Commonwealth Medical College 12 April 2012 - Revised
Bruce N. Ames Senior Scientist, Nutrition and Metabolism Center Children's Hospital Oakland Research Institute, Oakland, California;
Professor Emeritus University of California, Berkeley
I posited, and have buttressed, "triage theory" (1,2): metabolism responds to moderate deficiency of an essential vitamin or mineral (V/M) so that the scarce V/M is preferentially retained by V/M-dependent proteins necessary for short-term survival and reproduction. In contrast, proteins needed for long term health, which I term "longevity proteins" because they defend against the diseases associated with aging, lose the V/M and are disabled. Most of the world's population, including that of the U.S., are moderately deficient in one or more of the ~30 essential V/Ms. Moreover, since the damage from moderate deficiency is insidious, its importance for long-term health is not being appreciated. Strong support for triage theory comes from Joyce McCann's analyses of the literature on proteins dependent on vitamin K (3) and on selenium (4). Both have built into metabolism this trade-off between short-term survival and long-term health and each uses a different mechanism to accomplish this end. Theory and evidence suggest that this metabolic trade-off accelerates aging-associated diseases, such as cancer, cognitive decline, and cardiovascular disease.
Importantly, by the official U.S. Institute of Medicine measure of inadequacy,
the EAR (Estimated Average Requirement; the RDA is set at 2 SD above the EAR),
most of the U.S. population is below the EAR for one or more V/M.
Taking these long-term triage effects into account in setting EARs could lead to numerous changes.
We have calculated from the NHANES database that the percentages of the U.S. population that are below the EAR are:
- magnesium 56%;
- zinc 12%;
- iron 16% of menstruating women;
- vitamin B6 49% of elderly women;
- folate 16% of adult women.
The U.S. population also has very low intake of
- vitamin D,
- omega-3 fatty acids,
- vitamin K, and
- probably others,
and this is especially true for children, adolescents, elders, and the obese.
Longevity proteins, about half of those studied, indicate a mechanism that could be used for prevention by monitoring for insidious damage and suggest the existence of an undiscovered class of longevity V/Ms, which we are discovering. Our Choribar (V/M-dense, low-calorie, high-fiber, fruit-based) markedly improves metabolism in many human trials (5).
1. Ames, B (2006) Proc. Natl. Acad. Sciences, U.S.A., 103:17589-94.
2. Ames, BN (2010) J Nucleic Acids. doi:10.4061/2010/725071.
3. McCann JC and Ames BN (2009) Am J Clin Nutr. 90: 889-907. doi: 10.3945/ajcn.2009.27930.
4. McCann JC and Ames BN (2011) FASEB J. doi:10.1096/fj.11-180885.
5. Mietus-Snyder, et al. (2012) FASEB J. published online ahead of print doi: 10.1096/fj.11-201558._
Dr. Ames is a Professor of Biochemistry and Molecular Biology, Emeritus, University of California, Berkeley, and a Senior Scientist at Children's Hospital Oakland Research Institute. He is a member of the National Academy of Sciences and he was on their Commission on Life Sciences. He was on the board of directors of the National Cancer Institute, the National Cancer Advisory Board, from 1976 to 1982. His awards include: the General Motors Cancer Research Foundation Prize (1983), the Tyler Environmental Prize (1985), the Gold Medal Award of the American Institute of Chemists (1991), the Glenn Foundation Award of the Gerontological Society of America (1992), the Honda Prize of the Honda Foundation, Japan (1996), the Japan Prize, (1997), the Kehoe Award, American College of Occup. and Environ. Med. (1997), the Medal of the City of Paris (1998), the U.S. National Medal of Science (1998), the Linus Pauling Institute Prize for Health Research (2001), the American Society for Microbiology Lifetime Achievement Award (2001), the Thomas Hunt Morgan Medal from the Genetics Society of America (2004), and the American Society for Nutrition/CRN M.S. Rose Award (2008). His 540+ publications have resulted in his being among the few hundred most-cited scientists (in all fields). www.bruceames.org; bames at chori.org
Ames Video on Aging Summary below"
Mitochondrial decay, (a decrease in membrane potential, respiratory control ratio, cardiolipin, and cellular oxygen consumption, and an increase in oxidant by-products) appears to be a major contributor to aging and associated degenerative diseases. Oxidative damage to DNA, RNA, proteins, and lipids in mitochondrial membranes is a major consequence of this decay, resulting in functional decline of mitochondria, cells, and organs. Feeding the mitochondrial metabolites acetyl carnitine and lipoic acid to old rats rejuvenates the mitochondria and improves brain and other function. The degenerative diseases accompanying aging, such as immune dysfunction, cancer, cognitive decline, and stroke, might be delayed by an inexpensive intervention. About 40 essential micronutrients are required for metabolism and include minerals, vitamins, amino acids and fatty acids.
Micronutrient inadequacy ( EAR, i.e. 2 standard deviations below the RDA) is unusually widespread in the U.S. population (especially in the poor, children, adolescents, the obese, and the elderly) because of high consumption of calorie-rich micronutrient-poor unbalanced diets. Most of the world's population, particularly the poor, has inadequate intake of one or more micronutrients. Societal concern is low because no overt pathology has been associated with these levels of deficiency, e.g. 56% of the U.S. have intakes below the EAR for Mg and almost all African-Americans for vitamin D.
My triage theory explains why the pathology is insidious. When a micronutrient is inadequate, nature selects for a rebalancing of metabolism, that ensures survival of the organism at the expense of metabolism whose lack has only longer term consequences. I propose that during evolution micronutrient shortages were very common, e.g. the 15 essential minerals, which are not distributed evenly on the earth. The consequences of this homeostatic response are, for example, DNA damage (future cancer), adaptive immune dysfunction (future severe infection), and mitochondrial decay (future cognitive dysfunction and accelerated aging). Much evidence supports this idea that micronutrient shortages accelerate aging.
- Hypothesis: Age-related diseases due to lack of nutrients like vitamin K – Ames Triage Theory
- Omega-3: many benefits include helping vitamin D
- Serotonin regulated by Vitamin D – part 1 autism – Feb 2014 Ames is co-author
- Zinc and Vitamin D
- Less DNA repair if nutrient deficient (Vitamin D, Magnesium, Omega-3, Vitamin K, etc) – Ames Oct 2018
- Adaptive dysfunction of selenoproteins from the perspective of the triage theory: why modest selenium deficiency may increase risk of diseases of aging. June 2011 free full text online
- Prevention of mutation, cancer, and other age-associated diseases by optimizing micronutrient intake Sept 2010 free full text on-line
- Interview of Dr. Ames by Saul 2006
- LEF interview Aug 2011 Vitamin D not mentioned
the human body prioritizes the use of vitamins and minerals when it is getting an insufficient amount to keep functioning.
- Ames YouTube video on Aging May 2012
- Ames YouTube video (80 minute) Vitamin and Mineral Inadequacy Accelerates Aging