ly to be relied upon as a practical, sole source of B12.
Some anecdotal evidence suggests that vegans relying only on multivitamins have become deficient, with severe consequences.
Intrinsic factor – Intrinsic factor is a B12-transport protein that shuttles B12 from the digestive tract into intestinal cells. Intrinsic factor is efficient at absorbing a high percentage of a small dose of B12, but it becomes saturated after a meal containing an above-average amount of B12, and about 4 to 6 hours are required before it can efficiently absorb another dose (Institute of Medicine, 1998).
Passive diffusion – Passive diffusion is when B12 simply floats into the circulation unaided by a B12-transport protein. Only about 1% of any dose of B12 can be absorbed by passive diffusion. If being solely relied upon due to an absence of intrinsic factor, much higher doses of B12 are required than can be found in animal foods, fortified foods, or multivitamins.
Our B12 recommendations are made with the assumption that people have functioning intrinsic factor because most do.
This article examines the concerns regarding multivitamins in more detail.
Ideally, there’d be clinical trials in which vegans are randomized to different B12 regimens, including multivitamins, to see which regimens support a healthy B12 status. Unfortunately, we don’t have any such research. There’s also little observational research on vegans to draw on.
There’s been one clinical trial in nonvegetarians that suggested, on average, little benefit for B12 status from multivitamins. However, the multivitamins did improve B12 status in people who started the trial with poor B12 status.
Wolters et al. (2005) gave a daily multivitamin containing 9 µg of cyanocobalamin to 105 women aged ≥60 years for 6 months. The multivitamins also contained 150 mg of vitamin C. After 6 months, methylmalonic acid (MMA) levels, the most specific marker for B12 activity of a food or supplement, went from 164 nmol/l to 169 nmol/l which is essentially no change and by itself would indicate no benefit of the multivitamin.
But this study doesn’t allow us to conclude that multivitamins are ineffective. First, an average baseline MMA of 164 nmol/l is well within the healthy range (typically considered to be < 270 nmol/l) such that adding additional B12 shouldn’t make much difference in MMA levels. Second, the participants were instructed to take the multivitamin at breakfast which would dilute the effect of the B12 since it would be competing for absorption by intrinsic factor with the dietary B12 provided by animal foods. Most importantly, among the women who started out with a high baseline MMA, which indicates poorer B12 status, there was a substantial reduction in MMA over the course of the trial indicating a benefit from the multivitamin.
Because nonvegetarians receive multiple doses of B12 throughout the day from animal products, they have many opportunities to absorb a substantial amount of B12. In contrast, someone who only receives one dose of B12 per day, such as in a multivitamin, will have a more limited capacity for absorption via intrinsic factor.
In animal foods, B12 is attached to proteins which can protect it from damage from other molecules in the food, whereas in fortified foods and supplements, B12 is provided in a crystalline form that doesn’t offer such protection.
In Wolters et al.’s clinical trial of nonvegetarians, the multivitamin contained 9 µg of B12 which is almost twice the amount of VeganHealth’s minimum recommendation of 5 µg; but this shouldn’t be enough to make a practical difference. Using Walsh’s formula for cyanocobalamin absorption for adults, as described in Vitamin B12: Rationale for Recommendations, 1.26 µg of B12 would be absorbed from a 5 µg dose compared to 1.45 µg absorbed from a 9 µg dose. This difference is small enough to suggest that a 5 µg dose would also be effective.
An observational study using data from the United States National Health and Nutrition Examination Survey found a benefit from multivitamin use for B12 status among adults age ≥51 years (Frankenfeld, 2020). While somewhat reassuring, observational studies in nonvegetarians are limited for understanding the usefulness of multivitamins for vegans.
A study by Pawlak et al. (2018) could be interpreted to suggest multivitamins aren’t beneficial, but upon closer review, it doesn’t provide much evidence.
Pawlak et al. studied B12 supplement use among lactating vegans, vegetarians, and nonvegetarians. They found that multivitamin use was negatively correlated with breast milk B12 concentrations. This could be simply due to the fact that B12-only supplements typically contain much greater amounts of B12 than do multivitamins and in this study, the percentage of participants with high B12 levels (>1,122 pmol/L) in breast milk was significantly greater among those using B12-only supplements (26.5% vs. 5.5%). There’s no need to maximize B12 levels in breast milk, there simply needs to be enough to keep the infant healthy, and a negative correlation with multivitamin use doesn’t mean multivitamins were inadequate.
Of the 26 vegans, 5 had breast milk B12 levels of < 310 pmol/l, which was considered low. In private correspondence, Dr. Pawlak told me there was no supplementation pattern among the women with low B12 levels in breast milk; they weren’t relying solely on multivitamins.
Poor B12 absorption can be due to digestive problems, pernicious anemia, or specific medications; people diagnosed with B12 malabsorption shouldn’t rely on multivitamins. Vegans who haven’t had a reliable source of B12 for long enough to become deficient shouldn’t rely on multivitamins when initiating a B12 regimen.
Pernicious anemia is a disease in which someone doesn’t produce intrinsic factor, the protein responsible for intestinal absorption of B12. Pernicious anemia can be caused by a genetic autoimmune disorder or a gastrectomy. Most cases of the autoimmune version are diagnosed by age 2 (Medscape, 2019). In adults, Medscape reports that pernicious anemia is most prevalent among individuals of either Celtic or Scandinavian origin, and in those groups, 10-20 cases occur per 100,000 people per year. In adults, pernicious anemia normally presents in people 40 to 70 years old (Medscape, 2019).
The Mayo Clinic lists the following medications as reducing B12 absorption: Aminosalicylic acid (Paser), Colchicine (Colcrys, Mitigare, Gloperba), Metformin (Glumetza, Fortamet, others), and proton pump inhibitors.
The recommendations on VeganHealth are not appropriate for people with pernicious anemia, significant digestive disorders that could prevent B12 absorption, or people taking medications that can reduce B12 absorption. Instead, under the guidance of a physician, such people require large doses of oral B12 or B12 injections. People with B12 malabsorption can benefit from large doses of oral B12 because B12 can be absorbed through passive diffusion at a rate of ~1% of a dose. Relying solely on passive diffusion requires an amount of B12 magnitudes greater than food-based recommendations. If someone suspects they might not absorb B12 normally, they should speak to their physician who can test their B12 levels.
It’s generally thought that B12 deficiency can prevent intestinal cells from regenerating, leading to poor absorption. This raises a question for vegans who’ve gone some time without a source of B12: Could they be suffering from mild B12 deficiency such that the small amounts of B12 in multivitamins might not be enough to correct their deficiency?
I wasn’t able to find any reliable evidence or details regarding whether a mild B12 deficiency can exacerbate B12 malabsorption, but the possibility raises concerns. We’ve known about this possibility for decades and it’s why VeganHealth recommends that vegans who haven’t had a regular source of B12 take 2,000 µg once a day for 2 weeks to replenish their stores. Our rationale is that this B12 regimen is highly effective at replenishing stores (Kuzminski, 1998; Del Bo, 2019) and will allow the digestive system time to heal before transitioning to our general recommendations.
VeganHealth currently bases the lower range of our recommendations on the U.S. RDA and the upper range on the European Food Safety Authority’s recommendations. The U.S. RDA is intended to cover the needs of 97% to 98% of the population. Although some health professionals believe the RDA for B12 is too low for optimal health, there isn’t clear evidence for increasing it.
Degradation of B12 to inactive byproducts in multivitamins isn’t likely to pose a problem for vegans with normal digestion because 1) B12 transport proteins will protect it once dissolved, 2) intrinsic factor selects for active B12 over inactive analogs, 3) only a small percentage of B12 in multivitamins is typically degraded, and 4) manufacturers now typically add overages to supplements to cover degradation over the shelf-life of a supplement in order to be compliant with requirements.
Yamada et al. (2008) measured the B12 content of fortified beverages and multivitamins. Their paper’s abstract could be interpreted to suggest that the