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.

By Benjamin V. Treadwell, Ph.D.

A biological/biochemical mechanism, seemingly evolved to protect plant and animal life during hard times, may help us better understand the aging process and, perhaps, even slow it down in man.

The Xenohormesis Hypothesis

Do organisms respond to stress-signaling molecules produced by other species in their environment? This recent hypothesis may explain the connection between certain chemical compounds, polyphenols, especially common in plants during stressful environmental conditions (fungus, lack of sufficient water, etc.) and the effect they have on animals that eat the stressed plants.

The polyphenolic compounds put the plant into a hibernation-like biological state until conditions improve. When the low food-supply message is relayed to the animals, their biochemistry changes to a more life-sustaining state as well.

Less Food, Similar Effect

A similar life-sustaining and extending effect can be achieved with mammals using caloric restriction (CR). For instance, a rat's life span can be increased 30-50% with a 40% decrease in normal caloric intake.

More detailed analysis of the mechanism involved in this peculiar effect has shown that numerous biochemical pathways are reset, so to speak, to a more efficient and healthier state. For example, plasma insulin levels drop, insulin sensitivity increases, fat synthesis decreases, and virtually all health parameters measured improve. The caloric restricted animal has a lower incidence of cancer, heart disease and diabetes, and is mentally sharper as well as much more energetic.

The CR-stimulated increase in energy is the consequence of an increased production of a transcriptional factor, PGC-1 alpha, that turns on genes involved in the synthesis of the energy producing cellular organelles, the mitochondria. So how does that relate to the polyphenolic compounds present in stressed plants?

Plant Compound with CR-Like Effect

A number of years ago a group at MIT (Cambridge, MA) reported a gene present in the lowly yeast that was somehow involved in determining how long the yeast lived. The gene, SIR2, was later demonstrated to code for an enzyme, deacetylase, that acted on numerous biological molecules with life-extending consequences.

Many of these effects on cellular metabolism were later observed in other cells, including those of the fruit fly, and a nematode, C. elegans. It was also demonstrated that caloric restriction stimulated the synthesis of this enzyme in these lowly organisms.

One of the inquisitive post-doctoral students, David Sinclair, wondered whether it was possible to activate this enzyme by some other means than caloric restriction. Later, he set up his own laboratory and screened numerous compounds, discovering a chemical, commonly found in some plants and especially rich in fungus-infected grape skins, known as resveratrol.

With the introduction of resveratrol, the enzyme was activated in the yeast, the fruit fly and the nematode, and all three lived longer. What's more, if the organisms were CR-treated and then fed resveratrol, there was no additional effect on longevity. In other words, the biological mechanism by which caloric restriction and resveratrol extended life was similar, most likely via the activation of the SIR2 enzyme.

From Nematode to Mouse

So what? Extending the life of a yeast cell or a nematode is a far cry from doing the same to a mammal or man.

David Sinclair and colleagues apparently realized this. A very recent paper, published in Nature (see Research Update, this issue), reveals that resveratrol has similar health-promoting effects in a mammal, the mouse.

The excitement surrounding this work is that it demonstrates that mice fed a diet high in calories are, as expected, overweight and develop all the problems associated with obesity (diabetes, heart disease, liver disease, and decline in overall health parameters). However, mice on the same high-fat diet but also fed the resveratrol compound are, in virtually all respects, as healthy as the control animals fed a normal calorie diet. Furthermore, the resveratrol-treated, high-fat-diet mice are much more physically active than their resveratrol-less counterparts.

With analysis of liver and muscle cells, the investigators also discovered a significant increase in the number of mitochondria for the resveratrol-treated group, versus the high-calorie diet without resveratrol group. Since the mitochondria are the powerhouses of the cell, the increased energy is clearly the result of resveratrol-activated mitochondrial synthesis.

These experiments have not yet shown whether the mice on the resveratrol-high fat diet have extended life-spans. This result will not be known for a year or two as the mice have not reached their normal life-spans.

One caveat to this work is the dose of resveratrol used in the experiment. Each animal received a dose equivalent to an average size human ingesting 1.6 grams per day. The amount of resveratrol in an average bottle of red wine is about 1/70th of this dose. Do you want to drink 70 bottles of wine per day?

Actually, it turns out that resveratrol appears to be very non-toxic, as judged by animal studies even at this high dose. Furthermore, chemical compounds will most likely be synthesized that are much more active in eliciting the same or even better results at much lower doses.

From Mouse to Man

Whether resveratrol will produce similar results in humans remains to be seen, but the best guess is that it will, at minimum, have health benefits. How much we need is another question.

Overall, these studies should help us understand why certain diseases, such as diabetes, develop and why so many diseases are associated with aging. The results also show promise for the development of therapeutics to help reset the aberrant or dysfunctional biochemical pathways to prevent or attenuate the diseased state. The icing on the cake, of course, would be if this information helped extend our life span.