Information - Concepts In Nutrigenomics - Micronutrients

Deficiences Cause Disease

Approximately 40 micronutrients are required in the human diet. Deficiencies in micronutrients can cause DNA damage and are associated with a number of serious human diseases (Table 1).

Some cases of micronutrient deficiencies are due to poor diet while others are due to polymorphisms in genes encoding the enzymes involved in micronutrient metabolism. Approximately, 50 human genetic diseases can be attributed to enzyme polymorphisms and can be remedied or ameliorated by the administration of high levels of the vitamin component of the corresponding coenzyme. As many as one third of enzyme variants are due to increased Km for a coenzyme, resulting in a lower rate of reaction. The Michaelis-Menten constant, Km, is a measure of binding affinity of an enzyme for its ligand (substrate or coenzyme) and is defined as the concentration of ligand required to fill half of the ligand-binding sites. Intracellular concentrations of coenzyme may be increased by high doses of the corresponding vitamin, which would partially restore enzymatic activity and potentially ameliorate the phenotype. Changing substrate concentrations may be a general approach to circumvent decreased coenzyme binding or decreased enzymatic activities caused by a given coding SNP (cSNP).

Table 1

Micronutrient Deficiency and DNA Damage

Micronutrient

%US Population

DNA Damage

Health Effects

Folic acid

10% *

Chromosome breaks

Colon cancer, heart disease, brain dysfunction

Vitamin B12

4% (<half RDA)

Uncharacterized

Same as folic acid &  neurological damage

Vitamin B6

10% (<half RDA)

Uncharacterized

Same as folic acid

Vitamin C

15% (<half RDA)

Radiation mimic
(DNA oxidation)

 Cataracts (4X) Cancer

Vitamin E

20% (<half RDA)

Radiation mimic
(DNA oxidation)

Colon cancer (2X), Heart disease (1.5X), Immune dysfunction

Iron

7% (<half RDA)
(19% women 12-50 years of age)

DNA Breaks
Radiation mimic

DNA Breaks

Zinc

18% (<half RCA)

Chromosme breaks
Radiation mimic

Brain & Immune dysfyntion, Cancer

Niacin

2% (<half RDA)

Disables
DNA  repair
(polyADP ribose)

Neurological symptoms Memory loss

 * Prior to supplementation in US

Some examples of cSNPs include methylenetetrahydrofolate reductase (MTHFR) A222V (DNA: C677T) and FAD (in relation to cardiovascular disease, migraines and rages); NAD(P): quinone oxidoreductase 1 P187S (DNA:C609T) and FAD (in relation to cancer); glucose-6-phosphate dehydrogenase A44G (DNA:C131GP and NADP (in relation to favism and hemolytic anemia) and aldehyde dehydrogenase E487K (present in half of Asians) and NAD (in relation to alcohol intolerance, Alzheimer�s disease, and cancer.

Adjusting human metabolism through diet, which would be specific for individuals with similar genotypes and ages, may minimize damage to chromosomal and mitochondrial DNA optimizing health and prolonging the quality of life. Establishing optima micronutrient intakes for minimizing human DNA damage should reduce the risk and onset of certain cancers, and other degenerative diseases associated with aging. 

Further reading

Ames, BN and Wakimoto, P. 2002. Are micronutrient deficiencies a major cancer risk?  Nature Reviews Cancer 2, 694 � 704. PMID: 12209158