Triage Theory of Aging- Why You Must Take a MultiNutrient

If you want an in-depth, research-oriented version of this article, please read the “Research Version”.

Occasionally, a profound concept is developed that people must be informed. Such is the case with the Triage Theory of Aging, as proposed by Dr. Bruce Ames. The information in this article is derived from the extensive body of work by Dr. Ames and his colleagues. I am simply summarizing it, adding a few opinions, and presenting it for your consideration. I take no credit for these amazing discoveries.

This critical information provides specific answers as to why, if you want to improve health and delay premature aging, it is absolutely critical to consume a comprehensive Multinutrient on a daily basis. Essential nutrients consist of vitamins, minerals, and other essential and conditionally essential biochemicals that the body is unable to make and that must be obtained in food.

Before we answer why this is vital to your health, let’s look at some of the recent evidence that proves that Multinutrient supplements improve your health. Here is some recent research showing the benefits of consuming multinutrients.

1) This article emphasizes the importance of malnutrition and micronutrient deficiencies in Alzheimer’s disease (AD) and discusses recent supplementation trials. A number of epidemiologic studies have explored the associations between nutrients and AD.
2) Antioxidant supplementations have the potential to alleviate the atherosclerotic damage caused by excessive production of reactive oxygen species (ROS). This study evaluated the effects of prolonged antioxidant treatment on arterial elasticity, inflammatory and metabolic measures in patients with multiple cardiovascular risk factors. Antioxidant supplementation significantly increased large and small artery elasticity in patients with multiple cardiovascular risk factors. This beneficial vascular effect was associated with an improvement in glucose and lipid metabolism as well as decrease in blood pressure.
3) Daily tablets of certain B vitamins can halve the rate of brain shrinkage in elderly people who suffer from mild memory problems, an Oxford University study has shown. The team found that on average the brains of those taking the folic acid, vitamin B6, and B12 treatment shrank at a rate of 0.76% a year, while those in the placebo group had an average brain shrinkage rate of 1.08%. People with the highest levels of homocysteine benefited most, showing atrophy rates on treatment that were half of those on placebo. The team also monitored cognitive test scores, revealing that those with the slowest rate of shrinkage scored more strongly.
4) The incidence of esophageal adenocarcinoma (EA) and its precursor condition, Barrett’s esophagus, has risen rapidly in the United States for reasons that are not fully understood. This study evaluated the association between use of supplemental vitamins and minerals and risk of neoplastic progression of Barrett’s esophagus and EA. Use of multivitamins and single antioxidant supplements was associated with a significantly reduced risk of EA and markers of neoplastic progression among individuals with Barrett’s esophagus.
5) Use of multivitamin and mineral supplements is common among U.S. adults, yet few well-designed trials have assessed the reputed benefits. The objective of this study was to determine the effect of a daily multivitamin and mineral supplement on infection and well-being. Their conclusion: A multivitamin and mineral supplement reduced the incidence of participant-reported infection and related absenteeism in a sample of participants with type 2 diabetes mellitus and a high prevalence of subclinical micronutrient deficiency.
6) The objective of this report was to investigate how a long-term vitamin-mineral supplementation following the US Recommended Daily Intake (RDI) affected the plasma levels of selected nutrients in participants. Participants assigned to Centrum(R) showed a significant increase in plasma levels of vitamin E, beta-carotene, folate, vitamin B12, and an improved riboflavin status when compared with participants assigned to placebo..
7) Telomeres are located at the ends of chromosomes and regulate how many times a cell can divide. With each division, a little bit is clipped off, limiting the number of times a cell can divide. Telomere length may be a marker of biological aging.. This study provides the first epidemiologic evidence that multivitamin use is associated with longer telomere length among women.
8) Inadequate micronutrient intake among older adults is common despite the increased prevalence of fortified/enriched foods in the American diet. This study showed that supplementation with a multivitamin formulated at about 100% Daily Value can decrease the prevalence of suboptimal vitamin status in older adults and improve their micronutrient status to levels associated with reduced risk for several chronic diseases.
9) An analysis of nutrient intakes of 23,943 people, all free of cancer and heart disease was performed. After 11 years of data collection, the researchers data showed that users of antioxidant vitamin supplements at the start of the study had a significantly reduced risk of both cancer mortality and all-cause mortality, while people who started taking supplements after the study had started had significantly increased risks.
10) One month of supplementing with a multiple vitamin was associated with improvement in markers of pain, joint pain, strength,energy, and power in men and anxiety, energy, and balance in women. The study involved 54 people with an average age of 54 in this placebo control, cross-over study. IL-6 levels fell about 40%. “It therefore appears that a multi-nutrient supplement is beneficial to recovery, inflammatory status, and performance of active men and women” according to the researchers.

THE TRIAGE THEORY OF AGING

Triage is the process of determining the priority of patients’ treatments based on the severity of their condition. This rations patient treatment efficiently when resources are insufficient for all to be treated immediately. The basis for the Triage Theory of Aging (TTA) is that the body will sacrifice long-term survival for short-term survival. An apt analogy would be: If you were drowning would you trade a year of your life to be able to breathe? Of course you would.

In 2006, Professor Ames published his landmark article ‘Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage’. Ames found that many micronutrient deficiencies are associated with chromosome breaks and cancer in humans, and that such deficiencies caused DNA damage in rodents or human cells in culture. It had also been established that chromosomal breaks cause early aging. As a result Professor Ames proposed that DNA damage and late onset disease are consequences of a ‘triage allocation mechanism’ developed during evolution to cope with periods of micronutrient shortage. In other words, micronutrients, when scarce, are used for short-term survival at the expense of long-term survival. In a 2010 speech before the American Academy of Anti-Aging Medicine, Dr. Ames very clearly stated his theory:

“My triage theory (PNAS 103, 17589, 2006; AJCN 90, 889, 2009) posits that, as a result of recurrent shortages of micronutrients during evolution, natural selection developed a metabolic rebalancing response to shortage. The rebalancing favors micronutrient-dependent proteins needed for short-term survival while starving those only required for long-term health.
“Triage theory predicts that the consequence of moderate shortages of even a single micronutrient, though insufficient to cause overt clinical symptoms, will impair functions essential for long-term health. This impairment will result in insidious damage (e.g.: increased DNA damage) that, over time, leads to the acceleration of age-associated diseases (e.g.: increased cancer). As people with modest deficiencies have no overt clinical symptoms, there has been little incentive to correct these deficiencies, though this could change if it can be shown that they are resulting in biochemical changes (e.g.: chromosome breaks that are markers of increased risk of age-related diseases, such as cancer)”.

Dr Ames announced that ‘the theory explains why diseases associated with aging like cancer, heart disease, and dementia (and the pace of aging itself) may be unintended consequences of mechanisms developed during evolution to protect against episodic vitamin/mineral shortages’.

One example is when calcium is released from the bones into the blood stream as a short–term survival response to reduce metabolic acidosis caused by high protein intake, exercise, low potassium and magnesium, or kidney mal-function. This short-term emergency measure is essential for immediate survival but if repeated too often, results in osteoporosis.

CLINICAL EVIDENCE

No theory can stand without clinical evidence to support the hypothesis. The first research study performed by Dr. Ames was on Vitamin. This tested the basic premises of TTA. The results clearly showed that the test mice preferentially used Vitamin K, when scarce, for functions that were critical to short-term survival at the expense of those functions more important to long-term survival. The tradeoff was that the Vitamin K mice later suffered increased rates of osteoporosis, cancer and arteriosclerosis.

In another landmark study, Dr. Ames group showed that when a deficiency of folate (a B-complex vitamin) existed; it resulted in DNA incorporating a bio-chemical called uracil. This compound does not normally exist in DNA. When folate is deficient, uracil replaces the normally present guanosine, which may lead to increased rates of cancer due to this mutation. A vitamin B6 deficiency may make this situation worse, because B6 is needed to convert the inactive form of folate into the biochemically active form, so in essence, a B6 deficiency may create or aggravate a folate deficiency.

The next study confirming TTA involved the micro trace element, selenium. When only a modest selenium deficiency was created, the proteins that lost function first were the non-essential ones. The very same set of age-related diseases is associated with both selenium deficiency and genetic dysfunction of the non-essential selenium-containing proteins (cancer, heart disease and immune dysfunction), suggesting that selenium deficiency acts through long-term dysfunction of these non-essential proteins

Biotin is considered another B-complex vitamin that plays a key role in the mitochondria, the organelle that provides most of the energy that powers every cell in our body. There are four enzymes in the mitochondria, called carboxylases that contain biotin. These enzymes use amino acids (the building blocks of protein) to regenerate certain organic acids in the energy producing cycle (Kreb’s or Tri- Carboxylic Acid cycle) that supports energy production in the mitochondria. They took human lung cells and extracted the biotin. These cells died before the ones that had adequate biotin. They found that a deficiency of biotin led to a deficiency of another molecule called Heme, which is essential to energy production in mitochondria (as well as to carrying oxygen in the blood). This molecule must be made in the mitochondria. This, in turn, created a cascade of oxidative damage due to free radical production. Adding biotin restored function, more so in young cells. This showed the inter-relationship between biotin, energy production, Heme levels, and oxidative damage. Increased oxidative damage, uncoupling of energy production and lower levels of Heme and thus oxygenation are hallmarks of aging.

Additional studies on mitochondria showed that optimizing micronutrient intake optimized metabolism, resulting in decreased DNA damage with less cancer and other degenerative diseases of aging. This research focused on decreasing mitochondrial aging by supplementing rats with lipoic acid and acetyl carnitine. Decreased enzyme function results from protein deformation and loss of function due to an age-related decline in membrane fluidity, and mutations. The loss of enzyme function can be compensated by a high dietary intake of many of the B vitamins, which increases the level of the vitamin-derived coenzymes. Mitochondrial decay appears to be a major contributor to aging, degenerative diseases, cancer, and neural decay. Mitochondria from old rats compared to young rats generate increased amounts of mutagenic oxidant by-products, decreased membrane potential, respiratory control ratio, cellular oxygen consumption, and cardiolipin (a key lipid found in mitochondria). Oxidative damage contributes to this decay and leads to functional decline of mitochondria, cells, tissues, and eventually organs such as the brain, with an accompanying loss of cognition and ambulatory activity. Carnitine and lipoic acid improve function and reduce oxidative damage to mitochondria, thereby reducing oxidative damage to proteins, RNA and DNA and thus to aging.

Dr. Ames summarized 144 other research articles on the subject of micronutrient deficiencies as a primary cause of aging.
1) Folate Deficiency- causes chromosomal breaks, increased rates of cancer, increased chromosomal mutations due to incorporation of uracil into DNA, cessation of cell division, cell death, and decreased DNA repair. Vitamin B12 deficiency causes similar chromosomal breaks.
2) Magnesium- Approximately 56% of the US population is deficient. In humans, moderate magnesium deficiency has been associated with colorectal and other cancers, hypertension, stroke, osteoporosis, diabetes, and metabolic syndrome. In a study of 4,035 men followed for 18 years, the highest 25% compared with the lowest had a 40% decrease in all-cause mortality and cardiovascular disease and a 50% decrease in cancer deaths. In primary human cells in culture, magnesium deficiency leads to accelerated telomere shortening, activation of cell-cycle arrest proteins, premature aging, and mitochondrial DNA damage.
3) Vitamin B6- deficiency is associated with colorectal cancer; colorectal cancer decreased by 49% for every 100-pmol/mL increase in blood B6 level. Serum levels were inversely associated with lung cancer and gastric cancer. One possible mechanism is deficiency of B6 causing interference with Heme biosynthesis causing release of mutagenic oxidants. A sizeable percentage of the population not using supplements has inadequate B6 levels; 49% of elderly women have inadequate B6 intake. Low levels are also associated with depression and stroke.
4) Moderate deficiencies of calcium, niacin, vitamins A, C, or E are associated with chromosome damage. Severe deficiencies in rodents or human cell cultures for selenium, copper, niacin, choline, pantothenate, or riboflavin are also associated with chromosome breaks. Many of these and other moderate micronutrient deficiencies, when studied epidemiologically, are associated with cancer.
5) Mitochondrial decay occurs with age and results in increased production of mutagenic oxidant byproducts of electron transport. To the extent that the DNA damage is caused by oxidants released from mitochondria, mitochondrial DNA will be damaged before nuclear DNA. Mitochondrial decay appears to be a major contributor to both aging and its associated degenerative diseases.
6) Some micronutrient deficiencies impair Heme synthesis, which can result in oxidative stress, mitochondrial decay, DNA damage, and cell aging. Seven micronutrients (biotin, pantothenate, pyridoxine, riboflavin, copper, iron, and zinc) are required for Heme synthesis in mitochondria. A severe deficiency in any of these seven will cause a deficit of Heme and therefore of complex IV, of which Heme is an essential component. The normal complement of complex IV keeps oxidants to a minimum; deficits of complex IV result in oxidant leakage, DNA damage, accelerated mitochondrial decay, and cellular aging.
7) Iron deficiency is the most common micronutrient deficiency in the world. Iron deficiency anemia is associated with poor cognitive development in toddlers. Severe iron deficiency causes loss of mitochondrial complex IV in selected regions in the brain of neonatal rats. Iron deficiency or excess in rats damages mitochondria and causes oxidant release, oxidative DNA damage, and decreased mitochondrial efficiency at levels both below and above the optimum. Functional iron deficiency also is associated with diminished immune function and neuromuscular abnormalities.
8) Zinc inadequacy is common in about ~12% of adults. In cultured human cells, severe zinc deficiency causes complex IV deficiency and the release of oxidants, resulting in significant oxidative damage to DNA. Zinc deficiency also causes chromosome breaks in rats and is associated with cancer in both rodents and humans. base repair enzyme, leading to genetic damage.

9) Dr. Ames reviewed about 50 human genetic diseases due to defective enzymes, which were improved by giving high doses of the vitamin needed to make the enzyme function. The review points out that many of the B vitamins, given at levels 10–100 times the RDA, can raise enzyme activity levels by ten times or more, usually with minimal toxicity. It is common for proteins to become deformed with age; for example, membranes become stiffer by oxidation, deforming membrane proteins, and particularly in mitochondria. Vitamins and minerals that are necessary for enzymes to function may be elevated by supplementation and may enhance the activity of a deformed enzyme.

SUMMARY
In conclusion, cutting edge, contemporary research by Dr. Ames, his research group, and many other researchers clearly show that for every essential nutrient tested to date, even moderate, temporary deficiencies cause cellular aging by a number of mechanisms that cause chromosomal breaks and mutation, decreased function of mitochondria and oxidative damage. The result of this body of research is Dr. Ames “Triage Theory of Aging”. With the large body of supporting evidence, it would appear to this author that, at least for many essential nutrients, this is no longer a theory, but a fact. There is adequate research to document that widespread deficiencies of these nutrients are extremely common in the US today. There can be little doubt that as a population, we are suffering from an epidemic of chronic, degenerative diseases. Dr. Ames research provides an understanding as to a number of potential causes of this epidemic. What has not been discussed or researched is whether multiple essential nutrient disorders cause additive or exponential negative consequences. Dr. Ames research provides compelling evidence for the necessity of taking a comprehensive Multinutrient on a daily basis.