Homocysteine concentrations and the Mediterranean diet

Nutrition Research Newsletter, Nov, 2004

Multiple studies have shown that elevated total homocysteine (tHcy) concentrations may serve as an independent risk factor for cardiovascular disease. However, this has not been confirmed in all investigations. Some studies have considered tHcy more as a result than as a cause of arteriosclerosis, especially as a result of the confounding effect of various nutrient and genetic factors, particularly as a result of the confounding effect of various nutrient and genetic factors. The C-to-T substitution at nucleotide 677 (677CT mutation), which leads to the exchange of an alanine for a valine in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR; OMIM.236350), results in a thermolabile variant of MTHFR that produces a partially defective enzyme. MTHFR activity regulates 5-methyltetrahydrofolate, which is necessary for the re-methylation of tHcy to methionine and S-adenosylmethionine, the common methyl donor for the maintenance of DNA methylation. Raised tHcy concentrations have been related to homozygous MTHFR 677T, especially in the presence of low folate concentrations.

Several studies involving populations in Mediterranean countries, where traditional diets consist largely of foods of plant origin, have shown low rates of many chronic diseases and long life expectancies. While the mechanisms are not completely understood, carotenoids, folic acid, and fiber, all of which are abundant in the Mediterranean diet, appear to play important roles in the prevention of coronary artery disease.

While the effect of folic acid, vitamin B-6, and vitamin B-12 on plasma tHcy concentrations is well established, the association of a Mediterranean diet as a whole on tHcy is not known. Additionally, the presence of MTHFR genotypes that differentiate tHcy concentrations may influence the relation between a Mediterranean diet and tHcy. Therefore, researchers sought to evaluate the association of a gene-diet interaction between adoption of a Mediterranean diet and the MTHFR 677T mutation on tHcy concentrations in healthy adults from the ATTICA study.

Researchers studied demographic, lifestyle, clinical, biochemical, and genetic information from 322 men (x [ or -] SD age: 46 [ or -] 13 years) and 252 women (45 [ or -] 14 years) who had no clinical evidence of cardiovascular or any other chronic disease. Total plasma homocysteine concentrations, the distribution of the MTHFR genotype, and adherence to a Mediterranean diet, were measured.

The distribution of MTHFR genotypes was as follows: homozygous normal (CC), 41%; heterozygous (CT), 48%; and homozygous mutant (TT), 11%. Homocysteine concentrations were higher in persons with the TT genotype than in those with the CC and CT genotypes (x [ or -] SD: 15.8 [ or -] 9 compared with 11.3 [ or -] 8 AND 10.8 [ or -] 9 [micro]mol/L, respectively; P < 0.001). The Mediterranean diet score was not significantly associated with homocysteine concentrations (P = 0.89). However, after control for potential confounders, the stratified analysis showed that adherence to a Mediterranean diet was associated with reduced homocysteine concentrations in persons with the TT and CT genotypes (beta = -0.21, P = 0.002, and beta = -.014, P = 0.025, respectively) but not in those with the CC genotype (beta = -0.03, P = 0.38).

The observed association of an NTHFR 677C [right arrow] T gene-diet interaction on homocysteine concentrations may offer a pathophysiologic explanation for how a Mediterranean diet could influence coronary risk in individuals with elevated homocysteine levels.

G. Dedoussis, D. Panagiotakos, C. Chrysohoou, et al. Effect of interaction between adjerence to a Mediterranean diet and the methylenetetrahydrofolate reductase 677C T mutation on homocysteine concentrations in healthy adults: the ATTICA Study. Am J Clin Nutr; 80:849-854 (October, 2004). [Correspondence: DB Panagiotakos, 46 Paleon Polemiston St Glyfada, Attica 166 74m Greece. E-mail:d.b.panagiotakos@usa.net].