A critical role for B-vitamin nutrition in human developmental and evolutionary biology
Introduction
Few nutrients compare with folate and related B-vitamins for their impact on health. Indeed, the ancient precept “Let food be thy medicine and medicine be thy food” could not be more appropriate than when applied to this group of essential micronutrients. Although scientists are slowly becoming aware of the incredible breadth of involvement that folate has in critical life processes, few are aware of the likely role that folate nutrition and variants of folate dependent enzymes have in the evolutionary process. We provide a brief review of the molecular mechanisms that underpin the role of folate in disease processes, and show that some of these same mechanisms could explain why this vitamin may be an important factor in evolution. In addition, we present further experimental data to support this postulate, and to help provide an integrated and compelling argument for the importance of folate and related B-vitamins in the evolution of man.
Folate, vitamin B12, niacin (B3), pyridoxal phosphate (B6) and riboflavin (B2) are members of the B-group of vitamins that until recently were only of interest in the context of overt deficiency diseases such as anaemia and pellagra, or in generalised deficiency conditions where tissues that have a high cell turnover and increased energy demand (i.e. hematopoietic cells, skin, gut, nerve) show a distinct pathology. Recent research has changed this.
Section snippets
Molecular mechanisms
Folate in particular, plays several fundamental and direct roles in the synthesis, repair and expression of DNA [1], [2], while vitamins B2, B6 and B12 play a significant, but lesser role in these same epigenetic phenomena (see Fig. 1). Vitamin B3 as NAD+ acts as sole substrate for poly (ADP-ribose) polymerase-1 (PARP), which is required for cell differentiation, DNA repair, -expression and apoptosis [3]. However, NAD+ is also required as cofactor in nucleotide synthesis, and is co-substrate
Folate and evolution
Clearly, any role of folate in modulating risk for degenerative diseases like cancer, vascular disease or Alzheimer's cannot be considered a selection pressure in driving human evolution. However, at least three phenomena may well link folate metabolism to the evolutionary process.
Conclusion
Clearly, even within a single variant folate gene such as C677T-MTHFR, pleiotropism that stems from the central role of 5,10-methylene-H4folate in several critical biosynthetic pathways leads to either positive or negative modulation in the risk for both developmental and degenerative disorders (depending on folate nutritional status), and likely, by the same mechanisms, influences in utero survival, and hence human evolution.
It is not clear, however, whether folate nutrigenomics affect foetal
Acknowledgements
We acknowledge support provided by ASBAH, The Patrick Berthoud Charitable Trust, The British Heart Foundation and Cerebra.
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