PMID- 15485475 OWN - NLM STAT- MEDLINE DCOM- 20041130 LR - 20131121 IS - 0954-6820 (Print) IS - 0954-6820 (Linking) VI - 256 IP - 5 DP - 2004 Nov TI - Impairment of coronary circulation by acute hyperhomocysteinaemia and reversal by antioxidant vitamins. PG - 398-405 AB - 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 transthoracic 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 h following ingestion of the loads. RESULTS: The oral methionine load increased plasma homocysteine from 12.8 +/- 1.8 to 33.3 +/- 3.4 micromol 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. FAU - Coppola, A AU - Coppola A AD - Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy. toncop@tiscali.it FAU - Astarita, C AU - Astarita C FAU - Liguori, E AU - Liguori E FAU - Fontana, D AU - Fontana D FAU - Oliviero, M AU - Oliviero M FAU - Esposito, K AU - Esposito K FAU - Coppola, L AU - Coppola L FAU - Giugliano, D AU - Giugliano D LA - eng PT - Clinical Trial PT - Journal Article PT - Randomized Controlled Trial PL - England TA - J Intern Med JT - Journal of internal medicine JID - 8904841 RN - 0 (Antioxidants) RN - 0 (Cytokines) RN - 0 (Vitamins) RN - AE28F7PNPL (Methionine) SB - IM MH - Adult MH - Antioxidants/*therapeutic use MH - Coronary Circulation/*physiology MH - Coronary Disease/*etiology/prevention & control MH - Cross-Over Studies MH - Cytokines/metabolism MH - Female MH - Humans MH - Hyperhomocysteinemia/*physiopathology MH - Male MH - Methionine/therapeutic use MH - Vitamins/*therapeutic use EDAT- 2004/10/16 09:00 MHDA- 2004/12/16 09:00 CRDT- 2004/10/16 09:00 PHST- 2004/10/16 09:00 [pubmed] PHST- 2004/12/16 09:00 [medline] PHST- 2004/10/16 09:00 [entrez] AID - JIM1389 [pii] AID - 10.1111/j.1365-2796.2004.01389.x [doi] PST - ppublish SO - J Intern Med. 2004 Nov;256(5):398-405. doi: 10.1111/j.1365-2796.2004.01389.x.