QWhat’s the deal with adding on omega-3 supplementation in your isotretinoin patients?

Medically reviewed on 1.15.25 by Mark Lebwohl, MD

Lately there’s been more talk about adding on daily omega-3 pills for your isotretinoin patients – and for good reason. Two actually. Taking one 1000mg omega-3 supplement a day can reduce skin/mucous membrane dryness and potentially lower triglyceride levels in these patients.

As we know, one of the most commonly experienced side effects for your isotretinoin patients is dryness: their skin, their mucous membranes and sometimes even their eyes. We’ve all had those patients with super chapped lips and nosebleeds, especially during the winter months.

In one randomized double-blind clinical trial, a total of 118 patients with moderate or severe acne were randomly divided into two (case and control) groups. The control group was treated with isotretinoin 0.5 mg/kg, and the case group was treated with the same dose of isotretinoin combined with oral omega-3 (1 g/day). The treatment lasted for 16 weeks and mucocutaneous side effects of isotretinoin were recorded and compared between the two groups at weeks 4, 8, 12, and 16. Cheilitis, xerosis, nose dryness and dryness of eyes were less frequent in the group that received isotretinoin combined with oral omega-3 compared to the group that received isotretinoin alone. At week 16 the rate of dry lips was 25.6% in the isotretinoin-only group compared to 14% in the combination group. For dry nose at week 16, the rates were 11.1% in the isotretinoin group compared to 0% in the combination group, and for dry skin it was 11.1% in the isotretinoin group at week 16 compared to 2% of patients in the combination group. It’s theorized based off animal studies that fish oil supplementation reduces transepidermal water loss, increases skin hydration, and consequently decreases skin dryness.

And we know that some of our patients on isotretinoin have an increase in their triglycerides while on therapy. In fact, as many as 44% of patients with baseline triglyceride levels within the reference range who are treated with isotretinoin develop hypertriglyceridemia. And very high levels can have significant consequences such as acute pancreatitis (not typically seen until triglycerides reach >1000 mg/dL, however).

In a small longitudinal survey, 39 patients with acne were treated with isotretinoin for a median of 5.87 months, and triglyceride levels during therapy were reviewed retrospectively.  Comparison of the mean percentage increase in triglyceride levels in patients with and without omega-3 supplement use and with preexisting elevated triglyceride levels demonstrated that patients not using the supplements had a greater increase in triglyceride levels during treatment from baseline compared with patients using the supplements: 49 to 13.91% respectively.

So, it’s probably worth bringing up omega-3 supplementation from the start with your isotretinoin patients to help mitigate some of the medication’s potential side effects.

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References:

1. Mirnezami M, Rahimi H. Is Oral Omega-3 Effective in Reducing Mucocutaneous Side Effects of Isotretinoin in Patients with Acne Vulgaris? Dermatol Res Pract. 2018 May doi: 10.1155/2018/6974045
2. Zane  LT, Leyden  WA, Marqueling  AL, Manos  MM.  A population-based analysis of laboratory abnormalities during isotretinoin therapy for acne vulgaris.  Arch Dermatol. 2006;142(8):1016-1022.
3. Krishna S, Kim J. Influence of ω-3 Fatty Acids on Triglyceride Levels in Patients Using Isotretinoin. JAMA Dermatol. 2015 Jan doi: 10.1001/jamadermatol.2014.2402
4. Munoz M, Babu B. Acute pancreatitis secondary to hypertriglyceridemia. Cleveland Clinic Journal of Medicine. December 2020, 87 (12) 742-750; DOI: https://doi.org/10.3949/ccjm.87a.19156
5. Barcelos R. C. S., de Mello-Sampayo C., Antoniazzi C. T. D., et al. Oral supplementation with fish oil reduces dryness and pruritus in the acetone-induced dry skin rat model. Journal of Dermatological Science. 2015;79(3):298–304. doi: 10.1016/j.jdermsci.2015.06.015.