. 
— Hippocrates

I would rather have questions that can’t be answered than answers that can’t be questioned.
— Richard Feynman

[D&S Comment: This reminds us of “The science is settled” that is supposed to be the answer (according to some) to any possible question of climate change.]

 

KETONES PART II

The birth of the ketogenic diet

IF YOU PLAN TO TAKE C-8 MCT OIL… BE SURE TO TAKE IT WITH FOOD.

Your brain on ketones: the aging brain is highly dependent on ketones for energy—when it can’t get enough

Brain connections depend upon white matter: the search for the lost connections

AUTOIMMUNITY: causes neuroinflammation to the brain’s astrocytes, damaging myelin and impairing memory

The aging female brain is particularly susceptible to white matter catabolism

Another major risk factor for white matter cannibalization is the apoE4 allele

Why the high fat, low carbohydrate diet is ketogenic

Exercise reduces anxiety by altering fatty acids in the brain

The Birth of Neurogenesis

Hesperidin Protects Newborn Neurons From Culling

Voluntary Running And Neurogenesis

Constituent Of Turmeric Induces Neural Stem Cell Proliferation In Vivo

EGCG Increases Neurogenesis In Adult Mice And Increases Neural Stem Cells In Areas Of Brain Damage

Fluoxetine Makes New Neurons Grow Faster

Increased Gray Matter In Brain Of People Who Learn To Juggle

Fear Reduced By Ketone Body Supplementation Threat: Escape from a predator (with a little help from C-8 MCT Oil)

Sex Hormones on the trading floor

Grapefruit juice may be hazardous to your health, but not necessarily for the reason you think

Quick Bits

When It’s Just On The Tip Of Your Tongue

References

KETONES: THE NEW FAST ENERGY REVOLUTION
PART II

Contents of PART I of this series for those who didn’t read it:

  1. Medium chain triglycerides and ketones derived from MCTs
  2. Ketones and the ketogenic diet
  3. How ketones protect myelinated nerve tracts in the brain, necessary for brain areas to get connected to each other
  4. Neurodegenerative diseases of aging are associated with damage to myelinated nerve tracts
  5. Maintaining a healthy weight with ketones from C-8 MCT OIL; a ketone supplemented diet may increase levels of brown fat
  6. Ketones can mimic the effects of insulin, helping to maintain healthy blood sugar levels
  7. Best of all: How to benefit from a ketogenic diet (high fat, low carbohydrate) without having to limit your intake of carbohydrates. We repeat this section of PART I just below because it is so important in understanding why you can benefit from ketones without having to limit your carbohydrate intake, a very major difference from the ketogenic low-carb diet.

How to Benefit from a Ketogenic High-Fat Diet Without Having to Limit Carbohydrates or Raise LDL

THE C-8 SOLUTION

It is possible to enter a state of mild ketosis, where you attain a level of ketones adequate to give you the beneficial effects of a ketogenic diet, without having to cut your carbohydrate intake, if you ingest adequate quantities of the C8:0 medium chain triglyceride (1,2,3-propanetriol trioctanoate), a common food ingredient made from glycerin and fatty acids from coconut oil. (Henderson, 2009) Another paper (Hashim, 2014) noted: “When administered orally in controlled dosages, these esters [of ketone bodies] can produce plasma KB [ketone bodies] levels comparable to those achieved by the most rigorous KD [ketogenic diet], thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD [Alzheimer’s disease], and Parkinson’s disease.”

IF YOU PLAN TO TAKE C-8 MCT OIL …
TAKE C-8 MCT OIL WITH FOOD
TO AVOID POSSIBLE GASTROINTESTINAL UPSET
While the benefits of ketone supplementation can be quite considerable, like many foods and nutrient supplements you can experience gastrointestinal discomfort when you take too much or too fast. You should take your C-8 MCT OIL along with food to prevent this. First, start with 1 teaspoon per meal for a few days. Then, increase your serving size to 1 tablespoon per meal. Finally, we suggest you then drink an ounce of the oil from a shot glass once with a meal.

The reason for the stomachache, when it occurs, is that the C-8 MCT OIL is rapidly hydrolyzed to free fatty acids and the eight carbon backbone fatty acid (octanoic acid, also called caprylic acid), which is the main component of the C-8 MCT OIL, can cause irritation. This is perfectly natural and can be avoided by taking it with food and gradually increasing your serving size.

“…a woman’s chance of developing AD [Alzheimer’s disease] is now greater than her chance of developing breast cancer.”

— from David E. Bredesen. Reversal of cognitive decline: A novel therapeutic program. Aging. 6(9):707-17 (2014).

In a 90 day randomized, double blind, placebo controlled study of Alzheimer’s patients with mild to moderate symptomology (Henderson, 2009), the C8:0 MCT described in the paragraph above (which was called AC-1202) had a significantly improved cognition score compared to placebo (but only for those who did not have an apoE4 allele). There was no difference detected for those who had that allele. However, see next paragraph.

In a very recent paper (Newport, 2015), a case history of a single patient who had developed severe Alzheimer’s disease (he had difficulty finding his way around his own house, for example) and was treated with beta-hydroxybutyrate, a ketone made by the liver during fasting or on a ketogenic diet, was described. The patient had an apoE4 allele but had very significantly improved cognitive abilities on the ketone. The authors of this paper (Newport, 2015) suggest that the Henderson study (Henderson, 2009) that found no statistically significant improvement in cognition in patients with mild to moderate cognitive dysfunction who also had an apoE4 allele, might have come about because of a lack of statistical power to detect changes in those with the allele or that improvement might have been seen if studied for a longer period of time and/or at a higher dose of ketone treatment.

“In patients with Alzheimer’s disease, administration of medium-chain triglycerides [MCT] improved memory and the degree of improvement correlated with blood levels of BETA-HYDROXYBUTYRATE. (Emphasis added.) Further, direct application of beta-hydroxybutyrate protected cultured hippocampal neurons against Abeta [amyloid beta] toxicity. Finally, exogenous administration of either beta-hydroxybutyrate or acetoacetate reduced neuronal loss and improved neuronal function in animal models of hypoxia, hypoglycemia, and focal ischemia.” (Emphasis added) (Maalouf, 2009)

A 2015 review paper (Morrone, 2015) noted that “[t]he ketogenic diet aims to create a state of fasting within the body. This reduces metabolic induced stresses, including damage from reactive oxidative species and pathogenic mitochondrial biogenesis. Ketogenic diets may also decrease the production of advanced glycation end products, which accumulate on Abeta [amyloid beta] plaques, potentially assisting in one of the aforementioned clearance cascades by decreasing reuptake of Abeta by RAGE [the advanced glycation endproduct receptor].”

You may not be familiar with a ketogenic diet and, therefore, not realize how substantial the benefits of such a diet can be. Some of these benefits are quite remarkable.

The Birth of the Ketogenic Diet

There was an apparent Biblical reference to a diet of this type (Paoli, 2013) in the story of a cured epileptic (The New Testament, Matthew 17:14-21). The ketogenic diet has been known in more modern times since 1863, when William Banting (the discoverer of insulin) found that he could treat his own obesity with a low carbohydrate diet. He published the story of his recovery from obesity in the 1863 monograph “Letter on Corpulence.” Severe childhood epilepsy was treated with a low carbohydrate (ketogenic) diet in the 1920’s but it wasn’t until the 1970’s, with the appearance of the Atkins’ diet, that use of a high fat low carbohydrate diet, in this case to lose weight, became popular. But, as we will show later in this paper, it is possible to enter a state of mild ketosis WITHOUT reducing dietary carbohydrates.

A study was published (Westman, 2008) in which an Atkins-style ketogenic diet (high fat, low carbohydrate) was found to be superior in maintaining glycemic control (in subjects with type 2 diabetes) as compared to a low-glycemic index diet.

YOUR BRAIN ON KETONES
THE AGING BRAIN IS HIGHLY DEPENDENT
ON KETONES FOR ENERGY
WHEN IT CAN’T GET ENOUGH

Imagine this: As your brain ages, it becomes unable to get all the energy it needs from glucose and as time goes on it needs to obtain more and more of its energy from ketones. The horrifying part of this process is that the liver, as IT ages, becomes unable to supply enough ketone bodies to the brain and the brain cannibalizes some of its own lipids in order to generate ketones. The lipids that it uses to make ketones have been identified as being found in WHITE MATTER (Klosinski, 2015), in which myelin coats and insulates neurons, enabling different brain areas to become connected to each other. The loss of these connections is a major degenerative process involved in ALZHEIMER’S DISEASE (AD) and also occurs in aging. Sandy hypothesized in an earlier Durk & Sandy newsletter that the loss of connections to where memories are located is the reason for the failure of memory processes, rather than the loss of memories themselves.

Researchers have studied the switch to ketones from glucose as a fuel in the brain of patients with early AD, concluding that the observed loss of white matter integrity could be a result of the switch from glucose as a fuel to that of fats. The ketones derived from the fats that would be supplied by the liver may have to be obtained by the brain from digesting its own myelin (degrading the white matter). Importantly, the loss of white matter takes place when the brain begins to digest its own myelin but not when the brain is supplied by supplemental (exogenous) ketones. The loss of white matter that occurs when the brain switches from the use of glucose to INTERNALLY obtained (not supplemental) ketone bodies is clearly a disaster, the brain cannibalizing itself for fuel and doing immense harm in the process. Nevertheless, “[t]he catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand.” (Klosinski, 2015)

GRAY MATTER IS MYELINATED, TOO

We were surprised to read in a 2012 paper (Bartzokis, 2012) that “[w]hile most think of myelin as a component of white matter, in humans, gray matter is also extensively myelinated [ ] and the key role of this intracortical myelin (ICM) component in optimizing brain function have generally been overlooked.” The extensive myelination of the human brain, exceptionally so compared to other species, imposes a very large metabolic demand (the procurement of energy). (Bartzokis, 2012)

BRAIN CONNECTIONS DEPEND UPON WHITE MATTER, MYELINATED NERVE TRACTS IN THE BRAIN

The loss of white matter, and the resulting loss of myelinated neuronal tracts that are necessary for access to memories, may play a major role in ALZHEIMER’S DISEASE. One way to help prevent this loss would be to supply ketone bodies that the brain would otherwise get by the degradation of myelin in white matter.

AUTOIMMUNE ATTACK AS A SOURCE OF DAMAGE TO MYELIN AND SUBSEQUENT MEMORY IMPAIRMENT

“…invading autoreactive periphral immune cells destroy myelin, the lipid insulation around neuronal axons that facilitates rapid action potential propagation.” (Osso, 2015) The neuroinflammation that results when the autoreactive immune cells invade the brain is caused by excessive release of tumor necrosis factor alpha (TNF-alpha), a major inflammatory cytokine.

A recent paper (Habbas, 2015) shows that TNF-alpha is indeed causative in the observed demyelination.

The Aging Female Brain is Particularly Susceptible to White Matter Catabolism

Klosinski, 2015 also explains that the loss of estrogen accompanying menopause is an additional risk factor for loss of white matter. “[l]oss of estrogenic control of glucose metabolism in brain during menopause can lead to decreased glucose utilization, diminished aerobic glycolysis and altered oxidative phosphorylation, which together generates a hypometabolic phenotype.”

Another Major Risk Factor for White Matter
Cannibalization is the apoE4 Allele

“The main modulator of induced ketosis appears to be the carriage status of APOE4 [whether an individual has the APOE4 allele, either one or two of them]. It may not be a coincidence that APOE4 is also the major genetic risk factor for late onset AD [Alzheimer’s disease]. The failure of APOE4 carriers to respond to ketosis may indicate a more insidious metabolic problem. APOE4 carriers may be over reliant on glucose and, hence, over a lifetime, cerebral neurons are deprived of the metabolic advantages conferred by ketone body metabolism and this may be crucial to etiology of AD.” (Henderson and Poirier, 2011)

Why the High Fat, Low Carbohydrate Diet is Ketogenic

Any excess glucose beyond that required for immediate use as energy is converted via lipogenesis into fat and is stored. Either dietary or stored fat can fuel cellular respiration using ketone bodies (a byproduct of the breakdown of fatty acids mostly in the liver.)

After glucose or glycogen (stored glucose) are depleted, the switch to fats for energy begins. It may start when carbohydrate consumption falls below 50-60 g/day. However, as we explain below, it is possible to induce a state of mild ketosis without a change in diet, which is a great relief because for most people restricting their intake of carbohydrates to 50 to 60 grams a day is very difficult to impossible on an ongoing basis. Just to give you an example of the carbohydrate content of foods you don’t even think of as carbohydrate-rich, there are 31 grams of carbohydrates in 100 grams of cooked pasta, which may be considered a low- or medium-glycemic index food, and 7 grams of carbohydrate in 100 grams of raw broccoli.

The characteristic sweet smell of the breath of uncontrolled diabetes is acetone, one of the ketones produced in diabetics who are unable to metabolize carbohydrates and must use other fuels, in this case ketones.

[END OF MCT PART]

References

  • Neuropharmacology: myelination as a shared mechanism of action of psychotropic treatments.Neuropharmacology. 62(7):2137-53 (2012).
  • Coates and Herbert. Endogenous steroids and financial risk taking on a London trading floor. Proc Natl Acad Sci U S A. 105(16):6167-72 (2008).
  • Draganski, Gaser, et al. Changes in grey matter induced by training. 427:311-312 (2004).
  • Change in the brain’s white matter. Science.330:768-769 (2010).
  • Fuhr et al. Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br J Clin Pharmacol.35:431-6 (1993).
  • Habbas, Santello et al, Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling. 163:1730-41 (2015).
  • Hashim and VanItallie. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester.J Lipid Res. 55:1818-26 (2014).
  • Hen et al. J Neurosci. Feb. 6, 2008 (as reported in Science News, 9, 2008 (p. 83)
  • Henderson et al. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond).6:31 (2009).
  • Henderson and Poirier. Pharmacologic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mind to moderate Alzheimer’s disease; a randomized, double-blind, placebo-controlled study. BMC Med Genet. 12:137 (2011).
  • Hucklenbroich, Klein, et al. Aromatic turmerone induces neural stem cell proliferation in vitro and in vivo. Stem Cell Res Ther.5:100 (2014).
  • Itoh, Imano, et al. (-)-Epigallocatechin-3-gallate increases the number of neural stem cells around the damaged area after rat traumatic brain injury.J Neural Transm. 119:877-90 (2012).
  • Kempermann, Kuhn, and Gage. Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci.18(9):3206-12 (1998).
  • Klosinski et al. White matter lipids as a ketogenic fuel supply in aging female brain: implications for Alzheimer’s disease.2:1888-904 (2015).
  • Maalouf et al. The neuroprotective properties of caloric restriction, the ketogenic diet, and ketone bodies. Brain Res Rev. 59(2):293-315 (2009).
  • Mobbs, Petrovic, et al. When fear is near: Threat imminence elicits prefrontal-periaqueductal gray shifts in humans. 317(5841):1079-83 (2007).
  • Morrone et al. Interaction between therapeutic interventions for Alzheimer’s disease and physiological Abeta clearance mechanisms.Front Aging Neurosci. 7 (article 64), (2015).
  • Naylor, Bull, et al. Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. Proc Natl Acad Sci U S A.105(38):14632-7 (2008).
  • Newport et al. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer’s. Alzheimers Dement.11(1):99-103 (2015).
  • Osso and Chan. Astrocytes underlie neuroinflammatory memory impairment. 163:1574-6 (2015).
  • Paoli et al. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr.67:789-96 (2013).
  • Santos-Soto et al. Voluntary running in young adult mice reduces anxiety-like behavior and increases the accumulation of bioactive lipids in the cerebral cortex. PLoS ONE.8(12):e81459 (2013).
  • Westman et al. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab (Lond). 5:36 (2008).
  • Yoo, Choi, et al. (-)-Epigallocatechin-3-gallate increases cell proliferation and neuroblasts in the subgranular zone of the dentate gyrus in adult mice. Phytother Res.24:1065-70 (2010).

 

THE BIRTH OF NEUROGENESIS

It may seem a long time that you’ve been reading about neurogenesis, the process whereby new neurons are created in the adult brain, but it is an amazingly few years—a little less than 20 years—since the first papers with direct evidence of neurogenesis began to appear on this subject. At the time, it was considered quite controversial, whereas now it is well established and the subject of some 41,962 papers in the literature as of today, May 14, 2016. For example, one of the earliest papers demonstrating that an enriched environment would result in the creation of new neurons in the adult brain (of mice) was published in 1998. “Neurogenesis was a hard thing for scientists to come to grips with,” said Fred Gage, a scientist at the time at the Salk Institute, who was a very early pioneer in the experimental work establishing neurogenesis. (Schwartz, 2002)

Later work was published showing that neurogenesis didn’t occur just in mice, but in humans as well. It came as quite a surprise to scientists, with its promise of improved cognition in both young and old.

These days, we are seeing ever more publications on ways to enhance neurogenesis, including a small number involving the use of nutrients or herbs that are safe and readily available. For instance, in one study (Tian, 2012), mice were lesioned with the neurotoxin 6-OHDA (6-hydroxydopamine), damaging and killing dopaminergic neurons. They were implanted with dopaminergic neurons and treated (or not) with sodium selenite. “The expression level of TNF-alpha [tumor necrosis factor alpha, an inflammatory cytokine] and iNOS [inducible nitric oxide synthase, an inflammatory factor] were decreased by 30% and 50%, respectively, in selenite treated group. The survival of implanted DA [dopamine] neurons and the rotational behavior of transplanted rats were also remarkably improved by selenite treatment.” Another paper (Molina-Holgado, 2007) reported that the expression of CB2 (cannabinoid receptor 2) promoted the proliferation of mouse neural stem cells. Activators of CB2 are found in a typical diet and include caryophyllene, a common constitutient of many culinary herbs (cloves, caraway, hops, basil, rosemary, cinnamon), and fruits and vegetables.

Another nutrient that has been found to enhance the numbers of newborn neurons and to protect them from the culling process that kills most newborn neurons is hesperidin. (Pathak, 2013) Hesperidin is a flavonone glycoside found abundantly in citrus fruits. It has a variety of protective properties including decreasing the permeability of capillaries, helping to prevent easy bruising. “Another study has shown the involvement of kappa opioidergic receptors in the antidepressant-like effect of hesperidin.” “Hesperidin seems to be a viable candidate for the treatment of major depression.” (Pathak, 2013) Our LITHIUM PLUS™ is one source of hesperidin.

VOLUNTARY RUNNING AND NEUROGENESIS

A potential benefit of voluntary running was described in a 2008 paper (Naylor, 2008). Young mice were exposed to radiation and then, after eight weeks, allowed to run freely in a running wheel. Though there was no difference in the distance the animals ran as compared to nonirradiated mice, the authors reported: “Voluntary running significantly restored precursor cell and neurogenesis levels after a clinically relevant, moderate dose of irradiation.” “Interestingly, voluntary running significantly increased the number of stem cells after irradiation…” (Naylor, 2008)

This particular study did not examine whether FORCED running would have similar effects (see Santos-Soto, 2013, described in the section above, where the anxiety reducing effects of voluntary running were not duplicated in animals subject to forced, rather than voluntary, running. This points to the complexity of brain processing. It isn’t just the motor activity that produces the beneficial effects, but other areas of the brain associated with the recognition of coercion also help determine how the motor information is interpreted and which biochemical pathways are then activated.

References

  • Neuropharmacology: myelination as a shared mechanism of action of psychotropic treatments.Neuropharmacology. 62(7):2137-53 (2012).
  • Coates and Herbert. Endogenous steroids and financial risk taking on a London trading floor. Proc Natl Acad Sci U S A. 105(16):6167-72 (2008).
  • Draganski, Gaser, et al. Changes in grey matter induced by training. 427:311-312 (2004).
  • Change in the brain’s white matter. Science.330:768-769 (2010).
  • Fuhr et al. Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br J Clin Pharmacol.35:431-6 (1993).
  • Habbas, Santello et al, Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling. 163:1730-41 (2015).
  • Hashim and VanItallie. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester.J Lipid Res. 55:1818-26 (2014).
  • Hen et al. J Neurosci. Feb. 6, 2008 (as reported in Science News, 9, 2008 (p. 83)
  • Henderson et al. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond).6:31 (2009).
  • Henderson and Poirier. Pharmacologic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mind to moderate Alzheimer’s disease; a randomized, double-blind, placebo-controlled study. BMC Med Genet. 12:137 (2011).
  • Hucklenbroich, Klein, et al. Aromatic turmerone induces neural stem cell proliferation in vitro and in vivo. Stem Cell Res Ther.5:100 (2014).
  • Itoh, Imano, et al. (-)-Epigallocatechin-3-gallate increases the number of neural stem cells around the damaged area after rat traumatic brain injury.J Neural Transm. 119:877-90 (2012).
  • Kempermann, Kuhn, and Gage. Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci.18(9):3206-12 (1998).
  • Klosinski et al. White matter lipids as a ketogenic fuel supply in aging female brain: implications for Alzheimer’s disease.2:1888-904 (2015).
  • Maalouf et al. The neuroprotective properties of caloric restriction, the ketogenic diet, and ketone bodies. Brain Res Rev. 59(2):293-315 (2009).
  • Mobbs, Petrovic, et al. When fear is near: Threat imminence elicits prefrontal-periaqueductal gray shifts in humans. 317(5841):1079-83 (2007).
  • Morrone et al. Interaction between therapeutic interventions for Alzheimer’s disease and physiological Abeta clearance mechanisms.Front Aging Neurosci. 7 (article 64), (2015).
  • Naylor, Bull, et al. Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. Proc Natl Acad Sci U S A.105(38):14632-7 (2008).
  • Newport et al. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer’s. Alzheimers Dement.11(1):99-103 (2015).
  • Osso and Chan. Astrocytes underlie neuroinflammatory memory impairment. 163:1574-6 (2015).
  • Paoli et al. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr.67:789-96 (2013).
  • Santos-Soto et al. Voluntary running in young adult mice reduces anxiety-like behavior and increases the accumulation of bioactive lipids in the cerebral cortex. PLoS ONE.8(12):e81459 (2013).
  • Westman et al. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab (Lond). 5:36 (2008).
  • Yoo, Choi, et al. (-)-Epigallocatechin-3-gallate increases cell proliferation and neuroblasts in the subgranular zone of the dentate gyrus in adult mice. Phytother Res.24:1065-70 (2010).

 

TURMERONE (CONSTITUENT OF TURMERIC ROOT) INDUCES NEURAL STEM CELL PROLIFERATION IN VIVO

There are other constituents of turmeric root that have beneficial effects besides CURCUMIN. That’s why we take a supplement of the whole turmeric root (in encapsulated powdered form). One of the other bioactive constituents is turmerone. “Curcumin and ar-turmerone [aromatic turmerone] are the major bioactive compounds of the herb Curcuma longa [turmeric].” (Hucklenbroich, 2014) Turmerone has not been studied nearly as extensively as curcumin, but the evidence to date supports antitumor and antiinflammatory properties against the inflammation associated with neurodegenerative diseases. A recent paper (Hucklenbroich, 2014) provides evidence that turmerone can induce neural stem cell proliferation in vivo.

Neural stem cells (NSC) are mobilized for regenerative processes when brain injury takes place, such as that caused by stroke, ischemia (deficient oxygen availability), or neurological disorders.

Fetal rats were given various doses of turmerone (ar-turmerone) and the effects on the proliferation of NSC (part of the neurogenesis process) determined in vitro as well as in vivo. “Both in vitro and in vivo data suggest that ar-turmerone induces NSC proliferation. Ar-turmerone thus constitutes a promising candidate to support regeneration in neurologic disease.” (Hucklenbroich, 2014)

An article by Will Block containing much more information on turmerone was published in the March 2015 issue of Life Enhancement magazine, pp. 11-13.

EGCG INCREASES NEUROGENESIS IN ADULT MICE

In another study of neurogenesis, adult mice were treated with EGCG (epigallocatechin gallate, the major bioactive constituent of green tea) for four weeks and then their brains were examined for cell proliferation in the subgranular zone of the dentate gyrus of the hippocampus. The hippocampus is one of the areas of the brain most vulnerable to damage. Hence, the ability to produce new cells for repair is highly beneficial and, importantly, these new cells can migrate to other areas of the brain. (Yoo, 2009)

The results showed that oral administration of EGCG increased the number of new cells in the dentate gyrus of the hippocampus in adult mice. We take EGCG in the form of our Green Tea Booster EGCG Capsules.

EGCG INCREASES THE NUMBER OF NEURAL STEM CELLS IN AREAS OF DAMAGED BRAIN

Another paper (Itoh, 2012) reported that EGCG increased the number of neural stem cells in the damaged area of rat brain after traumatic injury.

THE SSRI (SELECTIVE SEROTONIN REUPTAKE INHIBITOR) DRUG FLUOXETINE MAKES NEW NEURONS GROW FASTER

Fluoxetine (PROZAC®) is one of a large class of antidepressant drugs known as selective serotonin reuptake inhibitors (SSRIs), because it inhibits the reuptake of serotonin from neuronal synapses to the vesicles where it is stored for reuse. By inhibiting its reuptake, though, the drug keeps serotonin in the synapes, so that its signal is prolonged.

Fluoxetine (and some other SSRIs) have interesting effects besides prolonging the serotonin signal in the neuronal synapse. A 2008 paper (Hen, 2008) reported that fluoxetine increased the number of newborn neurons and, in addition, it caused these newborn neurons to grow more branch-like extensions called dendrites than cells not treated with fluoxetine. The extensions connect the neurons to other neurons and form networks.

SSRIs have been associated with rare incidents of impulsive violent events such as school shootings. The likely reason for this is that, because tryptophan is used to make serotonin and serotonin in the synapse is destroyed (unless it is taken back into the storage vesicles), a deficiency of tryptophan can occur in those taking SSRIs and who do not consume enough tryptophan in their diet. It is well known that tryptophan deficiency can result in increased impulsivity, including violent impulsivity (against others or self, even including suicide). So, if you want to try an SSRI, be sure to take a tryptophan supplement along with it. Some people do not have adequate quantities of tryptophan hydroxylase that converts tryptophan to 5-hydroxytryptophan in the conversion pathway to serotonin; for those people, a supplement of 5-HTP (5-hydroxytryptophan) is a good idea.

References

  • Neuropharmacology: myelination as a shared mechanism of action of psychotropic treatments.Neuropharmacology. 62(7):2137-53 (2012).
  • Coates and Herbert. Endogenous steroids and financial risk taking on a London trading floor. Proc Natl Acad Sci U S A. 105(16):6167-72 (2008).
  • Draganski, Gaser, et al. Changes in grey matter induced by training. 427:311-312 (2004).
  • Change in the brain’s white matter. Science.330:768-769 (2010).
  • Fuhr et al. Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br J Clin Pharmacol.35:431-6 (1993).
  • Habbas, Santello et al, Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling. 163:1730-41 (2015).
  • Hashim and VanItallie. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester.J Lipid Res. 55:1818-26 (2014).
  • Hen et al. J Neurosci. Feb. 6, 2008 (as reported in Science News, 9, 2008 (p. 83)
  • Henderson et al. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond).6:31 (2009).
  • Henderson and Poirier. Pharmacologic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mind to moderate Alzheimer’s disease; a randomized, double-blind, placebo-controlled study. BMC Med Genet. 12:137 (2011).
  • Hucklenbroich, Klein, et al. Aromatic turmerone induces neural stem cell proliferation in vitro and in vivo. Stem Cell Res Ther.5:100 (2014).
  • Itoh, Imano, et al. (-)-Epigallocatechin-3-gallate increases the number of neural stem cells around the damaged area after rat traumatic brain injury.J Neural Transm. 119:877-90 (2012).
  • Kempermann, Kuhn, and Gage. Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci.18(9):3206-12 (1998).
  • Klosinski et al. White matter lipids as a ketogenic fuel supply in aging female brain: implications for Alzheimer’s disease.2:1888-904 (2015).
  • Maalouf et al. The neuroprotective properties of caloric restriction, the ketogenic diet, and ketone bodies. Brain Res Rev. 59(2):293-315 (2009).
  • Mobbs, Petrovic, et al. When fear is near: Threat imminence elicits prefrontal-periaqueductal gray shifts in humans. 317(5841):1079-83 (2007).
  • Morrone et al. Interaction between therapeutic interventions for Alzheimer’s disease and physiological Abeta clearance mechanisms.Front Aging Neurosci. 7 (article 64), (2015).
  • Naylor, Bull, et al. Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. Proc Natl Acad Sci U S A.105(38):14632-7 (2008).
  • Newport et al. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer’s. Alzheimers Dement.11(1):99-103 (2015).
  • Osso and Chan. Astrocytes underlie neuroinflammatory memory impairment. 163:1574-6 (2015).
  • Paoli et al. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr.67:789-96 (2013).
  • Santos-Soto et al. Voluntary running in young adult mice reduces anxiety-like behavior and increases the accumulation of bioactive lipids in the cerebral cortex. PLoS ONE.8(12):e81459 (2013).
  • Westman et al. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab (Lond). 5:36 (2008).
  • Yoo, Choi, et al. (-)-Epigallocatechin-3-gallate increases cell proliferation and neuroblasts in the subgranular zone of the dentate gyrus in adult mice. Phytother Res.24:1065-70 (2010).

 

INCREASED GRAY MATTER IN THE BRAIN IN PEOPLE WHO LEARN TO JUGGLE

Probably any type of motor training would do it (maybe even golf), but a 2004 study (Draganski, 2004) of individuals learning from being rank amateurs to proficient jugglers (sustained juggling of 3 balls for 60 seconds) discovered increased gray matter in their brains by MRI. Gray matter is composed of myelinated neurons (as is the more well known myelinated white matter). Myelinated brain tracts are critical for connecting brain areas with each other and they are very susceptible to damage, with losses observed in aged humans.

The researchers reported a close relationship between the areas acquiring additional gray matter and the juggling performance.

An article in SCIENCE (Fields, 2010) also discussed the effects of juggling. Referring to a paper (Scholz, 2009), the author described the results as showing “increased white matter structural organization in a brain region important for visuo-motor control 6 weeks after learning to juggle.” He explains that the ability to form new myelin-forming oligodendrocytes “parallels the normal decline in human cognition and decrease in white matter volume after the age of 50.” He further notes that the loss of white matter correlates with the lower results of IQ tests as well as “certain psychiatric conditions” (such as schizophrenia) and suggests that white matter may play a direct role in learning and cognitive function.

References

  • Neuropharmacology: myelination as a shared mechanism of action of psychotropic treatments.Neuropharmacology. 62(7):2137-53 (2012).
  • Coates and Herbert. Endogenous steroids and financial risk taking on a London trading floor. Proc Natl Acad Sci U S A. 105(16):6167-72 (2008).
  • Draganski, Gaser, et al. Changes in grey matter induced by training. 427:311-312 (2004).
  • Change in the brain’s white matter. Science.330:768-769 (2010).
  • Fuhr et al. Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br J Clin Pharmacol.35:431-6 (1993).
  • Habbas, Santello et al, Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling. 163:1730-41 (2015).
  • Hashim and VanItallie. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester.J Lipid Res. 55:1818-26 (2014).
  • Hen et al. J Neurosci. Feb. 6, 2008 (as reported in Science News, 9, 2008 (p. 83)
  • Henderson et al. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond).6:31 (2009).
  • Henderson and Poirier. Pharmacologic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mind to moderate Alzheimer’s disease; a randomized, double-blind, placebo-controlled study. BMC Med Genet. 12:137 (2011).
  • Hucklenbroich, Klein, et al. Aromatic turmerone induces neural stem cell proliferation in vitro and in vivo. Stem Cell Res Ther.5:100 (2014).
  • Itoh, Imano, et al. (-)-Epigallocatechin-3-gallate increases the number of neural stem cells around the damaged area after rat traumatic brain injury.J Neural Transm. 119:877-90 (2012).
  • Kempermann, Kuhn, and Gage. Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci.18(9):3206-12 (1998).
  • Klosinski et al. White matter lipids as a ketogenic fuel supply in aging female brain: implications for Alzheimer’s disease.2:1888-904 (2015).
  • Maalouf et al. The neuroprotective properties of caloric restriction, the ketogenic diet, and ketone bodies. Brain Res Rev. 59(2):293-315 (2009).
  • Mobbs, Petrovic, et al. When fear is near: Threat imminence elicits prefrontal-periaqueductal gray shifts in humans. 317(5841):1079-83 (2007).
  • Morrone et al. Interaction between therapeutic interventions for Alzheimer’s disease and physiological Abeta clearance mechanisms.Front Aging Neurosci. 7 (article 64), (2015).
  • Naylor, Bull, et al. Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. Proc Natl Acad Sci U S A.105(38):14632-7 (2008).
  • Newport et al. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer’s. Alzheimers Dement.11(1):99-103 (2015).
  • Osso and Chan. Astrocytes underlie neuroinflammatory memory impairment. 163:1574-6 (2015).
  • Paoli et al. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr.67:789-96 (2013).
  • Santos-Soto et al. Voluntary running in young adult mice reduces anxiety-like behavior and increases the accumulation of bioactive lipids in the cerebral cortex. PLoS ONE.8(12):e81459 (2013).
  • Westman et al. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab (Lond). 5:36 (2008).
  • Yoo, Choi, et al. (-)-Epigallocatechin-3-gallate increases cell proliferation and neuroblasts in the subgranular zone of the dentate gyrus in adult mice. Phytother Res.24:1065-70 (2010).

 

FEAR AMELIORATION BY KETONE BODY SUPPLEMENTATION

Fear can be a debilitating emotion; just think of post-traumatic-stress disorder as an example. Hence, ways to reduce fear are being studied. One little known way is to supplement with ketone bodies, naturally produced during fasting or low carbohydrate diets or from an MCT (medium chain triglyceride) supplement OR by taking them exogenously.

Fear Processed By the Hippocampus and the Amygdala

“The fear-related memory and anxiety manifests, in mice, in freezing behavior. Contextual [in the context of an event] fear is associated with the hippocampal and amygdala neural circuitry, whereas tone-associated fear [where a tone is a cue for an electric shock] is more closely associated with amygdala pathways.” (Kashiwaya, 2014) The amygdala is an area of the brain involved in fear and anxiety, among other things, while the hippocampus is a brain hub for learning and memory.

In a mouse model of Alzheimer’s disease (AD), mice that were fed a ketone body diet exhibited significantly reduced freezing time in response to the tone signifying that the mouse is about to be shocked. Moreover, the mice had a reduced burden of amyloid beta in their brains. The results point to protection against age-associated deterioration of amygdala neurons. (Kashiwaya, 2014)

References

  • Neuropharmacology: myelination as a shared mechanism of action of psychotropic treatments.Neuropharmacology. 62(7):2137-53 (2012).
  • Coates and Herbert. Endogenous steroids and financial risk taking on a London trading floor. Proc Natl Acad Sci U S A. 105(16):6167-72 (2008).
  • Draganski, Gaser, et al. Changes in grey matter induced by training. 427:311-312 (2004).
  • Change in the brain’s white matter. Science.330:768-769 (2010).
  • Fuhr et al. Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br J Clin Pharmacol.35:431-6 (1993).
  • Habbas, Santello et al, Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling. 163:1730-41 (2015).
  • Hashim and VanItallie. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester.J Lipid Res. 55:1818-26 (2014).
  • Hen et al. J Neurosci. Feb. 6, 2008 (as reported in Science News, 9, 2008 (p. 83)
  • Henderson et al. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond).6:31 (2009).
  • Henderson and Poirier. Pharmacologic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mind to moderate Alzheimer’s disease; a randomized, double-blind, placebo-controlled study. BMC Med Genet. 12:137 (2011).
  • Hucklenbroich, Klein, et al. Aromatic turmerone induces neural stem cell proliferation in vitro and in vivo. Stem Cell Res Ther.5:100 (2014).
  • Itoh, Imano, et al. (-)-Epigallocatechin-3-gallate increases the number of neural stem cells around the damaged area after rat traumatic brain injury.J Neural Transm. 119:877-90 (2012).
  • Kempermann, Kuhn, and Gage. Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci.18(9):3206-12 (1998).
  • Klosinski et al. White matter lipids as a ketogenic fuel supply in aging female brain: implications for Alzheimer’s disease.2:1888-904 (2015).
  • Maalouf et al. The neuroprotective properties of caloric restriction, the ketogenic diet, and ketone bodies. Brain Res Rev. 59(2):293-315 (2009).
  • Mobbs, Petrovic, et al. When fear is near: Threat imminence elicits prefrontal-periaqueductal gray shifts in humans. 317(5841):1079-83 (2007).
  • Morrone et al. Interaction between therapeutic interventions for Alzheimer’s disease and physiological Abeta clearance mechanisms.Front Aging Neurosci. 7 (article 64), (2015).
  • Naylor, Bull, et al. Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. Proc Natl Acad Sci U S A.105(38):14632-7 (2008).
  • Newport et al. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer’s. Alzheimers Dement.11(1):99-103 (2015).
  • Osso and Chan. Astrocytes underlie neuroinflammatory memory impairment. 163:1574-6 (2015).
  • Paoli et al. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr.67:789-96 (2013).
  • Santos-Soto et al. Voluntary running in young adult mice reduces anxiety-like behavior and increases the accumulation of bioactive lipids in the cerebral cortex. PLoS ONE.8(12):e81459 (2013).
  • Westman et al. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab (Lond). 5:36 (2008).
  • Yoo, Choi, et al. (-)-Epigallocatechin-3-gallate increases cell proliferation and neuroblasts in the subgranular zone of the dentate gyrus in adult mice. Phytother Res.24:1065-70 (2010).

 

THREAT
CHASED BY A VIRTUAL PREDATOR,
HOW SCARY CAN IT BE?
C-8 MCT OIL
WHEN FEAR IS NEAR

Imagine this: As your brain ages, it becomes unable to get all the energy it needs from glucose and as time goes on it needs to obtain more and more of its energy from ketones. The horrifying part of this process is that the liver, as IT ages, becomes unable to supply enough ketone bodies to the brain and the brain cannibalizes some of its own lipids in order to generate ketones. The lipids that it uses to make ketones have been identified as being found in WHITE MATTER (Klosinski, 2015), in which myelin coats neurons, enabling different brain areas to become connected to each other. The loss of these connections is a major degenerative process involved in ALZHEIMER’S DISEASE (AD) and also occurs in aging.

The results of losing parts of the myelin sheath are dire. Your cognitive processes become slower and, worse yet, that process whereby the brain has to STEAL fats from the myelin sheath to make ketones, causes you to lose IQ POINTS.

Of course, a predator can get “closer” in time as well as in distance and this experiment we describe here is about a predator chasing an experimental subject through a virtual maze to get closer and closer and, then, actually has the ability to administer pain (via shocks, at a low level of one shock or a high level of three shocks (and, yes, they really hurt). Though the predator is merely a computer program, not a real animal, the reality of the pain makes this a very serious game that gives a clear picture of how the brain faces real danger.

When danger is imminent, your brain swings into high gear, engaging one area after another that alert you to that danger and then plan how to get you out of it. But as you age, you become slower because of the loss of the myelin sheath that insulates nerves—that myelin sheath increases the speed of information transmission. We know now something about how to keep myelin from being used as an energy source when the brain runs low on glucose. It could, when danger is near, save your life.

PREDATOR CHASES PREY
THE EXPERIMENT

A 2007 paper (Mobbs, 2007) describes an experiment involving human subjects who interacted with a computer program simulating a predator in a maze. They were stalked by the “predator” and the response of brain areas were imaged by fMRI to follow how their brains responded to the “predator” as it became closer and closer. The feature that provided the intensity to the ensuing drama was that the “predator” was designed to chase, capture, and inflict pain because the subjects were at risk of actually receiving painful shocks (one or three), which feel a lot like bites, if they failed to evade their pursuer. The researchers had hypothesized that the brain’s response would encompass three “‘core stages:’ ‘pre-encounter,’ where there is risk in the absence of immediate danger, ‘post encounter,’ where the threat is detected, and ‘circa-strike,’ defined as distal or proximal interaction with the threat stimulus.” “…distal threat elicits activity in the prefrontal cortices, which possibly reflects the complex planning of avoidance strategies…” while, when the threat becomes very close, midbrain structures such as the periaqueductal gray area (PAG) takes control. The PAG is a more ancient brain area that has evolved to control fast reflexive activity, such as fight or flight, under conditions where actual physical injury might occur.

That’s the experiment. Here is how this might look to you as you enter the maze.

You’re in a maze. (Mobbs, 2007) Suddenly, you sense “something” approaching. Your ventromedial prefrontal cortex comes onto alert. What is out there? You rapidly turn the pages of your memory backpages, looking for something you’ve met before. As the “thing” (whatever it is) keeps on moving toward you, your midbrain, including the periaqueductal gray, takes control. The situation has come into dangerous territory now, the territory where fast reactions and automatic solutions are needed, not careful thought and planning. Because you know that this “thing” will inflict pain. That is its mission in life, to track you down and make you feel pain. You grit your teeth as the “thing” makes its move and you are entirely on automatic—time has slowed down, as you wait to see if you’ve made it to safety.

You breathe deeply, feeling relief. You’ve evaded it and all is well, at least for now. You move cautiously through the maze now, alert to more danger, back into ventromedial prefrontal cortex territory again.

You feel fortunate that you have been taking C-8 MCT Oil for weeks now. Perhaps it made the difference.

References

  • Neuropharmacology: myelination as a shared mechanism of action of psychotropic treatments.Neuropharmacology. 62(7):2137-53 (2012).
  • Coates and Herbert. Endogenous steroids and financial risk taking on a London trading floor. Proc Natl Acad Sci U S A. 105(16):6167-72 (2008).
  • Draganski, Gaser, et al. Changes in grey matter induced by training. 427:311-312 (2004).
  • Change in the brain’s white matter. Science.330:768-769 (2010).
  • Fuhr et al. Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br J Clin Pharmacol.35:431-6 (1993).
  • Habbas, Santello et al, Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling. 163:1730-41 (2015).
  • Hashim and VanItallie. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester.J Lipid Res. 55:1818-26 (2014).
  • Hen et al. J Neurosci. Feb. 6, 2008 (as reported in Science News, 9, 2008 (p. 83)
  • Henderson et al. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond).6:31 (2009).
  • Henderson and Poirier. Pharmacologic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mind to moderate Alzheimer’s disease; a randomized, double-blind, placebo-controlled study. BMC Med Genet. 12:137 (2011).
  • Hucklenbroich, Klein, et al. Aromatic turmerone induces neural stem cell proliferation in vitro and in vivo. Stem Cell Res Ther.5:100 (2014).
  • Itoh, Imano, et al. (-)-Epigallocatechin-3-gallate increases the number of neural stem cells around the damaged area after rat traumatic brain injury.J Neural Transm. 119:877-90 (2012).
  • Kempermann, Kuhn, and Gage. Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci.18(9):3206-12 (1998).
  • Klosinski et al. White matter lipids as a ketogenic fuel supply in aging female brain: implications for Alzheimer’s disease.2:1888-904 (2015).
  • Maalouf et al. The neuroprotective properties of caloric restriction, the ketogenic diet, and ketone bodies. Brain Res Rev. 59(2):293-315 (2009).
  • Mobbs, Petrovic, et al. When fear is near: Threat imminence elicits prefrontal-periaqueductal gray shifts in humans. 317(5841):1079-83 (2007).
  • Morrone et al. Interaction between therapeutic interventions for Alzheimer’s disease and physiological Abeta clearance mechanisms.Front Aging Neurosci. 7 (article 64), (2015).
  • Naylor, Bull, et al. Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. Proc Natl Acad Sci U S A.105(38):14632-7 (2008).
  • Newport et al. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer’s. Alzheimers Dement.11(1):99-103 (2015).
  • Osso and Chan. Astrocytes underlie neuroinflammatory memory impairment. 163:1574-6 (2015).
  • Paoli et al. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr.67:789-96 (2013).
  • Santos-Soto et al. Voluntary running in young adult mice reduces anxiety-like behavior and increases the accumulation of bioactive lipids in the cerebral cortex. PLoS ONE.8(12):e81459 (2013).
  • Westman et al. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab (Lond). 5:36 (2008).
  • Yoo, Choi, et al. (-)-Epigallocatechin-3-gallate increases cell proliferation and neuroblasts in the subgranular zone of the dentate gyrus in adult mice. Phytother Res.24:1065-70 (2010).

 

SEX HORMONES ON THE TRADING FLOOR

Here we look at a study (Coates, 2008) of the effects of testosterone on 17 male traders who were actively engaged at buying such things as currency, commodities, bonds, and stocks, etc. (Coates, 2008) The study also examined the effects of the stress hormone cortisol, which was found to be increased by risk, e.g., cortisol levels rose on days when traders were “stressed by an above-average loss.”

A major find of the study was that “a trader’s morning testosterone level predicts his day’s profitability.” (Coates, 2008)

The paper explains the significance of testosterone as a marker of the traders’ risk preference and the reward they receive in their trading activities this way, “[i]t has also been found that testosterone and its metabolite, 3alpha-androstanediol, have rewarding and addictive properties, largely because they increase dopamine release in the shell of the nucleus accumbens, a brain region found to be stimulated in anticipation of irrational risk seeking.” They explain this by noting that a previous success in trading can lead to “androgen priming” (sometimes called the “winner effect”) and this can increase risky choices in the next round of trading. (Coates, 2008) These risky choices may eventually lead to irrational trading behavior with destructive results. “… testosterone has [ ] been found to lead to impulsivity and sensation seeking, to harmful risk taking and, among users of anabolic steroids, to euphoria and mania.” It may not have escaped your notice that these traits are similar to those seen in carriers of the DRD2 Taq1A gene.

References

  • Coates and Herbert. Endogenous steroids and financial risk taking on a London trading floor. Proc Natl Acad Sci U S A. 105(16):6167-72 (2008).

 

GRAPEFRUIT JUICE MAY BE HAZARDOUS TO YOUR HEALTH
BUT NOT FOR THE REASON YOU THINK

Many, perhaps most, of you know that grapefruit juice can alter how prescription drugs are metabolized and, hence, could interfere with your medicinal drug regime. But what you may NOT know is that the flavonone naringenin, its bitter principal, is the source of these metabolic effects because naringenin inhibits the cytochrome P-450 enzymes, CYP3A4 and CYP1A2, found in the liver and supposed to metabolize these drugs for excretion. (Fuhr, 1993) If there is too much CYP3A4, the prescription drugs it metabolizes may be eliminated from the bloodstream too rapidly, leaving you deficient as compared to the amount you need for your drug treatment.

Naringenin is available as a dietary supplement and, indeed, it appears to have many potential benefits, as do flavonones in general. Still, the fact that it interferes with the function of the CYP3A4 cytochrome P-450 enzyme makes it risky to use if a prescription drug you’re taking is metabolized by that enzyme, such as theophylline and calcium channel blockers (such as nimodipine and verapamil). (Fuhr, 1993)

Sandy learned about this the hard way. She thought that small amounts of grapefruit juice (an ounce or less added to flavor a fruit juice drink) would be too small an amount to have a significant effect on any of the prescription drugs she uses (which includes theophylline), but it appears she was wrong. The prescription drugs she takes for restless legs may have been affected because she noticed that just as she began drinking small amounts of grapefruit juice, her restless legs became worse and when she discontinued it, the restless legs went back to where it started before the grapefruit juice. If that was due to grapefruit juice, naringenin would be expected to have similar effects.

Reference

  • Fuhr et al. Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br J Clin Pharmacol.35:431-436 (1993).

 

QUICK BITS
WAY AHEAD OF HIS TIME…

Once the principle of movement has been supplied, one thing follows on after another without interruption.

— Aristotle

Aristotle here foresees Newton’s Law of Motion by an amazing (roughly) 2000 years: Newton’s Law I actually says: Every body persists in its state of being at rest or of moving uniformly straight forward, except insofar as it is compelled to change its state by force impressed.

Amazing.

 

WHEN YOU CAN’T REMEMBER
BUT IT’S JUST ON THE TIP OF YOUR TONGUE

It’s an old saying when people just can’t remember something to say that “it’s just on the tip of my tongue.” But the funny thing is that the memory MAY just be on the tip of their tongue. The area at the tip of your tongue is sensitive to sugar and sugar (glucose) is known to enhance human memory.

Study-Can one cup of coffee contribute to overweight and obesity in men?

Life Priority Blog 9.15.2015 Published-

Can one cup of coffee contribute to overweight and obesity in men?

Study: British Journal of Nutrition 28 Aug 2015

This is potentially big news because glucose is an important factor in our natural energy. If one cup of coffee can slow down the process of breaking down glucose, that temporary boost in energy is more costly than perceived. It could have longer lasting effects on our body that actually leave some people with less energy because the glucose in their body isn’t being broken down properly.

Almost everyone is looking for a morning or mid-afternoon pick-me-up and energy drinks and coffee are usually the solution. These caffeine infused drinks can provide short-term energy, but usually lead to a crash later. At the same time, energy drinks and coffee are not the healthiest solutions to the lack of energy dilemma someone might experience.

A recent study in the United Kingdom suggests that just one cup of coffee can affect glucose metabolism. They tested overweight men and varied the amount of caffeine the men received, and the results showed that just two grams of caffeine (equivalent to one cup of coffee) can make glucose metabolism and response worse.

An alternative to coffee could be Lift. Lift is an all-natural energy-drink mix (also available in capsule form) that can help boost energy. Lift doesn’t fill your body with caffeine; instead it uses L-phenylalanine to potentially help elevate your energy levels, mental clarity and happiness. Those three things are pretty important for everyone’s day so they might have a great one. So take your health into your own hands and start living more healthy. Think more about what you put into your system and try to make your health your top priority. Your diet alone can’t get you all the nutrients you need to stay healthy, so see if Lift is right for you.

To Your Health!

Sourced from: http://www.nutraingredients.com/Research/Just-one-coffee-affects-glucose-metabolism-in-overweight-men-Study

Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities.

*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.

*Any testimonials on this web site are based on individual results and do not constitute a guarantee that you will achieve the same results.

May 2016 Blog with Durk and Sandy

APPETIZERS

The marvelous thing about a joke with a double meaning is that it can only mean one thing.
— Ronnie Barker

The modern geography of the brain has a deliciously antiquated feel to it — rather like a medieval map with the known world encircled by terra incognita where monsters roam.
— David Bainbridge

The brain has no knowledge until connections are made between neurons. All that we know, all that we are, comes from the way our neurons are connected.
— Tim Berners-Lee

Creativity is a drug I cannot live without.
— Cecil B. DeMille

We started off trying to set up a small, anarchist community, but people wouldn’t obey the rules. 
— Alan Bennett

FLOW:
THINKING FAST AND THINKING SLOW

FLOW is a state that is often described as a “state of effortless concentration so deep that [people who experience it] lose their sense of time, of themselves, of their problems.” Such an “optimal experience” is probably not reached too often by most people, but when it is it gives you a sense of acting without conscious awareness, of time slowing down, of your senses perceiving you moving through a dreamlike state.

FLOW is a highly desired mental state because it allows one to do something that is pleasurable and that would otherwise require immense amounts of mental effort. It is what happens to people who drive racecars or motorcycles or even write a book (and we ought to know). When you’re in a state of flow, nothing distracts you from your goal, so all of your resources can be focused on it.

THINKING FAST and THINKING SLOW describes flow as what some artists experience in a creative state and that many others achieve “when enthralled by a film, a book or a crossword puzzle…[when] interruptions are not welcome…” Who hasn’t experienced FLOW? The trick is being able to produce it when you want it.

We knew a highly skilled champion racecar driver (Mickey Thompson, who sadly has died) who told us that using a BLAST family formulation of ours that we’d given him to try, he’d driven his automobile in a very long professional off-road auto race and time had slowed down with everything happening exactly right and without any conscious effort on his part. He said that it felt like the FLOW he experienced in his best races.

Time stands still if you go fast enough.

—Stephen F. Kaufman, martial arts professional, Ch. 19 on the subject of flow, in his book The Way of The Modern Warrior

The formulation that Mickey took was one of those we designed for our own use that contains phenylalanine. An interesting thing about phenylalanine is that, unlike tyrosine, another amino acid the brain can use to make DOPAMINE, a major neurotransmitter involved in all sorts of things having to do with reward and pleasure (such as auto racing!), phenylalanine can be converted by the brain into PHENETHYLAMINE (also called phenylethylamine). Phenethylamine has a remarkable property of providing mental energy (like caffeine), but may also be a stimulus barrier, a molecule that allows the brain to filter out undesired background noise in order to focus on what is important.

PHENYLALANINE is found in our BLAST family of dietary supplements, as well as in our ASCEND N’ SEE™ (no longer available).

Another of our formulations, called SMARTZ (which is, sadly, unavailable right now due to the lack of a distributor—you cannot order it from LIFE ENHANCEMENT, sorry) also contains phenylalanine. We like the flavor and the feeling it gives us and Sandy is sorely tempted to drink a can of our remaining supply, but it is a temptation that she resists because we will need samples if we ever want to locate a distributor.

Historical note: RHYTHM is Greek for FLOW. Or, as Hans von Bulow put it, “In the beginning was rhythm.” Rhythm has been called the heartbeat of music and scientists speculate that it is the sound of a mother’s heartbeat by a fetus in her womb that primes the brain to rhythm and to music. “Rhythm releases our motor reflexes, even if we do not respond with actual physical movement.” “In brief, we organize our perception of time by means of rhythm.” (SOURCE: Ch. 5 in The Enjoyment of Music by Joseph Machlis, W. W. Norton & Co., 3d edition, 1970),

The rhythms that the Ancients observed in Nature, such as the ebbing of the tides, the cycles of the Moon, the rising and setting of the Sun—these things had mystical qualities that caused the birth long ago of legends and myths concerning the rhythms of life. Today, we have greatly expanded our knowledge of these rhythms, identifying myriad changes in the physical and chemical aspects of the brain (and body) that cause these fascinating rhythms. In the end, everything is connected to everything else at the deepest level and you can use RHYTHM as a starting point of every phenomenon.

In the following section, quotes come from Thinking, Fast and Slow by Daniel Kahneman (winner of the NOBEL PRIZE in ECONOMICS for his work in psychology and decision-making), Farrah, Straus and Giroux, 2011.

The blurb by Steven Pinker, Prof. of Psychology at Harvard University and a well-known author of books on how the mind works notes that Dr. Kahneman’s work “has reshaped social psychology, cognitive science, the study of reason and of happiness, and behavioral economics …” This is a book that we highly recommend and have been reading and rereading.

THE ECONOMICS OF PAIN AND PLEASURE
“WANTABILITY”

Another chapter (CH. 35) in the book discussed above (Thinking, Fast And Slow)discusses pain and pleasure in the terms of an economist. UTILITY is a term of art in economics that means roughly a measure of worth or value. In biology, it would be used to assess pain or pleasure. The author of the book (Daniel Kahneman) chose to call it “experienced utility.” Somebody else in the book called it “wantability.” (One of the confusing but also amusing aspects of a newly developing field is the creation of a slew of names for it.)

Another word that is used in the context of utility (or pleasure and, occasionally, for pain) is the word HEDONIC. “The British economist Francis Edgeworth speculated about this topic in the nineteenth century and proposed the idea of a ‘hedonimeter,’ an imaginary instrument analogous to the devices used in weather-recording stations, which would measure the level of pleasure or pain that an individual experiences at any moment.” (Pg. 378 of the book.)

As most know, “electrical stimulation of specific areas in the rat brain (and of corresponding areas in the human brain) produce a sensation of INTENSE PLEASURE, so intense in some cases that rats who can stimulate their brain by pressing a lever will die of starvation without taking a break to feed themselves.” (Pg. 384.) The memory of this pleasure is what causes the animals to repeat the stimulation over and over. But it is usually only the very last moments of an experience of pleasure that are remembered and only at the very end the emotional evaluation emerges. This is very important because “tastes and decisions are shaped by memories and the memories can be wrong.” (Pg. 385.) How we remember pleasure and pain can be as important as the actual experience.

Quotes from the book say it best:

“A divorce is like a symphony with a screeching sound at the end—the fact that it ended badly does not mean it was all bad.”

“You are giving the good and the bad part of your experience equal weight, although the good part lasted ten times as long as the other.”

RISKY CHOICES:
AN ECONOMIC PERSPECTIVE

In economics, the difference between the preference for a small but certain reward (risk-averse) and preference for a larger but uncertain reward (risk-seeking) is an area of intensive study. (See, for example, MacKillop, 2013) Now, economists have extended the reach of their investigations to look at genetic and neurological correlates for these preferences, a new economic/scientific field called Behavioral Economics. As the author of a recent paper (MacKillop, 2013) says, “[t]here is growing interest in genetic influences on discounting and, in particular, the prospect of discounting as an endophenotype for addictive disorders…” Discounting is the way one adjusts his present valuation of a future reward based on the risk inherent in a delayed reward. It is the reason that you charge INTEREST when you loan money—the money is more valuable in your hands TODAY than the hypothetical possession of it sometime in the future. Delayed reward discounting is defined in one paper (MacKillop, 2013) as “how much a reward loses value based on its distance in the future.” This is also the Austrian School of Economics’ concept of time preference.

The term “endophenotype” simply means the expression of a particular genetic trait, in this case the preference for risk-aversion or risk-seeking. The DRD2 gene has been strongly supported as being involved in this preference (Zalocusky, 2016), with low levels of DRD2 activity associated in humans with risk-seeking behavior. The low levels of DRD2 can lead to addictive behaviors as individuals seek to increase dopamine release in the brain’s reward circuitry by engaging in these behaviors.

The researcher (MacKillop, 2013) thinks of the risk-seeking phenotype as “impulsive discounting.” He states his hypothesis: “…although not definitive, there is accumulating support for the hypothesis of impulsive discounting as an endophenotype for addictive behavior and a need for further systematic investigation.”

An early study of “impulsive discounting” was the famous marshmallow tests, where children had to decide whether to consume a second marshmallow (after eating one) or wait to receive yet another marshmallow. The children who waited were in later life seen to have higher educational and other life achievements; this trait continued for decades. Those who did not wait were more likely to misuse drugs at older ages.

References

  • Integrating behavioral economics and behavioral genetics: delayed reward discounting as an endophenotype for addictive disorders. J Exp Anal Behav.99(1):1-25 (Jan. 2013).
  • Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making. Nature.doi:10.1038/nature17400 (2016).

RISKY CHOICES AND DRD2

That the DRD2 dopamine receptor gene is a causative factor in risky decisionmaking is, we believe, becoming well supported, based on experimental evidence both in humans and that of animals. (Zalocusky, 2016). There is also mounting evidence of its involvement in addictions. Addiction appears to result when the brain’s cost-benefit analysis incorrectly causes individuals to choose risky behaviors such as those associated with addictive behaviors (e.g., excessive eating, compulsive sexual behavior, drug abuse, or gambling). The downgrading of the risks of an action while continuing to value its benefits can lead to highly maladaptive choices.

A recent study (Nasrallah, 2011) described the effects of alcohol use in adolescent rats, showing that subsequently the rats made more risky decisions. The researchers exposed adolescent rats to alcohol to assess its effects on risk-based decisions in the mesolimbic dopamine system, “the site of action for virtually all abused substances.” What they found was that “a history of adolescent alcohol use alters dopamine signaling to risk but not to reward.” “… the maladaptive bias toward large but risky outcomes displayed by these rats suggests that they overvalue larger rewards and/or fail to appropriately discount that value based on its diminished probability of occurrence.” “A corruption of reward valuation could promote maladaptive and suboptimal behavior by placing excessive priority on seeking rewards such as food, drugs, or sex.”

As reported in a later study, “…risk preferring rats could be instantaneously converted to risk-averse rats with precisely timed phasic stimulation of NAc [nucleus accumbens] D2R [DRD2] cells.” (Zalocusky, 2016) The implication is that stimulation of the DRD2 dopamine receptors would increase dopamine activity via these receptors and counteract the negative effect of (in this case) alcohol and possibly other forms of addiction (which are known to be associated with decreased DRD2 activity).

As noted in Reuter, 2006, “[g]eneral cognitive ability (intelligence, often indexed by IQ scores) is one of the most highly heritable behavioral phenotypes.” It has slowly come to be the general view among scientists that IQ does provide a rough measure of intelligence.” Creativity is not the same as intelligence, however, and heredity may, on the basis of twin studies, contribute perhaps 20% of the genetic contribution. This is controversial due to difficulties in measuring creativity. In the case of numerical creativity, there was a modest correlation with intelligence.

References

  • Reuter et al. Identification of first candidate genes for creativity: a pilot study. Brain Res.1069:190-7 (2006).
  • Nasrallah et al. Risk preference following adolescent alcohol use is associated with corrupted encoding of costs but not rewards by mesolimbic dopamine. Proc Natl Acad Sci U S A.108(13):5466-71 (2011).
  • Zalocusky, “Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making. doi:10.1038/nature17400 (2016).

CREATIVITY AND DOPAMINERGIC DRIVE

… no great genius was without a mixture of insanity.

—Aristotle

The problem is never how to get new, innovative thoughts into your mind, but how to get old ones out. Every mind is a building filled with archaic furniture. Clean out a corner of your mind and creativity will instantly fill it.

—Dee Hock

Creativity is not the same as intelligence. You can have one without having much of the other. That suggests that the basic mechanisms that result in creativity as compared to intelligence are different, at least in some respects. One of the differences is that creative people tend to generate more ideas, but at the same time many of those ideas may not be of high quality. It is intelligence that permits you to distinguish which ideas are the good ones. As Linus Pauling suggested, if you want to have good ideas, you need to have a lot of ideas and throw out the bad ones.

The basis for creativity is the recognition of patterns. A creative individual is able to see novel associations between things. Associational thinking has been identified in relation to music, writing, and other forms of obsessional mental effort. Hypergraphia (an urge to write incessantly, a trait probably shared by most writers) is an example of associational thinking, of creativity. Interestingly, hypergraphia was first characterized in temporal lobe epileptics, suggesting that damage to the temporal lobe is a contributing factor to hypergraphia, at least in those with epilepsy. White matter in the brain is the material that comprises the connecting tracts that allows different areas of the brain to communicate with each other. There is immense damage to white matter in Alzheimer’s disease, as well as in other neurodegenerative diseases (Parkinson’s, Huntington’s, epilepsy) and as part of aging in the brain.

Dopaminergic activity in the temporal lobes is an important player in creative drive. Mesolimbic dopamine influences novelty seeking and creative drive. Novelty seeking is a particular character trait exhibited by some people more than by others; it has recently been found to be linked to the DRD2 dopamine receptor. (Blum, 2011)

The DRD2 gene as well as the TPH gene—which induces the expression of tryptophan hydroxylase, the enzyme that converts tryptophan to 5-hydroxytryptophan on the pathway to serotonin— are both associated with creativity. (Reuter, 2006) The DRD2 gene is associated with verbal creativity, whereas the TPH gene is associated with numerical and figural creativity. (It is interesting to note that women have on average greater verbal abilities than men, while men typically have much greater numerical (mathematical) abilities than women. SAT scores reflect this, with most of those scoring high on the math SAT (over 700) being men. Average SAT scores don’t tell you about the distribution, where some scores fall far lower than average and others score much higher. Men have a much wider distribution, with a greater share of both the highest scores and the lowest.

As noted in Reuter, 2006, “[g]eneral cognitive ability (intelligence, often indexed by IQ scores) is one of the most highly heritable behavioral phenotypes. It has slowly come to be the general view among scientists that IQ does provide a rough measure of intelligence.” Creativity is not the same as intelligence, however, and heredity may, on the basis of twin studies, contribute perhaps 20% of the genetic contribution. This is controversial due to difficulties in measuring creativity. In the case of numerical creativity, there was a modest correlation with intelligence.

References

  • Reuter et al. Identification of first candidate genes for creativity: a pilot study. Brain Res.1069:190-7 (2006).
  • Blum et al. Generational association studies of dopaminergic genes in reward deficiency syndrome (RDS) subjects selecting appropriate phenotypes for reward dependence behaviors. Int J Environ Res Public Health.8:4425-59 (2011).

INCREASING CREATIVITY WITH SUPPLEMENTS: EEG ALPHA POWER

EGCG

All indications are that creativity tends to decline with age, though certain subjects (such as mathematics or physics) seem to appear in the creative works of some even into old age. It would certainly be nice to be able to continue the creative productivity that you see mostly in young persons. Think of music composers, for instance. The songwriters who produced the great rock music of the ‘60s seem to have lost the ability to compose music with the power of their early work. Wouldn’t it be wonderful to be able to recover those abilities, those youthful creative passions?

Creative idea generation has been linked to EEG alpha power. “Increases in EEG alpha power during creative ideation are among the most consistent findings in the neuroscientific study of creativity…” (Schwab, 2014)

It was recently discovered that supplementation with 300 mg of EGCG (epigallocatechnin gallate, highly enriched in green and white teas) was associated with “a significant increase in alpha, beta, and theta activity, also reflected in overall EEG activity…” (Scholey, 2012) Since EGCG increases EEG alpha power, it may be that EGCG could contribute to creative thinking.

NEUROGENESIS AND CREATIVITY

EGCG, as explained above, is associated with an increase in alpha waves in the brain, which, in turn, is associated with creativity, but EGCG also increases neurogenesis. (Yoo, 2010) Another nutrient that increases adult neurogenesis is taurine (Gebara, 2015), though we do not have data at this time on whether taurine enhances creativity. Both taurine and EGCG are found in our GREATER REWARDS.

Polyphenols, such as are found in tea, cocoa, and red wine) have been identified as a class of compounds that “can increase AHN” [adult hippocampal neurogenesis].” (Dias, 2012) Curcumin has been shown in published studies (So, 2008; Xu, 2007) to enhance adult hippocampal neurogenesis; in one of the studies (Xu, 2007), curcumin actually reversed impaired neurogenesis. We take curcumin in the form of turmeric root powder.

NEUROGENESIS AND SEX

Sex can initiate behavior that leads to pair-bonding in many, if not most, mammals. Scientists have begun to unravel this complex process. A recent paper (Leuner, 2010) reports that sexual experience (in rats) promotes adult neurogenesis. If one were to speculate, it seems plausible that neurogenesis resulting from sex may serve the purpose of creating new neurons dedicated to the establishment and maintenance of a pair bond.

Even ORGASM gets into the act. Another paper (Wang, 2013) describes a study in adult mice in which it was shown that the pulse of prolactin that immediately follows orgasm (Exton, 2001, this was a human study) stimulates adult neurogenesis in the subventricular zone and olfactory bulb.

References

  • Dias et al. The role of dietary polyphenols on adult hippocampal neurogenesis: molecular mechanisms and behavioral effects on depression and anxiety. Oxid Med Cell Longev.012:541971. doi: 10.1155/2012/541971. (2012).
  • Scholey et al. Acute neurocognitive effects of epigallocatechin gallate (EGCG). 58:767-70 (2012)
  • Schwab et al. The time-course of EEG alpha power changes in creative ideation. Front Hum Neurosci.13;8:310. doi: 10.3389/fnhum.2014.00310. (eCollection 2014).
  • Gebara et al. Taurine increases hippocampal neurogenesis in aging mice.Stem Cell Res. 14:369-79 (2015).
  • Yoo et al. Epigallocatechin-3-gallate increases cell proliferation and neuroblasts in the subgranular zone of the dentate gyrus in adult mice. Phytother Res.24:1065-70 (2010).
  • So et al. Curcumin stimulates proliferation of embryonic neural progenitor cells and neurogenesis in the adult hippocampus. J Biol Chem. 283(21):14497-505 (2008).
  • Xu et al. Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic expression in chronically stressed rats. Brain Res. 1162(1):9-18 (2007).
  • Leuner et al. Sexual experience promotes adult neurogenesis in the hippocampus despite an initial elevation in stress hormones. PLoS One.5(7):e11597 (July 2010).
  • Wang et al. Extracellular signal-regulated kinase 5 (ERK5) mediates prolactin-stimulated adult neurogenesis in the subventricular zone and olfactory bulb.J Biol Chem. 288(4):2623-2631 (2013).
  • Exton et al. Coitus-induced orgasm stimulates prolactin secretion in healthy subjects. 26:287-94 (2001).

WASH AND BE HEALED:

Cleanse Your Body
Wash Your Sins Away
The evidence of priming studies suggests that reminding people of their mortality increases the appeal of authoritarian ideas, which may become reassuring in the context of the TERROR OF DEATH.

…merely thinking about stabbing a co-worker in the back leaves people more inclined to buy soap, disinfectant or detergent than batteries, juice, or candy bars. Feeling that one’s soul is stained appears to trigger a desire to CLEANSE one’s body, an impulse that has been dubbed the LADY MACBETH EFFECT. (emphasis added)

—from Daniel Kahneman,
Thinking Fast And Slow, 
Farrah, Straus, and Giroux, 2011

DETERGERE, Latin for: to CLEANSE by rubbing. (So, you see, the Roman Empire didn’t fall, not entirely. Its language, LATIN, goes on and on. You did notice the similarity between DETERGERE and “detergent” of course.)

“Washing” and “cleansing” and “purification” and the like are almost ubiquitous in their occurrence in social contexts. “Wash your sins away,” “wash your mouth out with soap,” ethnic or political “purification,” “ethnic cleansing,” “cleanliness is next to godliness,” “washing your hands” of some problem, and the list goes on. Cleanliness, it seems, has a deeper meaning than just removing dirt.

For instance, a recent paper (Lee, 2010) describes how “[h]and washing removes more than dirt—it also removes the guilt of past misdeeds, weakens the urge to engage in compensatory [e.g. retaliatory] behavior and attenuates the impact of disgust on moral judgment.” The authors of the paper suggest that the “cleansing” that accompanies hand washing “may also reflect that washing more generally removes traces of the past by metaphorically wiping the slate clean.” The researchers here tested the hypothesis that hand washing might reduce a post-decisional dissonance effect (the uncomfortable feeling that you might have made the wrong decision).

In fact, that is just what they found. A group of 49 undergraduate students (quintessential research subjects!) examined 30 CD covers in a music store and ranked them by preference, then being offered by the researchers a choice of their fifth and sixth ranked CDs.

Then the students were asked to participate in a supposed consumer test of a soap, with some of them simply examining it and some of them actually washing their hands. They were again asked to rank order the CDs. It would have been expected that in the reassessment of the rank order, having received a particular CD would result in its moving up to a higher rank (as an example of “cognitive dissonance”). However, what was ACTUALLY found was that the students who had washed their hands did not increase the rank order for the CD they received (unlike the students who only examined the soap). Thus, the hand washing did in fact “cleanse” the mind of the need to rationalize that the CD they received was really better than they had first thought.

Voting for the lesser of two evils is a classic example of how a decision sure to create dissonance may be “remedied” by imagining that the lesser of the evils was better than you might have thought at first. We wonder whether making it possible for individuals to wash their hands at the polling station might leave people in a less agitated mood. But then, again, perhaps they should be if they have truly voted for somebody evil.

Reference

Lee and Schwartz. Washing away postdecisional dissonance,. Science. 328:709 (2010);

CLEANSING YOUR CONSCIENCE

The book (Thinking Fast And Slow) from which the quote at the start of this article was taken discussed how washing could be connected to moral “cleansing.” The author described an experiment in which people were induced to “lie” to a fictitious person on the telephone or by email. In doing so, it was likely expected to cause these “liars” (though they hadn’t actually LIED, they only simulated a lie) to nevertheless feel tainted and to attempt to “cleanse” themselves of their “moral lapse.” In fact, as the results showed, “people who had lied on the phone preferred MOUTHWASH over soap, and those who had lied in e-mail preferred SOAP to mouthwash.” (This preference referred to whether or not these individuals would buy mouthwash or soap, as assessed by a subsequent test.)

The idea that the participants would be highly motivated to “clean out their mouths” was substantiated. Parents used to admonish their children to “wash out their mouths” (we don’t know if they still do) after they had said or done something the parents considered wrong.

CLEAN YOUR CONSCIENCE AGAIN

In another paper (Schnall, 2010), researchers discuss how cleanliness can reduce the severity of moral judgments by toning down the desire to punish “wrongdoers.”

In this experiment, subjects were “primed” by hearing words that connote cleanliness whereas controls heard neutral words. After being “primed,” the participants were asked to rate six moral dilemmas, such as switching tracks so a train ran over one workman rather than five, killing (and eating) a terminally ill plane crash survivor to avoid dying of starvation, lying on a resume, etc. They were asked to rate their mood following these judgments. The results showed that the moral judgments of the hypothetical individuals making the decisions in the moral dilemmas was less severe when they had been “primed” with words connnoting cleanliness. The authors suggest that the thoughts of physical cleansing produced a sort of moral cleansing that reduced feelings of disgust associated with the decisions.

Reference

Schnall et al. With a clean conscience: cleanliness reduces the severity of moral judgments. Psychol Sci. 19:1219-22 (2010).

THE WATER-CURE MOVEMENT

Here, we will talk a bit about the “Water-Cure Movement” of the nineteenth century when there was a craze for CLEANSING yourself of your sins. This was a form of medicine called “hydropathy” that “was one of the most celebrated alternative forms of medical care.” (the latter phrase on the inner front jacket of a surprisingly well-referenced popular book—Wash and Be Healed by Susan E. Cayleff, Temple University Press, 1987). This was highly serious stuff at the time and appeared in the writings and speeches of many leading reformers and activists then.

The book Wash and Be Healed, from which this material was obtained, will only be touched upon here. The book contains 247 pages of mostly JUICY material (with hundreds of references), not all of which is suitable for a family (sort of) newsletter. So, moving right along to a few of its juicier bits…

It all started a long time ago… In Europe, one “took the cure.” In those early days, the water (meaning anything, the book says, from mud baths, mineral waters, stinking waters, putrid waters, to “holy” water) would be involved in highly ritualized “medical” treatments that could be little more than veiled approaches to group sex. And, of course, these “cleansing” rituals became VERY popular. Especially among women, who could endorse cleanliness while enjoying the sexual aspects of its practice (more on that follows).

Another little bit in the book introduces us to R. T. Trall, one of the co-founders of the movement. One of the innumerable doings of this man described in the book was his extensive and influential writing in the Water-Cure Journal, the “fanzine. of the time for the WATER-CURE movement.

In one of Trall’s articles, he suggested avoiding undesirable influences such as eating meat and devouring “pestilent literature” as he called it. He recommended the incredible treatment of “a towel wash or dripping sheet in the morning on rising, followed by thorough frictions with dry towels, or rubbing over the dry sheet [and] a hip or sitz bath twice a day…” (Makes you sweat just reading about this, doesn’t it?) (Wash and Be Healed, pg. 55.) The advice never ends but we have to end it with this: Trall suggests further that the water-cure adherent should “eliminate all seasonings, stimulants, and grease from the diet…”

Next, we learn that Trall has written an article on “The Physiology of Menstruation” containing a section entitled “The Sexual Orgasm.” In it, he admits: “[i]t is true that the sexual orgasm on the part of the female is just as normal as on the part of the male.” And in another article, “The Pleasure of Sexual Intercourse,” he asserts that, “it should be as pleasurable as possible to both parties.” “Surely,” he exclaims, “if sexual intercourse is worth doing at all, it is worth doing well.” (!)

We shall close out these comments with a look at the sexual pleasures that were part and parcel of a move- ment established ostensibly for the purpose of cleaning your sins away. That will have to be all for the WATER-CURE MOVEMENT.

As we had mentioned earlier in this discussion, the water cures included features such as “rubbing” and “friction massages.” T. L. Nichols, in his writings on the subject of “Diseases of Women” “urged the use of wet bandages ‘carefully and tightly applied’ in the pelvic area.” Yep, that ought to do it.

CLEANSING YOUR HAIR INSIDE AND OUT

We designed a shampoo for our own use that we call INNER SHAMPOO. We love the stuff. It won’t “wash your sins away” but it does a lot for your hair. It leaves hair delightfully shiny and squeaky clean, but with easy comb-ability. It has a stunning effect of actually REPAIRING split ends, as shown in photomicrographs of actual damaged hairs. Nothing else we have tried can compare to the resulting cleanliness and appearance and easy comb out of our hair after using it. And remarkably, we have not seen this combination of natural ingredients elsewhere—except when used as an emulsifier and dough conditioner in baked goods.

My Passion for Life Priority

I love Lift and Lift Caps, and have personally used these life-saving supplements for over 20 years.

I started using Lift/Lift Caps as a busy wife/mother of 3 small children (under 5) in 1991. At 66, my morning routine that helps me stay strong and gives me better mental focus is to go get my Lift Caps and do my daily devotional.

Lift was designed by two nutritional scientists and friends, Durk Pearson and Sandy Shaw (authors of Life Extension), for their own personal use. The formula was scientifically created for the ultimate brain support.

I love sharing the Lift/Lift Caps with anyone who wants to feel better and make better nutritional decisions for mental fatigue. I think you will find the Lift Caps a great addition to your day, especially after a long day/night! I love them.  Lift Caps provides your body with nutrients that help you have more energy and eliminate mental fatigue for 4-6 hours. Please feel free to call or email me with any questions!

Education is the Key to Wisdom. Wisdom is the Key to Good Health!

At Life Priority staying healthy is a family affair!

Sincerely, Michelle Pryor, co-Owner of Life Priority Inc.

Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities.

Information provided for educational purposes only. *These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease.

April 2016 Blog with Durk and Sandy

APPETIZERS

It’s necessary to be slightly underemployed if you are to do something significant.

— James Watson, Nobel laureate co-discoverer with Francis Crick of the DNA double helix

Gray hair is a blessing—ask any bald man.

— Jerry Smith

Fear is not real. The only place that fear can exist is in our thoughts of the future. It is a product of our imagination, causing us to fear things that do not at present and may not ever exist. That is near insanity, Kitai. Do not misunderstand me, danger is very real, but fear is a choice. We are all telling ourselves a story and that day mine changed.

— quote from the movie After Earth (2013) [D&S: We didn’t see the movie.]

No passion so effectually robs the mind of all its powers of acting and reasoning as fear.

— Edmund Burke (1729-1797)

Fairy tales are more than true; not because they tell us that dragons exist, but because they tell us that dragons can be beaten.

— G. K. Chesterton

I dream’d in a dream, I saw
a city invincible to the
Attacks of the whole of the
rest of the earth.

I dream’d that was the new City of Friends.

— Whitman

Those who dance are considered insane by those who can’t hear the music.

— Anon.

“If I wasn’t real,” Alice said — half laughing through her tears, it all seemed so ridiculous — “I shouldn’t be able to cry.”

“I hope you don’t suppose those are real tears,” Tweedledum interrupted in a tone of great contempt.

— Alice Through the Looking Glass (Lewis Carroll)

 

Introducing Durk Pearson & Sandy Shaw’s®
FLUSH Prune Juice

Durk Pearson & Sandy Shaw’s FLUSH®

The prune juice that flushes your regulation problems down the toilet.

 

Don’t put up with a poorly functioning regulatory system — Get regular with a morning constitutional with FLUSH

 

Did you know that the First Amendment protects you from health claim constipation?

Get it out — Get it ALL out with FLUSH!

 

FLUSH prune juice helps relieve chronic constipation. See your doctor first to ensure your regulation problem is not more serious than a need to increase your dietary fiber. Use one to four 8 ounce glasses per day as needed to help FLUSH your regulation problem.

— by Sandy Shaw

Gamma Oscillations — Key to Consciousness?

If one word were to describe the essence of a human life, that word might be conscious.

Serious research published in reputable peer-reviewed journals have studied the neural basis for consciousness. This work is closing in on what distinguishes the brain’s activity when we are conscious from that when it is operating unconsciously (which is most of what the brain does).

A little of the new research reveals:

1. Gamma oscillations may be importantly associated with and perhaps causal to consciousness (Singer, 1995) though there is no general agreement. In a 1999 paper (Engel, 1999), the author described the “gamma wave hypothesis” as follows: “[t]he hypothesis is that synchronization of neuronal discharges can serve for the integration of distributed neurons into cell assemblies and that this process may underlie the selection of perceptually and behaviorally relevant information.” “Gamma oscillations (y) [where y is the number of oscillations] (30-120 Hz), an emergent property of neuronal networks correlate with memory, cognition and encoding.” (Ferando, 2013).

2. GABA (gamma aminobutyric acid, an inhibitory neurotransmitter) appears to be involved in the creation of gamma oscillations. (Chen, 2014) “Among the rhythmic firing patterns observed in brain networks, gamma oscillations are generated by a specific class of inhibitory neurons with robust interconnectivity through fast GABA synapses.” (Proddutur, 2013) “…gamma oscillations may contribute to learning and memory…” (Proddutur, 2013) “We have previously shown how gamma oscillation frequency recorded in the CA3 [an area of the brain] in vitro is controlled by a delta-GABA(A)Rs-mediated tonic conductance of INs [inhibitory neurons], that is dynamically balanced by an NMDA-R mediated tonic excitation.” (Ferando, 2013)

3. Gamma oscillations may be important in working memory, a short term form of memory that is critical for complex thought. “During working memory tasks, increasing cognitive load is associated with an increase in gamma oscillations in healthy participants and epilepsy patients.” (Chen, 2014)

4. Gamma oscillations were shown to be associated with spontaneous recovery from depression in mice following chronic restraint stress (Khalid, 2016). When mice are subject to chronic restraint stress, they develop a depressive state that includes anhedonia, withdrawal from social interactions, reduced locomotor activity, much like the depression seen in humans. However, a few weeks after the chronic restraint stress is discontinued, most of the animals spontaneously recover from this depressive state. The recovery is associated with restoration of gamma activity at the network level.

5. In another paper (Rodriguez, 1999), researchers describe a new (as of that time) process in which “a transition between two distinct cognitive acts (such as face perception and motor response) should be punctuated by a transient stage of undoing the preceding synchrony and allowing for the emergence of a new ensemble…” (The gamma oscillations were associated with an increase in synchrony.)

PRODUCING GAMMA OSCILLATIONS

6. Lutz A, Greischar LL, Rawlings NB, Ricard M, Davidson RJ. Long-term meditators self-induce high-amplitude gamma synchrony during mental practice. Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16369-73.

References

 

 

  • Chen CM, Stanford AD, Mao X, Abi-Dargham A, Shungu DC, Lisanby SH, Schroeder CE, Kegeles LS. GABA level, gamma oscillation, and working memory performance in schizophrenia. Neuroimage Clin. Mar 20;4:531-9, 2014.; also see Bower B. Synchronized thinking. Brain activity linked to schizophrenia, skillful meditation. Science News. 166(20):310 (2004).
  • Engel AK, Fries P, König P, Brecht M, Singer W. Temporal binding, binocularrivalry, and consciousness. Conscious Cogn. 8(2):128-51 1999 Jun.
  • Ferando and Mody. Ferando I, Mody I. Altered gamma oscillations during pregnancy through loss of δ subunit-containing GABA(A) receptors on parvalbumin interneurons. Front Neural Circuits. 17;7:144 2013 Sep.
  • Khalid et al. Gamma oscillation in functional brain networks is involved in the spontaneous remission of depressive behavior induced by chronic restraint stress in mice. Bmc Neurosci. 17:4 (2016).
  • Lutz et al. Long-term meditators self-induce high amplitude gamma synchrony during mental practice. Proc Natl Acad Sci U S A. 101:16369-73 (2004).
  • Proddutur A, Yu J, Elgammal FS, Santhakumar V. Seizure-induced alterations in fast-spiking basket cell GABA currents modulate frequency and coherence of gamma oscillation in network simulations. Chaos. 23(4):046109. doi: 10.1063/1.4830138. PubMed PMID: 24387588; PubMed Central PMCID: PMC3855147 (2013 Dec).
  • Rodriguez E, George N, Lachaux JP, Martinerie J, Renault B, Varela FJ. Perception’s shadow: long-distance synchronization of human brain activity. Nature. 397(6718):430-3 (1999 Feb 4).
  • Singer and Gray, “Visual feature integration and the temporal correlation hypothesis,” Annu Rev Neurosci. 18:555-586 (1995).

SALINE SOLUTION MAY BE BETTER THAN SOAP FOR CLEANING CERTAIN WOUNDS

According to a report in the FEB 2016 Nature Medicine in their “Biomedical Briefing” section, there has been a study of 2,447 individuals whose wounds (a fractured bone had penetrated the skin) were cleaned either by saline solution or Castile soap. While 14.5% of those whose wound was cleaned by the soap required follow-up surgery, only 11.6% of those receiving the saline cleaning did. This is a small difference but saline solution is cheap so why not use it in place of soap. The doctors were happy with the results because when you look at the large number of people requiring the cleaning of wounds, the small difference would add up to a lot of people.

The study appeared in New England Journal of Medicine 373:2629-41 (December 2015).

The Nature Medicine report said that bacteria had been observed to grow back faster in a wound after soap treatment as compared to saline, though they did not know why that would be the case.

REWARD/PUNISHMENT DOPAMINE AND MECHANISMS OF REWARD AND PUNISHMENT

Punishment is becoming a growing element in today’s political arenas. Those who support Donald Trump have been suggested by some to be an anxious lot looking for some way to PUNISH those they hate and/or fear, such as illegal immigrants. Those who support Hillary Clinton and Bernie Sanders appear to be out to PUNISH the evil rich who have more than their “fair share.” Scientific studies are discussing the rise of punitive (e.g., punishing) gods, such as those in Christianity, Islam, and Judaism, considering the existence of such gods to promote cooperation in human society. (Johnson, 2016; Purzycki, 2016.) Everywhere we see a search for somebody to do the punishing that they believe needs to be done.

What is it in the Brain of Humans that Regulates the Pursuit of Reward or Punishment?

DOPAMINE

“One hallmark of adaptive behavior is the ability to learn from the outcomes of actions, whether these results are positive or negative.” (Paton and Louie, 2012) Recent research suggests that the neurotransmitter DOPAMINE plays a leading role in this adaptive behavior by signaling the difference between a REWARD and a PUNISHMENT and selecting the physical action to be taken in response to it.

A recent paper (Paton and Louie, 2012) identified two types of dopamine receptors, D1 and D2, that are instrumental in responding to reward and punishment, respectively. D1 dopamine neurons in the medial prefrontal cortex control food intake, for example (Land, 2014). Another recent paper (Engel, 2014) reported that some hormones have been identified as playing an important role in reinforcing food intake, an inherently rewarding process. This includes ghrelin and GLP-1 (glucagon like peptide-1). (Engel, 2014) GLP-1 has also been shown to control the rewarding properties of substances such as alcohol, nicotine, amphetamine, and cocaine. In sum, the authors of this paper (Engel, 2014) suggest that the gut hormones ghrelin and GLP-1 that activate the ghrelin and GLP-1 receptors may be novel targets for development of pharmacological treatments of alcohol and drug dependence.” And also for treatment of food addiction.

Moreover, a mechanism has been identified to explain in part how these molecules foster addiction: they activate the vitally important reward system in which the cholinergic and dopaminergic nervous systems interact. Importantly, this interaction links these neurotransmitter systems to experimental findings that show that eating is initiated by a dopaminergic signal and is terminated by a cholinergic signal. (Hoebel, 2007; Rada, 2000) This hub in which the neurotransmitter systems interact is a target for the complex process of food addiction as well as other addictions.

The story of punishment goes back a very long way. The Latin word for “PUNish” was/is “PUNire.” (Sandy’s Latin-English dictionary even shows that they had/have a specific name for losing half of your property (multare dimidia parte) and for loss of the priesthood and dowry (multare sacerdotio et uxoris dote). Et tu, Roman Empire??)

— John C. Traupman, PhD, editor (THE NEW LATIN and ENGLISH DICTIONARY, Third edition, Bantam Books, 2007)

The D1 receptors induce LTP (long term potentiation) by increasing the excitability of medium spiny neurons (a type of neuron responsive to the inhibitory neurotransmitter GABA), while the D2 receptors have the opposite effect, inducing LTD (long term depression) (Paton and Louie, 2012).

Stimulation of the D1 receptors (the “direct pathway” of dopaminergic signaling in the medium spiny neurons) “increased locomotion and decreased freezing” while stimulation of D2 receptors (the “indirect pathway”) resulted in decreased locomotion, increased freezing, and bradykinesis (slower movement). Thus, the rewarding pathway leads to movement and goal seeking of rewards, while the punishment pathway leads to signs of fear and anxiety (freezing) and depression (slower movement, less movement).

In their study, the researchers (Kravitz, 2012) reported that electrically stimulating the direct pathway in mice mimics reward, while the same treatment via the indirect pathway mimics punishment. Moreover, they found that there was an “asymmetry in the temporal longevity of stimulation effects, with positive reinforcement effects outlasting the transient punishment effects of activation.” “Overall, the results of Kravitz et al highlight a fundamental point about decision-making: selecting an action is never truly independent of reward learning (Paton and Louie, 2012).

The latter effect is interesting. People tend to pay more attention to the effect of positive information (that provides a REWARD because it supports your beliefs), as compared to negative information when they reconsider their beliefs.

References

  • Engel and Jerlhag. Role of appetite-regulating peptides in the pathophysiology of addiction: implications for pharmacotherapy. CNS Drugs. 28(10):875-86 (2014).
  • Hoebel et al. Accumbens dopamine-acetylcholine balance in approach and avoidance. Curr Opin Pharmacol. 7:617-627 (2007).
  • Johnson. Hand of the gods in human civilization. Nature. 530:205-207 (2016).
  • Kravitz AV, Tye LD, Kreitzer AC. Distinct roles for direct and indirect pathway striatal neurons in reinforcement. Nat Neurosci. 15(6):816-8 (2012 Jun).
  • Land BB, Narayanan NS, Liu RJ, Gianessi CA, Brayton CE, Grimaldi DM, Sarhan M, Guarnieri DJ, Deisseroth K, Aghajanian GK, DiLeone RJ. Medial prefrontal D1dopamine neurons control food intake. Nat Neurosci. 17(2):248-53 (2014 Feb).
  • Paton and Louie. Reward and punishment illuminated. Nat Neurosci. 15(6):807-9 (2012).
  • Purzycki et al. Moralistic gods, supernatural punishment and the expansion of human sociality. Nature. 530:327-330 (2016).
  • Rada PV, Mark GP, Yeomans JJ, Hoebel BG. Acetylcholine release in ventral tegmental area by hypothalamic self-stimulation, eating, and drinking. Pharmacol Biochem Behav. 65(3):375-9. (2000).

In the Political Realm

FEAR LEADS TO PUNISHMENT

Fear seems to be showing up pervasively among the populace. As an example, December of 2015 had the all time record for background checks on Americans in advance of their purchasing firearms. In the first two months of 2016, 5,218,000 background checks were processed. (Investyourself.com, Mar. 6, 2016).

Might those who fear some group of “others” be looking for somebody to punish these “others”? One might also surmise that the more fear, the more desire for punishment. In a world of mounting fear, the growing danger of the rise of a societal ethic based upon punishment is alarming.

… civilization means, above all, an unwillingness to inflict unnecessary pain. Within the ambit of that definition, those of us who heedlessly accept the commands of authority cannot yet claim to be civilized men.

— Harold J. Laski, “The Dangers of Obedience” (in Stanley Milgram’s classic Obedience To Authority (Harper & Row, 1975)

CHOCOLATE: TRUE BRAIN FOOD

Chocolate created a sensation in Europe during the 1600’s following its introduction by men who had been exploring Middle and South America. Extrapolating from Aztec medicine, chocolate was used in Europe to soothe stomach and intestinal disorders, to control diarrhea in children, to reduce fevers, to induce cough to expel mucus, and “promote strength before military or sexual conquests” (Wilson, 2010), among other things.

CHOCOLATE: a LIBIDO enhancer?

Chocolate was promoted as a libido enhancer early on. “In 1652, Antonio Colmenero de Ledesma’s ‘Chocolate; or, An Indian Drink’ promises it [chocolate] ‘Twill make Old Women Young and Fresh…” (Wilson, 2010)

References

  • ** Walter Freeman. Chocolate craving and the pharmacological implication. Neurophysiology Lab, Freeman Lab, University of California at Berkeley, Berkeley, CA 94720. This is apparently a term paper (code 869, categorized as “Neurochemistry”) obtained by fax Sept. 3, 2003 (paper is undated, with limited references; we included this for fun, not as serious scholarship).
  • Canli T, Lesch KP. Long story short: the serotonin transporter in emotion regulation and social cognition. Nat Neurosci. 10(9):1103-9 (2007).
  • Cassiday. A prescription for chocolate. Inform. 23(5):315-6 (2012).
  • Holzer and Izzo. The pharmacology of TRP channels. Br J Pharmacol.171:2469-73 (2014).
  • Michener W, Rozin P. Pharmacological versus sensory factors in the satiation of chocolate craving. Physiol Behav. 56(3):419-22 (1994).
  • Miller. Avenues for the development of therapeutics that target trace amine associated receptor 1 (TAAR1). J Med Chem. 55(5):1809-14 (2012).
  • Kamio et al. A single oral dose of flavan-3-ols enhances energy expenditure by sympathetic nerve stimulation in mice. Free Rad Biol Med. 91:256-63 (2016).
  • Williams RJ, Spencer JP. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radic Biol Med. 52(1):35-45. (2012)
  • Wilson PK. Centuries of seeking chocolate’s medicinal benefits. Lancet.376(9736):158-9. (2010).

PHENYLETHYLAMINE, A COMPONENT OF CHOCOLATE

Effects on LOVE and SEX

Phenylethylamine (also called β-phenylethylamine), found in chocolate, is “a compound that causes the brain to release mood-elevating and pain-relieving endorphins. Moreover, phenethylamine triggers the release of DOPAMINE, a neurotransmitter that stimulates creativity, sociability, and reward-seeking behavior. Phenethylamine is released in the brain when people FALL IN LOVE or become INFATUATED, which could explain the addictive properties of chocolate.” (Cassiday, 2012).

Phenylethylamine is also available as a metabolite of the amino acid phenylalanine, which is a constituent of our entire family of BLAST energy products. (The phenylethylamine is part of the BLAST! effect.) Phenylethylamine increases the stimulation of caffeine when the two are combined.

Women were reported to give the highest hedonic (pleasure) rating in a survey. It has been proposed that “phenylethylamine [aka β-phenethylamine] could be the critical factor…” because monoamine oxidase B, an enzyme that breaks down dopamine, may be reduced during the perimenstruum, a part of the menstrual cycle (Michener, 1994).

We have lost the reference for this point, but report it because we found it quite interesting. It was said that divorcing couples had elevated levels of phenethylamine in their brains. If true, this could certainly contribute to nasty divorce proceedings and even a heightened risk of murder at the time.

THEOBROMINE, another component of CHOCOLATE

Possible Effects on LOVE and SEX

THEOBROMINE, sometimes considered a contributing factor to the emotional state of “falling in love” is found in chocolate and provides milder stimulation than caffeine (also found in chocolate), which its chemical structure resembles. Theobromine also acts as a vasorelaxant and (purely a speculation) may support penile erection (the latter requires vasorelaxation).

COGNITIVE CONSEQUENCES OF FORCED COMPLIANCE SUCH AS WHEN THE GOVERNMENT MAKES YOU SAY THINGS YOU DON’T BELIEVE

There are many examples of government forcing people to say things they don’t agree with, such as the FDA requiring that you include warnings on your product with which you disagree. What might be the consequences to those having to lie to comply with government force? For example, if you sold Flush Pune Juice,™ the FDA would likely try to force you to say that your product was not for treating constipation.

This is an area of scientific research that has been studied for a long time. The famous Leon Festinger (whose paper on cognitive dissonance is considered a classic in the field of psychology (Festinger, 1957)), also published a paper in 1959 with James M. Carlsmith (Festinger and Carlsmith, 1959) on the cognitive consequences of forced compliance.

This paper explored what might happen when people had to say things that were in conflict with their private opinion. Two earlier papers by the same authors (Janis and King, 1954; King and Janis, 1956) showed that “if a person is forced to improvise a speech supporting a point of view with which he disagrees, his private opinion moves toward the position advocated in the speech. The observed opinion change is greater than for persons who only hear the speech or for persons who read a prepared speech with emphasis solely on elocution and manner of delivery.”

Festinger and Carlsmith analyzed an earlier paper that had found that when an individual was forced to say something that was opposite to that which he actually believed, the greater the promised reward for saying this falsehood or threatened punishment for not saying this falsehood, the less subsequent opinion change toward that falsehood took place, which was the opposite to what the author of the paper had expected. In their analysis, Festinger and Carlsmith suggest that “the magnitude of dissonance is maximal if these promised rewards or threatened punishments were just barely sufficient to induce the person to say [the falsehood]. From this point on, as the promised rewards or threatened punishment become larger, the magnitude of dissonance becomes smaller.” (Festinger and Carlsmith, 1959).

They continue: “One way in which the dissonance can be reduced is for the person to change his private opinion so as to bring it into correspondence with what he has said.” They suggest that “…the observed opinion change should be greatest when the pressure used to elicit the overt behavior is just sufficient to [induce them] to do it.”

This, then, is a view of what might happen inside the mind of someone who is coerced into making false statements by the threat of a punishment (as with the FDA). Surprisingly, it might be that, consistently with the results of the experiments carried out by and reported in Festinger and Carlsmith, 1959, that the lies end up being incorporated to some extent into a modified opinion that is more consistent with the lies and, hence, reduces the dissonance resulting from having made false statements.

References

  • Festinger. A theory of cognitive dissonance. Evanston, Ill: Row, Peterson, 1957.
  • Festinger L, Carlsmith Jm. Cognitive consequences of forced compliance. J Abnorm Psychol. 58(2):203-10 (1959 Mar).
  • Janis and King. The influence of role-playing on opinion change. J Abnorm Soc Psychol. 49:211-8 (1954).
  • King and Janis. Comparison of the effectiveness of improvised versus non-improvised role-playing in producing opinion changes. Hum Relat. 9:177-86 (1956).

FAST FACTS:

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“TOR [a growth promoting gene activated by food] inhibition [ ] stimulates AUTOPHAGY [cellular self-digestion], which, as in insulin/IGF-1 mutants, is REQUIRED FOR LIFE EXTENSION (at least in worms and flies).” (emphasis added) (That is, AUTOPHAGY is required for life extension in worms and flies. It may be required in other organisms.) (Cynthia Kenyon, Nature. Mar. 2010)

Autophagy is induced by limiting caloric intake, promoting the cellular self-digestion to obtain energy and raw materials in the absence of adequate amounts of food. However, some natural substances can also induce autophagy, including TREHALOSE, an osmolyte found in our FOLDRIGHT.

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CORRUPTION MARCHES ON…

Has anyone reading this newsletter failed to notice the unbelievable increase in governmental corruption at all levels in the U.S., local, State, and federal? Something to keep track of in the decline of Western civilization.

A recent study was published in Nature on the prevalence of rule violations and the intrinsic honesty of individuals living in different societies (Gachter, 2016). Among other things, the paper reports, “[s]ocieties with higher material security, as measured by Government Effectiveness [described in the paper as a proxy for ‘bureaucratic quality and material security’] tend to be more individualist, and more individualist societies tend to have less corruption.” The decline and fall of powerful historical societies (such as the Roman Empire) seem to coincide with rapidly increasing corruption.

Romans before the fall were as certain as we are today that their world would continue forever substantially unchanged. They were wrong.
— Bryan Ward-Perkins, historian

 

The study’s results further suggest that “for many people lying is psychologically costly.” One has to be very cautious in dealing with those who DO NOT find lying to be psychologically costly. They are very possibly sociopaths.

Reference: Gachter and Schulz. Intrinsic honesty and the prevalence of rule violations across societies. Nature. VOL 000: 00 MONTH 2016 [this is how the reference is given on our hardcopy]

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IF FASCISM IS A SUBMARINE THEN THE INCOME INEQUALITY MANTRA IS THE SNORKEL

“I read ‘Why the Germans? Why the Jews?’ by Gotz Aly. And I read ‘Mein Kampf.’ Of all the things there are to tell, the most alarming discovery to me was how the constant complaints of income inequality were synonymous with an ushering in of the fascist state. In ways I don’t fully understand, political messages that beat that drum — the constant barrage of political messages to the people that they are all victims — scares me.

On the surface I would not have thought cries of income inequality had anything to do with fascism, but I’m telling you it does. If fascism is a submarine then the income inequality mantra Is the snorkel.”

—Posted by John Walters
on FRIDAY SQUID BLOGGING:
SQUID SCIENTISTS ON TUMBLR

THE STALLION THAT COULDN’T COME
TRAGEDY RESOLVED BY DIETARY SUPPLEMENT

It is amazing how much of the science and technology discussed in our Life Extension, A Practical Scientific Approach is still just as useful today as it was in 1982, when the book was published. We include here one such useful item. It involved a case in which we acted as consultants to the owner of a valuable stud racehorse that simply could not reach orgasm.

We advised them to supplement the horse with niacin and histidine. The niacin releases histamine, required for orgasm, and histidine is the precursor to histamine. As we described the results in our book, “[t]he horse’s handlers told us later that the niacin worked beautifully for a few days but then he began having trouble again. We pointed out that the horse might not be making enough histamine and suggested they supplement his diet with histidine (which is made into histamine) and vitamin B6(required for this conversion).” They told us later that the combination worked great. In fact, they said that they had to restrain the horse, who was masturbating so frequently that they were afraid he would injure himself!

Incredibly, we were also told later (though this was not reported in the case history that we included in LIFE EXTENSION, pg. 754 of the hardcover edition) that the horse’s caretakers were using so much of it themselves that they were constantly asking us to send them some more. Which we did.

RECENT RESEARCH ON SEXUALITY REVEALS THAT WOMEN PREFER LARGER PENISES

Before we go any further, let us assure you that the authors averred that there was no funding for this study; perhaps the authors paid for it themselves. If so, nobody can complain that it was a waste of their tax money.

The authors managed to write a 17 page paper on this subject. Moreover, they claimed to have used a “new research method” to determine what size penis women preferred. The new research method turned out to be 3D models of penises, rather than the 2D photos said to be used in other people’s research. The 3D penis models used were, however, a bit, er, odd. You see, they looked like cylinders without any resemblance to actual penises at all. The authors said that there were no “mathematical descriptions available to accurately represent normal proportions of more complex penile structure” and that women might have a negative response to the appearance of an actual penis.

Hmmmm. Anyway, Figure 2 showed the model penises, which looked about as sexy as you might expect from the description above. Also, they were colored blue to avoid any possible racial connotation. The authors hypothesized that women might prefer larger penises for a one night stand as compared to a long term relationship since a larger penis might be perceived as more masculine, possibly preferable for a short term affair. The authors cite a reference that supports the contention that women prefer more masculine partners for a short term sexual relationship.

The results, using the 3D models, were that women preferred a larger penis (especially a larger circumference) for a one time partner, but the larger size preferred was only slightly larger than average and, in fact, women’s preferences for both relationship types was slightly larger than average. (Presumably a survey of erect penises determined what was “average.”*)


* One wonders how the penises were measured, though. Did they use actual penises attached to actual men or the inferior 2D photos alluded to in their paper?

The authors conclude by noting that “[t]his first use of 3D stimuli to assess preferences is promising.”

Just in case you wondered…

Prause et al. Women’s preference for penis size: A new research method using selection among 3D models. PLoS One, Sept. 2, 2015

Excerpts from Some LOVE POEMS
Selected by SANDY SHAW

(all except the first were published in “LOVE AND LONGING,” a collection of classic poetry and prose, edited by Kate Agnew, 2004, Wizard Books, Ltd., UK)

Someday he’ll come along
The man I love
And he’ll be big and strong
The man I love
And when he comes my way
I’ll do my best to make him stay.

He’ll look at me and smile
I’ll understand
And in a little while
He’ll take my hand
And though it seems absurd
I know we both won’t say a word

Maybe I shall meet him
Sunday, maybe Monday, maybe not
Still I’m sure to meet him one day.

He’ll buld a little home
Just meant for two…
The man I love.

Excerpts from “THE MAN I LOVE” (written
by Carolyn Leigh and Cy Nicoleman)
(c) SONY/ATV MUSIC PUBLISHING LLC/ WARNER/
CHAPPELL MUSIC, INC.

Why did you give no hint that night
That quickly after the morrow’s dawn,
And calmly, as if indifferent quite
You would close your term here, up and be gone
Where I could not follow
With wing of swallow
To gain one glimpse of you ever anon!

— from THE GOING by Thomas Hardy

She listened with a flitting blush,
With downcast eyes and modest grace;
For well she knew I could not choose
But gaze upon her face.”

— from LOVE by Samuel Taylor Coleridge

Say I’m growing old, but add,
Jenny kissed me.”

— from JENNY KISSED ME by Leigh Hunt

Look into her eyes
Do you see what I mean
Just look at her hair
And when she speaks, oh, oh what a pleasant surprise

How do you feel
Just look at her smile
Do you see what I mean
She is looking our way
Oh how I wish we could stay, just stay for a while
How do you feel

Just look at her walk
Do you see what I mean
She is coming our way
Oh, how my heart beats, I don’t even think I can talk.
How do you feel”

— from HOW DO YOU FEEL, Jefferson Airplane

February 2016 Blog with Durk and Sandy

APPETIZERS

A man minds his own business only if it is worth minding. Otherwise he will mind yours.

—anon

Science is a wonderful thing if one does not have to earn one’s living at it.

—Albert Einstein

We’ve got a hundred trillion bacteria in and on our bodies that have coevolved with us from the dawn of humanity. In many ways, we have colonized the bacteria as opposed to the other way around.

—Peter Dilaura, Chief Executive Officer,
Microbiome Start-up Second Genome
(Dec. 21, 2015, Chem Eng News)

War is when “your” government tells
You who the enemy is.
Revolution is when you figure it out
For yourself.

—no attribution given

I will never come and go, and
Fetch and carry, at the whistle
Of the great Man in the White
House, no matter who he is.

—Davy Crockett (supplied by the Tenth Amendment Center)

Rifles, muskets, long-bows and hand
Grenades are inherently democratic
Weapons. A complex weapon makes the
Strong stronger, while a simple
Weapon—so long as there is no
Answer to it—gives claws to the
Weak.

—George Orwell

(D & S: And those “claws” are what the federalies are so afraid of.)

It is impossible to strike the chains
From a slave who admires the glitter and
Shine of decoration added to their life.
Once it becomes modish to wear chains
Even the gullible among the free will
Wish to have them.

—tyr

 

And now for a change of pace…

My wife Mary and I have been married for forty-seven years and not once have we had an argument serious enough to consider divorce; murder, yes, but divorce, never.

—Jack Benny

 

The best thing about being attracted to unavailable men is that they’re always available.

—Meg Tilley

 

The two sexes mutually corrupt and improve each other.

—Mary Wollstonecraft

 

I told the doctor I was over-tired, anxiety-ridden, compulsively active, constantly depressed, with recurring fits of paranoia.

Turns out I’m normal.

—Jules Feiffer

RESISTING METABOLIC DYSFUNCTION WITH RESISTANT STARCH

RESISTANT STARCH—A NEGLECTED DIETARY COMPONENT

A recent review (Birt, 2013) explains what resistant starch is and how it benefits human health.

The review first notes that resistant starches (of which they describe four different types) improve health by “reduction of colon cancer precursors, systemic regulation of macronutrient [ie, carbohydrates] metabolism, and altered secretion of hormones…” as well as foster gut health largely via the production of butyrate and other short chain fatty acids. (Birt, 2013)

If these benefits aren’t enough, new research shows that resistant starches cause beneficial changes to the colonic microbiota and can also ameliorate the results of vitamin D deficiency (such as is associated with many diseases, including type I diabetes, dementia) (Littlejohns, 2014); and autoimmune, some cancers, type 2 diabetes, cardiovascular disease and infectious disease (Wacker, 2013).

The different types of resistant starch are identified in the review: Type I is found in the endosperm of cereal grains or seeds that are surrounded by protein matrix and cell wall material that interferes with digestion and also, importantly, reduces the glycemic response (just as if you had eaten a low glycemic index meal). Type II is the type found in uncooked potato starch; after cooking this type of resistant starch becomes highly digestible. Type III is characterized by high levels of amylose starch—the type of starch that has fewer branched chains as compared to amylopectin starch, which is easily digested. Type IV is “chemically modified starch” which is likely to be identified on food labels as “modified starch,” which is a natural form of starch that is complexed with a lipid.

See our article on cooking starchy foods with MCT oil and then refrigerating it, which will result in the formation of more resistant starch. [See “New Technology Doesn’t Have to Be Expensive or Complicated”, in the April 2015 issue of Life Extension News.]

As the review explains, [t]he botanical role of starch is to provide plants with a stable reserve of glucose for metabolism.” “Because the amylose component of starch is less branched than amylopectin, high-amylose starch tends to be more resistant to digestion than low-amylose starch.” (Birt, 2013).

It is interesting to know that “foods such as potatoes, rice, pasta, breakfast cereals, and bread are low in resistant starch (<2.5%, dry matter basis). Cooked legumes, peas, and cooked and cooled starchy foods are high in resistant starch (5.0-15%, dry matter basis).” You can continue to enjoy the foods low in resistant starch or not eat foods containing high quantities of resistant starch (if you don’t care for them) by taking resistant starch in the form of a dietary supplement. We take a resistant starch supplement and Durk also cooks his high fiber pasta with MCT oil to increase the Type IV resistant starch his (and sometimes Sandy’s) diet supplies.

Birt, Boylston, Hendrich, et al. Resistant starch: promise for improving human health. Adv Nutr. 4:587-601 (2013).

Littlejohns et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology.83:920-8 (2014).

Wacker and Holick. Vitamin D—effects on skeletal and extraskeletal health and the need for supplementation. Nutrients. 5:111-148 (2013).

[See “New Technology Doesn’t Have to Be Expensive or Complicated”, in the April 2015 issue of Life Extension News.]

AN EMERGING WORLD OF MEDICINE—LOW-DOSE MEDICATIONS—POINTS TO A REVOLUTION IN THE TREATMENT OF A DIVERSITY OF DISEASES

Recently, versions of common drugs that are used to treat diseases within a certain dose range (as defined in the FDA approved descriptive material that accompanies the drugs) have begun to appear in published experiments and in actual clinical use at far lower doses. These much lower doses have proven to often have rather different effects and to be useful for other conditions. Of course, at the reduced dosage the risk of adverse effects are reduced as well. The use of FDA approved drugs is not approved for their low dose forms, but as is well known, physicians are free to prescribe such usage to patients. These low dose forms are frequently manufactured by compounding pharmacies.

We note a few examples here. (In doing so, we are NOT either recommending or not recommending their use, but only giving them as examples of how the low dose medication field is advancing.)

LOW DOSE PROPRANOLOL

Low dose propranolol (where propranolol is a beta blocker, an antihypertensive medication used typically at 2 to 6 mg/kg per day, was administered to rats in a model of periodontal disease. They received propranolol at 0.1 mg/kg, 5 mg/kg, or 20 mg/kg per day. Divide these figures by 6.2 for the human equivalent dose. “Propranolol at 0.1 and 5 mg/kg reduced the bone resorption [loss of jawbone] as well as ICAM-1 and RANKL expression [markers of inflammation]. However, only the 0.1 mg/kg reduced IL-1beta, TNF-alpha and CTX levels as well as increased the expression of OPG…” RANKL induces oxteoclastogenesis (osteoclasts reduce bone mass). IL-1beta and TNF-alpha are powerful inflammatory cytokines. The human-equivalent dose used here is 1% or a bit less than the usual dose for hypertension, with no blood pressure lowering side effects at this dose!

A particularly interesting study showed that low-dose propranolol was effective in preventing postoperative supraventricular tachyarrhythmias (Silverman, 1982), a common cause of death in patients who have had heart attacks and then undergone surgery for graft replacement (coronary artery bypass). At the low dosage administered (10 mg orally every six hours starting the morning after surgery) patients exhibited no significant morbidity, “yet significantly decreased the incidence of postoperative SVT [supraventricular tachyarrhythmia].” (Silverman, 1982).

The authors of the low dose propranolol study for postoperative arrhythmias (Silverman, 1982) explained that propranolol has “proven efficacy” for the prevention and treatment of a variety of tachyarrhythmias, but that abrupt withdrawal could initiate “acute ischemic events.” Hence, they wanted to determine whether low dose propranolol might be effective and yet have a reduced risk of these adverse events.

Preoperatively, patients with stable angina had their propranolol treatment tapered to 40 mg every 6 hours by the day before surgery (if receiving a lower dose, they were continued on that dose) and then to 10 mg every six hours following surgery. Certain other medications were discontinued (details in paper). Three of 50 patients (6%), who were called Group I, developed supraventricular arrhythmias as compared to 50 patients (the controls) in which 14 (28% developed such arrhythmias. This result was significant.

The results of human and animal studies suggests that the low dose of propranolol has beneficial effects with fewer side effects as compared to the high dose of propranolol usually given to treat hypertensive patients.

LOW DOSE NALTREXONE

Naltrexone, an antagonist to opioid receptors, is often used to treat patients who have ingested an overdose of opiates. In the form of low dose naltrexone, however, it has been found to be useful in treating a variety of diseases, including several types of cancers (an example is pancreatic cancer, (Berkson, 2006)), COPD, itching pruritis, (Frech, 2011), ALS, Alzheimer’s disease, Systemic Lupus, Irritable Bowel Syndrome, and the list goes on (see Low Dose Naltrexone homepage, www.lowdosenaltrexone.org/ )—NOTE: we have not evaluated more than a sampling of the contents of this website. You should contact your physician, knowledgeable about the use of low dose naltrexone, before trying anything suggested here.)

LOW DOSE LITHIUM

LOW DOSE INSULIN

LOW DOSE CLONIDINE

Other substances or drugs that offer a different result when used at low doses as compared to higher doses include lithium enhancement of memory (Tsaltas, 2007); reduction of suicides (Ohgami, 2009); low dose insulin improves age-related cognitive deficits (Maimaiti, 2016); low dose clonidine (a blood pressure medication) shown to have beneficial effects on adolescents with chronic fatigue (Fagermoen, 2015) and many, many others. This field of medicine is expanding rapidly.

How Do The Low Dose Medications Work?

One hypothesis is that in some cases, low dose medicines may act as hormetic agents, where very small amounts of a substance induce counteracting mechanisms that provide protective effects.

Another possibility is based on the fact that a medication frequently works as an inverted “U” shaped curve, where at low doses, the pharmacological effects are different at the left side of the inverted U, and then at the peak of the curve and over to the right side toward higher doses, the effects again change. Of course, the higher doses are associated with a greater risk of undesirable off-target effects.

We suspect, in addition, that in some cases there may be a subset of receptors to which the drug bonds with unusually high affinity, thereby activating or blocking this subset with negligible effects at these low doses on most of the receptors.

Are Low Dose Medications the Same As Homeopathic Medicines?

No. Homeopathic medicines have rarely been subject to experimental testing, whereas there is a growing scientific literature on low dose medications. Homeopathy was founded by Samuel Hahnemann in Germany around 1800 (long before any scientific understanding of how highly diluted medications might work and in most cases they had never been shown to work by experiment or careful statistical analyses of patients being treated with them). The field was based upon vague ideas of “like cures like” and the “law of infinitesimals.” A propranolol dose of 1% of the usual is far different than a 1/10,000,000 homeopathic dose.

Naturally, in America, physicians saw homeopathy as competitive to their own sort of medicine, probably just as poorly understood, and fought its intrusion into “their” profession. Still, homeopathy attracted adherents and was able to evade FDA regulations for quite a long time. As an op-ed in the New England Journal of Medicine(Jan 21, 2016) explained: “In 1988, recognizing the increasing size of the homeopathic-drug market, the FDA issued a Compliance Policy Guide mandating conformity with good manufacturing practices and appropriate labeling regarding ingredients and directions for use. Homepathic drugs used for ‘serious’ conditions were to be prescribed by clinicians…” The FDA’s rules provide no informative education for the public, but appear to provide the FDA’s endorsement of homeopathic therapies by permitting them to be sold under FDA rules. All this will accomplish is to make homeopathic medicines more expensive, while increasing the FDA’s powers over the field of medicine. Better if the FDA stayed out of homeopathy altogether.

The article on the FDA’s new heavy handed policies over homeopathic medicine that was published in the Jan. 21, 2016 New England Journal of Medicine, typically for this medical journal, strongly supports the new power of the FDA over a competing branch of medicine. As the article’s last sentence puts it, “[t]he recent actions by the FDA and FTC may finally signal the end of homeopathic drugs’ century long evasion of regulatory scrutiny.” These folks have never seen anything, no matter how harmless or how many people it could help, that they didn’t want to regulate—making it harder to get and much more expensive. As Ronald Reagan described the government’s approach to command-and-control, “If it moves, tax it. If it slows down, keep on taxing it, and if it stops moving, subsidize it.”

References

  • Silverman, Wright, Levitsky. Efficacy of low-dose propranolol in preventing postoperative supraventricular tachyarrhythmias. Ann Surg. 196(2):194-7 (1982).
  • Berkson et al. The long-term survival of a patient with pancreatic cancer with metastases to the liver after treatment with the intravenous alpha-lipoic acid/low dose naltrexone protocol. Integr Cancer Ther. 5(1):83-9 (2006).
  • Frech et al. Low-dose naltrexone for pruritus in systemic sclerosis. Int J Rheumatol. 2011:804296. doi: 10.1155/2011/804296. Epub 2011 Sep 12 (2011).
  • Ohgami et al. Lithium levels in drinking water and risk of suicide. Br J Psychiatry. 194:464-5 (2009).
  • Tsaltas et al. Enhancing effects of chronic lithium on memory in the rat. Behav Brain Res. 177:51-60 (2007).
  • Maimaiti et al. Intranasal insulin improves age-related cognitive deficits and reverses electrophysiological correlates of brain aging. J Gerontology A Biol Sci Med Sci. 71(1):30-9 (2016).
  • Fagermoen et al. Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial. Bmc Pediatrics. 15:117 (2015).

HYDROGEN POWER

Hydrogen Gas Perfuses the Body, Promotes Better Health, By Following the Rules of Chemistry and Physics and NOW… Those of QUANTUM MECHANICS!

We have written earlier [see “Hydrogen Therapy” in the June 2012 issue of Life Enhancement] on the important protective effects of hydrogen gas, produced by fermentation by certain microbes in the gut, by scavenging the highly potent oxidant peroxynitrite as well as damaging hydroxyl radicals.

A new hypothesis proposes that hydrogen tunneling occurs in the enzymes of humans and other animals (Klinman, 2006). This phenomenal new vision points to how hydrogen changes the way enzymes such as alcohol dehydrogenase work. The idea is that “[h]ydrogen, like an electron [can tunnel] through an energy barrier…” The motions of the enzyme [in response to the movement of hydrogen] are critical for the quantum phenomenon to occur. The motions of the enzyme bring two sites, the acceptor and donor that are needed for the reaction to take place, very close together—so close that the hydrogen can move like a wave to get from one site to another.” (Mukhopadhyay, 2016).

This is amazing because, for one thing, hydrogen is 2,000 times heavier than an electron, which is known to tunnel.

The hypothesis is characterized (Mukhopadhyay, 2016): “The emerging picture is a ‘very different view of catalysis’,” says Klinman [Judith Klinman, University of California, Berkeley who, with her colleagues, did this work]. “The role of the whole protein, through these fluctuating conformations, is to bring things so close that quantum mechanics starts to take over, even at room temperature.”

This very new field of science, quantum biology, is sure to open up many new ways of looking at disease. In the case of hydrogen, as much as we now know of its beneficial effects on biological mechanisms, we can look forward to much more that it can do beyond that via the, perhaps, surprising field of quantum mechanics.

What this means is that hydrogen may be doing a great deal more in the body when hydrogen is generated by certain bacteria in the gastrointestinal tract than has been previously understood—for example, scavenging hydroxyl radicals and peroxynitrite. Incidentally, peroxynitrite, a powerful oxidant, has been identified as a key factor in the development of heart failure (Carnicer, 2013), of fibrosis (Daiber, 2013), and in others.

It is interesting to note that hydrogen is, by far, the fastest moving molecule in one’s body, even without the additional boost of enzymatic motions.

References

  • Klinman. Linking protein structure and dynamics to catalysis: the role of hydrogen tunneling. Philos Trans R Soc Lond B Biol Sci. 361(1472):1323-31 (2006).
  • Mukhopadhyay. Quantum Biology. ASBMB Today. www.asbmb.org/publications. (January 2016).
  • Carnicer, et al. Nitric oxide synthases in heart failure. Antioxid Redox Signal.18(9):1078-99 (2013).
  • Daiber et al. Protein tyrosine nitration and thiol oxidation by peroxynitrite—strategies to prevent these oxidative modifications. Int J Mol Sci. 14:7542-70 (2013).

Oh No, It Couldn’t Be, Could It??

THERE MIGHT BE A BASIS FOR PHRENOLOGY IN THE HISTONES OF DNA

LEM1602Phrenology274.jpgYou remember phrenology, right? That was a theory that is now considered bizarre if not outright nuts that the mentality of a person could be determined by the ridges and nooks and crannies of the outer surface of the skull. How could that possibly be? It turns out that HDAC8, histone deacetylase 8, “specifically controls the patterning of the skull. Mutations in the HDAC8 gene are associated with Cornelia de Lange disease, a syndromic form of intellectual disability characterized by facial dysmorphisms.” (Bassett, 2014). In other words, the ridges and nooks and crannies of the skull (the pattern) are partially determined by HDAC8 and, when HDAC8 is mutated, associated with a disease of deficient mentality. Phrenology might have been mostly a lot of hand waving, but there could have been a little grain of truth there, too, buried under a bushel of bad statistics. Histones are protein structures surrounding DNA in the nucleus (but not in mitochondrial DNA) that control access to DNA and, in this way, determine when genes are accessible for expression and when they are not (Bassett, 2014).

Reference

  • Bassett and Barnett. The role of dietary histone deacetylases (HDACs) inhibitors in health and disease. Nutrients. 6:4273-4301) 2014).

Oh, no, THIS couldn’t be, could it?

CRUMPLED PAPER AS A MODEL FOR CORTICAL FOLDING IN MAMMALIAN BRAINS

Phrenology is awfully strange and we know of no non-BS scientific papers to go with it.

Here is another view of brain folding that seems pretty weird, too, but researchers have some experimental evidence for their hypothesis.

Scientists have developed a mathematical model for what it looks like when the brain folds and it looks like… crumpled paper (Mota, 2015). The illustration in the commentary (Striedter, 2015) on the study showing the paper ball when crumpled, then expanding into its final folded form has the caption: “Folding increases with paper size, thicker paper has fewer folds. An analogous scaling rule applies to cortical folding in mammalian brains.”

The researchers here “provide a novel mathematical description of how the degree of neocortical folding in mammalian brains varies with other biological parameters, notably cortical thickness and surface area, and they offer the crumpling of a paper ball as a physical model to explain the observed scaling rules.” (Striedter, 2015). “For species with folded cortices (such as the human brain), total surface area increases faster than the exposed surface area (i.e., the slope is substantially greater than 1) [whereas the slope is 1 in species, such as rats and mice, that have smooth cortices].” Interestingly, whales and dolphins have more cortical folds than other mammals with the same cortical surface area (Striedter, 2015).

The researchers (Mota, 2015) crumpled paper balls to determine how the balls relaxed after being crunched. The result was consistent with the general scaling law as seen in the folding neocortex. As the commentary (Striedter, 2015) on the paper notes, “[t]he principal problem with the paper ball analogy is that it describes the folding of a structure that no longer grows, whereas the cortex folds during development.”

References

  • Striedter and Srinivasan. Knowing when to fold them. Science. 349:31-2 (2015).
  • Mota and Herculano-Houzel. BRAIN STRUCTURE. Cortical folding scales universally with surface area and thickness, not number of neurons. Science. 349:74-7 (2015).

THE BENEFITS OF AGED GARLIC MAY BE SOMEWHAT UNDERESTIMATED

A report from the BBC (30 March 2015) reports the potent effects of some awfully old medicine. A 9th Century Anglo-Saxon remedy for treating eye infections used onion, garlic, and part of a cow’s stomach was found in Bald’s Leechbook, an old English manuscript now held by the British Library. Scientists using this remedy were “astonished” to find that “it almost completely wiped out methicillin-resistant staphylococcus aureus, otherwise known as MRSA.” It is also otherwise known as a deadly killer, with a high mortality rate in humans. The remedy actually killed “up to 90%” of the MRSA bacteria, a phenomenal kill rate compared to what infected humans are currently being treated with in hospitals (where they are frequently infected in the first place).

These findings were said to be presented at the Annual Conference of the Society for General Microbiology in Birmingham, England. (As the conference was to have taken place in 2015, the findings have, presumably, already been presented).

Here is the actual formula for the remedy:

“Equal amounts of garlic and another allium (onion or leek), finely chopped and crushed in a mortar for two minutes.

Add 25 ml. (0.87 fl oz) of English wine [it MUST be English wine]—taken from a historic vineyard near Glastonbury [does this sound like an advert?]

Dissolve bovine salts in distilled water, add and then keep chilled for nine days at 4C.”

The bovine salts probably contained taurine (named after taurus—Latin for cattle—where is was first discovered). Taurine and chloride or bromide can be converted in one’s body to the powerful antimicrobials taurine chloramine and taurine bromamine, which are also anti-inflammatory molecules. [See “New Taurine & Bromine Formulation” in the September 2014 issue of Life Enhancement.]

The wine contained polyphenols with antimicrobial properties and garlic also has such properties.

That’s one way to look at it…

BEING SHORT CAN BE AN ADVANTAGE

“The shorter you are, the longer you’ll live if you’re a Japanese man, Hawaii-based researches concluded.”

“A study based on the Kuakini Honolulu Asia Aging Study showed shorter men were likelier to have a protective form of the longevity gene FOXO3, leading to smaller body size in early development and a longer lifespan. Shorter men were also likelier to have lower blood insulin levels and less cancer.”

—reported in the May 7 2014 PLoS ONE

Recipe

SANDY’S DELICIOUS CARBONATED ORANGE JUICE

Like carbonation in your orange drink? You don’t have to buy somebody’s not very tasty orange soda. Make your own. It’s SO easy and tastes GREAT.

All you need is about two cups of orange juice, fresh squeezed for best flavor but if you’re in a rush, a good quality commercial orange juice will do fine. You add about 1/4-1/2 teaspoon of baking soda to the juice (depending on how much carbonation you want) and stir briskly (maybe 20 seconds) until you see some fizz at the surface. Then drink it for a treat compared to plain OJ.

The small amount of baking soda (sodium bicarbonate) you’ve added to the orange juice will have NO effect on the flavor, but the bubbles from the carbonation will produce a nice tingling sensation on your tongue. You can do it with any fruit juice that is acidic, like pineapple juice.

Watch out for overflowing foam when you add the baking soda!

HOW TO DETECT LIES WITH A STORYTELLING TECHNIQUE

A hypothesis put forth by Andy Morgan, a forensic psychologist at Yale University who specializes in human memory and deception, purports to show that one can detect lies from analyzing stories subjects wrote about experiences they’d had. Morgan calls this “cognitive interviewing” and believes that the physical signs that are usually considered possible indications of lying such as blood pressure and respiration changes, alterations in skin such as sweating only achieves an accuracy of about 50% or, as he puts it, like flipping a coin.

What Morgan and his colleagues found, in interviewing 1200 people, was that stories describing the physical/sensory events in their experiences became much harder to put together when they were coming from liars. Morgan produced transcripts of each interview and showed that in nearly 85% of cases, “the transcripts that contained fewer unique words and fewer words overall related to the stories told by liars.” Morgan believes that this is because having to make stuff up reduces the richness of what is being said and the complexity of the language used to describe it.

This was reported in Criminal (podcast) episode 2—“Pants on Fire,” 14 February 2014

January 2016 Blog with Durk and Sandy

APPETIZERS

STARTING 2016 WITH A LAUGH… BY LOOKING ON THE BRIGHT SIDE

In theory, there is no difference between theory and practice. In practice there is.

—Yogi Berra

Listen carefully to first criticisms of your work. Note what it is about your work the critics don’t like—then cultivate it.

That’s the part of your work that’s individual and worth keeping.

—Jean Cocteau

 

Always listen to experts.
They’ll tell you what can’t be done and why.
Then do it.

—Robert Heinlein

 

Speak when you are angry, and you will make the best speech you will ever regret.

—Ambrose Bierce

 

THE POLITICOS CAN’T STAND IT WHEN THEY’RE THE BUTT OF LAUGHTER THEY’LL CRINGE AND THEN THEY’LL SLINK AWAY, INTO THE ZOMBIE HEREAFTER.

—Sandy (not a poet, just like to play with words)

 

In the Third Century AD, Emperor Caracalla of the bankrupt Roman Empire was said to have pointed to his sword and remarked “as long as we have this, we shall not run short of money.”

(D&S Comment: Nothing has changed
other than the weapons technology.)

 

THE WORLD STATE by G. K. Chesterton

Oh, how I love Humanity,
With love so pure and pringlish,
And how I hate the horrid French,
Who never will be English!
The International idea,
The largest and the clearest,
Is welding all the nations now,
Except the one that’s nearest.
This compromise has long been known,
This scheme of partial pardons,
In ethical societies
And small suburban gardens—
The villas and the chapels where
I learned with little labour
The way to love my fellow-man
And hate my next-door neighbor.

[D&S Comment:
A Good Fence makes a good neighbor,
And sure is worth the Labour!]

 

The truth will set you free…
But first it will piss you off!

—Anon Y Mous

 

Freedom is the oxygen of the soul.

—Moshe Dayan

 

UNAPPETIZING—

The Russians are very good at digging mass graves and filling them in, And the Europeans are very good at looking the other way.

—Durk Pearson

 

(D&S Comment: The above is just a thought as we watch developments in Europe, while Putin is on the sidelines plotting to take advantage of it. Of course, Obama has been sold to the highest bidder (hint: not the U.S. taxpayers) and the European militaries will not be doing anything to interfere with a takeover of Europe by Islamic extremists demanding Sharia law. Meanwhile while our traitorous President wants to import hundreds of thousands of Islamic immigrants—just funded yesterday (12-17-15) by our helpful Congress—immigrants who will be thoroughly background checked,* avers Kerry. Think of this as hiring a thousand agents provocateur. Ever get the feeling that this is not a case of stupidity or ignorance, but of a plan to dismantle the America we were born in? Thank the Second Amendment activists for seeing to it that we have not been disarmed.)

 


* In a report with the headline “Senior Obama officials have warned of challenges in screening refugees from Syria” (The Washington Post, 11/17/15, we get the picture that the risks associated with importing 300,000 Syrian refugees into the United States are severe and there is a substantial problem in imagining what could possibly justify this, e.g., how does the United States benefit from this? What, one has to wonder, is the agenda that the powers that be have in mind?

 


 

The Post article (see footnote) quotes FBI director James Cooney as saying in Congressional testimony last month that, although the vetting process for checking out refugees has “‘improved dramatically,’ Syrian refugees will be even harder to check because, unlike in Iraq, U.S. soldiers have not been on the ground collecting information on the local population. ‘If we don’t know much about somebody, there won’t be anything in our data,’ he said, ‘I can’t sit here and offer anybody an absolute assurance that there’s no risk associated with this.’” One might say that he COULD offer an absolute assurance that terrorists will get into the United States via such a plan.

WHEN HISTORY REPEATS— THE COLLAPSE OF THE ROMAN EMPIRE

Rome’s collapse meant staggering loss. People forgot how to read, how to farm, how to govern themselves, how to build houses, how to trade, and even what it had once meant to be a human being.

—lost source

 

WHO STEALS THE MOST STUFF IN THE UNITED STATES?

“Law Enforcement took more stuff from people than burglars did last year” proclaimed a headline in the Washington Post 11/23/2015. The Post reports that, as pointed out in the blog from Martin Armstrong of Armstrong Economics the week before and as Armstrong learned from the Institute for Justice, the Treasury and Justice departments deposited more than $5 BILLION into their respective asset forfeiture funds last year, while the FBI reports that burglary losses topped out at $3.5 BILLION. (Needless to say, the total amount of private burglary losses is likely to be underestimated overall but, on the other hand, an unusually large asset seizure can have a very large impact on the total. The article reports that the Bernie Madoff judgment amounted to $1.7 billion, which was said to have reverted largely to the victims (though you have to wonder how much the lawyers got).

All in this paragraph was reported
in Wonkblog by Christopher Ingraham.

QUICKIES

Chen et al. Activation of TRPV1 channel by dietary capsaicin improves visceral fat remodeling through connexin43-mediated Ca2+ influx. Cardiovasc Diabetol.14:22 (2015).

The above paper discusses the stimulation by capsaicin (hot pepper) of the burning of fat by adipocytes in visceral fat. Niacin, a TRPV1 agonist, signals brown fat and other types of cells to use fat as a fuel rather than glucose, though we do not have a reference at hand that niacin signals such a switch in fuel use in adipocytes in the heart nor do we know whether capsaicin does that in the heart. This could be important as the heart is highly dependent on fat burning for the production of energy. See Virtue et al. A new role for lipocalin prostaglandin D synthase in the regulation of brown adipose tissue substrate utilization. Diabetes. 61:3139-47 (2012). Prostaglandin D synthase is activated by niacin during the niacin flush. For more, see Sandy Shaw’s niacin flush paper in the August, September, and October Life Enhancement website. Li et al. TRPV1 activation impedes foam cell formation by inducing autophagy in oxLDL-treated smooth muscle cells. Cell Death Dis. 5:e1182 (2014).

Foam cells are a major part of the atherosclerotic process. Here, the researchers used smooth muscle cells derived from mice. Capsaicin was used to activate TRPV1.

Suggestion: Take capsaicin capsules as a daily supplement

VITAMIN D3 promotes the recovery of amyloid beta clearance by phagocytes in ALZHEIMER’S DISEASE macrophages derived from human patients.

Reference

  • Mizwicki et al. Genomic and nongenomic signaling induced by 1alpha,25(OH)2-vitamin D3 promotes the recovery of amyloid-beta phagocytosis by Alzheimer’s disease macrophages. J Alzheimer’s Dis. 29(1):51-62 (2012)

DAYDREAMS: NOREPINEPHRINE facilitates what is called “task unrelated thoughts” or (more commonly) daydreams.

Reference

  • Smallwood et al. Insulation for daydreams: a role for tonic norepinephrine in the facilitation of internally guided thought. PLoS ONE. 7(4):e33706 (2012).

LYCOPENE—A CAROTENOID WITH POWERFUL ANTI-INFLAMMATORY POWERS

The data in a paper (Rafi, 2007) indicated potent anti-inflammatory effects of the carotenoid lycopene that, as part of a natural chemical pathway, inhibits COX. Via its two forms COX1 and COX2, COX converts arachidonic acid to inflammatory prostaglandins, such as the powerful inflammatory prostaglandin E2 (PGE2) (though under some conditions PGE2 can be anti-inflammatory). PGE2 is a known factor in virtually all inflammatory diseases, including cardiovascular disease, cancer, diabetes type 2, arthritis, inflammatory bowel disease, epilepsy, Alzheimer’s disease, and many others.

COX-1 is constitutively expressed, while COX-2 is an inducible enzyme that “mediates acute and chronic inflammation, pain, and cellular repair mechanisms.” (Rafi, 2007) The authors believe that the results of data from studies of lycopene “suggest that inhibition of COX2 may be effective in preventing infammatory-associated cancers.” (This suggestion, from 2007, was supported by later work.) The authors concluded: “Therefore, using lycopene or [lycopene-containing] tomato-based products to regulate the production of NO and COX-2 may be classified as a therapeutic approach for the treatment or prevention of chronic inflammatory disease.”

Sandy Gets Some Relief From The Pain Of Her Arthritic Knees With Lycopene

Unfortunately, Sandy has a moderate case of knee osteoarthritis. We had run out of lycopene and after a few days to a couple of weeks she had noticed more pain in her knees. The day she went back on lycopene (we both used 15 mg a day, though Sandy has upped hers to 30 mg a day now that she has felt the difference), she was aware of much more comfort in walking. The best way to take it is with the fattiest meal of the day, as it is absorbed best with fats.

It is also interesting that lycopene is another one of the natural products that inhibits formation of inflammatory prostaglandins. See (Shaw, 2015) “Why the Niacin Flush May Be Surprisingly Beneficial to Your Health” by Sandy Shaw for a discussion in Part I under the subheading “What Is the Niacin Flush? of inflammation and the prostaglandins that play such a major role in it, particularly PGE2 and PGD2. PGD2 is prostaglandin D2 that is released, causing the niacin flush, and which counters the effects of inflammatory PGE2 when released as a pulse, but there are many ways other than taking niacin to interfere with PGE2-induced inflammation. Lycopene is one such effective antiinflammatory nutrient.

Note that COX-2 inhibitors such as Celebrex are widely used for treating arthritis and, unlike the prescription COX-2 inhibiting drugs, there is no evidence that lycopene increases the risk of cardiovascular disease. Indeed, lycopene reduces the risk, possibly (at least in part) because of its powerful antioxidant activity.

Sandy Shaw (2015) paper, Part I, is found in the Life Enhancement website, www.life-enhancement.com, August 2015.

Reference

  • Rafi, Yadav, Reyes. Lycopene inhibits LPS-induced proinflammatory mediator inducible nitric oxide synthase in mouse macrophage cells. J Food Sci.72(1):S69-S74 (2007).

NEUROGENESIS CAN BE OVERDONE JUST LIKE EXERCISE
IT IS INITIATED BY ELECTRICAL ACTIVATION OF NEURAL STEM CELLS, SAME TYPE OF ELECTRICAL ACTIVITY THAT TRIGGERS EPILEPTIC SEIZURES

Like any physiological process, there is a level at which too much neurogenesis can lead to adverse effects (Hsieh and Schneider, 2013). The effects of various levels of electrical activity on neurogenesis have been described (Hsieh and Schneider, 2013) as follows: “It may be that the neurogenesis response of stem progenitor cells to [electrical] activity is an adaptive mechanism to maintain regional homeostasis: increasing stem cell production when local circuitry activity levels are low, and restoring quiescence when activity levels are high.” The point here is that when activity levels are too high, you have electrical activation that becomes pathologically high as occurs during an epileptic seizure. As the authors go on to explain: “A potential ‘cost’ of excitable stem cells is inappropriate activation after pathological forms of activity, such as seizures.”

The authors also describe a possible excitation signal as follows: “A possible mechanism for excitation-neurogenesis coupling is GABA-mediated depolarization, previously described in mouse embryonic neuronal progenitor cells. Depolarization causes an increase in intracellular Ca2+ concentration similar to that evoked in cultured neural stem/progenitor cells. This excitation signal is relayed to the genome wherein the transcription factor NeuroD is rapidly activated to promote neurogenesis.” “…excitation signaling in the form of GABA is also necessary to drive the functional integration of newborn neurons.”

In another paper (Veyrac, 2013), the authors explain, “Newborn DGCs [dentate granule cells] are initially tonically activated by ambient depolarizing GABA….” Following hyperpolarization (by process that includes expression of glutamate receptors), “…they are hyperexcitable, display properties of ehanced synaptic plasticity, and are prone to integrate the existing hippocampal neurocircuitry.”

Importantly, the authors point out, “As their functional maturation progresses, however, newborn DGCs compete to survive, leaving the majority eliminated by cell death. Several behavioral manipulations, in particular hippocampal dependent learning, can regulate their rate of survival.” In this paper (Veyrac, 2013), the authors identify the Zif268/egr1 gene as controlling the selection, maturation, and functional integration of adult hippocampal newborn neurons by learning.”

Immediate Early Genes Are Transiently And Preferentially Induced In Newborn DGCs During Their Critical Period Of Maturation

Zif268/egr1 is one such immediate early gene and, as explained in the paper, actively controls the survival of newborn DGCs during their critical period of maturation in the first 2-3 weeks of their birth.”

The requirement for excitation during the early phase of newborn neuronal maturation may be a reason that the decline in arachidonic acid in cell membranes of the brain with aging is a negative factor in cognition (McGahon, 1997). Despite the fact that the metabolic products created by arachidonic acid are often involved in damage due to excessive inflammation, arachidonic acid is there for some reason(s) and this might be one of those reasons. Rice oil is relatively rich in arachidonic acid. Perhaps this is one reason that the Japanese who live in Japan, who consume a lot of rice and use rice oil in cooking, may live longer than those in other countries.

DHA Protects the Brain Against Inflammation

As we have written before, one way to protect the brain against arachidonic acid-associated inflammation is to take supplementary DHA, docosahexaenoic acid, as found in fish oils. (Basselin, 2012).

References

  • Hsieh and Schneider. Neural stem cells, excited. Science. 339:1534-35 (2013).
  • Veyrac, Gros, Bruel-Jungerman, et al. Zif268/egr1 gene controls the selection, maturation and functional integration of adult hippocampal newhorn neurons by learning. Proc Natl Acad Sci U S A. 110(17):7062-67 (2013).
  • McGahon, Clements, Lynch. The ability of aged rats to sustain long-term potentiation is restored when the age-related decrease in membrane arachidonic acid concentration is reversed. Neuroscience. 81(1):9-16 (1997).
  • Bresselin, Ramadan, Rapoport. Imaging brain signal transduction metabolism via arachidonic acid and docosahexaenoic acid in animals and humans. Brain Res Bull. 87(2-3):154-71 (2012).

LIVE LONGER AND ENJOY BETTER ORGASMS, TOO?

ORGASM: How the Brain Makes You Feel SOOOOO Good
by Sandy Shaw

HYPOTHESIS: ORGASM is like a small, self-limited epileptic seizure in terms of temporal electrical activity, that takes place in the “pleasure center” area of the brain and also in the lower part of the spinal cord. Feeling good is an important part of what makes life worth living and orgasms make you feel so good.

It is known that people experiencing epileptic seizures may also concurrently have orgasms. An early paper Sandy got after she hypothesized that orgasm might be a sort of small epileptic seizure provides support for that hypothesis (Heath, 1972). It is surprising how some of the oldest papers in a field provide information that has not been referred to in later papers. So, in researching how orgasm works, Sandy decided to look at the early stuff. The Heath, 1972 paper was useful, as was Gil-Vernet, 1994, which provided an amazingly detailed series of events that take place in the ejaculatory mechanisms accompanying orgasm (that include, for example, urethra, prostate, bladder neck, and so on), all via endorectal ultrasonography. Incredible work!

Interestingly, epilepsy has been very recently reported to be associated with activation of the TRPV1 receptor (Naziroglu, 2015), for which capsaicin (component of hot pepper) is an agonist. Anti-epileptic medications which reduce the sensitivity of the TRPV1 receptor to its agonists, tend to increase the difficulty of reaching orgasm. The TRPV1 receptor can also cause pain and itch and, it may not be coincidental that orgasm in some individuals can be enhanced by pain. “It is well known that neurogenic inflammation is associated with the activation of nociceptors [pain receptors] sensitive to capsaicin …” (Origoni, 2014, pg. 5).

The NIACIN FLUSH and the TRPV1 “Capsaicin” receptor—the connection to better orgasms

Durk has commented that he finds that experiencing the niacin flush while having an orgasm produces a stronger orgasm. (Sandy has noticed that, too.) Recently, niacin has been discovered to activate the TRPV1 receptor (Linlin, 2014) and this is thought by the researchers who made that discovery to be a part of the niacin flush of itching and increased cutaneous (skin) blood flow with the sensation of warmth. Incidentally, we find here the return of the inflammatory prostaglandin PGE2 and its counteractive antiinflammatory prostaglandin PGD2 in the pain activation at the irritant receptor TRPA1 (related to and interactive with TRPV1). The TRPA1 receptor is activated by pungent, warming spices, such as mustard, garlic, and cinnamon (Materazzi, 2008). As explained in Sandy Shaw’s paper on the niacin flush (see Life Enhancement website for August, September, and October 2015), the pulsatile release of PGD2 by immediate release (not extended release) niacin is the cause of the niacin flush. Niacin has been shown to activate, as part of the niacin flush, the TRPV1 receptor (as does capsaicin) (Linlin, 2014) and perhaps, like capsaicin, this activation could desensitize the TRPV1 receptors.

These anecdotal observations and very recent scientific discoveries are consistent with TRPV1 activation being part of orgasm.

It is known that, “Sexual experience promotes adult neurogenesis in the hippocampus despite an initial elevation in stress hormones,” as it says in the title of a paper by Leuner, Glasper, Gould, PLoS ONE July 2010. This is consistent with the increased neuronal excitation required for neurogenesis and, thus, neurogenesis and orgasm may be cousins in terms of electrical pathways. Now if only we could figure out how to generate orgasms at will and perhaps lengthen them (much too short, like life itself, don’t ya think?)

It may be that a simple way to increase the strength and/or length of orgasms is to activate the TRPV1 receptors at the time that you want to experience an orgasm. Hence, eating hot pepper, cinnamon, ginger, mustard, garlic, or other “hot” foods and spices just before you want to “come” might be just the ticket. In fact, “hot” foods and spices have long been thought to be aphrodisiac and the TRPV1 receptor activation may be a large part of why they appear to have sex enhancing effects. Hot Indian spices are indeed used in Tantric yoga sex ceremonies as we found when we were guinea pigs in studies of tantric sex by doctors Hartman and Fithian in the 1970s.

IN FACT, HOT FOODS AND SPICES
MAY HELP YOU LIVE LONGER

TRPV1 Regulates Longevity and Metabolic Health in Mice

Indeed, TRPV1 does a lot more than regulate pain and itch and (perhaps) orgasms. It has recently been found that TRPV1 knockout mice (mice that have no TRPV1 receptors, with the result looking as if their TRPV1 receptors are entirely desensitized) are exceptionally long-lived, “displaying a youthful metabolic profile at old age.” “These data suggest that ablation of select pain sensory receptors or the inhibition of CGRP [calcitonin gene-related peptide, which promotes neurogenic inflammation or antagonizes insulin release] are associated with increased metabolic health and control longevity” (Riera, 2014). This suggests that the niacin flush and the consumption of “hot” foods and spices may be beneficial to one’s health and longevity.

TRPA1: a Gatekeeper for Inflammation

TRPA1 has been described as a “gatekeeper of chronic inflammatory disorders of the skin, airways, and gastrointestinal tract” (Bautista, 2013).

It has been linked to diseases that include asthma, cough, inflammatory bowel disease, colitis, and many others (Bautista, 2013). Hence, consuming hot foods and spices that activate the TRPA1 receptor—including mustard, garlic, cinnamon, etc.—is a way to desensitize the TRPA1 receptor, which studies show to decrease inflammation in the skin, airways, and GI tract, and possibly to extend life and induce stronger orgasms. WOW! What more could you ask?

TRPV1 Desensitization Also Improves Cognitive Function

You might add to the list of potential benefits of TRPV1 desensitization that, “TRPV1 inactivation [via desensitization] also improves cognitive functions” (Steculorum, 2014). TRPV1 has been reported to be highly expressed in brain areas important in cognitive function including the cortex and hippocampus and to modulate hippocampal synaptic plasticity including long term potentiation (Mezey, 2000). A more recent paper reported that, in mouse brain slices, capsaicin-induced changes in long term potentiation (LTP, a learning/memory process) in the lateral amygdala were mediated by TRPV1 (Zschenderlein, 2011).

Sandy (and Durk) have both noticed a REALLY remarkable improvement in Sandy’s visuo-spatial capabilities since using TRPV1 desensitization agonists as adjunct treatments for her temporal lobe epilepsy. This is an anecdotal report, not PROOF that TRPV1 activation followed by desensitization can improve visuo-spatial capabilities. Incidentally, the downside of this improved cognition via TRPV1 was, for Sandy, a concurrent increase in irritability, as well as impatience, so if you are prone to outbursts of irritability, be careful, and if you aren’t but your best friend using these supplements is, you might also be careful. Depending on how sensitive an individual is to the TRP system, changes in dietary constituents that affect TRP channels could have a noticeable effect on personality. The effect might be considered desirable by friends, but also might be undesirable—depending on how you use the supplements.

CAUTIONARY NOTES FOR THE USE OF SUPPLEMENTS THAT ACTIVATE OR DESENSITIZE TRP CHANNELS:

    1. In using natural substances (spices and herbs) that activate the TRPV1 and/or TRPA1 receptors (which are part of a family of 28 different Transient Receptor Potential channels), you have to be very cautious as some individuals are much more sensitive to activation than others. Highly activated, TRPV1 (for example) can produce states of irritability and even rage that go beyond the energy-increasing levels that most people would find comfortable. Just consider how much variation there is in how sensitive people are to capsaicin (hot pepper) to give you an idea of what could happen to some that you might want to avoid. A minor example: Durk gets a bellyache when he takes capsaicin capsules on an empty stomach, whereas Sandy doesn’t.
    2. Some animals used in research (principally rodents, but also dogs and others) respond to TRPV1 and TRPA1 activation very differently than humans do. Hence, when you read a scientific paper that lists purported “agonists” for the TRP receptors, be aware that whether the agonists in the list are really agonists in humans depends critically on what animals were used in the research and DO NOT assume that humans will have a similar response. A good example is peppermint (a TRPA1 agonist); people like it, rodents hate it and stay away from it (making peppermint a useful rodent repellant). The animals may not like the sensations in their mouth or throat or possibly even how it makes them feel.
    3. It may be that what is called an “agonist” could be an “antagonist” and that the dosage is what makes the difference, so that anything called an “agonist” might be an “antagonist” depending on dose and you can’t necessarily expect the substance to be committed to being an “agonist” or “antagonist” because a research paper found it to be so under certain conditions.
    4. Indeed, whether a substance is an agonist or antagonist depends not only on the species in which the substance is tested, not only on the dosage used, but also on the time of the day, the stresses the animal (or human) is under at the time, and other factors that make it far from a simple proposition to determine what effect you are going to get. The tried and true careful self-experimentation, recording the conditions under which the experiment was conducted, is really the best we have at present for personal use. Simple noninvasive tests would be very helpful.

References

  • Naziroglu. TRPV1 channel: a potential drug target for treating epilepsy. Curr Neuropharmacol. 13:239-47 (2015).
  • Linlin, Lee, Mao, et al. Nicotinic acid activates the capsaicin receptor TRPV1—a potential mechanism for cutaneous flushing. Arterioscler Thromb Vasc Biol. 34(6):1272-80 (2014).
  • Origino, Maggiore, et al. Neurobiological mechanisms of pelvic pain. Biomed Res Int. 903848. doi: 10.1155/2014/903848. (2014).
  • Materazzi, Nassini, Andre, et al. COX-dependent fatty acid metabolites cause pain through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A. 105(33):12045-50 (2008).
  • Riera, Huising, Follett, et al “TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling. Cell. 157:1023-36 (2014).
  • Bautista, et al. TRPA1: a gatekeeper for inflammation. Annu Rev Physiol.75:181-200 (2013).
  • Mezey, Toth, Cortright, et al. Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human. Proc Natl Acad Sci U S A. 97:3655-60 (2000).
  • Steculorum and Bruning. Die another day: a painless path to longevity. Cell. 157:1004-6 (2014).
  • Gil-Vernet JM, et al. Ejaculation in men: a dynamic endorectal ultrasonographical study. Br J Urology. 73:442-8 (1994).
  • Heath. Pleasure and brain activity in man. Deep and surface electroencephalograms during orgasm. J Nerv Ment Dis. 154(1):3-18 (1972).
  • Zschenderlein et al. Capsaicin-induced changes in LTP in the lateral amygdala are mediated by TRPV1. PLoS ONE. 6(1):e16116 (2011).

 


TRPV1 Sensitization May Be Part of Opiate (or Sex?) Withdrawal 
by Sandy Shaw

There is a scientific literature describing connection between opioids and TRPV1 receptors (Hakimizadeh, 2014). In this particular paper, it was reported that in rats, morphine reduced the expression of TRPV1 receptors in the amygdala but not in the hippocampus. The amygdala is an important brain center involved with, among other things, the emotion of fear. The researchers (Hakimizadeh, 2014) found that in morphine-dependent rats, there was a significant decrease in TRPV1 gene expression in the amygdala and that this suggests that, “TRPV1 receptors may be involved in morphine-induced dependence.”

Sex addiction might be an example of what happens when endogenous (or exogenous) opioids interact with TRPV1 receptors, but it is quite complex because, for one thing, there are 28 different known Transient Receptor Potential (TRP) channels, and these may interact with each other, with feedback effects and compensatory activity that complicates the interpretation of these interactions (Kaneko, 2014).

For those with deficient interest in sex (the so-called “hypoactive sexual desire disorder”), TRPV1 activators (capsaicin and ginger, for example) may be useful in jazzing up sexual interest. Perhaps that is a reason that ginger beer (real beer, not a soft drink) is so popular. Actually, the soft drink would work, too, but small amounts of alcohol boost the TRPV1 effect of the ginger.

References

  • Hakimizadeh, et al. Morphine reduces expression of TRPV1 receptors in the amygdala but not in the hippocampus of male rats. Iran J Med Sci. 39(3):261-7 (2014).
  • Kaneko and Szallasi. REVIEW: Transient receptor potential (TRP) channels: a clinical perspective. Br J Pharmacol. 171:2474-2507 (2014).

 


COMING UP: perhaps in next Durk & Sandy newsletter:

TRPV1 And Drugs, Sex, (And Rock & Roll?)

Hmmmm. I wouldn’t be surprised if TRPV1 plays a role in rock & roll by being part of the system that, particularly in young men (but also some young women) puts the energy and the sexual drive into rock & roll that you don’t see too much in aging rock performers. Does this mean that old rock performers can be “rejuvenated” by TRPV1 agonists??? A fun thought for the future of rock & roll.

Also, as noted above (see section on TRPV1 improvement of cognition), this receptor may be involved with visuo-spatial abilities (only a hypothesis), as Sandy and Durk have noted in Sandy, who has sensitivity to TRPV1 receptors. If so, then here is another way that TRPV1 agonists might be beneficial to aging musicians.

RECIPE
SCINTILLIA’S HOLIDAY CHEESECAKE

Yummy and SO easy to make. Other than shopping for the ingredients, prep time is only about 10 minutes.

Nutritional benefits: 1. sweetened with erythritol, 2. the whipped topping is made of low fat, low sugar content chocolate mousse yogurt with live cultures. Erythritol is not only free of sucrose or sweeteners, both natural and synthetic, with various adverse effects, but it is a scavenger of damaging hydroxyl radicals. 3. Vanilla is a mild agonist to the TRPV1 receptor, while nutmeg in the quantities used for the cheesecake will give you, in a serving, a mild agonist dose to the TRPA1 receptor. Ever think of eating as a virtual chemistry book of ingredients and their effects? These days, it can seem a lot like that. Your taste buds won’t know the difference, though. It will all just taste wonderful to them.

Ingredients you’ll need:

• Canned pineapple slices in pineapple juice, six or seven slices

• 1 prepared graham cracker pie crust

• 1 pkg (8 oz) of cream cheese, softened

• Two or three 6 oz. servings of Yoplait whipped chocolate

• Mousse yogurt

• 2 teaspoons vanilla extract

• Powdered nutmeg

• 1⁄3 cup erythritol

TIP: You don’t need to bake the prepared pie crust, though the package wrapper is likely to suggest it if you want a “golden” crust. The flavor difference is not very much whether “golden” or not.

1. Use a hand mixer or whip to blend the softened cream cheese and vanilla in a small bowl.

2. Line the pie crust with the drained slices of pineapple.

3. Pour the cream cheese and vanilla mixture evenly over the pineapple slices.

4. Sprinkle nutmeg over the cream cheese/vanilla layer to your taste.

5. Gently spoon out the chocolate mousse yogurt over the cream cheese/vanilla until even, without pressing down on it (so as to avoid squeezing out the air whipped into the mousse).

6. That’s it! You cover your pie shell containing its fillings with the plastic cover that generally comes with the prepared pie crust and refrigerate for three hours. Then ENJOY!!

December 2015 Blog with Durk and Sandy

HAPPY NEW YEAR!!!!

APPETIZERS

HOW DOES HE KNOW WHEN YOU’VE BEEN NAUGHTY OR NICE?
You’d better watch out,
You’d better not cry,
You’d better not pout,
I’m telling you why,
Santa Claus is tapping
Your phone.

He’s bugging your room,
He’s reading your mail,
He’s keeping a file,
And running a tail,
Santa Claus is tapping
Your phone.

He hears you in the bedroom,
Surveils you out of doors,
And if that doesn’t get the goods,
Then he’ll use provocateurs.

So—you mustn’t assume
That you are secure,
On Christmas Eve
He’ll kick in your door,
Santa Claus is tapping
Your phone.

Our thanks to Eugene Volokh,
THE VOLOKH CONSPIRACY,
posted 9 Sept. 2013

When I played drunks I had to remain sober
Because I didn’t know how to play them
when I was drunk.
— Richard Burton

LSD is a drug that causes psychotic and aberrant behaviors in people who have not taken it.
— tyr

If that’s an army, they are too few. If it’s a diplomatic embassy, they are too many.
— Tigranes the Great of Armenia at Tigranocerta in 69 BC, surveying the 12,000 Roman soldiers who were about to tear apart his army of some 135,000 men (from The Classical Compendium by Philip Matyszak, Thames & Hudson, 2009)

Love is not altogether a delerium, yet it has many points in common therewith.
— Thomas Carlyle

Love is a great beautifier.
— Louisa May Alcott

There is pleasure in the pathless woods.
— Lord Byron

Joy is not in things; It is in us.
— Richard Wagner

Random processes produce many sequences that convince people that the process is not random after all. You can see why assuming causality could have evolutionary advantages. It is part of the general vigilance that we have inherited from our ances- tors. We are automatically on the lookout for the possibility that the environment has changed. Lions may appear on the plain at random times, but it would be safer to notice and respond to an apparent increase in the rate of appearance of prides of lions, even if it is actually due to the fluctuations of a random process.

— Daniel Kahneman, Thinking, Fast and Slow (Farrar, Straus and Giroux, 2011) (pg. 115)

(D & S Comment: The automatic vigilance is described in the book as being part of System 1, the intuitive way of thinking. So while it is certainly good to be vigilant of marauding lions even if you think their appearance is caused by the boogie man, the fly in the ointment is that the belief in an incorrect assumption of a cause can, in the world of politics, end up costing a huge amount of money if the process is random rather than caused by what people believe intuitively. And, unfortunately, as the author points out earlier in the book (pg. 91) the people who are most likely to make snap (intuitive) judgments of the competence of political candidates on the basis of whether they have a “competent” face were those that were most politically uninformed and who watched a lot of television.

Francis Crick (Nobel Prize Winner, Medicine, 1962) must have been bom- barded with mail following his receipt of the Nobel Prize. Here is a response he is reported to have sent out: Dr. Crick thanks you for your letter but regrets that he is unable to accept your kind invitation to: send an autograph/ help you in your project/ provide a photograph/ read your manu- script/ cure your disease/ deliver a lecture/ be interviewed/ attend a conference/ talk on the radio/ act as chairman/ appear on TV/ become an editor/ speak after dinner/ write a book/ give a testimonial/ accept an honorary degree.

— reported in David Frost’s The Impossible Takes Longer the 1,000 wisest things ever said by Nobel prize laureates (Walker & Co. 2003)
(D & S Comment: We think we know how he felt. After the publication of “Life Extension, a Practical Scientific Approach” and our very extensive publicity tours in 1982 and 1983, we received over 500,000 letters with nearly all of the above requests.)

To be secure, take the advice of a 19th century Boston politician, Martin Lomasney: “Never write if you can speak, never speak if you can nod, and never nod if you can wink…“

I was asked at a lecture by someone in the audience who said, why can’t I clone myself and keep the copies as spare parts? And my answer was, be careful, one of the copies might keep you for spare parts.
—Sydney Brenner, Nobel Prize for Medicine, 2002

A common principle often invoked in scientific discourse is Occam’s Razor. This principle dictates that the simplest or most parsimonious explanation should be favored. However, one shouid keep in mind that a simple explanation that does not explain the facts is to be discarded. Sydney Brenner introduced the concept of “Occam’s Broom,” which is used to sweep inconvenient truths under the rug to salvage the ‘simplest’ explanation. Recognizing when to use the razor and avoid the broom is a use- ful reflection in evaluating scientific models as the subtle Mendel and McClintock examples attest.
— pg. 11, Birchler, Mendel, Nechanism. Models, Marketing, and More in the Sept. 24, 2015 Cell

The philosopher Friedrich Hayek, who led the debate against social and economic planning in the mid-twentieth century, noted a paradox that applies today. As science advances, it tends to strengthen the idea that we should “aim at more deliberate and comprehen sive control of all human activities.” Hayek pessimistically added, “It is for this reason that those intoxicated by the advance of knowledge so often become the enemies of freedom.“
— Nico Stehr, in an oped (“Democracy is not an inconvenience”) in the 24 Sept. 2015 Nature

(D & S Comment: Scientific journals are disproportionately full of opeds propos ing regulations before, during, and after any technology not fully understood (as they all are). In the end, their agenda ends up attempting to regulate nearly all human activities, thus supporting Hayek’s pessimistic suggestion above.)

FDA “PROTECTS” PUBLIC FROM CANCER DETECTION BLOOD TEST

In another move toward police state medicine, the FDA has notified Pathway Genomics that it cannot market a blood test to screen for various cancers in healthy people because the company didn’t get the FDA’s permission to do so. In a 21 Sept. 2015 warning letter, the FDA declared the company’s test blood collection tubes a “medical device” and therefore, their use comes under the agency’s jurisdiction. The test, which would have allowed the public to determine whether they had cancer cells circulating in their bloodstream at a cost of $299 to $699 will probably never become available because the cost of getting FDA approval is prohibitive. Meanwhile, the FDA calls the test, which simply collects blood for analysis by their Pathway Cancer Intercept Detect service, the results to be sent to the patient’s doctor (who has to order the test), a “high risk test that has not received adequate clinical validation and may harm the public health.”

Where is the “high risk” the FDA claims exists here and how might it “harm” the public health, provided a disclaimer truthfully explains limits to the test’s ability to provide conclusive proof of having or not having cancer, a disclaimer we would be amazed if the company didn’t already provide for legal protection, if for no other reason.

The FDA is a dangerous entity backed by little more than government force that is immensely harmful to the public health. The agency pursues a vigorous agenda of extending its jurisdiction by decree (they simply proclaim authority over whatever suits their fancy), without Constitutional or statutory basis, to more and more of new medical technologies, effectively eliminating most of them from public access. In the meantime, courts regularly “defer” to the FDA and other regulatory agencies, providing little in the way of an effective check to their power-seeking. The result is the shrinking of choices available in the medical marketplace. And for THIS, we pay taxes??? We’d be better off shredding the money.

  • FDA warning on cancer test reported in the 2 Oct. 2015 Science, pg. 12

HYDROGEN ADMINISTERED IN HYDROGEN RICH SALINE IMPROVES MEMORY IN A RAT MODEL OF AMYLOID BETA INDUCED ALZHEIMER’S DISEASE

The researchers of a paper studying the above subject (Li, 2010) wanted to learn whether hydrogen could reduce inflammation and improve cognition in a rat model of Alzheimer’s disease. The 84 rats were divided into three groups: sham operated (icv injection that did not include amyloid beta1-42), amyloid beta 1-42 icv, and amyloid beta 1-42 icv plus hydrogen saline. Hydrogen saline was injected into the third group of rats for 14 days after intracerebroventricular (icv) injection of Amyloid beta1-42. They were tested for inflammatory cytokines IL-6, and TNFalpha and the lipid peroxidation product malondialdehyde (MDA), as well as testing the rats in the (uh oh) Morris Water Maze and open field trial to test for learning and memory function.

The hydrogen-enriched saline significantly improved animal performance in the Morris Water Maze and enhanced LTP (long term potentiation), an important process in learning, in the hippocampus, where LTP is blocked by amyloid beta1-42. The treatment also reduced levels of the inflammatory cytokines and the malondialdehyde, as well as reducing the hyperactive immune response to HNE and GFAP, which was induced by amyloid beta1-42.

So far, the experiments with hydrogen treatment for various medical conditions have used only hydrogen gas or hydrogen in saline or water. Why nobody is using hydrogen generated by the hydrogen producers residing in the gut microbiota for this purpose is not clear. It is possible that the reason is that a test for evaluating how much hydrogen is generated by the microbiota and which then diffuses into the tissues has not yet been developed; it is much simpler to know how much hydrogen the animals were administered when it is done by gas or by water or saline saturated with hydrogen.

Unlike hydrogen administered by gas or in water/saline, the ingestion of fermentable fibers, such as long chain fructooligosaccharide (long chain inulin), which is a particularly good fuel for the hydrogen producers in the gut, is a simple inexpensive way to get hydrogen into your system, PLUS it is not limited to the short time following the breathing of the gas or the drinking of the hydrogen containing liquid for exposure to hydrogen.

We are both enthusiastic users of our hydrogen power supplement. It is a powder that is not miscible in water, but mixes in very well when added to oatmeal, which is one way we use it. You could also add it to smoothies, casseroles, thick soups, etc. It is stable when cooked.

  • Li, Wang, Zhang, et al. Hydrogen-rich saline improves memory function in a rat model of amyloid beta-induced Alzheimer’s disease by reduction of oxidative stress. Brain Res. 1328:152-61 (2010).

WHITE MATTER IN THE BRAIN MAY BE A KEY TO DEGENERATIVE CHANGES LEADING TO ALZHEIMER’S

Recently it has become a focus of much attention in Alzheimer research on the lesions in white matter that are so strongly associated with the disease. White matter is the myelinated tracts that connect neural networks of the brain that are found in gray matter, such as the visuo-spatial processing area that is severely impaired in Alzheimer’s disease. In our last newsletter, Sandy hypothesized that Alzheimer’s might not be a disease where memories are lost, but where the areas containing memories are disconnected from being accessed by other brain areas. If this is the case, then the white matter tracts that constitute these connections might be the key to Alzheimer’s via their vulnerability to damage. White matter lesions have been found in imaging studies of Alzheimer brains and are attracting scientific attention as an important factor, possibly a key factor, in the disease (Godin, 2009; den Heijer, 2006; Stebbins, 2009). Interestingly, depression in older individuals is often accompanied by white matter abnormalities. An earlier paper (Alexopoulos, 2005, cited in Alexopoulos, 2010) proposed that, “white matter abnormalities compromising frontolimbic circuitry may predispose to geriatric depression and interfere with its response to pharmacotherapy.”

One scientist who has done considerable work on the white matter changes in Alzheimer’s disease, George Bartzokis, M.D., has proposed that “white matter may be the primary origin of the complex process that comes to present as AD [Alzheimer’s disease]. That is, white matter involvement may precede, not follow, cortical degeneration. In a series of thoughtful papers, Bartzokis has presented the ‘myelin model’ as an alternative to the traditional conceptualization of the pathogenesis of AD.” “Although still theoretical, the myelin model draws support from many neuroimaging studies.” For example, individuals at familial risk of AD or late onset AD associated with the ApoE4 allele have been found to have white matter abnormalities in memory-related tracts, such as the parahippocampal white matter, cingulum, inferior occipitofrontal fasciculus and splenium of the corpus callosum. “A particularly intriguing DTI study of normal ApOE4 carriers found decreased microstructural integrity of temporal lobe tracts with normal hippocampal and entorhinal cortical volumes.” (quotes in this paragraph come from pp. 305-306 of Christopher M. Filley’s book The Behavioral Neurology of White Matter, 2nd edition, (Oxford University Press, 2012).

VITAMIN D AND THE RISK OF DEMENTIA AND ALZHEIMER’S DISEASE

A 2014 paper (Littlejohns, 2014) reports the interesting finding that severe deficiency of Vitamin D (<25nmol/L) and deficiency of Vitamin D (≥25 to <50 nmol/L) was associated with a substantially increased risk of all-cause dementia and Alzheimer disease.

Vitamin D has been shown to mitigate age-related cognitive decline, possibly by reducing inflammation and decreasing amyloid beta burden (Briones and Darwish, 2012). Another paper reported that vitamin D prevents cognitive decline and enhances synaptic function in the hippocampus in aging mice (Latimer, 2014). A recent paper (Mizwicki, 2014) reported that vitamin D3 promoted the recovery of impaired amyloid beta phagocytosis by Alzheimer’s disease macrophages. This is important because the rate of production of amyloid beta in Alzheimer’s brains has been found not to differ from that of normal brains, but the ability of the Alzheimer’s brain to clear amyloid beta is impaired compared to that of normals.

Interestingly, multiple sclerosis is also a disease where damage to myelinated white matter tracts is responsible for failure of linkages between areas of the brain that send commands to motor areas and the motor areas that are supposed to receive those messages. The damage to the white matter tracts blocks these communication pathways. Moreover, multiple sclerosis is known to be increased at higher latitudes, that is the farther north you live, the higher the risk of getting multiple sclerosis. Vitamin D deficiency is associated with that higher risk and, of course, people at higher latitudes are exposed to less sunlight and consequently get less vitamin D via its manufacture in the skin. It may be a stretch but it is still tempting to extend the vitamin D association to Alzheimer’s disease as well.

Moreover, a paper (Huebbe, 2011) has shown that the apoE4 allele, which increases the risk of Alzheimer’s disease, is associated with higher vitamin D levels in targeted replacement mice (where the human apoE4 is substituted for their apoE) and in humans. This is consistent with the fact that in Europe, the apoE4 allele distribution is positively correlated with geographic latitude, with a greater than 4-fold greater frequency in the north than in the south (e.g., 22.7% in Finland vs. 5.2% in Sardinia. The authors (Huebbe, 2011) interpret this to possibly mean that the apoE4 allele may be beneficial early in life but then have a cost in later life (beyond reproductive age). Another paper (Norberg, 2011) also found that there was a north-south difference in the cognitive impairment resulting from apoE4 in non-demented subjects, with data coming from 16 centers across Europe. The latter study showed apoE4 carrier prevalence was 62.7% for the northern region, 42.1% in the middle region and 31.5% in the southern region. “Similar to AD [Alzheimer’s disease], APOE4 status is also associated with white matter (WM) abnormalities that may contribute to age- and disease-related neurodegeneration.” (Foley, 2014).

Durk hypothesizes that taking high dose vitamin D to get into the higher concentration of vitamin D that is still safe may be a way to reduce the damaging effect of having an apoE4 allele, because the gene’s expression may be plausibly assumed to be increased when vitamin D levels are low. Taking high dose vitamin D may, therefore, decrease the expression of apoE4 and reduce its deleterious effects thereby. This is an exciting possibility and one we hope will be tested soon. In the meantime, taking vitamin D at levels up to 4000 iu per day may be reasonable for most.

References

  • Littlejohns et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology. 83:920-8 (2014).
  • Huebbe, Nebel, Siegert, et al. ApoE4 is associated with higher vitamin D levels in targeted replacement mice and humans. FASEB J. 25:3262-70 (2011).
  • Latimer, Brewer, Searcy, et al. Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats. Proc Natl Acad Sci U S A. 111(41):E4359-66. (Sept. 29, 2014).
  • Briones and Darwish. Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden. J Neuroinflammation. 9:244 (2012).
  • Mizwicki, Menegaz, Zhang, et al. Genomic and nongenomic signaling induced by 1 alpha,25(OH)2-vitamin D3 promotes the recovery of amyloid-beta phagocytosis by Alzheimer’s disease macrophages. J Alzheimers Dis. 29:51-62 (2014).
  • Stebbins and Murphy. Diffusion tensor imaging in Alzheimer’s disease and mild cognitive impairment. Behav Neurol. 21:39-49 (2009).
  • Godin, Tzourio, Maillard, et al. Apolipoprotein E genotype is related to progression of white matter lesion load. Stroke. 40:3186-90 (2009).
  • den Heijer, Sijens, Prins, et al. MR spectroscopy of brain white matter in the prediction of dementia. Neurology. 66:540-544 (2006).
  • Norberg, Graff, Almkvist, et al. Regional differences in effects of apoE4 on cognitive impairment in non-demented subjects. Dement Geriatr Cogn Disord.32(2):135-42 (2011).
  • Alexopoulos, Glatt, Hoptman, et al. BDNF Val66met polymorphism, white matter abnormalities and remission of geriatric depression. J Affect Disord. 125(1-3):262-8 (2010).
  • Alexopoulos. Depression in the elderly. Lancet. 365:1961-70 (2005).
  • Foley, Salat, Stricker, et al. Interactive effects of apolipoprotein e4 and diabetes risk on later myelinating white matter regions in neurologically healthy older aged adults. Am J Alzheimer’s Dis Other Demen. 29(3):222-35 (2014).

BILE ACIDS INDUCE EXPRESSION OF GENES IN BROWN FAT THAT INCREASE METABOLIC RATE (THERMOGENESIS)

The physiological functions of bile acids have been found to extend beyond that of regulating the absorption and catabolism (breakdown) of fats such as cholesterol and triglycerides. It is reportedly involved in the liver’s metabolism of fatty acid and triglyceride synthesis and VLDL (very low density lipoproteins) production mediated by sterol-regulatory-element-binding protein 1c and bile acids have been shown to inhibit high fat diet induced hyperglycemia and obesity in C57BL/6J mice (Ikemoto, 1997). Not too long ago, a paper (Watanabe, 2006) reported that bile acids increased energy expenditure in brown fat (this was in mice) and prevented obesity and insulin resistance. Remarkably, they found that cholic acid, a bile acid, induced the enzyme (D2, iodothyronine deiodinase type 2) that converts the biologically inactive thyroid hormone T4 to its active form T3. Cholic acid increased D2 activity and oxygen consumption in brown fat, preventing obesity and increasing fat oxidation (thus increasing insulin sensitivity). Incidentally, as an aside, niacin (via the pulsatile release of prostaglandin D2) also increases the oxidation of fats by signaling the conversion of cellular energy use from glucose to fats (Virtue, 2012); this appears to be one of the mechanisms by which niacin beneficially affects the metabolism of lipids.

Iodothyronine diodinase type 2 (D2) is also expressed in skeletal muscle. The researchers (Watanabe, 2006) found that skeletal muscle cells from the mice treated with cholic acid also had increased D2 activity and therefore served as a source of the active form of thyroid hormone.

D2 Is a Selenoprotein

One way to improve the function of D2 is to take adequate amounts of selenium as the enzyme is a selenoprotein (Curcio, 2001). Inadequate selenium intake is one way that people can be hypothyroid even when they secrete adequate amounts of T4 because D2 is needed to convert that T4 to its active form T3.

References

  • Curcio et al. The human type 2 iodothyronine deiodinase is a selenoprotein highly expressed in a mesothelioma cell line. J Biol Chem. 276:30183-7 (2001).
  • Watanabe, Houten, Mataki, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 439:484-9 (2006).
  • Ikemoto, Takahashi, Tsunoda, et al. Cholate inhibits high-fat diet-induced hyperglycemia and obesity with acyl-CoA synthetase mRNA decrease. Am J Physiol. 273 (Endocrinol Metab 36): E37-E45 (1997).
  • Virtue, Feldmann, Christian, et al. A new role for lipocalin prostaglandin D synthase in the regulation of brown adipose tissue substrate utilization. Diabetes.61:3139-47 (2012).

NUTRITION AND THE BRAIN DIETARY
Protection Against Autoimmune Diseases In the Brain
BARLEY BETA GLUCANS

Short Chain Fatty Acids (acetate, propionate, butyrate) Protection Against Autoimmunity (especially by propionate) in the Central Nervous System (in an animal model of multiple sclerosis)

Interestingly, the fermentation of beta glucans takes place in the large intestine (in contrast to many other more readily digested fibers that are usually fermented in the small intestine) as a result of the action of colonic microflora (Kim and White, 2010). Here, the fermentation of beta glucans results in the formation of short chain fatty acids—acetate, propionate, and butyrate—which are now known to provide protection to the gastrointestinal (GI) tract by inhibiting the growth of pathogenic bacteria, reducing cholesterol, as well as helping in the absorption of essential minerals including calcium and magnesium (Kim and White, 2010).Barley and oats are two excellent sources of beta glucans, a component of fiber, that has been shown to reduce cholesterol by lowering the reabsorption of bile acids, thus increasing the excretion of cholesterol (which is converted to bile acids) in the feces (Kim and White, 2010). Bile acids are described as “physiological detergents that play important roles in facilitating the absorption of dietary lipids and fat-soluble vitamins and biliary excretion and disposal of endogenous metabolites and xenobiotics.” “In the liver, bile acids inhibit both triglyceride synthesis and gluconeogenesis.” “…bile acids activate a G protein coupled receptor TGR5, which stimulates energy expenditure in brown adipocytes. TGR5 agonists have been shown to improve obesity and insulin resistance.” (last three quotes from Li, 2010). [More on the effect of bile acids on obesity in the article just following this one.]

A very new paper (Haghikia, 2015) now reports that long chain fatty acids enhanced the formation of T helper 1 (Th1) and/or Th17 cells that are involved in autoimmune diseases (Haghikia, 2015). Short chain fatty acids, particularly propionate, were shown in the Haghikia et al paper to ameliorate experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. The mechanism involved the ability of the short chain fatty acids to beneficially influence the creation of T regulatory (Treg) cells that restrain excessive immune system activity as seen in autoimmune diseases. As the authors note, the Treg cell effector cell balance “is disturbed in MS [multiple sclerosis] patients.” They also point out the exceptional effect of propionate, “[o]f particular interest is the ability of PA [propionic acid] to beneficially influence the generation of Treg cells. Our study posits PA as a potent compound with the capacity to restrain CNS [central nervous system] autoimmunity via restoration of the altered Treg cell effector T cell balance, which is disturbed in MS patients.” Moreover, the researchers note “growing evidence for the lasting dietary effect [of propionic acid] on microbiome composition” and indicate their opinion that “a rapid translation of PA therapy from clinical studies to clinical trials in MS patients seems reasonable.”

We agree that clinical trials with propionate seem reasonable, but as propionate is an unpatentable compound, widely available and inexpensive, it is unlikely to interest pharmaceutical companies in investing millions for research and with economic conditions as bad as they are, government money is unlikely to be forthcoming for this research either.

How to Get More Propionate from Your Diet

One way to get increased amounts of propionate (which cannot be taken orally as a supplement because it will not survive passage through the liver) is to ingest digestive resistant fiber. Our hydrogen power formulation is a fructo-oligosaccharide or long chain inulin and the published literature indicates it as an extremely good source of fiber that is fermented to short chain fatty acids, with especially large amounts of propionate as compared to other fibers (Kim and White, 2010). Of course, the hydrogen power formulation is specifically intended to be used as a fuel by hydrogen producing gut microbes in the lower digestive tract, where the hydrogen diffuses throughout the body, passes through the blood-brain barrier and into mitochondria, and provides protection against hydroxyl radicals, the most dangerous biological radical, and peroxynitrite (Ichihara, 2015). Our barley nuggets, flour, and flakes are from a special barley strain that is very high in beta glucans. Our resistant starch is also a good precursor to propionate.)

Interestingly, there may be autoimmune components to Alzheimer’s disease (AD) (as indicated by a literature search we did on October 20, 2015; also see Bartzokis, 2011) and, thus, there is the possibility that a fiber that is fermented to propionate and other short chain fatty acids might also help prevent or mitigate the autoimmune involvement in AD. We have not seen a paper specifically testing this hypothesis.

References

  • Kim and White. In vitro bile-acid binding and fermentation of high, medium, and low molecular weight beta-glucan. J Agric Food Chem. 58:628-34 (2010).
  • Haghikia, JIorg, Duscha, et al. Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine. Immunity. 43:817-29 (2015).
  • Li, Chanda, et al. Glucose stimulates cholesterol 7 alpha-hydroxylase gene transcription in human hepatocytes. J Lipid Res. 51:832-42 (2010).
  • Ichihara, Sobue, Mikako Ito, et al. Beneficial biological effects and the underlying mechanisms of molecular hydrogen—comprehensive review of 321 original articles. Med Gas Res. 5:12 (2015), 21 pp.
  • Bartzokis. Alzheimer’s disease as homeostatic responses to age-related myelin breakdown. Neurobiol Aging. 32(8):1341-71 (2011).

PROSTAGLANDINS AS MAJOR FACTORS IN INFLAMMATION, BOTH AS PRO-INFLAMMATORY AND ANTI-INFLAMMATORY

SANDY STUDIES THE NIACIN FLUSH AND LEARNS A LOT ABOUT THE REGULATION OF INFLAMMATION BY PROSTAGLANDINS

In the course of writing the paper, she learned a lot about how the niacin flush works (a major effect is the pulsatile release of prostaglandin D2, which suppresses the inflammatory prostaglandin E2, which appears to be a factor in every inflammatory disease. She also learned that finding out what was known at any particular time was very difficult, requiring many extensive literature searches, due to the disseminated understanding of a particular aspect of science, the “balkanization” of science (where many areas of science are not very well connected to other areas), and the level of understanding differing from one scientist to another. Sometimes it seemed that a particular fact that had been discovered years ago had to be rediscovered due to a sort of failure of the earlier knowledge to be kept alive in ongoing discussions. This is why the disclaimer “we are the first to discover what we report in this paper, to the best of our knowledge” has become ubiquitous, because you can never be entirely sure.When Sandy wrote her paper on the niacin flush (see the July, August, and September issues of the Durk & Sandy newsletter at the Life Enhancement website (www.life-enhancement.com), her purpose was to find out whether it was a good idea to eliminate the niacin flush in order to make niacin supplementation more pleasant for those who didn’t like the flush. It was not self-evident whether the flush played a part in the protective effects of niacin (the immediate release form that causes flushing) or whether it could be suppressed without reducing the very powerful beneficial effects of niacin in protecting against non-fatal heart attacks (the most common kind) and reducing the risk of a variety of diseases associated with dyslipidemia and inflammation, such as diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and many others.

A good example of the last point, that you can find work that predates new research and anticipates its findings is the following: Sandy just found a 1998 paper (Prasad, 1998), a review that proposed that “PG [prostaglandin] induced elevation of Abeta [amyloid beta] may lead to an increased binding of Abeta…” and they report their prior work in which they show that “prostaglandins (PG), which are [] released during inflammatory reactions, cause rapid degenerative changes in differentiated murine neuroblastoma (NB) cells in culture.”

Sandy became very interested in prostaglandins D2 and E2 and their apparent ubiquitous appearance in inflammatory diseases. It seemed that the papers she read did not distinguish between the PULSATILE release of PGD2, which appeared to be an important anti-inflammatory signal, as compared to CHRONIC release of PGD2, which was pro-inflammatory, as she learned was the case in Alzheimer’s disease. Even now, this distinction does not seem to be mentioned in papers.

A recent paper (Das, 2011) describes inflammation and its resolution as follows: “During the early phase of inflammation, COX-2 derived PGs [prostaglandins] and TXs [thromboxanes] and lipoxygenase-derived LTs [leukotrienes] initiate exudate formation and inflammatory cell influx. TNF-alpha causes an immediate influx of neutrophils concomitant with PGE2 [prostaglandin E2] and LTB4 [leukotriene B4] production, whereas during the phase of resolution of inflammation, an increase in LXA4 [lipoxin A4, a pro-resolution molecule derived from arachidonic acid], PGD2 [prostaglandin D2] and its product 15deoxydelta12-14PGJ2 formation occurs that induces resolution of inflammation with a simultaneous decrease in PGE2 synthesis that stops neutrophil influx and enhances phagocytosis of debris.”

References

  • Das. A defect in the activities of delta6 and delta5 desaturases and pro-resolution bioactive lipids in the pathobiology of non-alcoholic fatty liver disease. World J Diabetes. 2(11):176-88 (2011).
  • Prasad, Hovland, La Rosa, et al. Prostaglandins as putative neurotoxins in Alzheimer’s disease. Proc Soc Exp Biol Med. 219:120-5 (1998).

AGE-ASSOCIATED DECREASE IN ARACHIDONIC ACID AND EPA, DHA

A paper (Das, 2011) reviews changes with age that result in reduced levels of arachidonic acid and the long chain omega 3 fatty acids (found in fish oils) EPA and DHA and, consequently, low-grade systemic inflammation due to a reduced level of the important antiinflammatory, inflammation resolving molecules that are derived from them, lipoxins, resolvins, and protectins, respectively. It may surprise you to learn that arachidonic acid, which is the source of highly inflammatory prostaglandins, can also be converted to lipoxins, that have antiinflammatory effects. The chemical pathways are described in Das, 2011: “TNFalpha [tumor necrosis factor alpha, a major inflammatory cytokine] causes an immediate influx [to the inflamed tissues] of neutrophils concomitant with PGE2 [prostaglandin E2, a powerful inflammatory prostaglandin] and LTB4 [leukotriene B4] production, whereas during the phase of resolution of inflammation, an increase in LXA4, PGD2 [prostaglandin D2, which can function as an important antiinflammatory molecule via pulsatile release, as in the niacin flush] and its product 15 deoxydelta 12-14PGJ2 formation occurs that induces resolution of inflammation with a simultaneous decrease in PGE2 synthesis that stops neutrophil influx and enhances phagocytosis of debris.” The authors explain that this is a process in which there are two waves of release of arachidonic acid, one in which it and its metabolites are involved in inflammation and one in which they are involved in the resolution of inflammation. They note that high fat diets, trans-fat, and cholesterol block the action of the enzymes (delta5 and delta6 desaturases) that are required to produce GLA (gamma linolenic acid), DGLA (dihomogammalinolenic acid), AA (arachidonic acid) EPA, and DHA, thus exacerbating inflammatory conditions.

DECREASE IN MEMBRANE ARACHIDONIC ACID IN HIPPOCAMPUS WITH AGE SHOWN TO IMPAIR COGNITION

Another paper (McGahon, 1997) described how the age-associated decrease in membrane arachidonic acid (AA) observed in the dentate gyrus of the hippocampus of rats resulted in impaired long-term potentiation, an important process in learning and memory. Giving the aged animals a diet supplemented with arachidonic acid and its precursor, gamma-linolenic acid, resulted in reversal of the decreased membrane AA and sustained long term potentiation “indistinguishable from four month controls.”

We both take supplemental gamma linolenic acid.

References

  • Das. A defect in the activities of delta6 and delta5 desaturases and pro-resolution bioactive lipids in the pathobiology of non-alcoholic fatty liver disease. World J Diabetes. 2(11):176-88 (2011).
  • McGahon et al. The ability of aged rats to sustain long-term potentiation is restored when the age-related decrease in membrane arachidonic acid concentration is reversed. Neuroscience. 81(1):9-16 (1997).

PHENOLIC ACIDS IN PLANTS SUPPRESS LIPOLYSIS IN ADIPOCYTES (FAT CELLS) VIA ACTIVATION OF THE NIACIN RECEPTOR GRP109A (ALSO CALLED HM74A/PUMA-G)

The phenolic acids (including the important polyphenols you get in your diet and probably also take in supplement form), found ubiquitously in the plant kingdom, have been reported in a recent paper (Ren, 2009) to suppress lipolysis via activation of the same receptor by which niacin also suppresses lipolysis, one of the major protective effects of niacin against cardiovascular disease.

The phenolic acids tested and reported (Ren, 2009) to inhibit adipocyte lipolysis were shown in Table 1 and included (showing the dose that inhibits lipolysis by 50%, the IC50): niacin (nicotinic acid) at 0.2, caffeic acid at 14, gallic acid at 30 and others less well known, such as protocatechulc acid at 20. Note that niacin is much more effective at inhibiting lipolysis, but keep in mind that the dose of niacin being reported here is the pharmacological dose used in conventional therapy for reducing LDL cholesterol and increasing HDL cholesterol and is far higher than the physiological amount of niacin found in a good diet. The other compounds are presumably reported at doses closer to the physiological amounts one can get in a diet.

The authors explained how they became interested in the possible activity of phenolic acids at the niacin receptor: “ …both phenolic acids and nicotinic acid are small carboxylic acids with close structural similarity. We also note that application of certain phenolic acids, such as benzoic acid, also induces a flushing response and prostaglandin D2 release in a manner similar to that of nicotinic acid treatment. We thus asked whether phenolic acids could act as GPR109A agonists [activators].”

The authors conclude in their paper’s abstract: “Activation of GPR109A by phenolic acids may thus contribute to a cardiovascular benefit of these plant-derived products.” They also note in the text of the paper that, “while considered on an individual basis, the amount of a given phenolic acid may be low, and a combined phenolic acid content could be quite high.” They give as an example of combining different phenolic acids, “…addition of 80 mm of trans-cinnamic acid, p-coumaric acid, or benzoic acid alone led to a suppression of lipolysis by 17, 26, and 3%, respectively. However, when the same concentrations of these three compounds were combined, a suppression of 53% was observed.”

References

  • Ren, Kaplan, Hernandez, Cheng, et al. Phenolic acids suppress adipocyte lipolysis via activation of the nicotinic acid receptor GPR109A (HM74a/PUMA-G). J Lipid Res. 50:908-14 (2009).

LIPOLYSIS MAY MEDIATE THE PROINFLAMMATORY EFFECTS OF VERY LOW DENSITY LIPOPROTEIN (VLDL)

In a 2006 paper (Saraswathi and Hasty, 2006), researchers studied the effect of incubating mouse peritoneal macrophages with 100 μg/ml VLDL for six hours, finding that it resulted in 2.8 to 3.7 fold increases in intracellular triglycerides and free fatty acids, respectively, via intracellular hydrolysis (lipolysis). There were significant increases of at least two fold in inflammatory proteins as well, including TNFalpha, IL-1beta, MCP-1 (monocyte chemoattractant protein-1, intercellular adhesion molecule 1, matrix metalloproteinase 3 (MMP3), and macrophage inflammatory protein 1alpha. The authors suggest that these changes point to a direct proatherogenic effect of VLDL. The increases in triglycerides and free fatty acids was eliminated by Orlistat, an OTC weight-loss drug.

Interestingly, VLDL is known to be the lipoprotein carrier for apoE4. “ApoE3 binds preferentially to HDL and apoE4 to VLDL.” (Tetali, 2010). The fact that the ApoE4 gene is being carried by a potentially proinflammatory lipoprotein suggests the possibility of an interplay that may increase the adverse effects of apoE4. Suggestion: keep your VLDL level down. Niacin is very effective at this, as is fish oils.

References

  • Saraswathi and Hasty. The role of lipolysis in mediating the proinflammatory effects of very low density lipoproteins in mouse peritonial macrophages. J Lipid Res. 47:1406-16 (2006).
  • Tetali, Budamagunta, Simion, et al. VLDL lipolysis products increase VLDL fluidity and convert apolipoprotein E4 into a more expanded conformation. J Lipid Res. 51:1273-83 (2010).

RESTLESS LEGS: OTHER POSSIBLE REMEDIES

QUININE MIGHT WORK FOR SOME

Quinine in the form of tonic water, a very popular mixer with spirit alcohol, has been found to have the very interesting effect (Talavera, 2008) of inhibiting the TRPM5 channel-dependent response of taste receptors to sweet taste. This is part of a recently discovered facility of bitter compounds to frequently inhibit the sweet taste transduction pathway.

Dr. xxxx, the new editor/author of the “Nutrition & Healing” newsletter, formerly written by Jonathan V. Wright, M.D., suggests that 2-4 ounces of tonic water with quinine may be able to stop ongoing restless legs in some. I’ve tried it. Sometimes it helps. But don’t drink too much of it. Though there is no warning on a bottle of tonic water, there is about 75 mg of quinine in a bottle (1 liter) and some people have been reported to be sensitive to as little as 30 mg. (See “Wikipedia” article on quinine.) Those sensitive to it can end up having a kind of hangover that includes lower blood pressure (even to the point of fainting), lightheadedness, and difficult in walking (as if you were drunk on alcohol). This may possibly be due to the decreased response of the taste receptors to sucrose, which is supposed to release insulin that then releases noradrenaline. Reduced noradrenaline can lower blood pressure and might lead to lightheadedness, fainting, memory problems, and motor clumsiness.

Scaring Away Restless Legs

A possibility (per an experience of Sandy’s) is that a scary incident can frighten away restless legs, just as hiccups can also be eliminated that way. (You may have to be totally unprepared for the surprise fright.) This suggests (but doesn’t prove) that a bolus release of (probably) noradrenaline/adrenaline might be what counteracted the restless legs in this case. On the other hand, a chronic release (as compared to a bolus release) of noradrenaline/adrenaline might make restless legs worse so don’t take a long-acting adrenergic agonist and necessarily expect it to give you longtime relief.

Sandy has found agonists of the adrenergic alpha2 receptor to be usually effective at suppressing restless legs. Such agonists include the anti-hypertensive/sedative drug clonidine and dopamine (with L-dopa as its precursor). Alpha 2 adrenergic agonists suppress noradrenergic neurons in the locus coeruleus; these neurons “fire during waking, fire less during sleep and their activity increases just before waking, suggesting they promote wakefulness.” (Zhang, 2015). The scientists who produced that paper (Zhang, 2015) found that a drug with alpha 2 adrenergic receptor agonism produced sedation that resembled closely recovery sleep following loss of sleep.

References

  • Talavera, Yasumatsu, et al. The taste transduction channel TRPM5 is a locus for bitter-sweet taste interactions. FASEB J. 22:1343-55 (2008).
  • Zhang, Ferretti, Guntan, et al. Neuronal ensembles sufficient for recovery sleep and t he sedative actions of alpha2 adrenergic agonists. Nat Neurosci.18(4):553-61 (2015).

ALPHA2 ADRENERGIC AGONISTS MAY MIMIC RECOVERY SLEEP

After not getting enough sleep, recovery sleep is an induced state that helps restore normal waking feeling and behavior. A paper (Zhang, 2015) reports that, “…recovery sleep and alpha 2 adrenergic receptor-induced sedation were not only similar behavioral states, but were both induced by activating similar neuronal populations in the PO [preoptic] hypothalamus.” The researchers found that GABAergic neurons in the LPO (preoptic hypothalamus) were required for the onset of dexmedetomidine-induced sedation. Desmedetomidine is an alpha2 adrenergic agonist used in clinical practice as an anesthetic.

This might be useful for people who have lost sleep and want to try using an alpha2 adrenergic receptor agonist to help them recover. Clonidine is such an agonist, a prescription drug that has been widely used as a sedative and is safe for most normal people at usual dosage prescribed. It will put you to sleep, so don’t take it when you plan to be working or driving. This drug may help relieve restless legs, but in Sandy’s experience it helped only when taken at night before bedtime. Natural products that act as agonists at alpha 2 adrenergic receptors are arginine and possibly agmatine (decarboxylated arginine found naturally in human serum) (Joshi, 2007). Clonidine potently lowers blood pressure, so be very cautious about dizziness-induced falls.

Interestingly, the authors (Zhang, 2015) note that, “candidate homeostat molecules, which accumulate proportionally to the amount of sleep deprivation and act locally in the preoptic area, include PGD2 [prostaglandin D2] and adenosine.” PGD2 is released in a pulse by immediate release niacin at doses of 50 mg or more, depending on individual sensitivity. We have found niacin to have a calming, sometimes nap-inducing effect.

References

  • Zhang, Ferretti, Guntan, et al. Neuronal ensembles sufficient for recovery sleep and the sedative action of alpha2 adrenergic agonists. Nat Neurosci. 18(4):553-61 (2015).
  • Joshi, Ferguson, Johnson, et al. Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells. Proc Natl Acad Sci U S A. 104(24):9982-7 (2007).
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