Impairment of coronary circulation by acute hyperhomocysteinaemia and reversal by antioxidant vitamins

Objective. To evaluate the effect of acute hyperhomocysteinaemia with and without antioxidant vitamins pretreatment on coronary circulation and circulating chemokine levels. Design. Observer-blinded, randomized crossover study. Setting. This study was conducted at a university hospital and at a general hospital in Italy. Subjects. Sixteen healthy hospital staff volunteers (nine men, seven women), aged 26-40 years. Interventions. Subjects were given each three loads in random order at 1-week intervals: oral methionine, 100 mg kg(-1) in fruit juice; the same methionine load immediately following ingestion of antioxidant vitamin E, 800 IU, and ascorbic acid, 1000 mg; and methionine-free fruit juice (placebo). Main outcome measures. Coronary flow velocity reserve (CFVR), assessed by noninvasive trans-thoracic Doppler echocardiography, blood pressure, heart rate, lipid and glucose, monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) parameters evaluated at baseline and 4 It following ingestion of the loads. Results. The oral methionine load increased plasma homocysteine from 12.8 +/- 1.8 to 33.3 +/- 3.4 mumol L-1 at 4 h (P < 0.001). A similar increase was observed with same load plus vitamins (P < 0.001) but not with placebo (P = 0.14). Circulating MCP-1 and IL-8 levels rose after the methionine load (P < 0.001), but not after placebo or methionine plus vitamins. The methionine load significantly reduced CFVR (decrease, 26 +/- 8.2%; P < 0.001). The methionine load with ingestion of vitamins partially prevented the impairment of CFVR (decrease, 11 +/- 4%; P < 0.001). Conclusion. Our data suggest that acute hyperhomocysteinaemia reduces CFVR and increases plasma MCP-1 and IL-8 levels in healthy subjects. Pretreatment with antioxidant vitamin E and ascorbic acid prevents the effects of hyperhomocysteinaemia, suggesting an oxidative mechanism.