By Benjamin V. Treadwell, Ph.D.

If we appear healthy, do we need to supplement our diets with vitamins, minerals and other nutrients? Thanks to evolution and inadequate nutrition, the answer seems to be yes.

Vitamins and Minerals 101

There are over 40 micronutrients, more commonly known as vitamins and minerals, that the body cannot manufacture but nevertheless requires for maximum health. Most of the micronutrients are familiar as they are contained in the common multiple vitamin-mineral pill many of us take on a daily basis. There are additional nutrients — the omega 6 and omega 3 fatty acids, for example — that are vitamin-like in that they are essential to our health but cannot be synthesized by our cells.
In addition to the essential nutrients, there are "conditionally essential nutrients" which can, to a limited extent, be made by the body, but at insufficient quantities under certain conditions. Those conditions include age-associated reduction in nutrient synthesis as well as diet deficiencies.

Biochemical Evolution
All organisms require nutrients not only to sustain life, but more importantly, to bring the organism to sexual maturity so it can reproduce. Over time, it is likely that sufficient quantities of these nutrients varied with environmental conditions. The evolving predecessors of humans became dependent on the nutrients available at the time to bring them at least to the reproductive age.
The biochemical constitution of modern man/woman is the product of those millions of years of continuous adaptations to the environment. The cells of the body have evolved to perform the work that is necessary for survival of the organism, and not much more. And metabolic pathways have evolved in a particular way that was partially determined by the availability of a variety of nutrients in the human diet.
In other words, nutrients that were plentiful to most diets promoted the development of certain enzymatic pathways. Since these nutrients were, in a sense, free for the taking, the cells of the evolving organism did not have to carry the blueprints for the machinery necessary to synthesize them. Consequently, the organism's survival became dependent on an external source, the diet, to supply these nutrients, now referred to as vitamins.
The scenario was different for nutrients that were often only available at suboptimal amounts in the diet of the evolving organism. It had to carry genetic information (blueprint) to synthesize these nutrients, but only at a rate to produce the balance of what was unavailable through diet. This more nebulous group of nutrients may include CoQ10, lipoic acid, L-carnitine and some amino acids, among others. They are commonly referred to as the "conditionally essential nutrients" because, under certain conditions like biological stress, genetics, poor nutrition and aging, the combination of nutrients provided by diet with those synthesized by the cell may still not be sufficient.
So, what does all this mean in terms of short- and long-term cellular health?

The Enzyme Triage Hypothesis
Bruce Ames, Ph.D.— formerly of the University of California, Berkeley, and currently at the Children’s Hospital Oakland Research Institute in Oakland, California — has proposed an interesting hypothesis: during times of low nutrient availability, a triage mechanism is activated, diverting scarce nutrients to the most critical cellular constituents to sustain life.
Furthermore, the major goal of the triage mechanism is to sustain life until either there are more available nutrients or until the organism has reached sexual maturity, and can reproduce. How does this occur?
Dr. Ames theorizes that the evolutionary process produced enzymes with different affinities for the vitamins they require to function in metabolic pathways, such as converting food to energy. (One can envision an enzyme as a tool composed of amino acids strung together, like beads on a string, to form a unique three-dimensional structure that contains pockets and clefts. One of the pockets is designed to accommodate a vitamin specific to that enzyme. The vitamin is held in place through interactions with chemical bonds in the pocket, like a key fits into a lock.)
Moreover, Ames' hypothesis states that enzymes involved as catalysts in metabolic pathways needed for immediate survival have the highest affinity for vitamins (such as the energy-producing pathways), while enzymes working the less survival-essential pathways have lower affinities for the corresponding vitamins (such as DNA repair enzymes). The net effect would be a transfer of the limited vitamins/nutrients to the enzymes necessary for short-term survival… but, as described below, not without a price.

The Triage Hypothesis and Your Health
Ames developed this hypothesis in an effort to explain the high correlation between vitamin deficiencies and diseases, particularly diseases common to the aged. He found that one of the more common effects of a variety of vitamin-mineral deficiencies is the accumulation of damage to the genetic code (DNA mutations).
Interestingly, DNA can function as a sink for toxic agents present in the environment and produced by cells during metabolism (free radicals). A deficiency in one or more vitamins can produce effects on the cellular blueprint that are similar to environmental toxins, i.e. cigarette smoke, toxic chemicals, and free radicals.
What is deceptive is that the damage to the DNA by toxic substances and vitamin deficiencies can go undetected for years, if not decades, without appearing to affect cellular health, at least for short-term appearance and survival. Unfortunately, it is likely the DNA damage that occurs early in life will often be expressed as a disease in later life.
In fact, after examining the medical literature, Ames observed an alarming correlation between populations with significant deficiencies in one or more micronutrients, and increased rates of diseases in later life, including cancer and other common age-associated degenerative diseases (see Research Update for more details).

Preventing Additional Damage
Vitamin deficiencies are common in this country due to a number of factors, including high consumption of nutrient-poor refined grain products and high-sugar foods and drinks. As we age, the absorption of nutrients from the foods we eat is also less efficient, which can partially explain the increased occurrence of certain vitamin deficiencies in the aged.
Ames believes that many of the degenerative diseases of aging could be reduced significantly with a lifestyle that ensures a healthy source of micronutrients. Starting a vitamin-enriched healthy diet today may not remove all the damage incurred to your DNA over the years, but it may help prevent or slow down the accrual of additional damage. And something as simple as taking a multiple vitamin / mineral supplement each day could give you many more healthy years.

Dr. Treadwell's article references a paper by Bruce Ames, Ph.D., published in the November, 2006 issue of Proceedings of the National Academy of Sciences. The paper examines the link between poor nutrition and the risk of diseases, particularly those associated with aging.

Dr. Ames discusses the widespread inadequacy of dietary intakes of vitamins and minerals (most likely due to excessive consumption of energy-rich, micronutrient-poor, refined food) and the potential of associated chronic metabolic disruption. He notes that DNA damage is caused by micronutrient deficiencies, some of which may also cause mitochondrial decay with oxidant leakage and cellular aging.

Observing that episodic shortages of micronutrients were common during evolution and that natural selection favors short-term survival at the expense of long-term health, Ames proposes that short-term survival was achieved by allocating scarce micronutrients by triage. He hypothesizes that today's micronutrient deficiencies trigger the same type of triage allocation response, accelerating cancer, aging, and neural decay but leaving critical metabolic functions intact.

To read the abstract, click here.
"Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage "
PNAS | November 21, 2006 | vol. 103 | no. 47 | 17589-17594

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.

QUESTION: I've heard there are two forms of alpha lipoic acid, one synthetic "S" and the other "R" natural. The body cannot metabolize the synthetic one and some people seem to be suggesting it is even harmful! I was also told that most alpha lipoic acid contains both S and R in roughly 50/50 proportions. Is any of this correct and what about Juvenon?
michael

ANSWER: The Juvenon™ Cellular Health Supplement contains a racemic mixture of lipoic acid, including both the R and S isomers. Both are active as antioxidants, but only the R+ form is found in our bodies...we make it. Furthermore, the R+ form is the isomer that is utilized by the enzymes of the mitochondria for the conversion of food metabolites to energy. The S form cannot substitute for the R+ in these reactions.

Juvenon will probably offer a product with the R+ form in the future, but only after we are certain it is, in fact, superior to the racemic mixture. Virtually all of the human studies to date (going back some 35 years) have utilized the racemic mixture with great results and a good safety record. No study to date has actually proven that either the R+ form or the racemic mixture is more effective for human health.

In fact, there is some evidence to indicate the R isomer, once isolated from the S isomer, is very unstable and forms polymerized products that are clearly not natural. This problem, we feel, must be worked out before we are comfortable with switching to the pure R form.

Send your questions to AskBen@juvenon.com.
For more questions and answers, go to juvenon.com/product/qa.htm.

Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor and member of Juvenon's Scientific Advisory Board.