Elevated plasma homocysteine levels in patients on isotretinoin therapy for cystic acne.
BACKGROUND
The use of Isotretinoin (Iso) for cystic acne (CA) therapy includes marked side-effects such as dyslipidemia, increased liver enzymes, and reduction of biotinidase activity. Moreover, Homocysteine (Hcy), an amino acid, is metabolized in the liver requiring folate, vitamin B6, vitamin B12, and the activity of enzymes, i.e. cystathionine-beta-synthase. Increased blood levels of Hcy are associated with premature occlusive vascular disease.


OBJECTIVE
The aim of this study was the evaluation of Hcy levels and the responsible vitamins for its metabolism in patients with CA on Iso treatment.


RESULTS
Twenty-eight patients with CA were submitted to laboratory examinations before (Value 1) and after (Value 2) 45 days on Iso (0.5 mg/kg/24 h) therapy. Blood levels of Hcy and vitamin B6 were evaluated by HPLC methods, and folate and vitamin B12 using a commercial Kit. Hcy levels (Value 1 = 7.86 +/- 1.6 micromol/L; Value 2 = 13.65 +/- 3.3 micromol/L; P < 0.001) were statistically significantly increased in patients on treatment. Vitamins were unaltered, and lipids and liver enzymes increased. Significant correlation between Hcy levels, vitamins, and liver enzymes was found. Methionine loading tests performed in nine patient-volunteers showed an abnormal response post-treatment.


CONCLUSIONS
It is suggested that the elevated Hcy levels in patients after 45 days on Iso therapy could be due either to the 'inhibition' of cystathionine-beta-synthase by the drug and/or their liver dysfunction. Daily vitamin supplementation along with frequent evaluations of Hcy blood levels are recommended for the prevention of a premature occlusive vascular disease.
Institute of Child Health, and Pharmacokinetics and Parenteral Nutrition Unit, Aghia Sophia Children's Hospital, Athens, Greece.
K H
KH
Schulpis
G A
GA
Karikas
S
S
Georgala
T
T
Michas
S
S
Tsakiris
D000152:Acne Vulgaris / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D005260:Female; D006710:Homocysteine / Q000097:blood / Q000187:drug effects*; D006801:Humans; D015474:Isotretinoin / Q000009:adverse effects / Q000627:therapeutic use*; D008111:Liver Function Tests; D008297:Male; D008715:Methionine / Q000097:blood / Q000187:drug effects; D016896:Treatment Outcome
D006710:Homocysteine; D008715:Methionine; D015474:Isotretinoin