in triglycerides and liver enzymes occurred in some patients, but they returned to baseline within 2-3 weeks after stopping treatment, similar to isotretinoin.
While oral vitamin A appears efficacious for mild to severe acne, studies done years ago would not meet current standards for drug approval, and our ability to provide a truly critical appraisal of the differences and similarities between oral vitamin A and isotretinoin is limited by the contrast in quality of isotretinoin and vitamin A trials. Side effects of oral vitamin A are similar to those of isotretinoin, including, importantly, teratogenicity. Acute vitamin A toxicity has been reported at initial doses of 25,000 IU/kg and chronic toxicity has been reported at doses of 4,000 IU/kg daily for a duration of 6-15 months.13 Signs of mild toxicity, such as mucocutaneous symptoms, are expected at the doses required for acne management and are similar to those of isotretinoin. Laboratory monitoring includes liver function tests, lipids, and pregnancy tests, in females of childbearing potential, as would be done with isotretinoin. The half-life of vitamin A is much longer than that of isotretinoin (12 days versus 24-29 hours, respectively), and female patients of childbearing age should be advised to wait at LEAST 3 months following treatment cessation before conceiving.14 Vitamin A is affordable and readily accessible over the counter in unit doses of 5,000 to 25,000 IU per capsule for about one tenth of the cost of isotretinoin.15 At doses of 50,000-300,000 IU daily, vitamin A may provide a substitute for acne management when isotretinoin is unavailable. Recommending an over-the-counter vitamin to which patients could have unlimited access without supervision by a medical provider should be done with very careful attention to patient selection and education.
While oral vitamin A appears efficacious for mild to severe acne, studies done years ago would not meet current standards for drug approval, and our ability to provide a truly critical appraisal of the differences and similarities between oral vitamin A and isotretinoin is limited by the contrast in quality of isotretinoin and vitamin A trials. Side effects of oral vitamin A are similar to those of isotretinoin, including, importantly, teratogenicity. Acute vitamin A toxicity has been reported at initial doses of 25,000 IU/kg and chronic toxicity has been reported at doses of 4,000 IU/kg daily for a duration of 6-15 months.13 Signs of mild toxicity, such as mucocutaneous symptoms, are expected at the doses required for acne management and are similar to those of isotretinoin. Laboratory monitoring includes liver function tests, lipids, and pregnancy tests, in females of childbearing potential, as would be done with isotretinoin. The half-life of vitamin A is much longer than that of isotretinoin (12 days versus 24-29 hours, respectively), and female patients of childbearing age should be advised to wait at LEAST 3 months following treatment cessation before conceiving.14 Vitamin A is affordable and readily accessible over the counter in unit doses of 5,000 to 25,000 IU per capsule for about one tenth of the cost of isotretinoin.15 At doses of 50,000-300,000 IU daily, vitamin A may provide a substitute for acne management when isotretinoin is unavailable. Recommending an over-the-counter vitamin to which patients could have unlimited access without supervision by a medical provider should be done with very careful attention to patient selection and education.
DISCLOSURES
The authors declare the following potential conflicts. Dr. Steven
Feldman has received research, speaking, and/or consulting
support from a variety of companies including Galderma, GSK/
Stiefel, Almirall, Leo Pharma, Baxter, Boeringer Ingelheim, Mylan,
Celgene, Pfizer, Valeant, Taro, Abbvie, Cosmederm, Anacor,
Astellas, Janssen, Lilly, Merck, Merz, Novartis, Regeneron,
Sanofi, Novan, Parion, Qurient, National Biological Corporation,
Caremark, Advance Medical, Sun Pharma, Suncare Research,
Informa, UpToDate and National Psoriasis Foundation. He is
founder and majority owner of www.DrScore.com and founder
and part owner of Causa Research, a company dedicated to
enhancing patients’ adherence to treatment. Madison K. Cook
and Patrick O. Perche have no conflicts of interest to report.
REFERENCES
1. iPLEDGE REMS. Home. Available at: https://ipledgeprogram.com/#Main. Accessed December 17, 2021.
2. Research C for DE and. iPLEDGE Risk Evaluation and Mitigation Strategy (REMS). FDA. Available at: https://www.fda.gov/drugs/postmarket-drugsafety- information-patients-and-providers/ipledge-risk-evaluation-andmitigation- strategy-rems. Published online December 16, 2021. Accessed December 17, 2021.
3. Medscape. iPLEDGE Rollout Described as a Failure, Chaotic, and a Disaster. Available at: http://www.medscape.com/viewarticle/964925. Accessed December 17, 2021.
4. Straumfjord JV. Vitamin A. Its effect in acne. A study of one hundred patients. Northwest Med. 1943;42:219-225.
5. Lynch, FW, Cook CD. Acne vulgaris treated with vitamin A. Arch Derm Syphilol. 1947;55(3):355-357.
6. Savitt LE, Obermayer ME. Treatment of acne vulgaris and senile keratoses with vitamin A: results of a clinical experiment. J Invest Dermatol. 1950;14(4):283-289.
7. Davidson DM, Sobel AE. Aqueous vitamin A in acne vulgaris. J Invest Dermatol. 1949;12(4):221-228.
8. Mitchell, GH, Butterworth T. Results of treatment of acne vulgaris by intramuscular injections of vitamin A. AMA Arch Derm Syphilol. 1951;64(4):428-430. doi:10.1001/archderm.1951.01570100045006
9. Kalkoff KW, Bickhardt R. Zur optimalen dosierung einer peroralen Therapie der akne mit Vitamin-A-palmitat [Optimal dosage in peroral therapy of acne with vitamin A palmitate]. Hautarzt. 1976;27(4):160-165.
10. Anderson JAD, Stokoe IH Vitamin A in Acne Vulgaris. Br Med J. 1963;2(5352):294-296.
11. Kligman AM, Mills OH Jr, Leyden JJ, et al. Oral vitamin A in acne vulgaris. Preliminary report. Int J Dermatol. 1981;20(4):278-285.
12. Drake WP. High dose vitamin A cures severe acne vulgaris. Int J Health and Science. 2021;10(2):687-691.
13. Chea EP, Lopez MJ, Milstein H. Vitamin A. In: StatPearls. StatPearls Publishing; 2021. Available at: http://www.ncbi.nlm.nih.gov/books/ NBK482362/. Accessed December 17, 2021.
14. Hon SL. Vitamin A. In: Wexler P, ed. Encyclopedia of Toxicology (Third Edition). Academic Press; 2014:960-961.
15. NOW Foods. Vitamin A 25,000 Softgels. Available at: https://www.nowfoods. com/products/supplements/vitamin-25000-softgels. Published January 29, 2016. Accessed December 17, 2021.
2. Research C for DE and. iPLEDGE Risk Evaluation and Mitigation Strategy (REMS). FDA. Available at: https://www.fda.gov/drugs/postmarket-drugsafety- information-patients-and-providers/ipledge-risk-evaluation-andmitigation- strategy-rems. Published online December 16, 2021. Accessed December 17, 2021.
3. Medscape. iPLEDGE Rollout Described as a Failure, Chaotic, and a Disaster. Available at: http://www.medscape.com/viewarticle/964925. Accessed December 17, 2021.
4. Straumfjord JV. Vitamin A. Its effect in acne. A study of one hundred patients. Northwest Med. 1943;42:219-225.
5. Lynch, FW, Cook CD. Acne vulgaris treated with vitamin A. Arch Derm Syphilol. 1947;55(3):355-357.
6. Savitt LE, Obermayer ME. Treatment of acne vulgaris and senile keratoses with vitamin A: results of a clinical experiment. J Invest Dermatol. 1950;14(4):283-289.
7. Davidson DM, Sobel AE. Aqueous vitamin A in acne vulgaris. J Invest Dermatol. 1949;12(4):221-228.
8. Mitchell, GH, Butterworth T. Results of treatment of acne vulgaris by intramuscular injections of vitamin A. AMA Arch Derm Syphilol. 1951;64(4):428-430. doi:10.1001/archderm.1951.01570100045006
9. Kalkoff KW, Bickhardt R. Zur optimalen dosierung einer peroralen Therapie der akne mit Vitamin-A-palmitat [Optimal dosage in peroral therapy of acne with vitamin A palmitate]. Hautarzt. 1976;27(4):160-165.
10. Anderson JAD, Stokoe IH Vitamin A in Acne Vulgaris. Br Med J. 1963;2(5352):294-296.
11. Kligman AM, Mills OH Jr, Leyden JJ, et al. Oral vitamin A in acne vulgaris. Preliminary report. Int J Dermatol. 1981;20(4):278-285.
12. Drake WP. High dose vitamin A cures severe acne vulgaris. Int J Health and Science. 2021;10(2):687-691.
13. Chea EP, Lopez MJ, Milstein H. Vitamin A. In: StatPearls. StatPearls Publishing; 2021. Available at: http://www.ncbi.nlm.nih.gov/books/ NBK482362/. Accessed December 17, 2021.
14. Hon SL. Vitamin A. In: Wexler P, ed. Encyclopedia of Toxicology (Third Edition). Academic Press; 2014:960-961.
15. NOW Foods. Vitamin A 25,000 Softgels. Available at: https://www.nowfoods. com/products/supplements/vitamin-25000-softgels. Published January 29, 2016. Accessed December 17, 2021.
AUTHOR CORRESPONDENCE
Madison Cook BS Madison.Kathleen.Cook@live.mercer.edu
