by Jack Norris, RD
- Clinical Trials in Nonvegetarians
- Extrapolating Wolters et al.’s Findings to Vegans
- Observational Studies
- B12 Malabsorption
- Degradation of B12 under Experimental Conditions
- Yamada et al.’s 2008 Study of B12 in Fortified Beverages and Multivitamins
- Kondo et al. and Herbert et al.’s Research on Multivitamins circa 1980
- Potential Improvements in the Accuracy of Nutrition Labeling
- B12 Transport Proteins and Multivitamins
- Observational Study of B12 in Fortified Non-Dairy Milks
- Anecdotal Reports
- Dangers of Recommending “Take a Multivitamin”
- Appendix A: Personal Experiment
Vegans who rely solely on a daily multivitamin for vitamin B12 should make sure it meets VeganHealth’s minimum recommendation for a daily dose, which is 5 µg for adults. This amount of B12 is tailored to meet the U.S. Recommended Dietary Allowance (RDA) after adjusting for absorption rates of a single daily dose.
Here are some suggestions for those who want extra assurance that they’re obtaining enough B12:
- If you’re concerned that your recent regimen has been inadequate, then for 2 weeks take 2,000 µg of B12 per day to replenish your stores.
- Aim for the upper range of VeganHealth’s recommendations.
- Use a B12-only supplement for whichever regimen you decide to follow.
- If taking a daily dose, divide it in half and take each half at least 4 hours apart to substantially increase absorption.
This article reviews the concerns about multivitamins being an adequate source of B12 for vegans. We conclude that the evidence is in favor of multivitamins being a reliable source.
When I first started writing about B12 around 2000, I was aware that Victor Herbert, one of the pioneers in vitamin B12 research, had expressed concerns about the efficacy of B12 in multivitamins, but I didn’t find the evidence convincing enough to avoid recommending them and on VeganHealth we’ve treated multivitamins like any other source.
I recently became aware that a respected vegan nutritionist has been strongly opposed to vegans relying on multivitamins and so I’ve given the subject another look.
Here are the specific concerns:
- Victor Herbert published dozens of papers from 1958 to 2003. He often cautioned that various ingredients in multivitamins, especially vitamin C, could damage B12 (Herbert, 1981; Herbert, 1982).
- Multivitamins normally contain only small amounts of B12, which might not be enough for vegans.
- There might be a significant degradation of B12 in multivitamins resulting in inactive B12 analogs that not only are useless but might interfere with the active B12 and hasten the onset of a deficiency.
- Some people suffer from mild B12 malabsorption, making the small amounts of B12 in multivitamins inadequate, whereas slightly higher doses might prevent such people from becoming deficient.
- People might take multivitamins too irregularly 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.
There are two routes for absorption of B12:
- 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.
Clinical Trials in Nonvegetarians
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.
Chen et al. (2022) conducted a randomized controlled trial providing a daily multivitamin to older adults who were taking medications that decrease the absorption of vitamins (average age 61.5 years). The multivitamin was Multi for Him 50+ by Nature Made which contains 25 µg of B12, 185 mg of vitamin C, and other nutrients thought to damage B12. After 8 weeks, the treatment group’s average serum B12 increased from 376 to 495 pmol/l while the placebo group’s decreased by 11 pmol/l. Methylmalonic acid levels weren’t measured so there’s a small possibility that the B12 wasn’t active.
B12 Absorption from Animal Products
Even if multivitamins work for nonvegetarians, they still might not be adequate for vegans for two reasons:
- 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.
We should mention that while being attached to protein in foods has benefits, it also has drawbacks, because the B12 must first be cleaved from the protein before it can be absorbed. Decreased digestive enzyme production or stomach acid, which can occur with aging, can reduce B12 absorption from animal products (Institute of Medicine, 1998). The Institute of Medicine recommends that “Since 10-30% of older people may malabsorb food-bound B12, it is advisable for those older than 50 to meet their RDA mainly by consuming foods fortified with B12 or a B12-containing supplement.”
Extrapolating Wolters et al.’s Findings to Vegans
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.
B12 in Breast Milk of 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.
Mild B12 Malabsorption in Vegans
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 under Experimental Conditions
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.’s 2008 Study of B12 in Fortified Beverages and Multivitamins
Yamada et al. (2008) measured the B12 content of fortified beverages and multivitamins. Their paper’s abstract could be interpreted to suggest that the B12 content in multivitamins was decreased by storage time, light exposure, temperature, and vitamin C. However, they didn’t test these variables for multivitamins.
In their study, Yamada et al. found that a B12-fortified beverage stored in an amber bottle experienced significant degradation compared to a beverage stored in a steel can, suggesting that light can do significant damage to B12. They also studied solutions containing 5 µg of B12 with vitamin C and found that 300 mg of vitamin C reduced the B12 content by about 40%. In a solution containing sugar, B12 was degraded by about 30%, and in a solution containing iron, B12 was reduced by about 20%.
These findings suggest that B12 shouldn’t be exposed to light during storage and that B12-fortified beverages might not be reliable, especially if they contain vitamin C, iron, or sugar.
Kondo et al. and Herbert et al.’s Research on Multivitamins circa 1980
While experiments by Kondo et al. and Herbert et al. raise concerns about B12 degradation from multivitamins in solution, their experiments can’t be extrapolated to human digestion in which B12 transport proteins protect B12 and select active B12 over inactive analogs. Although there’s almost always an inevitable amount of degradation of B12 in supplements over the course of the advertised shelf-life, companies today are encouraged to ensure enough B12 remains to meet the amount listed on the label.
Kondo et al. (1982) examined the contents of three multivitamin preparations and, after incubating them in water at 37°C (body temperature) for 2 hours, found that 20% to 90% of the B12 had degraded to inactive analogs. In further experiments, they pinpointed vitamin C, thiamin, and copper as the molecules causing the degradation of B12. A 90% degradation of B12 is an admittedly alarming amount, but this experiment can’t be extrapolated to what happens in normal B12 digestion given that they didn’t account for the protection of B12 by haptocorrin.
In a letter to the editor, Herbert et al. (1981) reported that their laboratory had found that incubation of cyanocobalamin for 30 minutes at body temperature and pH 7 with 500 mg of vitamin C resulted in the degradation of 1/3 of the cyanocobalamin. While this process was intended to mimic physiological conditions, it didn’t take into account that once a multivitamin dissolves in the digestive tract much of the B12 will bind to haptocorrin protecting it against damage from other molecules.
In another letter to the editor, Herbert et al. (1982) reported finding inactive B12 analogs in all of 15 commercial multivitamins they tested. There was an average of 17% inactive analogs.
If a multivitamin lists 5 µg on the label but actually contains 17% less, it would result in only 8.3 µg absorbed per week instead of the 8.4 µg that the RDA is based on, but this amount would still cover most people’s needs.
Potential Improvements in the Accuracy of Nutrition Labeling
In 1990, the United States passed the Nutrition Labeling and Education Act which gave authority to the Food and Drug Administration to regulate nutrition labeling. Manufacturers are encouraged to ensure Good Manufacturing Practices (GMP) which can include adding enough of an overage for each vitamin to ensure the amount listed on the label is maintained over the listed shelf-life of the product (Yoo, 2016).
The U.S. Pharmacopeia (USP) has a certification program to ensure a product’s contents; a certified product will contain the USP symbol. However, most products aren’t certified by USP and I couldn’t find any multivitamins with USP verification that were also vegan. There are other organizations that certify that a company uses GMP, such as the Natural Products Association, but this doesn’t appear to include testing the finished product’s contents.
While we don’t have proof of the extent to which improvements have been made since the early 1980s, there’s more awareness and more efforts to ensure accurate vitamin supplement labels.
B12 Transport Proteins and Multivitamins
Because the B12 transport protein, haptocorrin, binds B12 in the stomach, it might be best to take multivitamin supplements whole so that they don’t dissolve until they reach the stomach. Intrinsic factor should weed out most of the inactive B12 analog.
Vitamin B12 is transported by three different proteins whose nomenclature has changed over the years:
- Haptocorrin – secreted in the saliva; binds B12 in the stomach and protects it from stomach acid (also known as R-protein); carries B12 in the blood and transports it to the liver (Allen, 2018)
- Intrinsic factor – secreted in the stomach; binds B12 in the small intestines
- Transcobalamin – binds B12 in the intestinal cells and transports it through the blood to the body’s other cells where it’s utilized
For some time, haptocorrin was referred to as transcobalamin I in the blood and transcobalamin III in the saliva and digestive tract (Scott, 1974); during this time, transcobalamin was referred to as transcobalamin II.
People with a genetic defect for haptocorrin can have drastically reduced haptocorrin in the blood but not the saliva. The low haptocorrin in the blood results in low serum B12 levels without a functional deficiency (Carmel, 2009).
In a 1994 study on vegans, some of whom had trouble digesting a B12-supplement, Crane says, “Whether or not vitamin B12 encased in a multivitamin pill can be absorbed, remains to be determined. It may bypass combination with the ‘R’ factor [haptocorrin] in the mouth or stomach.”
In contrast, Yamada et al. (2008) note that “We have found, in preliminary experimental results, that haptocorrin can protect B12 from degradation by vitamin C. In liquid dietary supplements, B12 is in free form, and is easily exposed and degraded by vitamin C.” They cite Yamada 2004, which I haven’t been able to track down.
We’ve always encouraged vegans to chew B12-only supplements in order to aid passive diffusion which can take place in the mouth (Allen, 2018) and because some supplements were shown by Crane et al. (1994) to resist dissolving.
Crane implies that haptocorrin can bind B12 in the mouth, but I wasn’t able to verify this. So, it might be important for a multivitamin, which is more dependent on B12 transport proteins than a B12-only supplement, not to dissolve until it reaches the stomach. Not dissolving before reaching the stomach would protect the B12 from other contents of the multivitamin.
Once the multivitamin reaches the stomach and dissolves, haptocorrin binds the B12 and protects it from the stomach acid. When the B12-haptocorrin complex reaches the small intestines, haptocorrin releases the B12 where it then attaches to intrinsic factor.
While haptocorrin can bind to inactive B12 analogs, intrinsic factor is widely thought to be selective for only active B12 (Allen, 2008). In fact, Yamada et al. classified B12 as “inactive” by measuring the amount that wasn’t bound by intrinsic factor, such that the particular inactive analogs they measured wouldn’t present a problem for B12 metabolism.
Observational Study of B12 in Fortified Non-Dairy Milks
Because Yamada et al. (2008) raised concerns about obtaining B12 from fortified beverages, we should point out a reassuring study of B12-fortified, non-dairy milks which indicates they have a positive influence on B12 status.
Damayanti et al. (2018) measured B12 intake from multivitamins, fortified foods, B12 supplements, and animal products in a group of 67 vegans, 207 lacto-ovo-vegetarians, 78 pesco-vegetarians, 35 semi-vegetarians, and 341 nonvegetarians. Among the participants who didn’t take a B12-containing supplement (including multivitamins), intake of ≥0.51 µg/day of B12 from fortified, non-dairy milk was associated with higher serum B12 and holotranscobalamin (a measure of recent B12 intake).
There are anecdotal reports of vegans becoming B12-deficient after relying on multivitamins or prenatal supplements without an additional B12-only supplement. While disconcerting, these reports could have mitigating factors and the prenatal supplements likely didn’t contain enough B12 to meet our minimum recommendations.
The vegan nutritionist, whose concerns about multivitamins caused me to write this article, told me that she and several of her clients had become deficient while taking a daily vegan multivitamin containing 100 µg of B12. What she’s told me of her personal situation is consistent with pernicious anemia even though she claims not to have pernicious anemia. The other vegans might have malabsorption issues and are likely a self-selecting population given that people suffering from a nutrient deficiency would be more likely to seek out nutrition counseling.
This colleague also conducted a survey in which vegan women provided their B12 test results. There were several deficient women who were taking a multivitamin, containing 10-400 µg, as their source of B12 whereas none who were taking a B12-only supplement three times a week or more were deficient (defined as serum B12, holotranscobalamin, or mean corpuscular volume (MCV) outside of the reference range of the multiple labs used).
This same colleague points out that the most popular supplement in her country contains only 2.6 µg of B12, that she knows two vegan women who’ve had infants with neural tube defects while relying on a popular prenatal supplement that contains only 2.6 µg of B12, and she knows people who have died or become permanently disabled as a result of B12 deficiency. She also referenced an Italian vegan woman who had been taking a prenatal containing B12 during pregnancy who gave birth to a B12-deficient baby who is now permanently disabled, as well as vegan babies in Australia who have died of B12 deficiency.
VeganHealth recommends that pregnant and breastfeeding women receive at least 10 µg per day. Earlier in this article, we noted that there isn’t much of a difference between 5 µg and 9 µg in a single dose of B12. However, based on absorption rates, there is a significant difference between 2.6 µg and 10 µg which would result in 1.0 and 1.5 µg absorbed per dose, respectively.
The Italian woman mentioned above was the subject of a case report (Guez, 2012). Her child was exclusively breastfed until 5 months old when he was hospitalized with failure to thrive. The mother apparently only started supplementing during her 2nd trimester with a multivitamin containing 2.5 µg of B12 and stopped after giving birth. This amount of B12 falls far short of our recommendations.
In contrast to the above anecdotal reports, the UK Vegan Society sells a multivitamin, VEG 1, that contains 25 µg of B12 and without any vitamins or minerals thought to degrade B12. The reports they’ve received haven’t raised concerns about the adequacy of the B12 amount in their supplement (private correspondence with Stephen Walsh in August 2021). But this alone doesn’t provide much evidence regarding a typical multivitamin containing 5 µg of B12.
I spoke with another colleague who relies on a DEVA multivitamin with 100 µg of B12 plus occasional fortified foods with no signs of deficiency.
While concerning, the anecdotes of harm coming to vegans by relying on multivitamins have too many uncertainties to cause us to change the methodology we use for our recommendations.
Dangers of Recommending “Take a Multivitamin”
I’m resistant to increasing recommendations to compensate for the possibility that people won’t follow them—how would we know how much more to recommend?
But given that some multivitamins don’t contain enough B12 to meet our minimum recommendations, I’m sympathetic to the idea that it could be dangerous for vegan health professionals, and the greater vegan community, to promote the idea that for B12 vegans can “just take a multivitamin.”
After the discussion with my colleague and reviewing the research, I see a need for vegan advocates to emphasize that when relying on daily multivitamins as a sole source of B12 vegans need to make sure it meets our minimum recommendations. For my part, I’ll be reviewing Vegan Outreach’s materials to make it clear that multivitamins must have at least 5 µg for adults if taken only once per day.
The concerns about multivitamins as a source of B12 have focused on the potential risk of degradation and whether there’s enough B12 in multivitamins to meet needs.
That enough B12 in multivitamins is degraded to make a significant difference in B12 status seems implausible because intrinsic factor should bind enough of the remaining active B12 to meet needs, presuming the multivitamin meets our minimum recommendation of 5 µg.
VeganHealth’s recommendation for meeting B12 needs through fortified foods and multivitamins assumes normal B12 absorption by way of intrinsic factor. Under these assumptions, the methodology we use is the least arbitrary we can think of for determining recommendations for vegans.
An alternative method would be to take the extremely cautious position of assuming people don’t have functioning intrinsic factor and base our recommendations on passive diffusion only. This would be a significant deviation from how nutrient recommendations are normally formulated which is to base them on most people’s needs rather than outlier cases that require special treatment. Such recommendations would be inconvenient for many people and could lead to some cases of acne-like symptoms in people sensitive to high doses of B12 (see Footnote B in Elevated Vitamin B12 Levels and Mortality). It’s worth remembering that passive diffusion is most accurately viewed as an accident of physiology that only plays a minuscule role without supplements.
We hope future research will provide more clarity, but based on the current evidence, it appears that a daily multivitamin supplement providing at least 5 ug of B12 should be sufficient for meeting needs in healthy adults with normal absorption.
Appendix A: Personal Experiment
After writing this article, I conducted an experiment on myself that indicated a daily multivitamin with 6 µg of B12 was enough to maintain my B12 status. I couldn’t find a multivitamin with 5 µg of B12, so I used a Deva multivitamin with 6 µg instead.
Here’s the timeline:
- October 7-20, 2021: No B12 intake.
- October 20, 2021 blood tests:
- serum B12: 281 pmol/l
- serum methylmalonic acid: 148 nmol/l
- serum homocysteine: 10.4 µmol/l
- October 20 (after blood draw): Began daily intake of Deva multivitamin containing 6 µg of B12 and 60 mg of vitamin C, with no other source of B12.
- January 26, 2022 blood tests:
- serum B12: 307 pmol/l
- serum methylmalonic acid: 112 nmol/l
- February 10, 2022 blood test:
- serum homocysteine: 10.3 µmol/l
These results, especially the reduction in methylmalonic acid to a low level, indicate that a daily multivitamin with 6 µg of B12 was enough to maintain a healthy B12 status.
Last updated February 2022
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