Decreased plasma folate concentration in young and elderly healthy subjects after a short-term supplementation with isotretinoin.

BACKGROUND: In the last two decades, there has been an increasing use of isotretinoin (13-cis-retinoic acid or 13-CRA) for treatment of severe, and recently mild and moderate, acne in Westernized populations. Recent human and animal studies emphasized alterations caused by 13-CRA administration on folate-dependent, one-carbon metabolism. Folate deficiency and subsequent hyperhomocysteinemia increase the risk of degenerative diseases.

OBJECTIVES: We determine whether a short-term supplementation with 13-CRA alters folate status and homocysteinemia in young and elderly healthy human subjects.

METHODS: Twenty young and 20 elderly (age mean, 26.1 and 65.4 years, respectively) healthy male volunteers were supplemented with approximately 0.5 mg/kg/day of 13-CRA for 28 days. Fasting plasma concentrations of 13-CRA, 5-methyltetrahydrofolate (5-mTHF) as the main circulating form of folate, and homocysteine (Hcy), as well as haematologic parameters and biochemical markers of liver and renal function, were measured at baseline and at the end of supplementation. Statistical analyses were carried out using two-way anova and standard tests.

RESULTS: In both groups, isotretinoin supplementation caused a dramatic increase in the circulating concentration of 13-CRA and its derivatives. It also led to significant increases in serum triglyceride (P < 0.0001) and creatinine (P = 0.002) concentrations and gamma-glutamyltranspeptidase activity (P = 0.0001) and decrease in serum level of urea (P = 0.027). However, the latter four parameters remained within normal ranges. These changes were accompanied by a 17.7% and 13.5% decrease in the plasma level of 5-mTHF (P = 0.001) in the young and elderly volunteers, respectively. Supplementation with 13-CRA did not cause significant variations in their plasma Hcy concentration. However, the latter parameter seemed to respond differently in each group of age (P = 0.046).

CONCLUSIONS: Our data indicate that a 28-day supplementation with isotretinoin alters the plasma folate in young and old healthy individuals. This stresses the necessity of studying the long-term effects of retinoid therapy on folate status and homocysteinemia in acne patients, given that alteration in the latter parameters is known to increase the risk of degenerative diseases.