Effects of Oral Isotretinoin on Serum Folic Acid Levels

September 2012 | Volume 11 | Issue 9 | Original Article | 23 | Copyright © September 2012

Objective: Acne vulgaris is one of the most common skin disorders, and oral isotretinoin has widely been used as a treatment for severe and resistant cases in recent years. This article considers the controversy over systemic isotretinoin's effect on the serum level of folic acid and its implications for health.
Methods: This study was conducted to assess the effect of systemic isotretinoin on the serum level of folic acid. Sixty-one patients, including 38 women and 23 men (mean age 23.6 ± 6 years) with severe or moderate acne that was resistant to conventional treatments, were supplemented with 0.5 mg/kg/d of oral isotretinoin for 30 days. They were instructed not to use any other drugs having an effect on the folic acid level nor change their diet. The serum levels of folic acid were measured at the baseline and at the end of the treatment period. Statistical analyses were carried out using the paired t test.
Results: Mean levels of folic acid were 26.75 ± 9.42 nmol/L at baseline, and and 23.6 ± 8.42 nmol/L after 30 days of isotretinoin supplementation. This showed a significant decrease in the serum level of folic acid (P=.008).
Conclusion: Given the significant decrease in the serum level of folic acid following a 30-day use of oral isotretinoin in acne patients, and considering the important role of folic acid in metabolic functions, we recommend further studies to assess the effect of longer periods of isotretinoin treatment, in addition to studies including other relevant factors in folic acid metabolism (e.g., serum homocysteine levels). Moreover, folic acid supplementation in acne patients using isotretinoin is recommended.

J Drugs Dermatol. 2012;11(9):e23-e24.


Acne vulgaris is one of the most common dermatologic diseases that affect more than 90% of individuals during their lifetimes.1 Caused by inflammation of the pilosebaceous glands, acne vulgaris is usually chronic and hard to treat, requiring long-term drug therapy.2
Severe acne has a considerable impact on patients' self-confidence and quality of life, and, from a psychological point of view, is comparable to chronic diseases such as epilepsy and asthma.3 Nowadays, oral isotretinoin is the most effective drug, widely used in severe cases, including in scarring and treatment-resistant forms of acne. Complications reported for this drug include dry skin and mucosa, headache, muscular and skeletal pain, and changes in liver enzymes and serum lipids.4
Recent investigations into the effects of oral isotretinoin on serum folic acid levels have delivered controversial results, with Schulpis and Polat concluding that oral isotretinoin does not change serum folic acid levels in patients with acne vulgaris, but Chanson et al's study results showing that it can lead to a decline in these levels.5-7
Considering the important role of folic acid in body metabolism, the fact that its decline can result in complications such as anemia, cardiovascular diseases, brain diseases, and colorectal cancer,8-10 and the growing consumption of oral isotretinoin by patients with acne vulgaris, this study was designed to assess the effect of this drug on serum folic acid levels in patients with acne vulgaris who presented to the Shohada Ashaayer Hospital and private offices of Khorram Abad in Iran between 2008 and 2009.


Patient Selection

Following the diagnosis of severe, scarring, and moderate treatment-resistant forms of acne vulgaris by a dermatologist, patients were enrolled in the study after informed consent. Exclusion criteria were pregnancy; history of depression; treatment with drugs affecting folic acid levels, such as phenytoin, methotrexate, sulfasalazine, antacids, and alcohol; abnormal results for complete blood count, liver enzymes and markers, blood sugar, and serum lipids; and women of childbearing age not using contraception.

Data Collection

Venous blood samples were taken after 14 hours of fasting, and serum folic acid levels were measured using a specially designed kit (MP Biomedicals GmbH, Germany). After the baseline measurement of serum folic acid, oral isotretinoin 0.5 mg/kg/d (Decutan®; Actavis, Iceland) was prescribed for 30 days. Patients were instructed to use the drug between meals, not to change their regular diet, and not to consume folic acid supplements,