Individuals with the MTHFR 677 TT genotype had a significantly higher risk of CHD, particularly in the setting of low folate status. These results support the hypothesis that impaired folate metabolism, resulting in high homocysteine levels, is causally related to increased risk of CHD.

Objective: We quantified the public health benefit of fruits and vegetables on the prevention of cancer and cardiovascular disease (CVD), using currently available human data. Design: We reviewed over 250 observational studies on cancer and CVD. Relative risks (RRs) for high versus low intake of fruits and vegetables were obtained. The preventable proportion of chronic diseases, i.e. the per cent of cases attributable to low consumption of fruits and vegetables, was estimated using three scenarios: best guess, optimistic (using stronger RRs) and conservative (using weaker RRs and eliminating the contribution of smoking and/or drinking). The preventable proportion was calculated for increasing average intake from the current 250 g day −1 to the recommended 400 g day −1 among the general Dutch population.

Objective: To study the effects of prolonged intake of cafetiere coffee, which is rich in the diterpenes cafestol and kahweol, on serum aminotransferase and lipid concentrations. Design: Randomised parallel controlled trial. Subjects: 46 healthy men and women aged 19 to 69. Intervention: Consumption of five to six strong cups (0.9 litres) a day of either cafetiere (22 subjects) or filtered coffee (24 subjects) for 24 weeks. Main outcome measures: Mean changes in serum aminotransferase and lipid concentrations. Results: Cafetiere coffee raised alanine aminotransferase concentration by up to 80% above baseline values relative to filtered coffee. After 24 weeks the rise was still 45% (9 U/l (95% confidence interval 3 to 15 U/l), P = 0.007). Alanine aminotransferase concentration exceeded the upper limit of normal in eight of the 22 subjects drinking cafetiere coffee, being twice the upper limit of normal in three of them. Cafetiere coffee raised low density lipoprotein cholesterol concentrations by 9–14%. After 24 weeks the rise was 0.26 mmol/l (0.04 to 0.47 mmol/l) (P = 0.03) relative to filtered coffee. Triglyceride concentrations initially rose by 26% with cafetiere coffee but returned close to baseline values within six months. All increases were reversible after the intervention was stopped. Conclusions: Daily consumption of five to six cups of strong cafetiere coffee affects the integrity of liver cells as suggested by small increases in serum alanine aminotransferase concentration. The effect does not subside with prolonged intake. High intakes of coffee brews rich in cafestol and kahweol may thus be responsible for unexplained increases in this enzyme activity in apparently healthy subjects. Cafetiere coffee also raises low density lipoprotein cholesterol concentration and thus the risk of coronary heart disease. Key messages This randomised study found that cafetiere coffee also increased alanine aminotransferase and low density lipoprotein cholesterol concentrations, and they were still raised after six months of daily intake. Filtered coffee had no effect The increase in liver enzyme activity could be innocuous, but the increase in cholesterol concentration may increase coronary risk and could be a reason to advise patients to drink filtered coffee

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SummaryElevated homocysteine levels are associated with an increased cardiovascular disease (CVD) risk, but the underlying mechanism is still unclear. High homocysteine might affect the endothelium, and consequently lead to impaired haemostasis. In a randomized placebo controlled trial among 276 older adults with plasma total homocysteine concentrations above 13 mM at screening, we investigated the effect of homocysteine lowering by folic acid supplementation (0.8 mg/day) for 1 year on markers of endothelial function (vonWillebrand factor), coagulation (tissue factor, factor VIIa, fragments 1+2), and fibrinolysis (fibrin degradation products, tissue-type plasminogen activator), and inflammation (C-reactive protein). Despite a 24% reduction in plasma homocysteine concentration and four-fold increase in serum folate concentration in the folic acid group compared to the placebo group, there was no clear change in any of the haemostasis markers, nor CRP. Although homocysteine is associated with vascular disease risk in the general population, marked lowering of slightly elevated homocysteine concentrations by one-year folic acid supplementation does not influence haemostasis markers.

SummaryHomocysteine may have an effect on risk of cardiovascular disease by stimulating procoagulant factors and/or impair anti-coagulant mechanisms or fibrinolysis. However, data in humans of such effects are sparse. In this intervention study, we examined the effect of homocysteine lowering by B-vitamin supplementation on prothrombin fragments 1 and 2 (F1+2), thrombin-antithrombin complex (TAT), and fibrin degradation products (D-dimer). The study comprised 118 healthy volunteers, 50 with homocysteine > 16 µmol/L and 68 with homocysteine ≤ 16 µmol/L, who were randomized to placebo or highdose B-vitamin supplements (5 mg folic acid, 0.4 mg hydroxycobalamin, and 50 mg pyridoxine) daily for 8 weeks. Although homocysteine concentrations were 27.7% (p < 0.0001) reduced in the Bvitamin group compared to the placebo group, no effect on F1+2 and TAT concentrations was observed. A 10.4% reduction was observed for D-dimer (p = 0.08).In conclusion, it appears that in healthy subjects homocysteine reduction by B-vitamin supplementation has a modest beneficial effect on clotting activation.

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