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 – or remediate – 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.
Vitamins
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).
