THE ROLE OF ORAL SUPPLEMENTS IN MITIGATING COMMON ISOTRETINOIN SIDE EFFECTS: A COMPREHENSIVE REVIEW

Keywords: Isotretinoin, Oral Supplements, Side Effects, Acne Vulgaris, Vitamin E, Vitamin D, Omega-3 Fatty Acids, Folic Acid, Vitamin B12, Biotin

Abstract

Acne vulgaris, a chronic inflammatory dermatosis, affects approximately 9% of the global population. This condition arises from the multifactorial interplay of genetic predisposition, hormonal imbalances, excessive sebum production, hyperkeratinization of follicular infundibula, and proliferation of Cutibacterium acnes, culminating in inflammation and comedone formation. While various therapeutic modalities exist, including topical retinoids, antibiotics, and hormonal agents, oral isotretinoin remains one of the most efficacious treatments for acne vulgaris. Notwithstanding its superior effectiveness, the drug is associated with a spectrum of adverse effects that warrant mitigation strategies.

The primary aim of this narrative review is to evaluate the efficacy and rationale for employing oral supplements to alleviate the most prevalent isotretinoin-related side effects. By synthesizing extant research, this study appraises the benefits and limitations of select supplement interventions. The central clinical question addressed is: What is the role of oral supplements in mitigating common adverse effects among patients receiving isotretinoin therapy? Findings are expected to furnish clinicians and patients with evidence-based guidance on adjunctive supplement use to enhance treatment tolerability.

References

Aksaç, S. E., Bilgili, S. G., Yavuz, G. Ö., Yavuz, İ. H., Aksaç, M., & Karadağ, A. S. (2021). Evaluation of biophysical skin parameters and hair changes in patients with acne vulgaris treated with isotretinoin, and the effect of biotin use on these parameters. International Journal of Dermatology, 60(8), 980. https://doi.org/10.1111/ijd.15485

Aktürk, A. Ş., Güzel, S., Bulca, S., Demirsoy, E. O., Bayramgürler, D., Bilen, N., & Kıran, R. (2013). Effects of isotretinoin on serum vitamin E levels in patients with acne. International Journal of Dermatology, 52(3), 363. https://doi.org/10.1111/j.1365-4632.2012.05676.x

Al‐Dhubaibi, M. S., Alhetheli, G., Alsenaid, A., & Elneam, A. A. (2021). Serum Vitamin D Levels at Different Stages of Acne Vulgaris Patients Treated with Isotretinoin: A Prospective Study. The Open Dermatology Journal, 15(1), 11. https://doi.org/10.2174/1874372202115010011

Almohanna, H. M., Ahmed, A., Tsatalis, J. P., & Tosti, A. (2018). The Role of Vitamins and Minerals in Hair Loss: A Review [Review of The Role of Vitamins and Minerals in Hair Loss: A Review]. Dermatology and Therapy, 9(1), 51. Adis, Springer Healthcare. https://doi.org/10.1007/s13555-018-0278-6

Alting, K., & Hunsel, F. van. (2018). Curling of Hair in Two Female Patients Taking Alitretinoin. Drug Safety - Case Reports, 5(1). https://doi.org/10.1007/s40800-018-0092-1

Brelsford, M., & Beute, T. C. (2008). Preventing and managing the side effects of isotretinoin. Seminars in cutaneous medicine and surgery, 27(3), 197–206. https://doi.org/10.1016/j.sder.2008.07.002

Carmel, R. (2008). How I treat cobalamin (vitamin B12) deficiency. Blood, 112(6), 2214. https://doi.org/10.1182/blood-2008-03-040253

Cassano, N., Benedittis, M. D., Petruzzi, M., Carbonara, M., Agnusdei, C. P., Alessandrini, G., Bellini, M., Callea, A., Carriera, M. L., Coviello, C., Gasparro, E. C., Dattola, S., Ferrari, A. P., Gabellone, M., Gravante, M., Ligori, P., Liguori, G., Mancino, A. T., Manco, S., … Vena, G. (2003). Topical Vitamin E Acetate for the Treatment of Cheilitis: A Multicentre Experience. European Journal of Inflammation, 1(3), 125. https://doi.org/10.1177/1721727x0300100306

Chu, S., Michelle, L., Ekelem, C., Sung, C. T., Rojek, N. W., & Mesinkovska, N. A. (2020). Oral isotretinoin for the treatment of dermatologic conditions other than acne: a systematic review and discussion of future directions [Review of Oral isotretinoin for the treatment of dermatologic conditions other than acne: a systematic review and discussion of future directions]. Archives of Dermatological Research, 313(6), 391. Springer Science+Business Media. https://doi.org/10.1007/s00403-020-02152-4

Drozd, M., Marzęda, M., Blicharz, A., & Piecewicz‐Szczęsna, H. (2020). Is the effect worth the risk? - The most common complaints during oral isotretinoin anti-acne therapy and controversies around its adverse effects. Journal of Education Health and Sport, 10(9), 549. https://doi.org/10.12775/jehs.2020.10.09.066

Elangovan, R., & Baruteau, J. (2022). Inherited and acquired vitamin B12 deficiencies: Which administration route to choose for supplementation? [Review of Inherited and acquired vitamin B12 deficiencies: Which administration route to choose for supplementation?]. Frontiers in Pharmacology, 13. Frontiers Media. https://doi.org/10.3389/fphar.2022.972468

Elgharably, N., Abadie, M. A., Abadie, M. A., Ball, P., & Morrissey, H. (2022). Vitamin B group levels and supplementations in dermatology: Review of the literature. Dermatology Reports. https://doi.org/10.4081/dr.2022.9511

Feily, A. (2019). Successful Treatment of Isotretinoin Induced Musculoskeletal Pain by Vitamin B12 and Folic Acid. Open Access Macedonian Journal of Medical Sciences, 7(21), 3726. https://doi.org/10.3889/oamjms.2019.799

Ghani, M. U., Bakhtawar, A., & Tariq, I. (2025). Comparison of Low-Dose Isotretinoin and Conventional Dosing Regime for the Management of Acne Vulgaris. Biological and Clinical Sciences Research Journal, 6(7), 19. https://doi.org/10.54112/bcsrj.v6i7.1863

Ghiasi, M., Mortazavi, H., & Jafari, M. (2018). Efficacy of Folic Acid and Vitamin B12 Replacement Therapies in the Reduction of Adverse Effects of Isotretinoin: A Randomized Controlled Trial. Skinmed, 16(4), 239–245.

Goforousha, F., Azimi, H., & Goldust, M. (2013). Efficacy of Vitamin E to Prevent Dermal Complications of Isotretinoin. Pakistan Journal of Biological Sciences, 16(11), 548. https://doi.org/10.3923/pjbs.2013.548.550

Gökalp, H., Bulur, İ., & Gürer, M. (2014). Decreased Vitamin B12 and Folic Acid Concentrations in Acne Patients After Isotretinoin Therapy: A Controlled Study. Indian Journal of Dermatology, 59(6), 630. https://doi.org/10.4103/0019-5154.143533

Gurram, A., Cavanagh, M., & Ross, L. (2025). Isotretinoin and Hair Loss: A Clinical Perspective and Literature Review. SKIN The Journal of Cutaneous Medicine, 9(5), 2584. https://doi.org/10.25251/n5hj2f33

Hamdy, D. A., Ali, M. A., Mahmoud, A. Allah, & Mohammed, G. (2025). Serum homocysteine level in Acne patients before and after oral Isotretinoin. Aswan University Medical Journal/Aswan University Medical Journal , 0. https://doi.org/10.21608/aumj.2025.365183.1203

Hussein, R., Bindayel, S., & Abahussein, O. (2023). Prospective study of the effects of isotretinoin and vitamin D levels on severe acne vulgaris. TURKISH JOURNAL OF MEDICAL SCIENCES, 53(6), 1732. https://doi.org/10.55730/1300-0144.5742

Ibrahim, M., Khan, S., Pathak, S., Mazhar, M., & Singh, H. (2023). Vitamin B-Complex and its Relationship with the Health of Vegetarian People. Natural Resources for Human Health, 3(3), 342. https://doi.org/10.53365/nrfhh/169824

Johansson, S., & Melhus, H. (2001). Vitamin A Antagonizes Calcium Response to Vitamin D in Man. Journal of Bone and Mineral Research, 16(10), 1899. https://doi.org/10.1359/jbmr.2001.16.10.1899

Kamal, M., & Polat, M. (2015). Effect of different doses of isotretinoin treatment on the levels of serum homocysteine, vitamin B 12 and folic acid in patients with acne vulgaris: A prospective controlled study. JPMA. The Journal of the Pakistan Medical Association, 65(9), 950–953.

Kangari, H., Eftekhari, M. H., Sardari, S., Hashemi, H., Salamzadeh, J., Ghassemi‐Broumand, M., & Khabazkhoob, M. (2013). Short-term Consumption of Oral Omega-3 and Dry Eye Syndrome. Ophthalmology, 120(11), 2191. https://doi.org/10.1016/j.ophtha.2013.04.006

Kapała, J., Lewandowska, J., Placek, W., & Owczarczyk-Saczonek, A. (2022). Adverse Events in Isotretinoin Therapy: A Single-Arm Meta-Analysis. International Journal of Environmental Research and Public Health, 19(11), 6463. https://doi.org/10.3390/ijerph19116463

Kim, H. J., Lee, S. M., Lee, J. S., Lee, S. Y., Chung, E. H., Cho, M. K., Lee, S. H., & Kim, J. E. (2019). Homocysteine, folic acid, and vitamin B12 levels in patients on isotretinoin therapy for acne vulgaris: A meta‐analysis [Review of Homocysteine, folic acid, and vitamin B12 levels in patients on isotretinoin therapy for acne vulgaris: A meta‐analysis]. Journal of Cosmetic Dermatology, 19(3), 736. Wiley. https://doi.org/10.1111/jocd.13059

Kuş, S., Gün, D., Demirçay, Z., & Sur, H. (2004). Vitamin E does not reduce the side‐effects of isotretinoin in the treatment of acne vulgaris. International Journal of Dermatology, 44(3), 248. https://doi.org/10.1111/j.1365-4632.2004.02072.x

Mirnezami, M., & Rahimi, H. (2018). Is Oral Omega-3 Effective in Reducing Mucocutaneous Side Effects of Isotretinoin in Patients with Acne Vulgaris? Dermatology Research and Practice, 2018, 1. https://doi.org/10.1155/2018/6974045

Miziołek, B., Bergler-Czop, B., Stańkowska, A., & Brzezińska-Wcisło, L. (2019). The safety of isotretinoin treatment in patients with bone fractures. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 36(1), 18-24. https://doi.org/10.5114/ada.2019.82822

Most Common Isotretinoin Therapy Side Effects on Egyptian Acne Females in Dakahlia Governorate. (2024). The Egyptian Journal of Hospital Medicine, 96(1), 2860. https://doi.org/10.21608/ejhm.2024.374386

Qudsia, F., & Riaz, S. (2021). Therapeutic Effect of Folate and Cobalamin in Diabetics. In IntechOpen eBooks. IntechOpen. https://doi.org/10.5772/intechopen.96447

Rajput, I., & Anjankar, V. (2024). Side Effects of Treating Acne Vulgaris With Isotretinoin: A Systematic Review [Review of Side Effects of Treating Acne Vulgaris With Isotretinoin: A Systematic Review]. Cureus. Cureus, Inc. https://doi.org/10.7759/cureus.55946

Reyes-Hadsall, S., Ju, T., & Keri, J. (2023). Use of Oral Supplements and Topical Adjuvants for Isotretinoin-Associated Side Effects: A Narrative Review [Review of Use of Oral Supplements and Topical Adjuvants for Isotretinoin-Associated Side Effects: A Narrative Review]. Skin Appendage Disorders, 10(1), 1. https://doi.org/10.1159/000533963

Rohde, C. M., Manatt, M., Clagett‐Dame, M., & DeLuca, H. F. (1999). Vitamin A Antagonizes the Action of Vitamin D in Rats. Journal of Nutrition, 129(12), 2246. https://doi.org/10.1093/jn/129.12.2246

Sakaniya, L. R., Dvoriankova, E. V., Niewozinska, Z. A., Badlueva, K. V., Andrienko, E. S., Beley, T. V., & Korsunskaya, I. M. (2025). Isotretinoin-LIDOSE: 15 years of experience in acne therapy. A review. Consilium Medicum, 27(6), 328–332. https://doi.org/10.26442/20751753.2025.6.203323

Saraç, G., Koca, T. T., Şener, S., & Hakverdi, G. (2018). Effect of 6-Month Isotretinoin Treatment on 25-Hydroxyvitamin D Levels in Patients With Acne Vulgaris. Journal of Clinical Medicine of Kazakhstan, 1(47), 25. https://doi.org/10.23950/1812-2892-jcmk-00537

Sitohang, I. B. S. (2021). ISOTRETINOIN FOR TREATING ACNE VULGARIS. International Journal of Applied Pharmaceutics, 20. https://doi.org/10.22159/ijap.2021v13i2.40045

Soutou, B., Sleiman, J., Tomb, R., Kechichian, E., & Hélou, J. (2022). Prevalence of adverse events varies with the different oral isotretinoin brands in acne treatment: a retrospective observational study. . Research Square (Research Square). https://doi.org/10.21203/rs.3.rs-1897757/v1

Strauss, J. S., Gottlieb, A. B., Jones, T. M., Koo, J., James, W. D., Lucky, A. W., Pappas, A. A., McLane, J. A., & Leach, E. E. (2000). Concomitant administration of vitamin E does not change the side effects of isotretinoin as used in acne vulgaris: A randomized trial. Journal of the American Academy of Dermatology, 43(5), 777. https://doi.org/10.1067/mjd.2000.110391

Subject Index Vol. 108, 2002. (2002). Acta Haematologica, 108(4), 248. https://doi.org/10.1159/000067760

Tylczyńska, K., Tylczyńska, N., Skiba, J., Skiba, Z., Kowalik, K., Michalska, M., Zielińska, A., Szypulski, S., Iwaniuk, S., & Maciejewski, I. (2024). Outcomes and adverse effects of isotretinoin in acne treatment: a systematic review. Quality in Sport, 33, 56178. https://doi.org/10.12775/qs.2024.33.56178

Vigarios, É., Comont, T., Piroth, M., Cougoul, P., & Sibaud, V. (2019). Severe aphthous stomatitis secondary to vitamin B12 deficiency with isotretinoin therapy. JAAD Case Reports, 5(6), 563. https://doi.org/10.1016/j.jdcr.2019.05.005

Weise, C., Ernst, D., Tol, E. A. F. van, & Worm, M. (2013). Dietary polyunsaturated fatty acids and non‐digestible oligosaccharides reduce dermatitis in mice. Pediatric Allergy and Immunology, 24(4), 361. https://doi.org/10.1111/pai.12073

Xu, C. (2024). Prevention of Isotretinoin-Induced Oxidative Stress and Hepatotoxicity. MATEC Web of Conferences, 404, 4005. https://doi.org/10.1051/matecconf/202440404005

Yelich, A., Jenkins, H., Holt, S., & Miller, R. (2024). Biotin for Hair Loss: Teasing Out the Evidence. The Journal of clinical and aesthetic dermatology, 17(8), 56–61.

Zainab, Z., Malik, N. A., Obaid, S., Malik, S., Aftab, K., Mumtaz, M., Pervez, A., & Syed, Z. (2021). Effectiveness Of Oral Omega 3 In Reducing Mucocutaneous Side Effects Of Oral Isotretinoin In Patients With Acne Vulgaris. Journal of Ayub Medical College, Abbottabad : JAMC, 33(1), 60–63.

Tlish, M. M., & Shavilova, M. E. (2024). Recurrence of acne after treatment with systemic isotretinoin: causes and methods of prevention. Vestnik Dermatologii I Venerologii, 100(6), 92–100. https://doi.org/10.25208/vdv16809

Published
2025-12-24
Citations
How to Cite
Maria Gierasimiuk, Adam Januszkiewicz, Wiktoria Januszkiewicz, Wojciech Machulski, Martyna Ciarkowska, Jan Makulski, Kamil Franczyk, Karolina Swierk, Damian Podkościelny, & Michal Gorski. (2025). THE ROLE OF ORAL SUPPLEMENTS IN MITIGATING COMMON ISOTRETINOIN SIDE EFFECTS: A COMPREHENSIVE REVIEW. International Journal of Innovative Technologies in Social Science, (4(48). https://doi.org/10.31435/ijitss.4(48).2025.4508

Most read articles by the same author(s)