The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 19 No. 5 • June 2016



The birth of the ketogenic diet


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



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


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.”


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

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

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

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

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

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

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

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

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

The Birth of the Ketogenic Diet

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

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

Your Brain on Ketones
The Aging Brain is Highly Dependent
on Ketones for Energy
When It Can’t Get Enough

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

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


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)


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.


“...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.



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