Ensuring Adequate Vitamin B12 Status on a
Stewart D Rose* and Amanda J Strombom
1Plant-Based Diets in Medicine, USA
Submission: May 07, 2019; Published: July 09, 2019
*Corresponding author: Stewart Rose, Plant-Based Diets in Medicine, 12819 SE 38th St, #427, Bellevue, WA 98006, USA
How to cite this article: Stewart D Rose, Amanda J Strombom. Ensuring Adequate Vitamin B12 Status on a Plant-Based Diet. Adv Res Gastroentero
Hepatol. 2019; 13(3): 555862. DOI: 10.19080/ARGH.2019.13.555862.
Vitamin B12 is a water-soluble vitamin. All naturally occurring B12 is produced by bacteria in the soil. Animals ingest these bacteria along with their feed, resulting in their presence in animal-derived foods. It is also added to other foods as an enrichment and is available as a dietary supplement. Since patients on a plant-based diet eat no animal-derived foods, and only plant-foods cleaned of soil residue, they must rely on supplementation or fortified foods. Status is typically assessed via serum or plasma vitamin B12 levels. Injected Vitamin B12 appears to be equivalent to oral vitamin B12, but there is no evidence that sublingual delivery offers any advantage over other oral preparations. Vitamin B12 has been demonstrated to be safe in doses up to 1,000 times the recommended dietary allowance and is safe in pregnancy.
It is vital that patients on a plant-based diet have adequate levels of Vitamin B12. Vitamin B12 deficiency is characterized by megaloblastic anemia, fatigue, weakness, constipation, loss of appetite, and weight loss. Neurological changes, such as numbness and tingling in the hands and feet, can also occur. Due to conservation through enterohepatic recirculation, the body’s stores of B12 may last the patient some time which can lead to complacency and give the patient a false sense of security. Therefore, the physician should emphasize the importance of vitamin B12 supplementation and the rationale for it.
Vitamin B12 is a water-soluble vitamin that is naturally present in animal-derived foods. It is added to others and is available as a dietary supplement and a prescription medication. Vitamin B12 exists in several forms and contains the mineral cobalt [1-4], so compounds with vitamin B12 activity are collectively called “cobalamins”. Methylcobalamin and 5-deoxyadenosylcobalamin are the forms of vitamin B12 that are active in human metabolism .
Vitamin B12 is required for proper red blood cell formation, neurological function, and DNA synthesis [1-5]. Vitamin B12 functions as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase. Methionine synthase catalyzes the conversion of homocysteine to methionine [5,6]. Methionine is required for the formation of S-adenosylmethionine, a universal methyl donor for almost 100 different substrates, including DNA, RNA, hormones, proteins, and lipids. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to succinyl-CoA in the degradation of propionate [3,5,6], an essential biochemical reaction in fat and
protein metabolism. Succinyl-CoA is also required for hemoglobin synthesis. Thus, maintaining adequate vitamin B12 status is vital for good health.
Vitamin B12, bound to protein in animal-derived foods, is released by the activity of hydrochloric acid and gastric protease in the stomach . When synthetic vitamin B12 is added to fortified foods and dietary supplements, it is already in free form and thus does not require this separation step. Free vitamin B12 then combines with intrinsic factor (IF), a glycoprotein secreted by the stomach’s parietal cells, and the resulting complex undergoes absorption within the distal ileum by receptor-mediated endocytosis [5,7].
Vitamin B12 status is typically assessed via serum or plasma vitamin B12 levels. Values below approximately 170–250 pg/mL (120–180 picomol/L) for adults  indicate a vitamin B12 deficiency. However, evidence suggests that serum vitamin B12 concentrations might not accurately reflect intracellular
concentrations . Elevated methylmalonic acid levels (values
>0.4 micromol/L) might be a more reliable indicator of vitamin
B12 status because they indicate a metabolic change that is highly
specific to vitamin B12 deficiency [5-9].
The following Table 1 lists the current RDAs for vitamin B12
in micrograms (mcg) . For infants aged 0 to 12 months, the
Food and Nutrition Board established an adequate intake (AI) for
vitamin B12 that is equivalent to the mean intake of vitamin B12
in healthy, breastfed infants.
Approximately 56% of a 1mcg oral dose of vitamin B12 is
absorbed, but absorption decreases drastically when the capacity
of intrinsic factor is exceeded (at 1–2 mcg of vitamin B12) .
After the age of 50, the amount of intrinsic factor available is
reduced, leading to malabsorption in many seniors. However,
approximately 1% of oral vitamin B12 can be absorbed passively
in the absence of intrinsic factor [8,9]. For example, only about 5
mcg of a 500-mcg oral supplement is actually absorbed in healthy
The bioavailability of sublingual vitamin B12 appears to
be equivalent to oral vitamin B12, but there is no evidence that
sublingual delivery offers any advantage over oral preparations
. Given the lower cost and ease of administration of oral
vitamin B12, this might be a reasonable choice for replacement in
many patients .
Vitamin B12 has been demonstrated to be safe in doses up to
1,000 times the recommended dietary allowance and is safe in
pregnancy . The Institute of Medicine (IOM) did not establish an
upper limit for vitamin B12 because of its low potential for toxicity.
The IOM states that “no adverse effects have been associated with
excess vitamin B12 intake from food and supplements in healthy
individuals” . Findings from an intervention trial support these
conclusions. In the HOPE 2 trial, vitamin B12 supplementation
(in combination with folic acid and vitamin B6) did not cause any
serious adverse events when administered at doses of 1.0 mg for
5 years .
All naturally occurring B12 is produced by microorganisms
. The only organisms to produce vitamin B12 are certain
species of bacteria. Some of these bacteria are found in the soil
around the grasses that ruminants eat. They are taken into the
animal, proliferate, form part of their gut flora, and continue to
produce vitamin B12 . Since patients on a plant-based diet
eat no animal-derived foods, and only plant-foods cleaned of soil
residue, they must rely on supplementation or fortified foods
Fortified breakfast cereals are a readily available source of
vitamin B12 with high bioavailability for vegetarians [5,8,9,15,16].
Some nutritional yeast products also contain vitamin B12.
Fortified foods vary in formulation between brands and over time,
so it is important to read product labels regularly to determine
which added nutrients they contain.
Several studies have shown varying prevalence of B12
deficiency with those on a plant- based diet [17-19]. For instance,
one study showed that (52%) of those following a plant-based diet
were B12 deficient (<118 pmol/L) . However, other studies
have found a lower incidence of B12 deficiency . As expected,
those taking B12 containing supplements have lower incidences
of B12 deficiency .
Vitamin B12 is secreted in bile and then most is reabsorbed via
the enterohepatic circulation by ileal receptors which require IF.
In healthy individuals most of this B12 is reabsorbed and available
for metabolic functions . This gives the body an effective
mechanism to conserve its B12, so deficiency can take as long as
several years to present. This sometimes leads to complacency
among patients following a plant-based diet. Development of
vitamin B12 deficiency is likely to be more rapid in patients with
pernicious anemia since IF is lacking .
Vitamin B12 deficiency is characterized by megaloblastic
anemia, fatigue, weakness, constipation, loss of appetite, and
weight loss [2,3,22]. Neurological changes, such as numbness and
tingling in the hands and feet, can also occur [5,23]. Additional
symptoms of vitamin B12 deficiency include difficulty maintaining
balance, depression, confusion, dementia, poor memory, and
soreness of the mouth or tongue . The neurological symptoms
of vitamin B12 deficiency can occur without anemia, so early
diagnosis and intervention is important to avoid irreversible
Large amounts of folic acid can mask the damaging effects of
vitamin B12 deficiency by correcting the megaloblastic anemia
caused by vitamin B12 deficiency [2,24] without correcting the
neurological damage that also occurs [2,24].
Vitamin B12 crosses the placenta during pregnancy and is
present in breast milk. Exclusively breastfed infants of women
who consume no animal products may have very limited reserves
of vitamin B12 and they can develop vitamin B12 deficiency
within months of birth [5,25]. Undetected and untreated vitamin B12 deficiency in infants can result in severe and permanent
neurological damage. During infancy, signs of a vitamin B12
deficiency include failure to thrive, movement disorders,
developmental delays, and megaloblastic anemia .
Vitamin B12 deficiency is sometimes treated with vitamin
B12 injections, since this method bypasses potential barriers to
absorption. However, high doses of oral vitamin B12 may also
be effective. In a 2005 review of randomized controlled trials
comparing oral with intramuscular vitamin B12, patients who
received high dosages of oral vitamin B12 (1 to 2 mg daily) for 90
to 120 days had an improvement in serum vitamin B12 similar
to patients who received intramuscular injections. The authors
concluded that 2,000 mcg of oral vitamin B12 daily, followed by
a decreased daily dose of 1,000 mcg and then 1,000 mcg weekly,
can be as effective as intramuscular administration [8,9]. These
results were consistent in patients regardless of the etiology of
their vitamin B12 deficiency, including malabsorption states
and pernicious anemia. Overall, an individual patient’s ability to
absorb vitamin B12 from the diet is the most important factor in
determining whether vitamin B12 should be administered orally
or via injection .
The American Dietetic Association recommends supplemental
vitamin B12 for vegans and lacto-ovo vegetarians during both
pregnancy and lactation to ensure that enough vitamin B12 is
transferred to the fetus and infant . Pregnant and lactating
women who follow strict vegetarian or vegan diets should consult
with a pediatrician regarding vitamin B12 supplements for their
infants and children .
In previous eras and under primitive conditions, man may have
absorbed adequate vitamin B12 through the soil left on his food,
when there was little to no washing and peeling. Now, however,
patients following a plant-based, or vegan diet, must supplement
with vitamin B12. Due to conservation through enterohepatic
recirculation, the body’s stores of B12 may last the patient some
Some vegetarian and vegan patients are complacent when
it comes to vitamin B12 supplementation. The long lag time
until symptoms present can add to the complacency and some
patients may become convinced, they don’t need supplemental
B12. Therefore, the physician should emphasize the importance
of vitamin B12 supplementation and the rationale for it. The
physicians should also make the patient aware of the consequences
Given the higher rate of B12 deficiency in vegans and
vegetarians, they should have the lab work done initially. If a
deficiency is found, or there is non-compliance with recommended
supplementation, then more frequent lab work is called for.
Vitamin B12 deficiency is easy to prevent. Vitamin B12 is
included in many multivitamins as well as being sold separately.
While some foods are fortified with B12, this cannot be relied
upon due to dietary preference variations and commercial
500mcg and 1,000mcg vitamin B12 supplements, as well as
smaller doses, are widely available and affordable and can be used
to prevent or treat deficiency, regardless of etiology, without the
need for intramuscular injections. Considering the exceptionally
low toxicity, vitamin B12 can be prescribed in generous doses if
the clinician considers it best to err on the side of safety with a