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.


METHODS
Observer-blinded, randomized crossover study.


METHODS
This study was conducted at a university hospital and at a general hospital in Italy.


METHODS
Sixteen healthy hospital staff volunteers (nine men, seven women), aged 26-40 years.


METHODS
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).


METHODS
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).


CONCLUSIONS
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.
Coppola
A
A
Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy. toncop@tiscali.it
Astarita
C
C
Liguori
E
E
Fontana
D
D
Oliviero
M
M
Esposito
K
K
Coppola
L
L
Giugliano
D
D
D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000502:physiology*; D003327:Coronary Disease / Q000209:etiology* / Q000517:prevention & control; D018592:Cross-Over Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D020138:Hyperhomocysteinemia / Q000503:physiopathology*; D008297:Male; D008715:Methionine / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use*
D000975:Antioxidants; D016207:Cytokines; D014815:Vitamins; D008715:Methionine