Is folic acid the ultimate functional food component for disease prevention?

Abstract

Introduction Mankind has been relatively unsuccessful in the search for the ultimate panacea for all ills; however, in the field of functional foods, few nutritional components have so many fundamental and diverse biological properties as folic acid and related B group vitamins. Moreover, few nutrients can claim to modulate, if not overtly benefit, such a wide array of clinical conditions. Around 2500 years ago Hippocrates first espoused the “food as medicine” philosophy, which fell into obscurity by the 19th century. The first 50 years of the 20th century saw the discovery of the essential elements and vitamins, particularly in the context of deficiency diseases. Indeed, by 1912 Casimir Funk had put forward the “vitamine theory,” proposing four different “vitamines” that would cure scurvy, pellagra, beri-beri, and rickets. During the 1970s the shift in emphasis from undernutrition to overnutrition and disease led to a flood of public health guidelines on optimising nutritional parameters. By the 1990s, with an ageing health conscious population, scientists from academia and the commercial world coalesced their thinking to create the trend we now know as functional foods. Enrichment of flour as a US government programme to correct problems with nutrient deficiency was probably the first modern attempt to design a food for functional purposes related to nutritional outcome. The first consequence of this was the eradication of pellagra with niacin, and a current programme in the United States aims to do the same for neural tube defects through mandatory fortification of grain with folate at source.1 2 The ramifications of this mass use of folate as a functional food are likely to have even wider effects. Folate status and common variations in genes that code for folate dependent enzymes are linked to many types of cancer, vascular disease, birth defects, and complications of pregnancy.3 This arises because several molecular mechanisms that underpin the genomic machinery are sensitive to B vitamin status and, in particular, are responsive to the interaction between folate nutrition and folate dependent enzyme polymorphisms (folate nutrigenomics). Mechanisms that may be affected include the maintenance of genomic CpG methylation patterns for regulated gene expression and the proficient synthesis of nucleotides to prevent DNA strand breakage.4 5 The same nutrigenomics also influence plasma homocysteine status and thus risk for vascular disease.3 These relations are shown in figure 1. View larger version: In this window In a new window Fig 1 Molecular mechanisms affected by dietary folate Summary points B vitamins, particularly folate, may give considerable protection against serious diseases such as cancer, heart disease, and birth defects The method of protection is by lowering homocysteine or through epigenetic mechanisms Common single nucleotide polymorphisms of several genes coding for folate dependent enzymes can modulate risk for several serious clinical conditions The level of risk or protection with some single nucleotide polymorphisms is further influenced by a person's nutritional folate status; this is the basis of a new subdiscipline within human nutrition—“nutrigenomics” Folate used in food fortification is not a natural coenzyme; we do not know the long term biological effects of exposure to unmodified synthetic folate Future trends will emphasise dietary practices that complement the genetic variation of an individual person