Can I Take Vitamin B12 with Vyvanse?

What the Vyvanse Label Actually Lists

The drug interaction section of the Vyvanse prescribing information names five groups: MAO inhibitors (contraindicated, including within 14 days of stopping one), serotonergic drugs, CYP2D6 inhibitors, urinary alkalinizing and acidifying agents, and tricyclic antidepressants [1]. Vitamin B12 is not among them.

The closest thing to a nutrient interaction on that list is the pH entry. Acidifying agents such as ascorbic acid lower amphetamine blood levels, and the label says to increase the dose based on clinical response; alkalinizing agents such as sodium bicarbonate raise amphetamine levels, and the label says co-administration should be avoided [1].

The label also states that lisdexamfetamine is an inactive prodrug converted to dextroamphetamine mainly in the blood by red blood cells, not by cytochrome P450 enzymes [1]. For timing, the label says to take Vyvanse in the morning and avoid afternoon doses because of insomnia [1].

Metformin Is the Real Reason B12 Comes Up

Metformin reduces B12 absorption, and the effect shows up in long-term data [7][2].

In the Diabetes Prevention Program Outcomes Study, participants received metformin 850 mg twice daily or placebo for 3.2 years; participants assigned to metformin then received open-label metformin [2]. B12 at or below 203 pg/mL was found in 4.3% of the metformin group versus 2.3% of the placebo group at 5 years (p=0.02), and 7.4% versus 5.4% at 13 years, a difference that was not statistically significant [2]. Combined low and borderline-low B12 at or below 298 pg/mL was more common with metformin at both 5 years (19.1% versus 9.5%) and 13 years (20.3% versus 15.6%) [2]. Each year of metformin use raised the odds of deficiency (OR 1.13, 95% CI 1.06-1.20), and neuropathy was more common in metformin users with low B12 [2].

A second trial, published in the BMJ, followed 390 adults with type 2 diabetes on insulin who were randomized to metformin 850 mg three times daily or placebo for 4.3 years. Mean B12 fell 19% with metformin compared with placebo (95% CI -24% to -14%), and the absolute risk of B12 below 150 pmol/L was 7.2 percentage points higher [8].

A 2018 review makes an important qualification: metformin, PPIs and H2 blockers clearly lower serum B12 by reducing absorption, but it is unclear whether that translates into more functional or clinical deficiency, and randomized trials using multiple-marker testing are still needed [7]. Metformin use for more than four months is one of the risk factors that may justify screening, although screening average-risk adults is not recommended [9].

Acid-Suppressing Drugs

A case-control study using records from a large Northern California health system compared 25,956 adults with a new B12 deficiency diagnosis to 184,199 people without one. Two or more years of PPI supply was associated with B12 deficiency (OR 1.65, 95% CI 1.58-1.73), and two or more years of H2 blocker supply with an OR of 1.25 (95% CI 1.17-1.34) [3]. This is an association drawn from pharmacy and laboratory records, not a randomized trial [3].

The mechanism is food-bound B12: less stomach acid means less release of B12 from dietary protein. The synthetic B12 in supplements and fortified food is not protein-bound and does not need that acid [4]. More than 12 months of PPI or H2 blocker use is listed as a screening risk factor [9].

Who Is Actually Low on B12

About 2% to 3% of US adults are deficient [6]. Risk factors include malabsorption from gastric or small-bowel surgery or autoimmune gastritis, low intake from vegan or strict vegetarian diets, metformin and proton pump inhibitors, and older age [6]. Deficiency causes megaloblastic anemia and neurologic, psychiatric and thromboembolic problems [10].

The RDA is 2.4 mcg a day for adults and teens 14 and older, 2.6 mcg in pregnancy and 2.8 mcg while breastfeeding [5]. The NIH Office of Dietary Supplements advises adults over 50 to get most of their B12 from fortified foods or supplements, because many older adults make too little stomach acid to release the B12 bound to protein in food [5]. People who have had bariatric surgery should take 1 mg of oral B12 daily indefinitely [9].

Testing: What a Low or Borderline Result Means

A serum B12 below 180 pg/mL is diagnostic for deficiency, and 180 to 350 pg/mL is borderline and should be followed by a methylmalonic acid measurement, which confirms deficiency if elevated [6]. No single cutoff is universal, and most laboratories call a level below 200 or 250 pg/mL subnormal [4][10].

An MMA above 0.271 micromol/L suggests deficiency, though MMA also rises with kidney impairment and tends to be higher in older adults; the Office of Dietary Supplements notes that experts suggest checking MMA when serum B12 is 150 to 399 pg/mL [4]. Measuring at least 2 of 4 markers (serum total B12, holotranscobalamin, homocysteine, MMA) raises sensitivity and specificity for diagnosing deficiency [7].

A persistently high serum B12, above 1,000 pg/mL on two measurements, has been associated with solid tumors, hematologic malignancy and cardiovascular death. That is an association that should prompt evaluation, not evidence that B12 supplements cause these conditions [6].

B12 Dosing and What the Numbers Mean

There is no Tolerable Upper Intake Level for vitamin B12, because no safety concern has been identified even at high doses [4]. Supplements commonly contain 500 to 1,000 mcg, far above the 2.4 mcg RDA, and the body absorbs only a small percentage of a large oral dose [4].

For treating a diagnosed deficiency, oral B12 at 1 to 2 mg daily is as effective as intramuscular injection for correcting anemia and neurologic symptoms in most patients; injections are 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 (low-quality evidence), and one trial using 2,000 mcg daily produced a higher mean serum B12 than injection (difference 680 pg/mL, 95% CI 392.7 to 967.3). No trial measured symptoms [11]. Oral B12 is available through HealthRX.com as vitamin B12.

Does B12 Change ADHD Symptoms or Vyvanse's Effect?

Nothing in the Vyvanse label describes B12 as changing how lisdexamfetamine behaves in the body [1]. B12 deficiency on its own causes neurologic and psychiatric problems [10], so a confirmed deficiency is worth correcting for its own sake.