Vitamin C therapy ameliorates vascular endothelial dysfunction in treated patients with homocystinuria.
OBJECTIVE
We sought to investigate the effects of short- and long-term vitamin C therapy on endothelial dysfunction in patients with homocystinuria.


BACKGROUND
Untreated homocystinuria due to cystathionine beta-synthase deficiency is associated with premature atherothrombotic disease; 25% of untreated patients suffer a vascular event by the age of 16 years and 50% by 29 years. Treatment directed at reducing homocysteine accumulation significantly reduces this risk. However, despite 'optimal' treatment and compliance, hyperhomocysteinaemia usually persists and individuals exhibit endothelial dysfunction indicative of an adverse cardiovascular prognosis. Additional intervention is therefore required to further reduce cardiovascular risk.


METHODS
We investigated the endothelial effects of acute (2 g single dose) and chronic (1 g/day for 6 months) administration of oral vitamin C in 5 patients with homocystinuria (mean age 26 years, 1 male) and 5 age- and sex-matched controls. Brachial artery endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent responses to nitroglycerin (NTG) were measured using high-resolution ultrasonic vessel wall-tracking.


RESULTS
Baseline: Plasma total homocysteine was 100.8 +/- 61.6 and 9.2 +/- 1.9 micromol/L in the patient and control groups, respectively (p < 0.001). FMD responses were impaired in the patient group (20 +/- 40 microm) compared with the controls (116 +/- 30 microm) (p < 0.001). Vitamin C administration: FMD responses in the patient group improved both acutely, 160 +/- 65 microm at 4 h (p < 0.001), and chronically, 170 +/- 70 microm at 2 weeks (p < 0.001) and 170 +/- 40 microm at 6 months (p < 0.001). FMD responses in the control group were unaltered (p = 0.526). Within both groups, neither the vascular response to NTG nor plasma homocysteine was altered (p > 0.4).


CONCLUSIONS
Vitamin C ameliorates endothelial dysfunction in patients with homocystinuria, independent of changes in homocysteine concentration and should therefore be considered as an additional adjunct to therapy to reduce the potential long-term risk of atherothrombotic disease.
Cardiovascular Sciences Research Group, Wales Heart Research Institute, Cardiff, UK.
C H
CH
Pullin
J R
JR
Bonham
I F W
IF
McDowell
P J
PJ
Lee
H J
HJ
Powers
J F
JF
Wilson
M J
MJ
Lewis
S J
SJ
Moat
D000328:Adult; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D001783:Blood Flow Velocity; D001794:Blood Pressure; D001916:Brachial Artery; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate; D006711:Homocystine / Q000097:blood; D006712:Homocystinuria / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008715:Methionine / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D013763:Tetrahydrofolates / Q000097:blood; D014664:Vasodilation
D013763:Tetrahydrofolates; D009569:Nitric Oxide; D006711:Homocystine; D008715:Methionine; D005996:Nitroglycerin; D001205:Ascorbic Acid; C005984:5-methyltetrahydrofolate