Human geneticists have known for hundreds of years that metabolic disorders can be passed down through generations. Explorers since the 17th century have understood the link between the vitamins in food and serious disease. However, it has only been in the last decade that scientists have been able to associate genetic variation with vitamin utilization and thus begin to unravel their combined effects on human health and disease. Completed in 2003, the human genome sequence created an informational infrastructure that provides scientists with critical tools in understanding human health and disease. Perhaps the most valuable product of these efforts was a nearly comprehensive catalog of common genetic variation at the single nucleotide level (SNPs), which represents the genetic basis for defining and distinguishing individuals.
The MTHFR Example
Recent genetic and biochemical research studies have focused on the biological effects of SNP variation in enzymes that require a vitamin as a cofactor for function. An interesting example is the A222V variant in methylene-tetrahydrofolate reductase (MTHFR)1. MTHFR is an enzyme of enormous clinical interest, as it is a member of the folate / homocysteine pathway, which has been implicated in neural tube defects as well as a potential risk factor for stroke and coronary heart disease. The biological effects in people with either one or two copies of mutant form of MTHFR can be reversed by elevated folate in their diets; the folate-remedial variant of MTHFR occurs in 3 out of 10 people of all ethnicities. This well studied example with MTHFR highlights two interesting characteristics of vitamin-responsive genes: (1) Genetic variation effecting biological function occur commonly in the general population, and (2) Enzyme systems with vitamin cofactors are involved in pathways associated with medical conditions involving serious disease.
1. Yamada K, et al., (2001) Proc Natl Acad Sci USA 98:14853-14858
Function & Remediation
Most genetic variation occurs in regions of the genome that do not affect enzyme structure and thus will have little or no physiological effect. Examining genetic variations within the coding regions of enzyme genes provides an efficient strategy to identity SNPs that will affect function. SNPs that impact function are the best candidates for comprising enzyme activity and thus will most likely have clinical consequences. Unlike many of the genetic association studies published in the last few decades, a focus on functional variation identifies genetic associations with high statistical significance and reliability.
Scientists at UC Berkeley and VitaPath Genetics published recently on a unique property of SNPs in vitamin responsive genes by showing that their negative effects could be corrected vitamin supplementation1. In this study, we showed that common genetic variants in folate-dependent enzymes function substantially below their peak level; however; the function of these enzymes can be restored to their normal levels through supplementation with elevated doses of folate. The ability to correct â€“ or remediate â€“ the effect of functional variants is a unique characteristic of the vitamin-responsive genes with significant clinical potential. 1. Marini N. et al., (2008) Proc Natl Acad Sci USA 105:8055-8060
Genetics & RDAs
Correlations in the vitamin-responsive enzymes between genetic variation and metabolic impact were not possible previously since the full landscape of common genetic variation has only recently emerged. Thus, when the Recommended Daily Allowances (RDAs) were established in the middle of the 20th century, it was not possible to describe or incorporate individual genetic variation in the recommendations. Moreover, even with the wealth of genetic information available to date, no dietary guideline currently in place is based on either genetic information or from an understanding of an individual’s unique profile.
From VitaPath’s research, we now know that certain mutations in these enzymes require significantly higher levels of their vitamin cofactor for normal performance. This suggests two important conclusions: (1) the current RDA is inadequate to the needs of many individuals and (2) individuals with defined genetic profiles can mitigate their effects with over-the-counter products that carry minimal risk of side effects when taken in doses that are higher than the RDA but are still within a reasonable therapeutic window.
A vitamin is a small organic molecule required in small amounts by an individual. In humans, a molecule is defined as a vitamin when it cannot be made in sufficient quantities by us, and thus must be obtained from the diet. Until the early1900s, vitamins were obtained solely through food intake. As the scientific understanding of vitamins increased, it was recognized that dietary habits and the seasonal availability of food could significantly alter the types and amounts of vitamins ingested. To provide a constant and continued source of vitamins, inexpensive pills containing synthesized vitamins were developed allowing for supplementation of the dietary intake.
Vitamins are essential for normal metabolism, growth, development and regulation of cell function. Vitamins participate in diverse array of biochemical functions, including functioning as hormones (Vitamin D), antioxidants (Vitamin E), and regulators of cell and tissue growth (Vitamin A). The largest number of vitamins (B complex vitamins) function as precursors for enzyme cofactor molecules (or coenzymes ) that ultimately act as catalysts or substrates in metabolism. When acting as part of a catalyst, vitamins are bound to enzymes and are called prosthetic groups. For example, biotin is part of the enzymes involved in making fatty acids. Vitamins also act as coenzymes that carry critical chemical groups between enzymes. For example, folic acid carries various forms of carbon within the cell for use in many biochemical reactions. Although vitamins do perform other important roles in cellular biochemistry, their role in assisting enzyme reactions is the best-known and most well studied function.
The 13 Essential Vitamins
In humans there are 13 essential vitamins. Nine are classified as water-soluble (Eight B vitamins and vitamin C) and four are classified as fat-soluble (A, D, E and K). Water-soluble vitamins dissolve easily in water, and unused vitamins are readily excreted from the body. Because they are not readily stored, consistent daily intake is important.
Fat-soluble vitamins are absorbed through the intestinal tract with the help of lipids. Because they are more likely to accumulate in the body, they are more likely to lead to high storage levels and thus more potentially toxicity than are water-soluble vitamins.
Vitamin Chemical Name
- Vitamin A Retinol
- Vitamin B1 Thiamine
- Vitamin B2 Riboflavin
- Vitamin B3 Niacin
- Vitamin B5 Pantothenic acid
- Vitamin B6 Pyridoxine
- Vitamin B7 Biotin
- Vitamin B9 Folic acid
- Vitamin B12 Cyanocobalamin
- Vitamin C Ascorbic acid
- Vitamin D Calciferol
- Vitamin E Tocopherol
- Vitamin K Phylloquinone
In Nutrition & Disease
Vitamins are essential for the normal growth and development of an organism. Using the DNA blueprint inherited from its parents, a fetus begins to develop from the nutrients it absorbs. It requires certain vitamins and minerals to be present at certain times. These nutrients facilitate the chemical reactions that produce among other things, skin, bone, and muscle. If there is serious deficiency in one or more of these nutrients, a child may develop significant disease. Once growth and development are completed, vitamins remain essential nutrients for the healthy maintenance of the cells, tissues, and organs. They also enable an individual to efficiently use chemical energy provided by food it eats, and to help process the proteins, carbohydrates, and fats required by biochemical reactions. People who eat a varied diet are unlikely to develop a severe vitamin deficiency. In contrast, restricted diets have the potential to cause prolonged vitamin deficits, which may result in serious or deadly disease. Because human bodies do not store most vitamins, humans must consume them regularly to avoid deficiency. Increasing scientific evidence shows that an individual’s genetic make-up plays an important role in effective and efficient vitamin utilization (see Genes & Vitamins).