APPETIZERS

No matter how much you push the envelope, it will always be stationery. 
— unknown

… used to think that the brain was the most wonderful organ in my body. Then I realized who was telling me this.
— Emo Philips, comedian

Awareness … is the endpoint of a cascade of processing steps that occur below the surface. “By the time consciousness kicks in, most of the work has already been done.”
— John-Dylan Haynes***

There is a saying among women scientists who attend highly specialized engineering universities, where the girl-to-guy ratio is decidedly in their favor: “The odds are good, but the goods are odd.”
— Michio Kaku, in his book The Future of the Mind, pg. 143 (Doubleday, 2014)****

Thinking differently from others is therefore a prerequisite for creativity.
— (Power, 2015)

WHERE MOST OF THE WORK IS DONE BEFORE YOU KNOW IT

John-Dylan Haynes (*** see quote just above) is a scientist who studies decision making in the areas of the brain that process information without your conscious knowledge. In a fairly recent study, Dr. Haynes and his collaborators determined what areas of the brain were involved in making a decision by human subjects to press a button (Soon, 2008). The conscious motor decision took place after activity in other brain areas was detected. “The predictive information in the fMRI [functional magnetic resonance imaging] signals from this brain region [frontopolar cortex] was already present 7s before the subject’s motor decision. Taking into account the sluggishness of BOLD [blood oxygen level-dependent] responses, the predictive neural information will have preceded the conscious motor decision by up to 10s.” “Thus, there appears to be a double dissociation in the very early stages between brain regions shaping the specific outcome of the motor decision and brain regions determining the timing of a motor decision.”

“… it has been argued that the brain had already unconsciously made a decision to move even before the subject became aware of it (Soon, 2008).”

Indeed, as Dr. Haynes said. By the time consciousness kicks in, most of the work has already been done.”

Reference

Soon, Brass, Heinze, & Haynes. Unconscious determinants of free decisions in the human brain. Nature Neurosci. 11(5):543-5 (2008).

MAGNESIUM REDUCES ALL-CAUSE MORTALITY, INCLUDING STROKE, HEART FAILURE, AND DIABETES

A very recent paper (Fang, 2016) examined the association between dietary magnesium and health. In this dose-response meta-analysis from 40 prospective cohort studies that included over one million (1,000,000) participants, the researchers found that, for each 100 mg/day increase in magnesium intake, the risk of stroke decreased by 7% (RR (relative risk):0.93; 95% CI (confidence interval):0.89-0.97, and was associated with a 10% lower risk of mortality. The highest category of magnesium intake, as compared to the lowest category, was found in the participants to reduce the risk of type 2 diabetes (RR: 0.74 (95% CI: 0.69-0.80).

“A dose-response analysis revealed that a 100 mg/day increase in dietary magnesium intake is significantly associated with a 7%, 22%, 19%, and 10% decrease in the risk of stroke, heart failure, type 2 diabetes, and all-cause mortality.” However, there was no clear association between magnesium and the risk of cardiovascular disease. In the U.S. and in Europe, the daily intake of magnesium does not generally meet the recommended amount. Epidemiological studies indicate that low levels of serum magnesium are associated with diseases such as chronic obstructive pulmonary disease (COPD), type 2 diabetes, and Alzheimer’s disease, among others (Fang, 2016).

We highly recommend taking supplemental magnesium. We take 400-600 mg per day of magnesium from our On Target Magnesium Plus.™

Reference

Fang et al. Dietary magnesium intake and the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies. BMC Med. 14:210 (2016)

ARGININE FOR PAIN: SICKLE CELL DISEASE

Preliminary clinical studies are showing promising results in the treatment of pain in patients with sickle cell disease. Pain is the hallmark of sickle cell disease, with some patients in pain all of the time. Arginine has been found in these preliminary clinical studies to be effective against the pain due to vaso-occlusive blood clots. “Phase II clinical trials of arginine therapy for sickle-related pain are underway and a Phase III randomized controlled trial is anticipated in the near future (Bakshi, 2016).”

Sickle cell disease is described as an “arginine deficiency syndrome (Bakshi, 2016).” The “global arginine bioavailability ratio” (GABR) was developed to assess the state of arginine sufficiency as expressed in the ratio of arginine to arginine metabolites (ornithine and citrulline). The GABR is low, not only in sickle cell disease, but also in diabetes. Moreover, a low GABR “has been shown to be a strong predictor of cardiovascular disease and early mortality in general (Bakshi, 2016).”

Arginine can be found in our Inner Power,™ with each serving containing 6 grams of arginine. Suggested use is 1 to 3 servings a day on an empty stomach—at bedtime, upon awakening, or before exercise.

Reference

Bakshi and Morris. The role of the arginine metabolome in pain: implication for sickle cell disease. J Pain Res. 9:167-75 (2016).

RUTIN, A COLD MIMETIC, ACTIVATES BROWN ADIPOSE TISSUE TO INCREASE ENERGY EXPENDITURE FOR WEIGHT LOSS

The safest way to increase BAT (brown adipose tissue) thermogenesis is by exposure to cold (Yuan, 2017). Rutin is a dietary flavonoid shown, in a very recent study to increase energy expenditure like exposure to cold, “greatly increas[ing] core body temperature when animals were exposed to a cold environment (4 degrees C, 4 h) Genetically obese mice were able to switch energy sources from oxidizing glucose to oxidizing fat, a flexibility that is normally impaired in obese animals (Yuan, 2017).

In the study, genetically obese mice (Db/Db) and diet-induced obese mice (DIO) were treated with rutin (1 mg/ml added to their drinking water for 10 weeks). Increased thermogenesis in BAT was detected by the induction of “beige” tissue formation (in which WAT, white adipose tissue, is converted to a more BAT-like form, a process called “browning”), activating SIRT1/PPARgamma coactivator (PGC)-1alpha/mitochondrial transcription factor, increasing the number of mitochondria, and increasing UCP1 (uncoupling protein 1) activity. “Indeed, the expression levels of BAT markers, such as UCP1, Cidea, and Prdm16 were dramatically increased in BAT from rutin-treated DIO or Db/Db mice (Yuan, 2017).” These are changes that are seen in cold-exposed BAT. SIRT1 activation is particularly interesting as it has been associated with increased longevity in many studies.

Activated brown adipose tissue (BAT) has beneficial effects on lipid metabolism—for example, after cold exposure BAT “promotes the clearance of excessive triglycerides in the plasma by increasing lipid uptake into BAT,” where it is subsequently metabolized to create heat (thermogenesis) (Yuan, 2017).

Though certain FDA-approved drugs can promote the “browning” of white adipose tissue (WAT), they may be far more likely to have unwanted side effects than rutin—for example, rosiglitazone or beta-adrenergic agonist drugs (such as clenbuterol) have been reported to promote such “browning,” but are said not to be used in clinical practice for this purpose due to side effects.

The researchers (Yuan, 2017) conclude: “These findings reveal that rutin is a novel small molecule that activates BAT and may provide a novel therapeutic approach to the treatment of metabolic disorders.”

Each serving (2 capsules) of our AGEless™ contains 125 mg of rutin. This formulation was designed to protect against glycosylation (an aging mechanism in which glucose combines with proteins to form AGEs, advanced glycation endproducts). The prevention of AGE formation is another beneficial effect of rutin. We’ve been taking AGEless for umpteen years.

PERSISTENT INFECTIONS CAN BE SILENT KILLERS: HELICOBACTER PYLORI

It is generally accepted that persistent infections (viral, bacterial, fungal, parasitical, etc.) can have serious effects on health by inducing hyperactivation of the immune system, such as by increasing the release of inflammatory cytokines. One such persistent infection is Helicobacter pylori (H. pylori), now well known for increasing the risk of ulcers and of gastrointestinal cancers (Herrera, 2009). The bacterium, believed to infect 40-50% of the world’s population, has been linked to many systemic diseases, including cardiovascular disease (Danesh, 1999) and cancer and some evidence suggests that it indirectly contributes to the development of Alzheimer’s disease. (Malaguarnera, 2004). In fact, a recent paper reports that H. pylori triggers double-strand breaks in DNA, which is consistent with its carcinogenic properties (Toller, 2011).

PARKINSON’S DISEASE

A presentation at a scientific meeting by M. Niehues and A. Hensel was reported in the journal Planta Medica (Niehues and Hensel. In vitro interaction of L-Dopa with bacterial adhesins [responsible for the adhesion of the bacterium to gastric epithelial cells] of Helicobacter pylori: an explanation for clinical differences in bioavailability?” Planta Medica 75:877-1094 (2009). The researchers here reported the surprising effect of H. pylori on the availability of L-Dopa taken by Parkinson’s disease patients. The L-Dopa became attached to bacterial adhesins from the H. pylori, leaving less unbound L-Dopa for actually treating Parkinson’s. The authors of the presentation suggest that this mechanism may explain why Parkinson’s patients infected with H. pylori do less well on a similar amount of L-Dopa as patients who are not infected with H. pylori.

Thus, Parkinson’s disease patients might benefit by eliminating or reducing H. pylori present in their systems. A dietary supplement available for this purpose that is both safe and effective (as well as inexpensive) is mastic, the gum resin of the mastic tree, Pistacia lentiscus L. Sandy takes Life Enhancement’s Bye-Lori Plus,™* which contains mastic, because Durk was infected with H. pylori for decades before eradicating it with antibiotics and Sandy wants to make sure she didn’t “catch” it from him.

HELICOBACTER PYLORI AND ARGININE

Pathogens such as Helicobacter pylori and Toxoplasma gondii defend themselves against their host’s immune system by producing arginases that limit nitric oxide (a powerful pathogen-killing substance) production by depleting L-arginine (Grohmann, 2010). Thus, increasing L-arginine might be another way to help eradicate Helicobacter pylori infections. We both take L-arginine (6-12 grams/day) in Inner Power Plus,™ available from Life ­Enhancement Products.

References

• Danesh et al. Helicobacter pylori infection and early onset myocardial infarction: case-control and sibling pairs study. Br Med J. 319(30):1157-62 (1999).
• Grohmann and Bronte. Control of immune response by amino acid metabolism. Immunol Rev. 236:243-64 (2010).
• Herrera and Parsonett. Helicobacter pylori and gastric adenocarcinoma. Clin Microbiol Infect. 15(11):971-6 (2009).
• Malaguarnera et al. Helicobacter pylori and Alzheimer’s disease: a possible link. Eur J Int Med. 15:381-6 (2004).
• Toller et al. Carcinogenic bacterial pathogen Helicobacter pylori triggers DNA double-strand breaks and a DNA damage response in its host cells. Proc Natl Acad Sci U S A. 108(36):14944-9 (2011).

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TIME IS ON MY SIDE … YES, IT IS

by Sandy Shaw

The difference between drug use and addiction or eating and metabolic diseases is time. The amount of time we take a potentially addictive drug determines whether we become addicted; this is also true for eating—eating for only a limited period of time can prevent the development of metabolic diseases, such as diabetes type 2 (Hatori, 2012).

An example of how time can determine the result of eating: a recent study of male mice fed a high fat diet found that restricting feeding to only eight hours a day WITHOUT REDUCING CALORIES as compared to being free to eat at any time prevented metabolic diseases (such as obesity, hyperinsulinemia, fatty liver, and inflammation).

Dopamine is required for the estimation of time by the internal clock. “Interval timing, the ability to discriminate durations in the seconds-to-minutes range, is a form of temporal cognition that requires an optimal level of dopaminergic function in cortico-striatal circuits in order to control time sharing and regulate clock speed.” A time interval is initiated by cortical oscillators in the ventral tegmental area of the brain by a burst of dopamine accompanied by a burst of theta power, which act as the “start gun” (Kononowicz, 2015).

The internal clock is critically controlled by dopaminergic agonists and antagonists. Dopamine agonists such as cocaine and methamphetamine (“speed”) have been shown to increase the speed of the internal clock, while dopamine antagonists such as haloperidol and raclopride have been shown to decrease the speed of the internal clock (Cheng, 2007).

In another study (Sysoeva, 2010), researchers found that there is an association of serotonin (5-HT) related genes with time perception. In their experiment, forty-four Russian Caucasian males (right handed and with a mean age of 22) compared two durations (they had to indicate which of them was shorter) on a computer monitor. “Many studies have reported an association between duration representation parameters and personality, specifically impulsivity and psychoticism.” Unsurprisingly, other studies have found psilocybin, a 5-HT (serotonin) receptor agonist, to affect time perception (Sysoeva, 2010).

“Despite the evidence … suggesting the centrality of DAergic [dopaminergic] modulation in mediating the drug-induced euphoria and timing distortions reported here, this explanation is likely an oversimplification of the processes underlying the individual differences observed in this study. Neuromodulators such as serotonin, GABA, glutamate, and norepinephrine, have also been found to influence time perception and to interact with DA [dopamine] in complex ways (Lake, 2013).” Another neuro­transmitter with important effects on drug addiction and incentive-motivated behaviors is acetylcholine (Lester, 2010).

WHEN TIME SLOWS DOWN

You’ve all experienced it—the times when sudden danger appears, such as your car is about to hit a tree, and time slows release of adrenaline as you rapidly close in on the tree. As explained above, stimulants such as methamphetamine cause a large release of dopamine and this increases the speed of the internal clock. A hypothesis proposes that the reason this feels like time is slowing down is that your brain sees time as the amount of information it processes—the more bits of information is counted as a longer period of time compared to the usual number of bits you experience as “regular” time (Eagleman, 2005).

In a similar fashion, seeing an event in “slow motion” causes observers to believe that more time had passed than actually had (Caruso, 2016). Thus, time is under­estimated.

A very recent paper (Soares, 2016) reported how mice judged the passage of time (judging the duration of intervals). Using a pharmacogenetic method to suppress dopaminergic neuronal activity in the substantia nigra pars compacta, they found that “[s]ituations in which DAergic [dopaminergic] activity is elevated naturally, such as states of high approach motivation, response uncertainty, or cognitive engagement are associated with underestimation of time. Conversely, situations that decrease DAergic activity, such as when fearful or aversive stimuli are presented are associated with overestimation of time.”

The bottom line: “… pleasurable events boost dopamine release, which should cause your internal clock to run faster … so that short intervals seem longer than they are (Simen, 2016).”

FLOW

Time stands still if you go fast enough.

—Stephen F. Kaufman, marial arts professional (Ch.
19 in his book “The Way Of The Modern Warrior”)

Who hasn’t experienced FLOW? The trick is being able to produce it when you want it.

Flow is often described as a state of effortless concentration so deep that people who experience it lose their sense of time. It gives you a sense of acting without conscious awareness, of time slowing down, of perceiving yourself to be moving through a dreamlike state.*

We knew a highly skilled champion racecar driver (Mickey Thompson) who told us that using a BLAST family formulation of ours had, in a very long off-road auto race (the BAJA 1000, when it was 1000 miles rather than 1000 kilometers) resulted in time slowing down, with everything happening exactly right and without any conscious effort on his part. He said that it felt like the flow he had experienced in his best races. The formulation that Mickey took was one of those we designed for our own use that contains the amino acid phenylalanine. Phenylalanine can be converted into tyrosine (which is then converted to dopamine) but also into phenethylamine (also called phenylethylamine), a neuromodulator that provides mental energy like caffeine, but also acts as a stimulus barrier (helps to filter out distractions). Phenylalanine is found in our BLAST formulas.

Caffeine provides mental energy in a different way than phenylalanine (see above). Phenylalanine is a natural compound that increases dopamine (via conversion to tyrosine) but, unlike caffeine (a xenobiotic), it does not mimic the effects of amphetamine and cocaine, like caffeine can do at 4-5 times the average human consumption of coffee. At high doses (300-800 mg), caffeine can increase feelings of anxiety, nervousness, and insomnia. Caffeine does NOT have addictive potential at the usual level of human consumption (50-300 mg or 1-3 cups of coffee), but induces feelings of well-being, alertness, energy, and ability to concentrate. Most of the effects of caffeine are reported to take place at adenosine receptors, where caffeine is an inhibitor (Nehlig, 2000). There are other changes, though, which include a 26-30% increase in the densities of cortical muscarinic and nicotinic cholinergic receptors; the evidence supports significant alterations in adenosine, adrenergic, serotonergic cholinergic, and GABAergic systems (Shi, 1993).

NUTRIENTS THAT MODIFY THE SPEED OF THE INTERNAL CLOCK

The amino acid tyrosine is precursor to dopamine, that is, converted to dopamine. (The amino acid phenylalanine is converted to tyrosine, so it is an indirect precursor to dopamine.) As noted above, dopamine agonists increase the speed of the internal clock (Cheng, 2007; Meck, 1987). This feels like time is slowing down. (Interestingly, “flow” is a process in which time does feel as though it is slowing down.)

WHEN PLEASURE BECOMES A HABIT

In the scientific literature, addiction is often called habit formation. Habit formation differs immensely from goal-directed activity. Where goal-directed activity is influenced by the outcome of performing an action, addictive activity is not—a negative outcome does not influence it.** If an action is habitual, “then devaluation should have no effect on performance, since habits are elicited by antecedent stimuli which are not affected by devaluation. “… habitual behavior is not controlled by the action-outcome contingency … (Yu. 2009)”

This can be seen in lever pressing by experimental animals. “At first lever pressing is goal-directed and sensitive to manipulation like outcome devaluation. Under certain conditions, it can become more habitual and impervious to changes in the value of the outcome … Studies in flies, mice, rats, horses, monkeys, and humans have shown some version of this transition from more flexible and goal-directed behavior to inflexible and habitual behavior.” (Yu, 2009)

It was purely the feeling that had captivated me, made me sacrifice everything to it, gladly, joyfully. It was a seashell’s pristine whisper in my ear, warm sun rising in my heart, fireflies winking in the nerves.

—Will Bohnaker, Haunts of The Aardwolf, on the allure of caffeine

EATING: DELAY DISCOUNTING

A recent paper (Johnson, 2010) points to a proposal that “deficits in reward processing may be an important risk factor for the development of obesity, and that obese individuals may compulsively consume palatable food to compensate for reward hyposensitivity.” This is another way of saying “self-medication.”

The dopaminergic nervous system is critically involved in the perception of pleasure from eating and sex. In fact, “the degree of pleasure from eating correlates with [the] amount of dopamine release (Stice, 2008).” The chronic overeating of high fat and high sugar foods causes a decrease in the sensitivity of dopaminergic neurons as a result of downregulation (reduced signaling). Animal studies have found similar effects from overeating and also in response to chronic drug use. Both overeating and the use of addictive drugs cause downregulation of dopamine D2 receptors and decreased D2 sensitivity.

A deficiency in the release of dopamine in the dorsal striatum may also be seen in individuals with a certain variant (allele) of the D2 dopaminergic receptor gene, the Taq1A A1 allele; it is interesting to note that this allele is involved in impulsivity, which is defined as “the relative preference for a smaller reward, sooner in time, compared to a larger reward, later in time … (Eisenberg, 2007)” This is called delay discounting—and “non-human research suggests that corticostriatal mesolimic substrates mediate delay discounting performance and that dopamine is the critical neurotransmitter involved.” (Eisenberg, 2007) The famous marshmallow experiments were a particularly notable example of delay discounting.

MONOAMINE OXIDASE A (MAOA) AND IMPULSIVITY

Monoamine oxidase A (MAOA) is a gene importantly affecting impulsivity. “… the risk imparted by the specific genetic variation studied here [MAOA] contributes to the impulsive dimension of this complex behavior [aggression].” The monoamine oxidase A (MAOA) gene, is of two types—MAOA-L (the low expression variant) and MAOA-H (the high expression variant). MAOA-L is associated with an increased risk of violent behavior. “Arguably, the clearest link between genetic variation and aggression exists for monoamine oxidase A (MAO-A) … a key enzyme in the catabolism [breakdown] of monoamines, especially serotonin.” The enzyme catabolizes dopamine, serotonin, and norepinephrine, reducing their availability for signaling at neuronal synapses (Meyer-Lindenberg, 2006). Hence, reduced catabolism, as with the MAOA-L variant, will not decrease the availability of dopamine, serotonin, and norepinephrine for signaling as much as the MAOA-H variant.

Goal-directed dimensions of aggression have been associated with psychopathy, often accompanied by diminished empathy and remorse. In their study (Meyer-Lindenberg, 2006), the researchers found that “men, but not women, carrying the low-expression MAOA genotype showed increased [emotional] reactivity during retrieval of negatively valenced emotional material.” Interestingly, men have only one allele (copy) of the MAOA gene, whereas women have two. The reason for this is that men have only one X chromosome (where the MAOA gene is located), while (of course) women have two. Interestingly, estrogens have been shown to affect the expression of MAOA in the brain (Meyer-Lindenberg, 2006).

Higher dominance has been associated with the low expression variant of MAOA (MAOA-L) and aggression in males in studies of primates.

SEROTONIN AND IMPULSIVITY

As noted above, serotonin deficiency is associated with impulsive behavior. This can be corrected by taking tryptophan, the amino acid that is converted to 5-hydroxytryptophan by the enzyme tryptophan hydroxylase and then to serotonin. However, some individuals are unable to make this conversion in sufficient amounts because their version of the enzyme lacks adequate potency. A way to overcome this is to take 5-HTP (5-hydroxytryptophan), which bypasses the need for tryptophan hydroxylase. We suggest taking 25 to 50 mg of 5-HTP at bedtime. We get ours from our Serene Tranquility with 5-HTP.™

DELAY DISCOUNTING MEETS THE GRASSHOPPER AND THE ANT

Another experiment on delay discounting (like the marshmallow experiments) was performed in human subjects, who made a series of choices between early and delayed monetary rewards while they were examined by fMRI (functional magnetic resonance imaging) (McClure, 2004). As a result, the researchers developed a hypothesis for how the brain decides between the early and later rewards. “… we hypothesize that short-run impatience is driven by the limbic system, which responds preferentially to immediate rewards and is less sensitive to the value of future rewards, whereas long-run patience is mediated by the lateral prefrontal cortex and associated structures, which are able to evaluate trade-offs between abstract rewards, including rewards in the more distant future.” They allude to the metaphor of the grasshopper and the ant. The grasshopper spends its time enjoying the present and ignoring what may come later, while the patient ant works diligently preparing for the future. The authors call delay discounting the competition between the “impetuous limbic grasshopper” and the “provident prefrontal ant.” (McClure, 2004).”

In sum, the researchers suggest that “human behavior is often governed by a competition between lower level, automatic processes that may reflect evolutionary adaptations in particular environments, and the more recently evolved, uniquely human capacity for abstract, domain-general reasoning and future planning.”

Another hypothesis on the neuro­chemistry of delay discounting (Kravitz, 2012) proposes that addiction (in which the future consequences of using drugs are ignored) depends upon the interaction between dopamine D1 receptors and dopamine D2 receptors: dopamine D2 receptors counteract dopamine D1 receptors in determining the probability of performing a future action. The D1 receptors induce persistent reinforcement, while the D2 receptors induce transient “punishment” (negative signaling) for the performance of a future action. “In contrast, depression is marked by impaired reinforcement from positive stimuli and heightened punishment from negative stimuli (Kravitz, 2012).”

SPEAKING OF ANTS …

Yes, speaking of ants, a recent paper appeared in the “Research Highlights” section of the 29 Sept. 2016 Nature which reported that ants can get hooked on morphine. The ants were given access to sugar water laced with morphine. Then, over the course of several days, the amount of sugar in the water was reduced while the morphine content was increased, until eventually there was NO sugar in the water, only morphine. The ants, given a choice between sugar water and the sugar-free morphine solution, preferred the sugar-free morphine by 65% to 35%. Plus the ants’ brains showed elevated levels of dopamine, just as addicted mammals do. The authors were said to suggest that ants might make a good model for studying addiction in humans. Durk wonders why 35% of the ants DIDN’T choose morphine … Sandy suggests that maybe those ants had a different version of the D2 dopamine receptor.

HIGH IMPULSIVITY PREDICTS THE SWITCH TO COMPULSIVE COCAINE-TAKING

Rats, like humans, can get addicted to drugs. When rats are exposed to cocaine, 15-20% of them become addicted, which is similar to that observed in humans (Belin, 2008).

“… the essential feature of addiction … [is] … the persistence of drug-seeking in the face of negative consequences …” explain researchers in a 2008 paper (Belin, 2008). In their study, they found that high impulsivity “predicts the development of addiction-like behavior in rats … [and they note that, in humans,] … there is a high comorbidity between drug addiction and disorders characterized by impulsive behavior, such as attention deficit-hyperactivity disorder.”

Low serotonin levels are thought to be a cause of impulsivity. For example, reducing serotonin levels by tryptophan-restricted diets results in more impulsive choices in experiments. A recent paper (Bevilacqua, 2010) found that a mutation in the serotonin 2B receptor predisposed a Finnish population to severe impulsivity.

Lithium may reduce impulsivity, but studies reporting this association have involved doses much higher than the low-dose form that we use. One such study (in rats) found that a “moderate” dose of lithium (20 mg/kg) suppressed impulsive behavior (Ohmura, 2012). Research involving the low concentrations of lithium found in mineral waters and in some tap water has reported reduced impulsiveness and suicide in people.

Another way to reduce impulsivity is to take tryptophan (precursor to serotonin). See above in “Eating: Delay Discounting.”

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WHATEVER YOU MAY THINK OF MR. TRUMP …

Whatever you may think of Mr. Trump, he has revolutionized the way this government functions. This is not just the election of a “new” president, but the initiation of a truly new way to govern where each individual has a voice, where each man or woman can speak directly to the president, something that has NEVER before been possible.

Trump uses social networking, something no president has done before. In so doing, his “tweets” can be answered by anyone. The bureaucracy and the mainstream media are both bypassed.

A post (Feb. 2, 2017) by John Robb at Global Guerillas puts it this way, “National governance isn’t just in Washington [DC] anymore. It’s [] conducted everywhere at once. Everyone, from the government bureaucrat to the corporate executive to the owner of a Twitter account is now an active participant. It is now MUCH more participatory than it has EVER been. (emphasis on MUCH added).”

The post continues, “Bureaucratic governance mass media coverage focuses on one problem at a time (serially) … In contrast, networked governance can focus on many [problems] in parallel. This makes it very difficult for gatekeepers to exercise control.”

This is how Mr. Trump is flummoxing the media and his political enemies: he tweets and he distracts them from other, more important issues. They can’t respond to everything at once and he has sent them off in directions of his choice to keep them busy.

In a second post (Feb. 10, 2017), at Global Guerrillas, John Robb adds to his well-done analysis of the merging of social networking and politics. He sees social networking as containing three political networks: insurgency, orthodoxy, and participatory. The insurgency is the way that Trump became president without much advertising—about 10% of Hillary’s—and despite the opposition of most of the press. Trump was the catalyst here.

The orthodoxy “arose out of the ashes of the political parties and it is growing without any formal leadership (from the Feb. 10, 2017 post).” It is the part of social networking that fiercely opposes Trump. “Trump feeds the outrage that fuels it,” says Mr. Robb.

The participatory group is something of a combination of the insurgency and the orthodoxy.

In a recent article (Egerstedt, 2011), the author commented on a paper (Liu, 2011) about social networking, specifically, how they can be controlled. The conclusion was that they are VERY difficult to control. “… both social networks and naturally occurring networks, such as those involving gene regulation, are surprisingly hard to control.” (Egerstedt, 2011)

The article contained an analysis of how you choose the most influential individuals (the driver nodes). “The nodes are individual decision makers … The edges [the connections] are the means by which information flows and is shared between nodes.” The analysis continues: “… driver nodes tend to avoid the network hubs. In other words, centrally located nodes are not necessarily the best ones for influencing a network’s performance … the most influential members may not be those with the most friends.” What I think this means is that the most influential decision makers may not be “joiners.” They are influential because of their ideas, which can be reached by large numbers of others without these influential people having any knowledge of who these “others” are.

A social network is a very different form of social connection, because it is not necessary to actually KNOW anybody. You can be a hermit living on a mountain top nowhere near anybody else and still be as connected to the network as “people who need people.” Something like 24,000,000 people are following Trump at Twitter, but few are actually likely to know him or to “need” him.

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References

• * Daniel Kahneman (winner of the Nobel Prize in Economics), Thinking, Fast and Slow (Farrah, Straus and Giroux, 2011)
• ** Addiction is like a 0% interest rate because it makes the performance of an action insensitive to future cost.
• *** Haynes quoted in “Brain scans can reveal your decisions 7 seconds before you decide,” Exploring The Mind!, http://exploringthemind.com/the-mind/brain-scans-can-reveal-your-decisions-7-seconds-before-you-decide
• **** In the book (pg. 143), the author describes where this saying came from. Apparently, it was based on the fact that many intellectually brilliant individuals have a form of autism called Aspberger’s.
• ***** Caffeine can be addictive, but only at high doses.
• Belin et al. High impulsivity predicts the switch to compulsive cocaine-taking. Science. 320:1352-5 (2008).
• Bevilacqua et al. A population-specific HTR2B stop codon predisposes to severe impulsivity. Nature. 468:1061-6 (2010).
• Caruso et al. Slow motion increases perceived intent. Proc Natl Acad Sci U S A.113(33):9250-95 (2016).
• Cheng et al. Ketamine ‘unlocks’ the reduced clock-speed effects of cocaine following extended training: evidence for dopamine-glutamate interactions in timing and time perception. Neurobiol Learn Mem. 88:149-159 (2007).
• Eagleman et al. Time and the brain: subjective time relates to neural time. J Neurosci. 25(45):10369-71 (2005).
• Egerstedt. Degrees of control. Nature. 473:158-9 (2011).
• Eisenberg et al. Examining impulsivity as an endophenotype using a behavioral approach: a DRD2 Taq1 A and DRD4 48-bp VNTR association study. Behav Brain Funct. 3:2 (2007).
• Hatori et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 15:848-60 (2012).
• Johnson and Kenny. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 13(5):635-41 (2010).
• Kononowicz. Dopamine-dependent oscillations in frontal cortex index ‘start-gun’ signal in interval timing. Front Hum Neurosci. 12;9:331. doi: 10.3389/fnhum.2015.00331. eCollection 2015 (June 2015).
• Kravitz et al. Distinct roles for direct and indirect pathway striatal neurons in reinforcement. Nat Neurosci. 15(6):816-8 (2012).
• Lake and Meck. Differential effects of amphetamine and haloperidol on temporal reproduction: dopaminergic regulation of attention and clock speed. Neuropsychologia. 51:284-92 (2013).
• Lester et al. Acetylcholine-dopamine interactions in the pathophysiology and treatment of CNS disorders. CNS Neurosci Ther. 16:137-62 (2010).
• Liu et al. Controllability of complex networks. Nature. 473:167-73 (2011).
• McClure et al. Separate neural systems value immediate and delayed monetary rewards. Science. 306:503-7 (2004).
• Meck and Church. Nutrients that modify the speed of internal clock and memory storage processes. Behav Neurosci. 101(4):465-75 (1987).
• Meyer-Lindenberg et al. Neural mechanisms of genetic risk for impulsivity and violence in humans. Proc Natl Acad Sci U S A. 103(16):6269-74 (2006).
• Nehlig. Caffeine effects on the brain and behavior: a metabolic approach. Ch. 6 in Caffeinated Beverages, edited by Parliment, Ho, and Schieberle, (American Chemical Society, 2000).
• Ohmura et al. Lithium, but not valproic acid or carbamazepine, suppresses impulsive-like action in rats. Psychopharmacology. 219:421-32 (2012).
• Power et al. Polygenic risk scores for schizophrenia and bipolar disorder predict creativity. Nat Neurosci. 18(7):953-5 (2015).
• Shi et al. Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain. Cell Mol Neurobiol. 13(3):247-60 (1993).
• Simen and Matell. Why does time seem to fly when we’re having fun. Science.354(6317):1231-2 (2016).
• Soares et al. Midbrain dopamine neurons control judgment of time. Science. 354(6317):1273-7 (2016).
• Stice et al. Relation between obesity and blunted striatal response to food is moderated by Taq1A A1 allele. Science. 322:449-52 (2008).
• Sysoeva et al. Genetic determinants of time perception mediated by the serotonergic system. PLoS ONE. vol. 5 issue 9:e12650 (Sept. 2010).
• Yu et al. Genetic deletion of A2A adenosine receptors in the striatum selectively impairs habit formation. J Neurosci. 29(48):15100-3 (2009).
• Yuan et al. Rutin ameliorates obesity through brown fat activation. FASEB J. 31:333-45 (2017).

APPETIZERS

Thou shouldst not have been old till thou hadst been wise.
— King Lear (Shakespeare)

Gold IS money, everything else is credit.
— John Pierpont (J.P.) Morgan

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 modern nation-state, a massive and entrenched insurance company attached to an equally massive and entrenched standing army.
— W. Ben Hunt, Ph.D.
http://epsilontheory.com (posted Nov. 24, 2013)

The future is already here—it’s just not very evenly distributed.
— William Gibson, science fiction author

THE KING IS DEAD
LONG LIVE THE KING?

There are a number of meanings of the word “check,” but, it is said in a recent article, they all come from the same root: the game of chess.

First, the game of chess itself: the king, in Persian, is shah, and shah mat means ‘the King is dead.’ In Russian, the game of chess is itself called shakhmaty, and “check” is said shakh. This becomes scaccus in Latin, and from there you get echec in French, chess in English, and lots of other forms in different languages. (Note that echec is also the French word for ‘failure’—and this also comes directly from the chess concept.

—Sasha Volokh, THE VOLOKH CONSPIRACY, The Washington Post, Jan. 1, 2017 (NOTE: The words in Persian, Russian, Latin, and French do not contain the pronunciation punctuation (marks above letters).

HOW TO TAKE NIACIN THE RIGHT WAY

Oh, yes, there is a right way to take high-dose immediate release niacin. Take it at the right time and you can get a host of health benefits, especially reduced triglycerides, LDL, and VLDL and increased HDL—at the wrong time, you lose some of these benefits. Here’s why.

Niacin causes cellular metabolism to switch from primarily using glucose as a fuel to primarily using fats, except in the heart, where lipids are the primary fuel and niacin causes a switch to glucose (Carlson, 2005). This switch takes place postprandially, that is, right after you eat, which is when you experience the highest level of blood fats, high enough to increase the risk of a heart attack. That is why some people have a heart attack after eating a heavy meal.

The process of being able to switch between using metabolic substrates is termed metabolic flexibility … (Virtue, 2012).

After eating, fats are taken up and stored by adipose tissue, which releases fatty acids (a process called lipolysis) to the liver and to muscles. “During the fed state, net lipid flux into adipose tissue increases, whereas in the fasted state net lipid efflux predominates” (Virtue, 2012). Niacin prevents lipolysis, the release of these fatty acids from adipose tissue into the bloodstream. (The liver uses the fatty acids to produce triglycerides. The reduction in the availability of free fatty acids for the liver to make triglycerides is why niacin causes a reduction in triglycerides (Virtue, 2012; Kroon, 2017).

There is a strong negative correlation between plasma triglyceride levels and the concentration of HDL—as the level of triglycerides go up, HDL levels go down. The major components of VLDL (very low density lipoproteins) are triglycerides derived from the liver; the VLDL then carry triglycerides in the bloodstream. Reduction of the synthesis of triglycerides in the liver by niacin importantly increases HDL and reduces VLDL.

During the periods when you haven’t eaten (or at night when you sleep), your cells primarily use fats as primary fuel. Taking niacin can’t “switch” the choice of metabolic fuel to fats when you are already using fats as a fuel, but it can reduce the ability of cells to use glucose, which is why some people have a small increase in blood glucose when they use niacin. “We suggest that postprandial FFA [free fatty acid] lowering is the primary mechanism driving the metabolic improvements resulting from NiAc [nicotinic acid, niacin] timed to feeding. Reduced FFA supply to the tissues lowers substrate competition with glucose and improves insulin sensitivity just when it is needed the most (i.e., during the influx of dietary carbohydrate in the postprandial phase), resulting in reduced postprandial hyperglycemia and hyperinsulinemia (Kroon, 2017).”

Thus, the best way to use niacin as a supplement is to take it during or just after a meal, not at other times.

This, incidentally, is one reason why we do not recommend using extended-release niacin: it does not limit niacin to the times when it is best to take it, during or just after a meal.

THE EFFECTS OF EMOTIONAL STRESS REDUCED BY NIACIN

Another potential benefit from taking niacin is that niacin has been shown in healthy human subjects to reduce the elevated fatty acids and triglycerides that resulted from 2 hours of emotional stress as compared to similar human subjects receiving the same emotional stress but no niacin. (Carlson, 2005, p. 99)

References

Carlson. Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review. J Int Med. 258:94-114 (2005).

Kroon et al. Nicotinic acid timed to feeding reverses tissue lipid accumulation and improves glucose control in obese Zucker rats. J Lipid Res. 58:31-41 (2017).

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).

A GOOD TIME TO TAKE A DOSE OF NIACIN:
RIGHT AFTER YOU EAT SOME OF THIS WONDERFUL POTATO SALAD MADE WITH LOW GLYCEMIC INDEX, HIGH FIBER SWEET POTATOES

(Sandy adapted a recipe from one in POTATO SALAD by Debbie Moose (John Wiley & Sons, 2009))

For about 6 servings, you’ll need

2 pounds of sweet potatoes, cut into 1 – 1 1/2” long pieces

1/2 cup of crumbled blue cheese

1/4 cup chopped fresh chives

1/2 cup coarsely chopped walnuts (or any nuts of your choice)

3/4 cup sour cream

1/4 cup mayonnaise

1/2 tsp. salt

1/2 tsp. freshly ground black pepper

1 tsp. Ineffable Essence (optional—we ALWAYS use it)

1/2 cup chopped celery (or, a tsp or two of celery seed)

1/4 cup chopped onion (shallots are nice)

Cook sweet potatoes until they are soft when you poke them with a fork, 10 to 12 minutes (longer if you live at high altitude). Drain. Chop them coarsely until the texture is something like VERY lumpy mashed potatoes. Then put the lumped potatoes and all the other ingredients into a large bowl. Mix thoroughly.

This recipe is great either at room temperature or after refrigeration. (But do refrigerate the leftovers, if you have any.)

NOTE: Ineffable Essence is a condiment, one of our formulations, consisting of disodium inosinate (a nucleotide found naturally in foods such as meats, cheeses, and vegetables) and monosodium glutamate (yup, the supposed disaster area is found naturally in foods such as meats, cheeses, and vegetables at doses that have never caused any problems and that is how we use it). Ineffable Essence adds natural substances that degrade in foods that contain them, to restore them to levels of fresh food and that add importantly to the flavor of fresh food.

GETTING CONNECTED WITH EGCG

EGCG is connected to lifespan
Lifespan is connected to stress
Stress is connected to obesity
Obesity is connected to cancer
Cancer is connected to diet
Diet is connected to eating
Eating is connected to drinking
And drinking—tea that is—
Is connected to Y O U.

—this silly ditty written by Sandy

The reality is that green tea (in particular, its major polyphenol EGCG (epigallocatechin 3-gallate), is an amazingly inexpensive source of important health benefits, which may include protection against neurodegenerative diseases and cognitive decline with aging to reducing stress-induced disorders to reducing the risk of cancer and cardiovascular disease to increasing lifespan of C. elegans and possibly even to reducing scarring after burns.

PROTECTION AGAINST INFLAMMATION BY EGCG

C-REACTIVE PROTEIN (CRP) REDUCED IN OLD RATS BY EGCG

Among its many benefits, EGCG has been reported in a number of studies to have anti-inflammatory activity. In one recent study (Kumaran, 2009), 3 months old and 24 months old male albino Wistar rats were studied. They were made hypercholesterolemic by being fed a diet of normal rat chow supplemented with 4% cholesterol and 1% cholic acid. Treated rats also received EGCG (100 mg/kg body weight/day) orally for 30 days. Unsurprisingly, the untreated old rats had abnormally elevated lipid levels, marker enzymes, and inflammatory enzymes in serum, as compared to the young rats. This EGCG dose is roughly equivalent to one of our green tea booster capsules taken three times a day, or 6 cups of green tea a day.

Results showed that treatment with EGCG partially reversed the elevated lipid levels and the inflammatory changes seen in the old rats. For example, elevated levels of TNF-alpha (tumor necrosis factor alpha), CRP (C-reactive protein), and fibrinogen (a clotting factor) were “reverted back to near control values upon supplementation of EGCG.” The authors add, “Plasma CRP, an acute phase reactant has proven remarkably robust as a marker of cardiovascular risk… (Kumaran, 2009). ”

As the researchers (Kumaran, 2009) noted in the introduction: “The lesions of atherosclerosis represent a series of highly specific cellular and molecular responses that is described best as an age-related inflammatory disease.”

EGCG AGAINST CANCER

One way that EGCG protects against cancer is to reactivate tumor suppressor genes that have been silenced by being methylated. DNA methylation is a method used in the body to make genes inaccessible for the purpose of being expressed. This can be reversed by reducing DNA methylation, which is what EGCG did in a recent study (Nandakumar, 2011). This is important, as DNA methylation increases with aging, one likely reason for the increasing susceptibility of older persons to get cancer.

Studies of green tea have revealed anti-cancer effects in a variety of different cancers, including stomach, small intestine, colon, lung, bladder, prostate, breast, oral cavity, prostate, melanoma, multiple myeloma, acute myelogenous leukemia, and chronic myelogenous leukemia, among others (Kumazoe, 2016). Several studies have shown that the active compounds in green tea extract are the catechins, with EGCG (epigallocatechin-3-gallate) as the most common form (Kumazoe, 2016).

PROSTATE CANCER INHIBITED BY EGCG

Despite some progress in the treatment of cancer, prostate cancer is still a major killer. Although it can often be brought into remission by blocking androgens, the cancer usually becomes insensitive to androgens and recurs in a different form—it can no longer be controlled by blocking androgens and is then very difficult to treat. Indeed, as of 2006, prostate cancer had become the second leading cause of cancer-related deaths among men in western countries (Bettuzzi, 2006).

A double-blind, placebo- controlled study of 60 men with high-grade prostate intraepithelial neoplasia, 30% of whom would be expected to develop prostate cancer within a year, reported that after a year only one tumor was found in the thirty men treated with green tea catechins (of which EGCG is the major component). The men took three capsules of 200 mg green tea catechins per cap each day for a year. The 30 men who received placebo had 9 tumors diagnosed. (Bettuzi, 2006) This study was particularly impressive considering that the men ALREADY had a form of early prostate cancer that was highly likely to progress to full blown prostate cancer.

In an epidemiological study of 49,920 Japanese men aged 40-69, consumption of green tea (5 or more cups a day) was associated with a dose dependent decrease in the risk of developing advanced prostate cancer, but not of local prostate cancer. The men were followed from 1990 (or 1993) to the end of 2004 (Kurahashi, 2008). These results show an association between green tea and a reduced risk of advanced prostate cancer but cannot be considered proof of causality.

EGCG INCREASES LIFESPAN OF CAENORHABDITIS ELEGANS

The famous model organism, C. elegans, a free living soil nematode worm, subject of numerous studies including studies of various treatments on lifespan, was in this study (Abbas, 2009) treated with EGCG (220 µm daily) throughout their complete lifespan. The mean lifespan of the treated worms was 16.11% greater than the untreated worms. In addition, when the animals were exposed to lethal oxidative stress, the EGCG-treated worms had a 65.05% increased survival.

GREEN TEA CATECHINS SLOW AGE-ASSOCIATED SENESCENCE IN MICE

For many people, their greatest fear of aging is a loss of mental capabilities or outright dementia. Hence, protecting the brain from decline with age is a powerful motivation.

One study of green tea catechins (with EGCG being the most abundant of these in the tea) followed SAMP10 mice especially bred to have accelerated brain aging (Unno, 2004). The treated mice received free access to food and tap water containing 0.02% green tea catechins for 12 months, while controls had free access to food but plain tap water during the same period. This is roughly equivalent to 400 mg per day of green tea catechins for an adult human (as calculated by body surface area to convert from the mouse dose). The animals were tested for their learning and memory abilities.

One of their memory tests involved the mice receiving a shock when they entered a dark area. Mice normally prefer the dark, so it was instinctive for them to seek darkness and avoid light. However, receiving a shock in dark areas caused the mice to learn to avoid dark areas. Staying in the light area for 300 seconds was used as a measure of the animals’ memories of the shock. Entering the dark area of a chamber divided into dark and light areas was consider a “failure.” The results showed that “[t]he failure ratio [the number of failures out of the total number of entries into the chamber] was significantly lower among the 12-month-old mice that had received GT-catechins than among similarly aged control mice.”

“Among the 12-month-old SAMP10 mice that had been given catechin water, there were fewer individuals with both marked cerebral atrophy and a longer learning time.” The authors discussed possible mechanisms for these results. They explained that green tea has potent antioxidant effects, but in addition to that, they induce increased expression of antioxidant enzymes. The researchers concluded that the preventive effects of GT catechins on brain senescence in these senescence-accelerated mice “may indicate a beneficial effect in maintaining the quality of life during old age.”

EGCG MAY REDUCE SCARRING

After reading about the benefits of EGCG described above, it may not seem nearly as important that it may reduce scarring after burns. But severe (hypertrophic) scars can, in addition to being unsightly, result in “itching, redness, and hard nodular scar tissue often with abnormal sensation.” Worst of all, they “can result in functional loss especially over joints such as in the hand.” This loss of function is the result of contracture as the hard scar tissue inhibits motion (Mehta, 2016).

The prevention and treatment of hypertrophic scars has not improved during recent years, even though survival following extensive burns has improved. Remedies for these severe scars are not readily available. Hence, it is good news that a widely available, inexpensive, and safe constituent of green tea (EGCG, epigallocatechin 3-gallate) has been shown “to inhibit a number of intracellular signalling pathways and reduce expression of pro-fibrotic molecules…” such as vascular endothelial growth factor (VEGF), TGF-beta1 (transforming growth factor beta-1), and CTGF (connective tissue growth factor) which promote the development of hypertrophic scars. (Mehta, 2016)

References

Abbas and Wink. Epigallocatechin gallate from green tea (Camellia sinensis) increases lifespan and stress resistance in Caenorhabditis elegans. Planta Med. 75:216-21 (2009).

Bettuzzi et al. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res. 66(2):1234-40 (2006).

Kumaran et al. Attenuation of the inflammatory changes and lipid anomalies by epigallocatechin-3-gallate in hypercholesterolemic diet fed aged rats. Exp Gerontol.44:745-51 (2009).

Kumazoe and Tachibana. Anti-cancer effect of EGCG and its mechanisms. Func Foods Health Dis. 6(1):70-8 (2016).

Kurahashi et al. Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidem. 167(1):71-77 (2008).

Nandakumar et al. (-)-Epigallocatechin-3-gallate reactivates silenced tumor suppressor genes Cip1/p21 and p16INK4a, by reducing DNA methylation and increasing histones acetylation in human skin cancer cells. Carcinogenesis. 32(4):537-44 (2011).

Nehta et al. The evidence for natural therapeutics as potential anti-scarring agents in burn-related scarring. Burns Trauma. 4:15 (2016).

Unno et al. Suppressive effect of green tea catechins on morphologic and functional regression of the brain in aged mice with accelerated senescence (SAMP10). Exp Geront. 39:1027-34 (2004).

ASSOCIATION OF FEAR OF TERROR WITH LOW-GRADE INFLAMMATION

The fear of terror from terrorists could be processed in the brain like fear from many severe sources of unpredictable danger. In each case, there are similar mechanisms, one of which is inflammation.

Israel is a place where the fear of terror is chronic, present on a day-to-day basis. Scientists from Tel-Aviv University and other Israeli institutions studied the effect of the fear of terror in 1,152 apparently healthy employed adults (721 men and 431 women aged 20-70) to test the hypothesis that “chronic fear of terror may be associated with low-grade inflammation” by measuring high sensitivity C-reactive protein (CRP), a commonly used indicator of inflammation (Melamed, 2004). (Chronically high levels of inflammation, as indicated by increased C-reactive protein, are associated with an increased risk of cardiovascular disease.)

The results were sexually dimorphic: “Chronic fear of terror in women, but not in men, is associated with elevated CRP levels, which suggests the presence of low-grade inflammation and a potential risk of cardiovascular disease.” “They [the women] not only appraised the situation as more threatening and expressed higher fear of terror, but this also appears to have negative implications to their physical health.” “Elevated CRP levels (>3.0 mg/L) were found in 24.5% of the men and 31.1% of the women.”

Since there is no way for an individual to control the uncertain occurrence of terrifying incidents, preventing the low-grade inflammation that mediates much of the negative health aspects of chronic fear is a possible way to maintain health while living in a state of fear. As noted above, EGCG has been shown in a study to reduce the level of CRP, C-reactive protein, in old rats.

A TERRORIZED POPULATION MAY HAVE A HIGHER LEVEL OF C-REACTIVE PROTEIN

As mentioned above, a recent study found that a “highly traumatized civilian population” had elevated levels of C-reactive protein, an inflammatory marker associated with high levels of stress and a biomarker for increased risk of cardiovascular and metabolic diseases. The “highly traumatized civilian population” were 2692 men and women who were recruited from an inner city hospital (Grady Memorial Hospital in Atlanta, GA) that treated primarily African Americans (Michopoulos, 2015).

Increased CRP was associated with PTSD (posttraumatic stress disorder) symptoms and fear physiology, including “hyperarousal” symptoms, all sounding very much like a “highly traumatized” population. “Individuals with PTSD show elevated levels of the inflammatory cytokines IL-6, IL-1beta, and IL-2…[and] peripheral levels of inflammatory molecules correlate with PTSD symptomology (Michopoulos, 2015).”

A second paper (Shenhar-Tsarfaty, 2014) also studied the relationship between C-reactive protein (CRP) and physiological correlates of chronic fear in a highly traumatized population, 17,380 apparently healthy adult volunteers in Israel. While average maximal pulse values tend to decrease with age (Shenhar-Tsarfaty, 2014), here they found 4.1% of the volunteers had annual pulse increases. Moreover, the observed pulse increases were correlated with elevated CRP levels. The authors concluded: “…consistent exposure to terror threats ignites fear-induced exacerbation of preexisting neuro-immune risks of all-cause ­mortality.”

They explain these results, in part, by noting that pulse is controlled by a number of genetic, environmental and other endogenous factors that “include excessive inflammation, shown to associate with pulse increases [and] to be controlled by cholinergic imbalance (decreased vagal tone or increased sympathetic activity), and to increase mortality (Shenhar-Tsarfaty, 2014).”

References

Melamed et al. Association of fear of terror with low-grade inflammation among apparently healthy employed adults. Psychosom Med. 66:484-91 (2004).

Michopoulos et al. CRP genetic variation and CRP levels are associated with increased PTSD symptoms and phy siological responses in a highly traumatized civilian population. Am J Psychiatry. 172(4):353-62 (2015).

Shenhar-Tsarfaty et al. Fear and C-reactive protein cosynergize annual pulse increases in healthy adults. Proc Natl Acad Sci U S A., published online Dec. 22, 2014, pp. E467-71.

C-REACTIVE PROTEIN LEVELS INCREASED IN THOSE WITH PTSD (POSTTRAUMATIC STRESS DISORDER)

Increased systemic inflammation has been linked to certain stress-induced psychopathologic disorders, such as posttraumatic stress disorder. In a recent paper (Michopoulos, 2015), researchers found that increased CRP (C-reactive protein) levels were associated with fear-related psychopathology and PTSD in subjects recruited from an inner city public hospital (Grady Memorial Hospital, Atlanta, GA) that primarily served African Americans.

(In addition, CRP levels were found to differ depending upon CRP gene variants, single nucleotide polymorphisms (SNPs). One particular SNP, rs1130864, was found to be significantly associated with increased PTSD symptoms.)

Since C-reactive protein is increased under inflammatory conditions and is itself a promoter of inflammation, a substance that can reduce the levels of C-reactive protein could possibly be beneficial to those under extreme stress or who have a stress-related disorders such as PTSD.

Delayed inhibition of stress or its prolongation can increase susceptibility to many conditions, including cardiovascular disease, diabetes, allergy, immune system disorders, cancer, schizophrenia, Alzheimer’s disease, and depression (Wong, 2010). In fact, C-reactive protein is considered a marker for increased risk of cardiovascular disease and is included in most lab test panels to evaluate CVD risk.

As mentioned above, EGCG was shown to reduce C-reactive protein levels in old rats.

References

Michopoulos et al. CRP genetic variation and CRP levels are associated with increased PTSD symptoms and physiological responses in a highly traumatized civilian population. Am J Psychiatry. 172(4):353-62 (2015).

Wong et al. Stress and adrenergic function: HIF1alpha, a potential regulatory switch. Cell Mol Neurobiol. 30:1451-7 (2010).

IF YOU TAKE SELENIUM TO HELP REDUCE YOUR RISK OF CANCER…

…You need to know that not all forms of selenium are equally effective in doing so and that selenite is likely to be more effective than some other forms, including ­selenomethionine.

DIFFERENT FORMS OF SELENIUM CAN HAVE VERY DIFFERENT EFFECTS

Selenium has anticarcinogenic effects, which is a major reason why the mineral is taken as a supplement by so many people. A recent paper (Olm, 2009) explains why, in terms of cancer prevention, selenate, selenocysteine, or selenomethionine may be less preferable than selenite. There, the authors explain what they have discovered about how different forms of selenium can exert different cytotoxic effects against cancer cells.

The researchers found that there is a reductive (anti­oxidant) microenvironment around cancer cells due to the secretion from cancer cells of cysteine that occurs as part of a cystine/cysteine redox cycle. This cycle is under the control of multidrug resistance protein pumps that operate in cancer cells to pump out intracellular molecules cytotoxic to cancer cells such as cysteine. This reductive extracellular microenvironment, in turn, activates selenium into forms that are cytotoxic because they are taken up into the cancer cells where they release deadly hydroxyl radicals. Selenate and selenomethionine were reported (Olm, 2009) to be less able to enter the cancer cells (less redox active). While selenocysteine is redox active, it has to be enzymatically degraded by the enzyme beta-lyase to selenide to achieve its full toxic potential. Moreover, selenocysteine may, the authors suggest, be partly secreted back to the extracellular compartment along the same pathway as cysteine.

The bottom line of this complex mechanism of selenium cancer protective effects is, as proposed in this paper, that there might be a “… possibility of a cancer-specific high-affinity selenium uptake mechanism that might explain cancer-specific selenite cytotoxicity at therapeutic selenite concentrations (μM range) (Olm, 2009).”

We hope that research is done on the use of sodium selenite as an adjunct to cancer chemotherapy. At least some of the cancer cells that are most resistant to chemotherapy will be particularly susceptible to selenite. The reason that chemotherapy so often eventually fails is that the cells that remain alive after that therapy are those that are able to pump the drugs out and, hence, are resistant and can continue to proliferate. The new resistant population is no longer treatable with the original chemotherapeutic regimen. These cells may be especially susceptible to the effects of selenite.

Meanwhile Back at the FDA the Selenium Evidence is Receiving Short Shrift

While considerable evidence supports a role for selenium in cancer risk reduction, the FDA has denied qualified health claims that selenium MAY have anticancer effects and MAY reduce the risk of several types of cancer. In the rarified atmosphere at the FDA, the belief persists that nothing can be communicated to the public as true about dietary supplements or foods unless the FDA first gives you their permission.

RARER THAN GOLD

Interestingly, the concentration of Se in the Earth’s crust is actually lower than that of gold, making it rarer than gold (Whanger, 2004). It should be no surprise, then, that there are many areas of the world where people live in a low-selenium environment.

UPPER TOLERABLE (SAFE) LIMIT OF SELENIUM SET BY THE INSTITUTE OF MEDICINE

The Institute of Medicine of the National Academy of Sciences (2000) has set 400 µg of selenium as the upper tolerable (safe) limit.

References

Olm et al. Extracellular thiol-assisted selenium uptake dependent on the xc-cystine transporter explains the cancer specific cytotoxicity of selenite. Proc Natl Acad Sci U S A. 106(27):11400-5 (2009).

Whanger. Selenium and its relationship to cancer: an update. Br J Nutr. 91:11-28 (2004).

LIVE LONGER WITH VITAMIN D3 OR
LIVE LESS LONG WITH LESS VITAMIN D3

Vitamin D deficiency has been linked to many chronic disorders, such as multiple sclerosis, inflammatory bowel disease, infections, immune deficiency, cardiovascular disease, hypertension, heart failure, sudden cardiac death, cancer, and Alzheimer’s disease (Gruber, 2015). But, even more than that, low vitamin D levels in serum are associated with increased mortality. In fact, in a recent meta-analysis of 42 randomized trials, taking vitamin D for three years or longer resulted in a significant 6% reduction in all-cause mortality.

In another meta-analysis (this one included 73 observational studies and 22 randomized controlled trials with 849,412 and 30,716 participants respectively), the observational studies were reported to show that “[e]ach decline of 25(OH)D [vitamin D] by 10 ng/mL was associated with a 16% increased risk of all-cause mortality (Gruber, 2015).”

Importantly, however, different forms of Vitamin D have different effects. In the randomized clinical trials noted in the paragraph above, “where vitamin D2 (dose range: 208-4500 IU/day) or vitamin D3 (dose range: 10-6000 IU/day) were given alone vs placebo or no treatment, vitamin D3 significantly reduced the mortality by 11%, whereas vitamin D2 increase[d] the mortality by 4%.” (The increased mortality seen with vitamin D2 was, however, seen with lower doses (<600 IU/day) and shorter average periods of supplementation (less than 1.5 years).) Vitamin D3 is the form of vitamin D that the two of us take.

A third meta-analysis that included 32 studies from January 1966 to January 2013 with more than 500,000 people (about 55 years old), found that serum 25(OH)D levels less than or equal to 30 ng/mL were associated with greater all-cause mortality, as compared to levels over 30 ng/mL. The authors of this meta-analysis also noted that the cutoff point for a deficient intake of vitamin D (20 ng/mL), as recommended by the federal government’s Institute of Medicine was too low to get all the health benefits of vitamin D (e.g., reduced risk of all-cause mortality and diseases such as cancer, autoimmune diseases, etc.). They suggested that the cutoff point should “not be set at 20 ng/mL, but at 30 ng/mL (Gruber, 2015).”

It is notable that the “Institute of Medicine recommended a daily tolerable upper intake (UL) for vitamin D for persons of nine years and older of 4000 IU and the Endocrine Society recommended for adults an UL of 10,000 IU vitamin D (Gruber, 2015).” We take 16,000 IU/day to attain a minimum-mortality sweet spot value of 60 ng/ml. NOTE: Do not take more than 10,000 IU/day unless you also have a blood test to verify that you are not taking too much.

It is also interesting to know that “obese individuals needed 2.5 times more vitamin D to raise the blood levels of 25(OH)D to the same degree as a normal weight person (Gruber, 2015).”

In conclusion, vitamin D3 is an inexpensive way to obtain a variety of potentially important health benefits, including the possibility of living longer.

Reference

Gruber et al. Live longer with vitamin D? Nutrients. 7:1871-80 (2015).

LONGER TELOMERES WITH VITAMIN D IN WOMEN

Telomeres are the ends of chromosomes that become shorter with each cellular replication—the shortening is associated with age and accelerated by oxidative stress and chronic inflammation. Arthritis, autoimmune diseases, and coronary heart disease have been associated with shorter telomeres (Richards, 2007).

Telomeres are commonly measured on leukocytes, white blood cells. A study of 2,160 women aged 18-79 years found that “[t]he difference in LTL [leukocyte telomere length] between the highest and lowest tertiles of vitamin D was 107 base pairs, which is equivalent to 5.0 years of telomeric aging (Richards, 2007).” This is a very substantial difference, especially considering that the vitamin D was the dietary source rather than supplemental.

With the advent of mostly indoor employment and the widespread use of sunscreens for outdoor recreation to protect against too much ultraviolet light, vitamin D deficiency has become endemic. It makes sense to take a supplement of D3­!

Reference

Richards et al. Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women. Am J Clin Nutr. 86:1420-5 (2007).

AND NOW! THIS VITALLY IMPORTANT NEWS ITEM

We have now learned why certain evil characters (such as Gollum, Smaug, and an orc) in J.R.R. Tolkien’s “The Hobbit” were all losers in their battles with humans, elves and dwarves: they had a severe vitamin D deficiency! Yes, they were felled as a result, thus answering a longstanding question concerning how such powerful, evil characters could have been such overwhelming losers.

As reported in the Christmas edition of the Medical Journal Of Australia, Nicholas Hopkinson, a doctor at Imperial College, London, and his son Joseph studied the diet, living conditions, and habitat of the characters in “The Hobbit” and made the Earth-shaking discovery that the evil characters were all living in the dark, with poor diets severely deficient in vitamin D.

Meanwhile the hobbit diet was varied, with plenty of vitamin D, and although Bilbo lived in a hole, he liked sitting in a sunny window as well as gardening, getting plenty of exposure to the sun.

The lesson to be derived from this story, according to the good doctor and his son, was that the triumph of good over evil could be explained to some extent by the poor diet of the evil characters and their lack of exposure to sunlight.

SO NOW WE KNOW…….?

(reported in the YAHOO NEWS, 12/15/13