August 2014 Issue

Vitamin B12
By Amelia R. Sherry
Today’s Dietitian
Vol. 16 No. 8 P. 20

Research suggests deficiencies in this vitamin are more common than we may think.

Dietitians are well aware that vitamin B12 is one of the key nutrients in which vegetarians and vegans are deficient, and that they need guidance on how to increase their intake. But can more be done to protect these clients against this nutrient shortfall and its severe consequences?

According to one researcher, the answer is yes. “Registered dietitian nutritionists should recommend that all vegetarians, including even semivegetarians, be tested for B12,” says Roman Pawlak, PhD, RD, an associate professor in the department of nutrition science at East Carolina University in Greenville, North Carolina.

It’s long been accepted that a vegan diet poses a high risk of vitamin B12 deficiency, but the notion that less restrictive vegetarians should be closely monitored for shortfalls remains controversial. Pawlak bases his recommendation for testing in part on a 2013 literature review he coauthored, in which 18 articles were examined that assessed the vitamin B12 status of vegetarians, including lacto-ovo-vegetarians, lacto-vegetarians, vegans, and those following a macrobiotic diet. The results showed that 62% of pregnant women, 25% to almost 86% of young children, 21% to 41% of adolescents, and 11% to 90% of elderly subjects were deficient in vitamin B12.1

Accurate Measures
Previous studies that have identified B12 deficiency among vegetarians have shown significantly lower prevalence rates than Pawlak’s 2013 literature review.2-4 Pawlak argues that his 2013 study paints a more realistic picture of the prevalence of B12 deficiency because he and his colleagues limited their research to studies assessing B12 status using only serum or urinary methylmalonic acid (MMA), holo-transcobalamin-II (holo-TCII), or both, which are considered more specific and accurate measures of vitamin B12 depletion and deficiency compared with the more commonly used serum B12 test.5,6 Notably, MMA and holo-TCII are the two tests, along with homocysteine, that the Academy of Nutrition and Dietetics (the Academy) currently recommends for determining B12 status in vegetarians.7

In fact, the widely used serum B12 test has been characterized as an unreliable measure of deficiency because the cutoff point for determining a deficiency is most often defined as 200 pg/mL or lower, which often is considered too low.8 In other words, researchers who use 200 pg/mL as the cutoff point are excluding a significant number of deficient patients with levels falling between 200 pg/mL and 350 pg/mL. “Symptoms of B12 deficiency have been noted up to a concentration of 350 pg/mL,” explains Katherine L. Tucker, PhD, a professor of nutritional epidemiology in the department of clinical laboratory and nutritional sciences at the University of Massachusetts Lowell.

Indeed, low serum B12 is considered a late indicator of deficiency in that by the time blood levels fall, clinical symptoms such as irreversible peripheral neuropathy already may be present. And serum B12 measures the total amount of B12 circulating in the blood, up to 80% of which may be inactive analogues, which can block B12 absorption.9 Holo-TCII, by comparison, is considered more sensitive because it measures just the active form of B12. MMA also is considered more sensitive because cobalamin is required to convert methylmalonyl coenzyme A to succinyl coenzyme A; therefore, rising MMA levels are an early indicator that active B12 has fallen.10

Jumping the Gun on Testing?
Despite the current research, not all dietitians are convinced that Pawlak’s 2013 review proves that all vegetarians should be tested for vitamin B12 deficiency. “The research studies that are available to be included in this review are limited, particularly with regard to Western countries in which B12-fortified foods are commonly consumed, though it’s not the fault of the review that the studies are limited; there just aren’t many out there,” says Reed Mangels, PhD, RD, LDN, an adjunct professor of nutrition at the University of Massachusetts Amherst and the nutrition advisor for the Vegetarian Resource Group.

“The only study on pregnant women was conducted in Ethiopia where a diet primarily composed of maize was eaten, for example. Also, while the studies spanned 22 years, very few recent studies, such as those conducted in the past 10 years, were available and included. In recent years, more vegetarians seem to be aware of the need to include reliable sources of B12 in their diets,” Mangels says, adding that she considers the evidence for across-the-board testing, which can be very costly, to be “shaky at best.”

Another weakness of the literature review: While MMA and holo-TCII are considered more accurate measures than serum B12, neither test, nor homocysteine, on its own is considered a gold standard diagnostic tool for identifying deficiency.10 For example, serum MMA may be elevated because of intestinal bacterial overgrowth, while urinary MMA may be high due to impaired kidney function. Holo-TCII levels may dip temporarily due to drug interactions or be affected by pregnancy, oral contraceptives, folate disorders, and alcoholism, plus folate, renal dysfunction, and vitamin B6 deficiency can impact homocysteine levels.10,11 For these reasons, it has been recommended that abnormal results of two or more tests be used to confirm a deficiency.10 In Pawlak’s 2013 literature review, only three of the 18 studies required two tests to establish a vitamin B12 deficiency. However, those studies that used two tests still revealed that deficiencies existed in 55% to 69% of vegetarians.

What’s more, because no universally established criteria exists for defining a vitamin B12 deficiency, the cutoff points for determining shortfalls differed among the studies examined. However, Pawlak believes that if uniform measures were used, prevalence would be even higher. “I am convinced that if authors of the published studies used appropriate B12 deficiency criteria, virtually all of their participants would have been diagnosed with a deficiency,” he says.

Stages of Deficiency
While across-the-board testing is expensive and remains controversial, understanding the usefulness of sensitive diagnostic tests is helpful for dietitians who suspect a client or patient may have a vitamin B12 deficiency. Mangels agrees that detecting B12 depletion before it becomes a deficiency is important. “You don’t want to wait until symptoms appear because by that time, there could be irreversible damage,” she says.

The early stages of B12 deficiency, also referred to as B12 depletion, often involves a fairly latent condition characterized by vague or no symptoms (eg, fatigue, forgetfulness), which can go unnoticed for months or years.8,12 Then suddenly, depletion can progress to later stages without warning and in as little as two months, lead to permanent peripheral neuropathy and cognitive damage.13

Sensitive tests can help a clinician detect B12 depletion (or a subclinical deficiency ) before it progresses. Specifically, the holo-TCII test can identify B12 depletion (also known as stages I and II of B12 deficiency), which is defined as having a negative balance of B12, or simply when the amount absorbed falls below the amount lost daily since it measures only the active amount of B12 circulating in the blood.4 Elevated MMA and homocysteine levels indicate a functional deficiency of B12, which is stage III. Total serum B12, which includes inactive and active forms, usually doesn’t fall until stage IV when more obvious clinical manifestations are apparent.

Counseling and Protection
When working with vegetarian and vegan clients, the first step for dietitians is to assess their B12 intake from foods and supplements to determine whether they’re meeting the Recommended Dietary Allowance (RDA), which is 2.4 mcg/day for adults and elders and 2.6 and 2.8 mcg/day for pregnant and lactating women, respectively. “This should include serving sizes, frequency, and sources,” Mangels says. “For example, taking a large supplemental dose once weekly may be fine, but eating eggs once or twice a week is not.”

Dietitians can recommend testing once a dietary assessment reveals a low intake. “I would especially recommend it for any client who is reluctant to supplement or eat fortified foods. If they feel they don’t need it, a test such as MMA, holo-TCII, or homocysteine can help prove to them otherwise,” Mangels says.

If these three, more sensitive tests aren’t available, “practitioners can use serum B12, but they should be aware that many lab values consider serum concentration even slightly below 200 as normal. So, in such a case, the dietitian needs to understand how to interpret the results rather than just accept the description from the lab,” Pawlak says.

For clients who resist testing altogether, RDs should stress the profound risks associated with vitamin B12 depletion and elevated MMA and homocysteine, such as anemia, Alzheimer’s and cardiovascular diseases, dementia, depression, and nerve degeneration, which may help change their minds.

When providing nutrition counseling to vegan and vegetarian clients, dietitians should recommend they eat foods fortified with vitamin B12 or suggest they take a supplemental amount that meets the RDA, says Toby Smithson, MSNW, RDN, LDN, CDE, a spokesperson for the Academy. However, controversy exists over whether the RDA is enough, since research has shown that anywhere between 4 and 10 mcg may be needed to raise B12 to appropriate levels in healthy subjects.14,15 For those who already have a deficiency or serum blood level below 350 pg/mL, some experts recommend amounts 40 to 100 times higher than the RDA.

Vegetarian elders also should eat fortified foods or take a supplement since the naturally occurring B12 found in food sources often is bound to protein. Atrophic gastritis, a condition affecting up to 30% of older adults, reduces the secretion of hydrochloric acid and thereby limits protein-bound vitamin B12 absorption. “Having a list handy of reliable sources of fortified foods, including plant milks, meat substitutes, breakfast cereals, some energy bars, and supplements, also can be helpful for all clients,” Mangels says.

Moreover, dietitians should be vigilant about discussing the importance of vitamin B12 supplementation when counseling pregnant and lactating women and children since the risks of deficiency, such as neurological damage and developmental delay, in these groups can be especially devastating.

— Amelia R. Sherry is a freelance writer, a dietetic intern at CUNY Hunter College School of Public Health in New York City, and the founder of the blog

1. Pawlak R, Parrott SJ, Raj S, Cullum-Dugan D, Lucus D. How prevalent is vitamin B12 deficiency among vegetarians? Nutr Rev. 2013;71(2):110-117.

2. Gilsing AM, Crowe FL, Lloyd-Wright Z, et al. Serum concentrations of vitamin B12 and folate in British male omnivores, vegetarians, and vegans: results from a cross-sectional analysis of the EPIC-Oxford cohort study. Eur J Clin Nutr. 2010;64(9):933-939.

3. Koebnick C, Hoffmann I, Dagnelie PC, et al. Long-term ovo-lacto vegetarian diet impairs vitamin B-12 status in pregnant women. J Nutr. 2004;134(12):3319-3326.

4. Waldmann A, Koschizke JW, Leitzman C, Hahn A. Homocysteine and cobalamin status in German vegans. Public Health Nutr. 2004;7(3):467-472.

5. Herrmann W, Obeid R. Cobalamin deficiency. Subcell Biochem. 2012;56:301-322.

6. Herbert V. Staging vitamin B-12 (cobalamin) status in vegetarians. Am J Clin Nutr. 1994;59(5 Suppl):S1213-S1222.

7. Craig WJ, Mangels AR. Position of the American Dietetic Association: vegetarian diets. J Am Diet Assoc. 2009;109(7):1266-1282.

8. Evatt ML, Mersereau PW, Bobo JK, Kimmons J, Williams J. Why Vitamin B12 Deficiency Should Be on Your Radar Screen: A Continuing Education Update. Published February 11, 2010. Accessed June 2, 2014.

9. Herbert V. Vitamin B-12: plant sources, requirements, and assay. Am J Clin Nutr. 1988;48(3 Suppl):852-858.

10. Carmel R. Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II. Am J Clin Nutr. 2011;94(1):348S-358S.

11. Herrmann W, Geisel J. Vegetarian lifestyle and monitoring of vitamin B-12 status. Clin Chim Acta. 2002;326(1-2):47-59.

12. Herrmann W, Obeid R. Causes and early diagnosis of vitamin B12 deficiency. Dtsch Arztebl Int. 2008;105(40):680-685.

13. Herrmann W, Schorr H, Obeid R, Geisel J. Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am J Clin Nutr. 2003;78(1):131-136.

14. Bor MV, von Castel-Roberts KM, Kauwell GP, et al. Daily intake of 4 to 7 microg dietary vitamin B-12 is associated with steady concentrations of vitamin B-12-related biomarkers in a healthy young population. Am J Clin Nutr. 2010;91(3):571-577.

15. Vogiatzoglou A, Smith AD, Nurk E, et al. Dietary sources of vitamin B-12 and their association with plasma vitamin B-12 concentrations in the general population: the Hordaland Homocysteine Study. Am J Clin Nutr. 2009;89(4):1078-1087.