Can I Take Omega-3 (EPA/DHA) with Tretinoin?

The Short Answer

The Renova 0.02% cream label does not point to an omega-3 interaction. Its drug-interaction section lists other topical products that irritate the skin and drugs known to be photosensitizers: thiazides, tetracyclines, fluoroquinolones, phenothiazines and sulfonamides [1]. Fish oil is not on that list.

Tretinoin is applied to the skin, and the effects the label describes are local: irritation, peeling and dryness, and, for Renova, mitigation of fine facial wrinkles [1]. The omega-3 concerns that appear in labels and trials relate to swallowing grams of EPA and DHA.

Topical Tretinoin Is Not Oral Isotretinoin

Topical tretinoin, including Renova cream, is a prescription retinoid [1]. It is a different drug product from oral isotretinoin, the capsule marketed under a restricted-distribution REMS called iPLEDGE because it is highly teratogenic [5]. Topical tretinoin labels carry no boxed warning.

Some tretinoin does get through the skin. The Renova label reports that radiolabeled 0.05% cream applied to healthy men was absorbed at less than 2%, with less bioavailability after 28 days of daily application, and that no percutaneous absorption study was done with the 0.02% cream [1]. Across topical formulations the label gives a range of 1% to 31% of the applied dose, depending on whether the skin was healthy or inflamed [1].

What the Renova Label Does Warn About

The label's concerns are local and sun-related. In the Renova studies of 339 patients, 32% had skin irritation that was severe, led to temporary discontinuation, or needed a mild topical corticosteroid, and about 4% discontinued because of adverse reactions [1]. Peeling, dry skin, burning, stinging and redness are the local reactions the label lists [1].

On sun, the Renova label recommends sunscreen of at least SPF 15 and protective clothing, says exposure to sunlight and sunlamps should be avoided or minimized, and says people with sunburn should not apply the cream until fully recovered [1].

The label says the photosensitizing drugs it names carry a possibility of augmented phototoxicity [1]. Omega-3 is not among the drugs named in that section.

What the Omega-3 Labels Actually Say

Prescription omega-3 comes in two forms: Vascepa, which is pure EPA ethyl ester, and omega-3-acid ethyl esters such as Lovaza, which supply about 465 mg EPA and 375 mg DHA per 1 gram capsule. Both are dosed at 4 grams a day [2].

Bleeding. The omega-3-acid ethyl esters label says omega-3-acids may prolong bleeding time. In the trials it describes, the prolongation did not exceed normal limits or produce clinically significant bleeding episodes. It says patients taking an anticoagulant or antiplatelet drug should be monitored periodically [2].

Atrial fibrillation. The same label describes a possible association with more frequent recurrence of symptomatic atrial fibrillation or flutter in people who already have paroxysmal or persistent atrial fibrillation, particularly in the first 2 to 3 months of therapy. In a trial of 663 such patients given 8 grams a day for 7 days and 4 grams a day thereafter, the combined hazard ratio was 1.25 (95% CI 1.00 to 1.40) [2]. A meta-analysis of seven cardiovascular outcome trials (81,210 patients) found more atrial fibrillation with marine omega-3 supplements overall (HR 1.25), and a higher hazard in trials testing more than 1 gram a day (HR 1.49, 95% CI 1.04 to 2.15) than in trials testing 1 gram a day or less (HR 1.12, 95% CI 1.03 to 1.22) [6].

Over-the-counter fish oil is a different category: not FDA-approved to treat or prevent heart disease, with side effects usually described as mild, including unpleasant taste, bad breath, bad-smelling sweat, headache and gastrointestinal symptoms [3]. Over-the-counter capsules vary widely in EPA plus DHA content, so the EPA and DHA amounts on the label matter more than the total fish oil milligrams.

Does Omega-3 Help With Acne?

The acne evidence is thin. In a 12-week study, 13 people with inflammatory acne took 3 grams of fish oil containing 930 mg of EPA alongside their existing acne treatments. Acne grading and inflammatory lesion counts did not change significantly at week 12, though 8 people improved, 4 worsened and 1 was unchanged [4]. A report of five cases suggests that EPA plus antioxidant nutrients may have improved inflammatory acne and calls for controlled trials [7].

The mechanistic case is plausible rather than proven. EPA and DHA partly inhibit several parts of the inflammatory response, including leukocyte chemotaxis, adhesion molecule expression, eicosanoid production from arachidonic acid and pro-inflammatory cytokines [8].

Practical Points

• The Renova label directs application once a day in the evening, using only enough to lightly cover the affected area, and says larger amounts have not been shown to work faster and may cause marked redness, peeling or discomfort [1].
• Read the EPA and DHA amounts on a supplement, not just the total fish oil figure [2].