Topic of the Month

Micronutrient insufficiency: Also a matter of genes

October 1, 2010

The human body needs micronutrients for several vital functions. Insufficient amounts in the body can increase the risk of multiple diseases. Micronutrient requirements vary from person to person and are dependant on age, sex, activity and performance levels, as well as physical and mental health condition. For a long time, insufficiency has been thought to be only a matter of inappropriate intake. Recent research has shown, however, that variable levels of micronutrients across populations seem also to strongly depend on the individual’s genetic profile: differences in DNA sequences, so-called ‘genetic polymorphisms’, among individuals can result in varying metabolic capabilities to utilize (absorb, transport, transform) vitamins etc. after intake. Thus, levels of micronutrients in blood and tissues might be limited by specific genetic variants, potentially increasing the risk of insufficiency and related diseases.


Consequently, scientists have suggested recommendations for micronutrient intakes should also consider genetics. People who have a gene-related reduced metabolic ability to convert a vitamin precursor to its active form, for example, could be advised to increase their vitamin intake. This also may have ramifications for public health through improved predictions of micronutrient insufficiency-related diseases and help to identify individuals who may benefit the most from eating certain foods or taking supplements. In addition, differences in individual genetics could help explain the results of some of the large-scale intervention studies which have not demonstrated a health benefit for micronutrient supplementation.


Beta-carotene and vitamin A

Vitamin A is essential for normal growth and development, immune system, vision and other functions in the human body. National survey data show that the intake of preformed vitamin A (retinol) – as such only present in animal products (especially liver) – is often critically low and does not meet the recommendations. As beta-carotene can be converted by the body to vitamin A, the carotenoid contributes significantly to balance inadequate vitamin A intake in large parts of the population. The bioavailability of beta-carotene is influenced by food-related factors including linkage strength in the food, food processing, dosage, and fat in the meal. Additionally, consumer-related factors such as vitamin A status, gut integrity and genetic variations determine the amount of beta-carotene used as vitamin A source.

The extent to which beta-carotene is converted to vitamin A is highly variable between well-nourished healthy individuals. Recent research has shown that almost 50% of women have a genetic variation which reduces their ability to produce sufficient amounts of vitamin A from beta-carotene. Such ‘poor converters’ seem to have a polymorphism in the gene coding the key enzyme responsible for beta-carotene conversion. Younger women carrying the genetic variation may be at particular risk as they tend to eat not enough vitamin A-rich foods relying heavily on the beta-carotene form of the nutrient.

Experts speculate that approximately 40 percent of all Europeans possess a gene variant that restricts the amount of beta-carotene their bodies can convert into vitamin A. If the gene-related restrictions are taken into account, the intake recommendations for beta-carotene would need to be increased for those who carry the genetic variation, they suggest. Further investigations in this direction are currently underway.


  1. Leung W. C. et al. Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers. The FASEB Journal. 2009; 23:1041–1053.
  2. Lietz G. and Hesketh J. A network approach to micronutrient genetics: interactions with lipid metabolism. Curr Opin Lipidol. 2009; 20(2):112–20.

B vitamins

The B vitamins play key roles in cell metabolism, promoting cell growth and division (DNA synthesis), enhancing immune and nervous system function, and maintaining healthy skin and muscle tone. B vitamin deficiency has been associated with increased risk of multiple chronic diseases. It has been hypothesized that insufficient levels of vitamin B9 (folate), B12 and B6 increase the production and decrease the degradation of homocysteine. High levels of this amino acid, mainly observed in the presence of low serum concentrations of folic acid, are seen as independent risk factor for cardiovascular and neurological diseases. In addition to B vitamin deficiency, genetic variations in enzymes involved in homocysteine metabolism may contribute to an increased disease risk.

In the last few years, several common genetic variants affecting metabolism and serum levels of homocysteine and B vitamins have been identified. Researchers suggest that these genetic polymorphisms may be important markers to identify people at risk for lifelong low B vitamin levels, high homocysteine concentrations and its consequences.


  1. Tanaka T. et al. Genome-wide Association Study of Vitamin B6, Vitamin B12, Folate,
    and Homocysteine Blood Concentrations. The American Journal of Human Genetics. 2009; 84:477–482.
  2. Miyaki K. Genetic Polymorphisms in Homocysteine Metabolism and Response to Folate Intake: A Comprehensive Strategy to Elucidate Useful Genetic Information. J Epidemiol. 2010; 20(4):266–270.

Vitamin C

Vitamin C (ascorbic acid) is essential for the synthesis of collagen and neurotransmitters. In addition, vitamin C as antioxidant is thought to contribute to the prevention of several chronic diseases such as atherosclerosis, type 2 diabetes, and cancer. Circulating concentrations of vitamin C in blood have been found to vary among individuals. Many characteristics are known to decrease vitamin C concentrations, including physical activity, alcohol consumption, and cigarette smoking.

Recently, a study analyzed blood samples obtained from over 15,000 women to assess the relationship between genetic variations involved in vitamin C metabolism and circulating concentrations of ascorbic acid. The researchers identified a polymorphism in the gene encoding a transport protein responsible for intestinal vitamin C uptake. The gene variant was associated with reduced ascorbic acid blood concentrations, which might be related to a restricted transport activity.

Whether this polymorphism increases the risk of vitamin C insufficiency and related chronic diseases is not known yet. Also it is not clear if the genetic limitations may be overcome by increased consumption of vitamin C in diet or supplements. Experts suggest that these results need to be considered in future studies and that they shed important light on previous research reporting on inconsistent relationships between vitamin C (supplement) intake or status and disease risk reduction.


  1. Timpson N. J. et al. Genetic variation at the SLC23A1 locus is associated with circulating concentrations of L-ascorbic acid (vitamin C): evidence from 5 independent studies with > 15,000 participants. American Journal of Clinical Nutrition. 2010; 92:375–82.
  2. Michels A. J. et al. A new twist on an old vitamin: human polymorphisms in the gene encoding the sodium-dependent vitamin C transporter 1. American Journal of Clinical Nutrition. 2010; 92:271–2.

Vitamin D

A sufficient intake of vitamin D is important as it helps the body to maintain normal bones, the immune system, inflammatory response, muscle function and cell division. The consequences of inadequate vitamin D concentrations are well established, and include childhood rickets, osteomalacia, and fractures. In addition, disorders such as diabetes, cardiovascular disease, and cancer have been linked to vitamin D insufficiency. Sufficient exposure to ultraviolet light or adequate intake from diet or supplements is needed to maintain vitamin D status, measured as 25-hydroxyvitamin D concentration in blood. Only about a quarter of the highly variable vitamin D concentrations between individuals is attributable to sun exposure or reported vitamin D intake. Results of twin and family studies suggest that genetic factors contribute substantially to this variability.

A recent study involving 16,125 people from the U.S., Canada and Europe identified genetic polymorphisms that more than double the risk of vitamin D insufficiency. Variants near genes coding enzymes involved in the synthesis of 25-hydroxyvitamin D and cholesterol, as well as a vitamin D transport protein seem to strongly affect vitamin D status. The scientists recommend these findings could assist identification of a subgroup of the population who are at increased risk of vitamin D insufficiency.

Current research indicates a correlation between polymorphisms in genes involved in vitamin D metabolism and an increased risk of developing diseases such as cancer, tuberculosis and autoimmune disorders.


  1. Wang T. J. et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010; 376:180–88.
  2. Köstner K. et al. The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature. Anticancer Res. 2009; 29(9):3511–36.
  3. Gao L. et al. Vitamin D receptor genetic polymorphisms and tuberculosis: updated systematic review and meta-analysis. Int J Tuberc Lung Dis. 2010; 14(1):15–23.
  4. Smolders J. The relevance of vitamin D receptor gene polymorphisms for vitamin D research in multiple sclerosis. Autoimmun Rev. 2009; 8(7):621–6.

Vitamin E

A sufficient intake of vitamin E is essential as it functions as an antioxidant, potentially protecting cells, tissues, and organs from damaging effects of free radicals, which can contribute to the development of several diseases. Low plasma levels of vitamin E (tocopherols) are associated with increased risk of chronic disorders. Serum levels after ingestion of a standard dose of vitamin E have been found to be extremely variable between individuals. Among numerous factors that can influence absorption, digestion, transportation, storage, chemical transformation, and excretion of vitamin E, also genetic variants seem to affect these mechanisms. Scientists have identified polymorphisms in a gene involved in vitamin E transport that strongly affects plasma concentrations of alpha-tocopherol and circulating lipids (e.g. triglycerides).

Recent research has suggested a correlation between genetic polymorphisms, a higher risk of developing cardiovascular diseases, respiratory tract infections and obesity, and potential benefits of increased vitamin E intake.


  1. Ferrucci L. et al. Common Variation in the b-Carotene 15,150-Monooxygenase 1 Gene Affects Circulating Levels of Carotenoids: A Genome-wide Association Study. The American Journal of Human Genetics. 2009; 84:123–133.
  2. Blum S. et al. Vitamin E Reduces Cardiovascular Disease in Individuals with Diabetes Mellitus and the Haptoglobin 2-2 Genotype. Pharmacogenomics. 2010; 11(5):675–684.
  3. Belisle S.E. et al. IL-2 and IL-10 gene polymorphisms are associated with respiratory tract infection and may modulate the effect of vitamin E on lower respiratory tract infections in elderly nursing home residents. Am J Clin Nutr. 2010; 92:106–14.
  4. Zillikens M. C. et al. Interactions between dietary vitamin E intake and SIRT1 genetic variation influence body mass index. Am J Clin Nutr. 2010; 91(5):1387–93.