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 UPSETWhile 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.