Prevention of Mutation, Cancer, and Other Age‐Associated Diseases by Optimizing Micronutrient Intake

Bruce N Ames

doi:10.4061/2010/725071

Abstract

I review three of our research efforts which suggest that optimizing micronutrient intake will in turn optimize metabolism, resulting in decreased DNA damage and less cancer as well as other degenerative diseases of aging. (1) Research on delay of the mitochondrial decay of aging, including release of mutagenic oxidants, by supplementing rats with lipoic acid and acetyl carnitine. (2) The triage theory, which posits that modest micronutrient deficiencies (common in much of the population) accelerate molecular aging, including DNA damage, mitochondrial decay, and supportive evidence for the theory, including an in-depth analysis of vitamin K that suggests the importance of achieving optimal micronutrient intake for longevity. (3) The finding that decreased enzyme binding constants (increased Km) for coenzymes (or substrates) can result from protein deformation and loss of function due to an age-related decline in membrane fluidity, or to polymorphisms or mutation. The loss of enzyme function can be compensated by a high dietary intake of any of the B vitamins, which increases the level of the vitamin-derived coenzyme. This dietary remediation illustrates the importance of understanding the effects of age and polymorphisms on optimal micronutrient requirements. Optimizing micronutrient intake could have a major effect on the prevention of cancer and other degenerative diseases of aging.

Highlights

Nutrition and Metabolism Center, Children’s Hospital Oakland Research Institute, 5700 Martin Luther King Jr
(2) The triage theory, which posits that modest micronutrient deficiencies accelerate molecular aging, including DNA damage, mitochondrial decay, and supportive evidence for the theory, including an in-depth analysis of vitamin K that suggests the importance of achieving optimal micronutrient intake for longevity
The importance of optimizing metabolic function to prevent mitochondrial decay is illustrated by feeding the mitochondrial metabolites acetyl carnitine (ALC) [13,14,15] and R-alpha lipoic acid (LA) [16] to old rats

Summary

Triage Theory Suggests a Cause of Much Preventable Mutation and Cancer

The “triage theory” [24,25,26] provides a unifying rationale for a causal link between chronic modest deficiency of a micronutrient (∼40 essential minerals, vitamins, amino acids, and fatty acids) and the many degenerative diseases accompanying aging such as cancer, immune dysfunction, cognitive decline, cardiovascular disease, and stroke. Human cells in culture, we found that severe deficiencies in zinc [42], iron [40], biotin [39], or vitamin B6 resulted in increased mitochondrial oxidative decay [24]. Zinc deficiency causes chromosome breaks in rats [73] and is associated with cancer in both rodents and humans [129] As discussed above, these observations reinforce the need to determine what degree of deficiency in humans results in DNA damage. Biotin deficiency in normal human lung fibroblasts in culture caused a 40–50% decrease in heme content, oxidant release, premature senescence, and DNA damage [39] The relationship of these effects to human intake amounts needs to be determined [133]. It should not be assumed that “too much of a good thing is wonderful.” Mae West, who said that, was not thinking about micronutrients

Ameliorating Some Consequences of Mutation

Conclusion

Findings

Conflict of Interest