Oral Isotretinoin for Acne Increases Plasma Homocysteine and Decreases Folic Acid

Isotretinoin therapy for acne is associated with elevated homocysteine and decreased folic acid and vitamin B12 plasma levels; higher homocysteine levels are related to an increased risk for cardiovascular diseases.

Treatment with oral isotretinoin is associated with changes in homocysteine and folic acid plasma levels in patients with acne, a study found. The results were published in the Journal of Cosmetic Dermatology.

Researchers reviewed selected studies that reported plasma levels of homocysteine, folic acid, and vitamin B12 during and after isotretinoin treatment in patients with acne. A total of 10 studies that included 592 patients with acne were pooled into a meta-analysis to identify changes in homocysteine, folic acid, and vitamin B12 plasma levels during and after isotretinoin therapy.

After isotretinoin therapy, patients with acne had significantly higher homocysteine levels (weighted mean difference [WMD], 2.99; 95% CI, 1.78-4.20; I2 = 86%). Conversely, isotretinoin was associated with significantly lower levels of folic acid (WMD, −1.03; 95% CI, −1.90 to −0.17; I2 = 89%) after therapy. Patients with acne who were treated for longer than 2 months had significantly lower plasma levels of vitamin B12 (WMD, −58.11; 95% CI, −80.30 to −35.92; I2 = 11%). There was no significant difference in vitamin B12 levels after isotretinoin therapy (WMD, −21.33; 95% CI, −43.01 to 0.36; I2 = 72%). In addition, no difference was found between vitamin B12 levels before or after isotretinoin in patients who were treated for less than 2 months (WMD, −7.23; 95% CI, −16.04 to 1.57; I2 = 0%).

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Limitations of the analysis include the small number of studies assessed as well as the potential for detection and reporting bias.

The study also suggested, according to the researchers, that higher homocysteine levels could be linked to an increased risk for cardiovascular disease. “Thus,” they wrote, “clinicians should be more concerned about the risk of [high homocysteine] when using [isotretinoin] therapy in acne patients.”

Disclosure: None of the study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Kim HJ, Lee SM, Lee JS, et al. Homocysteine, folic acid, and vitamin B12 levels in patients on isotretinoin therapy for acne vulgaris: A meta-analysis [published online July 5, 2019]. J Cosmet Dermatol. doi:10.1111/jocd.13059