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Juvenon Health Journal volume 10 number 1  january 2011

By Benjamin V. Treadwell, Ph.D.

Aging Brain Health: Rediscovering the Energy AlternativesWhether it’s abstract concepts or planning our day, why do we seem to think more slowly as we age? To date, there is no definitive answer, but an understanding of the aging brain and its energy requirements offers some clues.

Research has shown that, as we age, the mitochondria in our cells, including those of our central nervous system, produce less energy. For the brain, a decrease in available energy is more critical than for other organs. Although it comprises only two percent of the body’s weight (about three lbs.), the brain accounts for approximately 20 percent of the total energy expended by the body per day.

Moreover, unlike other tissues, including liver, heart, adipose and skeletal muscle, the brain cannot store burnable fuel in the form of glycogen/fat. Consequently, its cells need a constant supply of an energy source, primarily glucose. Even a small decrease in energy can result not only in impaired function of neurons and supporting cells, but also in brain cell death.

“Brain cells need a constant supply of an energy source primarily glucose.”

So, is it the condition of the mitochondria, the absence of enough fuel or a combination of the two that results in these energy deficits? Are they linked to age-associated neurodegenerative disorders? Can they be prevented or delayed? For some possible answers, this issue of the Health Journal examines the mechanisms involved, as well as some recent work implicating a specific class of fats with the potential to improve central nervous system/brain health.

Incapacitated Neurons
Studies have shown an age-associated loss of insulin receptors in the brain, which would cause a decrease in the capacity of the neurons to take up the fuel (glucose) that is burned by the mitochondria. There is also evidence that the excitatory neurotransmitter, glutamate, may be taken up by neurons (at synaptic vesicles) in excess with age, resulting in neuro-excitotoxicity and eventual death of the neuron.

So, it is reasonable to suspect the age-associated decline in brain function may be the consequence, at least in part (There are other potential contributing factors such as increase in cell-destructive oxidants.), of neuron dysfunction. In other words, the decline could be due to the aging brain’s impaired ability to regulate the flow of the primary fuel source, glucose, to its cells. (This theory seems to be supported by research that has linked type II diabetes with impaired cognition.)

Alternative Energy
Interestingly, although the brain and central nervous system (CNS) normally utilize glucose for energy, thanks perhaps to evolution, there is another option. Responding to pressures from the environment, in particular food shortages, animals, man included, have developed fuel depots in many tissues of the body. Liver, adipose and muscle tissue store glycogen and fat.

“The decline in brain function may be, in part, a consequence of neuron dysfunction.”

When food is scarce, the stored glycogen can be metabolized into glucose that can be converted to energy by the cells. Under extreme conditions of starvation, when all the glycogen stores are exhausted, fat is the next energy source. Metabolites, known as ketone bodies, are among the major products of fat metabolism under starvation conditions (lack of carbohydrates). The medical term for the increase in blood ketones, as a consequence of fats being used almost exclusively for energy, is ketosis.

Aside: Diabetics often produce these metabolites because, due to insulin resistance, glucose cannot enter their cells to be utilized for energy, therefore their muscle, liver, and fat cells use fat as a substitute. In fact, the characteristic odor of one ketone, acetone (active ingredient in nail polish remover), is readily recognized by diabetologists on the breath of those in ketosis.

Many tissues (liver excluded) can utilize ketones, themselves, as fuel for energy. Although brain and CNS cells cannot convert fat to energy, they can burn ketone bodies. In the scheme of evolution, an alternative energy source for the brain makes sense. After all, it is the control center necessary for survival, the most important organ required to devise a plan.

Studies seem to indicate that our ancestors most likely experienced long periods of near starvation, favoring the ketogenic condition. This raises a question pertinent to the health of modern man: has the brain become more accustomed/adapted to ketone bodies as a source of energy?

Neuron-calming Ketones
Speaking of brain health, it seems that ketones may also have a neuron-protective function. The first indications date back to the early part of the 20th century, when doctors often prescribed ketogenic diets, as well as more rigorous starvation diets, to induce ketosis in patients with intractable epilepsy. Although a large percentage of these patients experienced a seizure-free life after treatment, the exact mechanism was unclear and ketogenic diets were abandoned, for the most part, with the development of anticonvulsant drugs.

Recently, however, ketogenic diets have been “rediscovered” (and made more palatable) for patients with drug-resistant seizures. At the same time, researchers are beginning to learn how ketone bodies may reduce the frequency of seizures: by helping to maintain a normal balance between inhibition and excitation in the brain.

“Brain cells can burn ketones, products of fat metabolism in other cells, for energy.”

Experiments have shown that ketones interfere with the uptake of the neurotransmitter glutamate into those neuro-structures (synaptic vesicles), which are involved in its eventual release when the neuron is activated. An excess of glutamate can cause an over-charged neuro-electrical condition, leading to neuro-excitotoxicity and death of neurons comprising the circuit, in other words, a seizure.

Another recent study (See this issue’s “Research Update.”) demonstrated that artificially generated ketosis seems to improve cognitive performance in patients with mild to moderate Alzheimer’s disease. Although still speculative, the theory is that the mechanism may again involve ketone interference with excess-glutamate-induced neurotoxicity.

There is also evidence of improved mitochondrial health with increases in energy production (ATP synthesis) and levels of the antioxidant, catalase, as extrapolated from studies of animals on ketogenic diets.

Ketosis and Coconuts
The diet prescribed to the Alzheimer’s patients in the afore-mentioned study is actually a patented formula known as AC-1202 (similar in composition to coconut oil). Is it possible to enjoy the brain health benefits of ketosis without this kind of dietary restriction (or starvation)?

It seems there are foods on the market that may be as effective at producing ketones, but without a significant change in diet, other than cutting down on sugar-laden foods. One example is non-hydrogenated, virgin coconut oil (no trans fat).

“Coconut oil may be as effective at producing ketones as extreme dietary restriction.”

This food contains fatty acids with medium-length carbon chains, which are readily converted by the intestines and liver to ketones (as compared to most animal fat, which contains long-chain fatty acids, that are not readily converted to ketones). First used as an addition to the classic ketogenic diet in the 1960s, coconut oil allows one to obtain the health benefits of ketones while on a more typical diet with a variety of food choices, including healthy carbohydrates and protein.

Several studies have shown that coconut oil is safe for human consumption. Findings also seem to indicate possible benefits for weight loss, not to mention the potential neuro-protective benefits for age-associated neurodegenerative disorders. More research is definitely called for.


Research Update

An original research article, “Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial,” in BioMed Central’sNutrition&Metabolism journal, details the results of research by a group of investigators from Accera, Inc., a Colorado company developing therapeutic treatments for neurodegenerative conditions.

Based on observations that Alzheimer’s disease (AD) is characterized by early and region-specific declines in cerebral glucose metabolism and that ketone bodies are produced by the body during glucose deprivation and are metabolized by the brain, the team wanted to determine if artificially induced mild ketosis could improve cognitive performance. Specifically, they examined the effectiveness of a patented ketogenic compound, AC-1202, on improving the symptoms of AD.

The researchers were aware of previous in vitro studies, which showed that impairment in glucose uptake by brain tissue resulted in an energy deficit and death of involved neurons, while there were protective effects on neurons grown in the presence of ketones. The team was also familiar with in vivo work that had demonstrated improvement in mouse models of AD fed a diet containing ketones.

For this 90-day human trial, 152 subjects, previously diagnosed with mild to moderate AD, were randomly assigned to a diet containing AC-1202 or a placebo. In pre-study analysis, the AC-1202 diet produced a significant increase in ketone bodies two hours after ingestion.

All subjects took verbal and written tests, designed to measure cognition, to establish baselines before the start of the study. The tests were repeated on day 45 and again on day 90. An additional testing was administered two weeks after the trial period.

Test scores for dose-compliant subjects on the AC-1202 diet were significantly better at the 45-day testing, compared to the placebo group. Interestingly, subjects deficient in a specific genetic marker, APOE4, showed the greatest improvement at this point. The differences between APOE4 negative and positive subjects were not as great at the end of the study (90 days). There was no difference at the two-week, post-test evaluation.

The investigators acknowledged that more research is needed to determine why/how the absence of this specific genetic marker influences AC-1202 effectiveness. But they did conclude that chronic, artificially induced mild ketosis may “offer a novel strategy for AD that can be used with current therapies.”

Read abstract here.

This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.


Ask Ben

Dr.Treadwell answers your questions.

question: I will soon be taking the Juvenon Cellular Health supplement (new capsule size) in conjunction with CoQ10 — two 100 mg capsules per day that also have 20 mg L-carnitine per capsule — that I have been taking for a short while. My two questions are:

1) How do the functions or activities of the components of Juvenon Cellular Health compare and contrast with the functions or activities of the components of CoQ10 + L-carnitine supplements?
AND

2) How much overlap, if any, is there in the activity or function of Juvenon Cellular Health and CoQ10? Thank you for your attention to my questions. I appreciate the opportunity to get feedback on technical aspects of a supplement, a service I very rarely find with other, similar health products. — 

answer: The Juvenon formula provides a balance of alpha lipoic acid (ALA) and acetyl-L-carnitine (ALC). ALA is a powerful antioxidant and a cofactor (required for the function) of two major enzyme complexes involved in the production of energy. As we age, we need more of this cofactor than our cells can make or our diet can supply. This is also the case with ALC and L-carnitine.

ALC, like L-carnitine, is an amino acid that transports fatty acids into the mitochondria for conversion to energy. Although the two nutrients can have similar effects (with some overlap), it seems they are somewhat functionally different. Reportedly, the L-carnitine form penetrates heart and skeletal muscle cells, but not brain cells. In fact, animal studies and limited human trials have indicated not only that ALC improves the health and activity of the energy-producing mitochondria, but it also may enhance cognitive capability with a more rapid transport to the brain.

CoQ10 complements L-carnitine and the nutrients in the Juvenon supplement, functioning in electron transport in the energy-producing pathway. It also acts as an antioxidant, supporting the high-energy requirements of heart-cell mitochondria and protecting cellular components.

Although your CoQ10/L-carnitine supplement and Juvenon Cellular Health seem to be complementary, I recommend consulting with your health professional before adding to your daily dosages.

Benjamin V. Treadwell, Ph.D. is a former Harvard Medical School associate professor.

Summary
Article Name
Aging Brain Health: Rediscovering the Energy Alternatives
Description
Whether it’s abstract concepts or planning our day, why do we seem to think more slowly as we age? To date, there is no definitive answer, but an understanding of the aging brain and its energy requirements offers some clues.
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