Modest Vitamin/Mineral Deficiencies May Increase Age-Related Disease

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Released: 4/12/2011 1:40 PM EDT
Source: Children’s Hospital & Research Center Oakland
An analysis of the essential mineral selenium conducted by Children’s Hospital Oakland Research Institute (CHORI) scientists (1) suggests that adequate intake of essential mineral selenium could help to prevent age-related conditions such as immune dysfunction, cardiovascular disease, and cancer. Selenium is present in dietary plants if the soil has adequate amounts, which is generally true in the U.S., but not in parts of China, Russia, and most of Western Europe.
The analysis, conducted by CHORI Associate Staff Scientist, Joyce McCann, PhD, and Senior Scientist, Bruce Ames, PhD was designed to test Dr. Ames’ “triage” theory that provides a new basis for determining the optimum intake of individual vitamins and minerals by measuring long-term insidious damage associated with aging, and that has major implications for preventive medicine. The selenium analysis strongly supports the theory and is published in the March 2011 issue of the The Federation of American Societies for Experimental Biology (FASEB) Journal. The analysis provides a consistent scientific basis for establishing optimum vitamin and mineral intakes, which will add credence to recommendations for improving inadequacies in micronutrient intake of the American diet.
Dr. Ames proposed the triage theory in 2006 (2) to explain numerous observations from his own lab and the scientific literature. The triage theory explains why diseases associated with aging (and the pace of aging itself) may be unintended consequences of mechanisms developed during evolution to protect metabolic processes against episodic vitamin and mineral shortages. Dr. Ames reasoned that these mechanisms are focused on preserving vitamin and mineral-dependent functions required for animals to survive for reproduction, at the expense of other functions required to sustain long-term health — not a priority for evolution. As a result, Dr. Ames proposed that modest shortages in vitamin and mineral (against which (“essential”) functions are protected) lead to insidious metabolic damage in so-called “less critical functions” that over time accelerates aging and may lead to diseases of aging such as cancer, heart disease, and dementia. If correct, the triage theory has widespread implications for public health because modest vitamin and mineral deficiencies are quite common. It also suggests a new scientifically based and consistent strategy for establishing optimal vitamin and mineral intake standards, and it provides a research strategy to uncover early biomarkers of chronic disease.
This selenium analysis is the second in a series of literature-based studies conducted by Drs. McCann and Ames to test the basic premises of the triage theory by constructing triage-based biological profiles of individual vitamin and minerals. A previous analysis of published evidence on vitamin K (3), also strongly supported the theory.
The new analysis reviews about half of the 25 known mammalian selenoproteins; all of those with mouse knockout or human mutant phenotypes that could be used as criteria for a classification of “essential” or “nonessential”. On modest selenium deficiency, nonessential selenoprotein activities and concentrations are preferentially lost. Mechanisms include the requirement of a special form of tRNA sensitive to selenium deficiency for translation of nonessential selenoprotein mRNAs. The same set of age-related diseases and conditions, including cancer, heart disease, and immune dysfunction, are prospectively associated with modest selenium deficiency and also with genetic dysfunction of nonessential selenoproteins, suggesting that selenium deficiency could be a causal factor, a possibility strengthened by mechanistic evidence. Modest selenium deficiency is common in many parts of the world; optimal intake could prevent future disease, but as too much selenium is quite toxic, don’t overdo the supplementation.
The analysis of Drs. McCann and Ames has wider implications. If results for vitamin K and selenium can be generalized to other vitamin and minerals, as the triage theory proposes, not only experts aiming to set intake recommendations for optimal function, but scientists seeking mechanistic triggers leading to diseases of aging should look among micronutrient-dependent functions that have escaped evolutionary protection from deficiency. A brief summary of the triage theory and the vitamin K analysis has been published (4).
1. McCann JM & Ames BN (2011) Adaptive dysfunction of selenoproteins from the perspective of the triage theory: Why modest selenium deficiency may increase risk of diseases of aging. FASEB J, 25: in press.
2. Ames, B (2006) Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc. Natl. Acad. Sciences, U.S.A., 103:17589-94.
3. McCann JM and Ames BN (2009) Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr. 90: 889-907.
4. Ames, BN (2010) Prevention of mutation, cancer, and other age-associated diseases by optimizing micronutrient intake. Journal of Nucleic Acids Special Issue: DNA Damage, Mutagenesis, and DNA Repair. doi:10.4061/2010/725071.
About Children’s Hospital & Research Center Oakland
Children’s Hospital & Research Center Oakland is Northern California’s only independent not-for-profit regional medical center for children. Children’s Hospital Oakland is a national leader in many pediatric specialties and sub-specialties including hematology/oncology, neonatology, cardiology, orthopedics, sports medicine, and neurosurgery. The hospital is one of only two solely designated California Level 1 pediatric trauma centers with the largest pediatric inpatient critical care unit in the region. Children’s Hospital has 190 licensed beds, 201 hospital-based physicians in 30 specialties, more than 2,700 employees, and an annual operating budget of more than $350 million. Children’s is also a premier teaching hospital with an outstanding pediatric residency program and unique pediatric subspecialty fellowship programs.
Children’s research program, Children’s Hospital Oakland Research Institute (CHORI), is internationally renowned for taking state-of-the-art basic and clinical research and translating it into interventions for treating and preventing human diseases. CHORI has 300 members of its investigative staff, a budget of about $50 million, and is ranked among the nation’s top 10 research centers in National Institutes of Health funding to children’s hospitals. For more information, go to www.childrenshospitaloakland.organd


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