Can I Take Vitamin B12 with Tretinoin?

The Short Answer

Vitamin B12 is a water-soluble vitamin and a cofactor for methionine synthase, which converts homocysteine to methionine, and for methylmalonyl-CoA mutase [8][2]. Topical tretinoin is a prescription retinoid applied to the skin. The Renova label says it has not been established whether tretinoin's clinical effects are mediated through retinoic acid receptors, other mechanisms such as irritation, or both [1]. One is a vitamin used inside cells throughout the body, the other a drug applied to the face.

What the Tretinoin Label Lists as Interactions

Renova 0.02% cream is one FDA-approved tretinoin product, and its label is the one described here; Retin-A and Retin-A Micro are separate products with their own labeling [1].

The Renova drug-interaction section covers other topical medications, medicated or abrasive soaps, shampoos and cleansers, cosmetics with a strong drying effect, products with high alcohol content, astringents, spices or lime, permanent wave solutions, electrolysis, hair depilatories and waxes, and any product that may irritate the skin, all of which may increase irritation with tretinoin [1]. The label also says Renova should not be administered to a patient taking drugs known to be photosensitizers, such as thiazides, tetracyclines, fluoroquinolones, phenothiazines and sulfonamides, because of possible augmented phototoxicity [1].

Vitamin B12 is not named in that section [1].

Tretinoin's Own Side Effects

In Renova cream trials of 339 patients, almost all reported one or more local reactions such as peeling, dry skin, burning, stinging, erythema and itching; 32% had irritation that was severe, led to temporary discontinuation, or led to use of a mild topical corticosteroid, and about 4% discontinued because of adverse reactions [1].

What B12 Does and How Much You Need

The NIH Office of Dietary Supplements sets the adult RDA at 2.4 mcg per day, with 2.6 mcg in pregnancy and 2.8 mcg while breastfeeding [6]. There is no Tolerable Upper Intake Level, because no safety concern from high intake has been identified [5]. Supplements commonly contain 500 to 1,000 mcg, far above the RDA, and the body absorbs only a small percentage of a large oral dose [5].

Deficiency is uncommon in US adults, at roughly 2% to 3%. Risk factors are malabsorption (gastric or small-bowel surgery, atrophic or autoimmune gastritis, pernicious anemia), low intake on vegan or strict vegetarian diets, certain medicines (metformin, proton pump inhibitors) and older age [7]. Symptoms can include fatigue, brain fog, depression, peripheral neuropathy and ataxia [7].

For a diagnosed deficiency, oral vitamin B12 at 1 to 2 mg daily is as effective as intramuscular injection for correcting anemia and neurologic symptoms in most patients; injections work faster and are considered in severe deficiency or severe neurologic symptoms [9]. A 2018 Cochrane review of 3 randomized trials with 153 participants found oral 1,000 mcg daily normalized serum B12 as well as injections, on low-quality evidence; no trial measured clinical symptoms [10].

Medicines That Lower Vitamin B12

Metformin and long-term acid-suppressing medicines are the ones associated with lower B12. In the Diabetes Prevention Program Outcomes Study, B12 at or below 203 pg/mL was found in 4.3% of people on metformin vs 2.3% on placebo at 5 years [3]. In a Kaiser Permanente case-control study, 2 or more years of proton pump inhibitor supply was associated with a B12 deficiency diagnosis (OR 1.65), and 2 or more years of H2 blocker supply with OR 1.25 [4]. A 2018 review concludes these drugs lower serum B12 by reducing absorption, although whether that raises the risk of true functional or clinical deficiency is not settled [2].

Putting It Together

The Renova interaction text gives no time gap between an oral B12 supplement and the cream [1]. The label says Renova is applied to the face once a day in the evening [1].