Prof Bruce Ames has developed the concept of Triage consumption, where micronutrient needs and availability may not always be in synchronicity and has recommended that a larger overall consumption of micronutrients on a daily basis be considered a judicious way to limit DNA damage associated with aging and disease.
I have proposed that the expensive urine criticism is perhaps one of the most damaging of slights, and that Victor Herberts slur on the use of increased exogenous nutrients via supplementation has created more damage to human health than it has saved. A paper out in the American Journal of Nutrition, May 2010 has added some further clarity to this discussion.
Damage to the genome is recognised as a fundamental cause of developmental and degenerative diseases. Several micronutrients play an important role in protecting against DNA damage events generated through endogenous and exogenous factors by acting as cofactors or substrates for enzymes that detoxify genotoxins as well as enzymes involved in DNA repair, methylation, and synthesis. In addition, it is evident that either micronutrient deficiency or micronutrient excess can modify genome stability and that these effects may also depend on nutrient-nutrient and nutrient-gene interaction, which is affected by genotype.1
Essentially this paper looks at the ‘newish’ science of nutrigenomics, the study of the interaction between nutrients and genes in an attempt to develop a coherent approach to personalised interventions using suitable investigations.
It is generally accepted that unrepairable damage to our DNA contributes to the development of disease and that whilst RDA’s look to avoid the diseases of deficiency such as Beri Beri and Pellagra diseases of infertility, cancer, heart disease, neurodegenerative and immune diseases related to DNA injury modifiable by micronutrients – abound. Yet overconsumption especially of carbohydrates appears to compress longevity and promote disease.
In order for this to occur a combination of events need to be defined and qualified:
- Biomarkers used to study genome damage in humans and their validation,
- Evidence for the association of genome damage with developmental and degenerative disease,
- Current knowledge of micronutrients required for the maintenance of genome stability in humans, the effect of nutrient-nutrient and nutrient-genotype interaction on DNA damage, and
- Strategies to determine dietary reference values of single micronutrients and micronutrient combinations (nutriomes) on the basis of DNA damage prevention.
Biomarkers have been well studied and some 10 are used in the analysis of human DNA damage but not all show response to nutrient intervention assays in suitably qualified human trials. Just the micronuclei frequency index in the CBMN-Cyt assay in human lymphocytes has been substantially validated with respect to its sensitivity to changes in nutritional status in both cross-sectional and placebo-controlled trials and its association, via cross-sectional and prospective studies, with developmental and degenerative disease.
There is a substantive and developing body of evidence that links genome damage to a wide range of human health problems. These include infertility, cancer, cardiovascular disease, neurodevelopment disease, cognitive decline and increased risk of premature mortality.
What do we know about micronutrients keeping the DNA together and healthy? There is overwhelming evidence that a large number of micronutrients (vitamins and minerals) are required as cofactors for enzymes or as part of the structure of proteins (metalloenzymes) involved in DNA synthesis and repair, prevention of oxidative damage to DNA, and maintenance methylation of DNA., (See chart extracted from the lead article below)
The authors go on to explain that deficiency and excess of single micronutrients can cause genome damage and refer to a folate deficiency producing damage equivalent to 10x annual x ray exposure in cell cultures and further explores the essential role of nutrients such as zinc, B12 and methionine in key gene management systems.
A further study by the same author identified 9 key nutrients: calcium, folate, nicotinic acid, vitamin E, retinol, ß-carotene and high intake of pantothenic acid, biotin and riboflavin as being directly linked to genetic instability. The results from this study illustrated the significant effect of a wide variety of micronutrients and their interactions on genome health depended on amount of intake. The unexpected effects of these interactions highlighted the need to consider not only individual micronutrients but also micronutrient combinations at varying dosages and supports the need for increased understanding of nutrient gene interaction. Clearly one diet/micronutrient does not appear to suit all.
Food selection because of choice, religion, geography and age will greatly vary and it is unlikely that optimal food selection to limit genome based damage will be managed by dietary selection alone, supporting the position taken by Ames that a nutritional supplement will be required.
Multiple studies whilst short of unequivocal data do show that the effects of aging on the genome can be attenuated by selection of diet and supplement combinations.
Nutrient synergy also contributes to DNA protection efficacy as some may compete whilst others improve the protective effects of each nutrient, and may in principle explain some of the difficulties in translating single micronutrient studies into human research.
What About Tests?
So how would one test to see if the use of micronutrient combinations or individually would benefit the end user, and at what dose? Combinations are suggested of in vivo trials of foods and supplements using suitable placebos and genetic damage assays. Blood and tissue cultures perhaps from the buccal tissue are also recommeneded to provide accurate and relevant data collection.
Cross sectional analysis of differing age groups and populations will assist with the development of suitable assays and indications for use. Whilst this is yet to fully translate into individualised genetic based nutritional supplementation, the principle is clear.
Food and food concentrates are capable of modifying gene damage and gene expression, this makes it possible to apply a change of direction in the future risk for disease through the careful selection of food groups
– not news to Nutritional Therapists, but rather a chance of future medicine being moulded to individual outcomes rather than the just eat a balance diet approach that may be fine in principle for a public health message, but represents a very constraining approach for skilled intervention.
In the meantime I think the daily consumption of additional micronutrients beyond those obtained from foods in a collective form still represents a scientifically and socially sensible option.
 Fenech MF. Dietary reference values of individual micronutrients and nutriomes for genome damage prevention: current status and a road map to the future. Am J Clin Nutr. 2010 May;91(5):1438S-1454S. Epub 2010 Mar 10. View Abstract
 Li Y, Liu L, Tollefsbol TO. Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. FASEB J. 2010 May;24(5):1442-53. Epub 2009 Dec 17. View Abstract
 Fenech, M, Baghurst, P, Luderer, W, et al.. Low intake of calcium, folate, nicotinic acid, vitamin E, retinol, beta-carotene and high intake of pantothenic acid, biotin and riboflavin are significantly associated with increased genome instability: results from a dietary intake and micronucleus index survey in South Australia. Carcinogenesis 2005;26:991–9. View Full Paper
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