Coffee and gene interaction. The effect on methionine and lipid metabolism

Abstract: Background: Different dietary factors influence the risk of coronary heart disease (CHD), most likely in an interaction with genetic polymorphisms. The knowledge about such interactions is insufficient. Some observational studies have shown an association between coffee and CHD, others have not. Coffee consumption affects some CHD risk factors, e.g. plasma total homocysteine (tHcy) and serum total cholesterol. tHcy is negatively associated with folic acid, pyridoxine (vitamin B6) and vitamin B12, and is also influenced by the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. Serum cholesterol is affected by the APOE 2/ 3/ 4 polymorphism.Aims: To investigate if a supplement of 200 µg folic acid or 40 mg pyridoxine would decrease or eliminate the tHcy enhancing effect of coffee, and if the effect was dependent of the MTHFR C677T polymorphism. The study also gave the opportunity to study the serum cholesterol raising effect of filtered coffee and if the effect was influenced by APOE 2/ 3/ 4 polymorphisms.Method: The participants were 121 healthy non-smoking men (22%) and women (78%), 29-65 years old, not on blood lipid lowering drugs or vitamin B supplementation. The effect of coffee was studied in a prospective, controlled, double blind trial with four consecutive periods: 1. three weeks of coffee abstention (wash-out) 2. 4 cups (600 mL) coffee/day and 200 g folic acid/day or placebo for 4 weeks3. three weeks of coffee abstention (wash-out) 4. 4 cups (600 mL) coffee/day and 40 mg pyridoxine/day or placebo for 4 weeks.Results: Three weeks of coffee abstention resulted in a tHcy decrease of 1.04 mol/L for the whole group (95% CI -1.45, -0.62). During the subsequent coffee consumption period there was a further decrease of 0.17 mol/L in the folic acid group. In the placebo group there was a tHcy increase of 1.26 mol/L, the difference was 1.43 mol/L (95% CI 0.80, 2.07). Pyridoxine supplementation had no significant effect on the tHcy level.The homocysteine increasing effect of coffee was mainly seen in individuals homozygous for the MTHFR 677T genotype. Folic acid supplement reduced the tHcy increase in these individuals. The two coffee abstention periods resulted in a significant serum cholesterol decrease of 0.22 mmol/L and 0.36 mmol/L, respectively. Consumption of 4 cups filter brewed coffee/day resulted in a significant serum cholesterol increase of 0.25 mmol/L and 0.15 mmol/L, respectively. APOE e2 positive individuals had lower serum cholesterol at baseline than APOE e2 negative individuals, but the APOE polymorphism had no influence on the serum cholesterol increasing effect of coffee.Discussion: The results are consistent with earlier intervention studies on the association between coffee and tHcy. Individuals with hyperhomocysteinemia, often homozygous for the MTHFR 677T allele, should have an adequate intake of folic acid to limit the homocysteine raising effect of coffee. The magnitude of the serum cholesterol enhancing effect of filter-brewed coffee was surprising, and has been shown in only two earlier intervention studies. Individuals with high serum cholesterol should limit their coffee consumption regardless of their APOE genotype.

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