Key Concepts

  • A lot of people are deficient – especially vegans, vegetarians, and those with gut inflammation
  • Typical clinical tests (serum B12) are likely inadequate for assessing functional vitamin B12 status
  • Methylmalonic acid (MMA) urine or MMA serum test may provide better indication of B12 status
  • RDA – 2.4 mcg/day for adults
  • Fortified foods and most supplements in form of cyanocobalamin (1% absorption rate)
  • Methylcobalamin supplement appears to be most effective form of vitamin B12 supplement
  • B12 supplements are vegan friendly – they are synthesized from bacteria
  • No toxicity established – high doses appear safe
  • Food Sources – Liver, Salmon, Eggs
  • Vegetarian food sources are B12 analogs that they body cannot use – they also interfere with the absorption of the forms the body can use
  • Supplements: B Complex – $0.34/day | B12 – $0.07/day

Intro

Cobalamin (vitamin B12) is an important vitamin for everyone to pay attention to, whether your vegan, vegetarian, or eating a hamburger as you are reading this… This is because many people are deficient or at risk of becoming deficient, the test to detect B12 deficiency may not provide an accurate representation of functional B12 status, the main form of B12 supplement may not actually be doing anything, the food sources of B12 are limited, and the health challenges of clinical B12 deficiency may be irreversible.

Deficiency

Vitamin B12 is synonymous with energy, and most know that if you are deficient you will have low energy. To be more specific, vitamin B12 deficiency can lead to megaloblastic anemia, pernicious anemia, memory loss, dementia, and peripheral neuropathy.

Unfortunately, a lot of people are likely to have vitamin B12 deficiency. A study from Tufts University estimated showed that 40 percent of people between the ages of 26 and 83 have plasma B12 levels in the low normal range, 9 percent had outright deficiency, and 16 percent exhibited “near deficiency”. Neurological symptoms occurred for those individuals in the low normal range. Other studies have shown that 50-68% percent of long-term vegetarians and 80% of vegans were deficient in vitamin B12.

Its not only vegetarians and vegans at risk for vitamin B12 deficiency. Those with hypochlorohydria (low stomach acid), atrophic gastritis (chronically inflamed stomach), leaky gut syndrome, H. pylori infections (gastric ulcers), malabsorption conditions, and those who have had intestinal resections are also at risk. Anyone with irritable bowel syndrome (IBS), Chron’s Disease, under chronic strict, drinks alcohol excessively, have food sensitivities, or any other sort of inflammatory condition affecting the gut may be at risk for vitamin B12 deficiency. Ingesting medications including proton pump inhibitors, H2 blockers, cholestyramines, and metmformin may also increase risk of developing a vitamin B12 deficiency.

Digestion/Absorption

As you can see, a lot of people are at risk. Cobalamin is digested in as series of step that require a healthy stomach, pancreas, and small intestine for proper absorption. Vitamin B12 is usually bound to proteins in meat. Stomach acid and enzymes free the B12 from food. it is then bound to R-protein. In the small intestine (an alkaline) environment, R-proteins are degraded by pancreatic enzymes. This frees B12 and allows it to bind to intrinsic factor (IF). IF is produced by the parietal cells of the stomach. if the stomach is inflamed, IF’s release is hindered. The B12 bound to IF travels to the ileum (lowest part of small intestine) and is absorbed via cubulin (a transport protein) only in the presence of calcium (supplied by the pancreas). B12 is then released from cubulin in the enterocyte (intestinal cell) where it enters the blood and binds to holotranscobalamin II (holoTC2). B12 can then transported to all body tissues. Once the B12-holoTC2 complex arrives at the cell where it is needed, B12 is released from TC2 in the form of hydroxocobalamin. It is then turned into methylcobalamin or adenosylcobalamin. Two to 4 grams can also be stored in the liver. Due to B12’s ability to be stored, it may take 3-5 years to develop a deficiency.

Functions

Vitamin B12 plays essential roles in folate metabolism, in the synthesis of succinylcholine-CoA (a citric acid cycle intermediate), in homocysteine metabolism, and in red blood cell metabolism.

Recommended Dietary Allowance (RDA)

  • 2.4 mcg/day for adults

Toxicity

No upper level intake level (UL) is established for vitamin B12. Doses as high as 2 mg (2,000 μg) daily by mouth or 1 mg monthly by intramuscular (IM) injection have been used to treat pernicious anemia without significant side effects.

Stages of Vitamin B12 Deficiency

  • Stage I & II: blood plasma levels and cell stores of vitamin B12 become depleted; the concentration of holo-TC2 is reduced
  • Stage III: functional B12 imbalance characterized by elevated homocysteine and urinary MMA concentrations in the blood
  • Stage IV: development of clinical signs of B12 deficiency – megaloblastic anemia, pernicious anemia, memory loss, dementia, and peripheral neuropathy – these neurological symptoms may be irreversible

Clinical Testing for B12 Levels

Serum or plasma vitamin B12 levels are the typical way for assessing vitamin B12 status. Unfortunately, evidence suggests that serum vitamin B12 concentrations might not accurately reflect intracellular concentrations. An elevated homocysteine level (values >13 micromol/L) might also suggest a vitamin B12 deficiency; however, low vitamin B6 or folate levels can also cause elevated homocysteine levels and therefore can only point to the possibility of a vitamin B12 deficiency. Elevated methylmalonic acid (MMA) levels (values >0.4 micromol/L) might be a more reliable indicator of vitamin B12 status. MMA levels indicate a metabolic change that is highly specific to vitamin B12 deficiency. MMA can be measured in blood serum or in urine. Elevations in urinary MMA can also be caused by kidney dysfunction while elevation in serum MMA can be elevated in the presence of intestinal bacterial overgrowth. Holotranscobalamin II (holoTC2) appears to be the most sensitive test available to measure vitamin B12 deficiency. Unfortunately, the lab test does not appear to be available in the United States.

Food Sources

  • Clams, cooked, 3 ounces – 84.1 mcg – 1,402%
  • Liver, beef, cooked, 3 ounces – 70.7 mcg – 1,178%
  • Salmon, sockeye, cooked, 3 ounces – 4.8 mcg – 80%
  • Egg, whole, hard boiled, 1 large – 0.6 mcg – 10%

Plant sources such as fermented soy, spiraling, seaweed, and nutritional yeast contain vitamin B12 analogs called cobamides. This is not a useable form of vitamin B12 for humans and actually blocks the useable forms (methylcobalamin & adenoyslcobalamin).

Because B12 can be stored in the liver, it would make sense that even eating 1 serving of liver a week would provide adequate B12 in a person without B12 deficiency. But, I do not have a study which specifically proves that hypothesis.

Supplementation

Fortified foods and most standard supplements contain cyanocobalamin. As the name indicates, this type of cobalamin contains cyanide. It does not mean it will kill you, but it could potentially inhibit cytochrome C oxidase in the electron transport chain. Additionally, it is estimated that only one percent of cyanocobalamin is converted to active cobalamin. So, cyanocobalamin may serve no benefit and may actually be harmful, although the level of cyanide it contains is very minimal.

Hydroxycobalamin is the form typically given as an intramuscular (IM) shot/injection.

It appears that the most useful form for oral supplementation is methylcobalamin. Methylcobalamin is a metabolically active form of vitamin B12 and can be converted to the other metabolically active form, adenoyslcobalamin, as needed.

A few studies have suggested that high dose oral B12 supplementation may be as effective as injections for those with B12 malabsorption problems. However, most B12 experts still recommend injections for people with clinical B12 deficiency.

It appears that the B12 found in supplements is sourced from bacterial cultures. Therefore, no animals are harmed in the creation of the products making it vegan and vegetarian friendly.

The B complex contains all the B vitamins. I could not find a B complex without the potential to cause a niacin flush. Due to the way B vitamins work in the body taking them together makes the most sense. I also included a B12 individual supplement in the event your health care professional has recommended its sole usage. If this is a case consulting with a physician may be wise as they can provide an injection which can correct a deficiency.

Our Gut Bacteria Produces B12

An interesting fact is that cobalamin is produced in our colon by bacteria, although it is not bioavailable because the receptors necessary for absorbing the vitamin are found in the small intestine. The vitamin B12 produced by gut bacteria is currently being explored as a modulator of gut microbial ecology.

Conclusion

Supplementing appears warranted. This B Vitamin Complex Supplement contains active forms of all B vitamins. This Methyl B12 vitamin contains methylcobalamin.

 

References/Resources

Peer-Reviewed Articles

  1. https://www.ncbi.nlm.nih.gov/pubmed/10552882
  2. https://www.ncbi.nlm.nih.gov/pubmed/12011576
  3. http://ajcn.nutrition.org/content/78/1/3.long
  4. http://ajcn.nutrition.org/content/78/1/131.full
  5. https://www.ncbi.nlm.nih.gov/pubmed/18234134?dopt=Abstract
  6. Holotranscobalamin, a marker of vitamin B12 status
  7. Stages of B12 Deficiency
  8. Vitamin B12 as a modulator of gut microbial ecology
  9. Presence and formation of cobalamin analogues in multivitamin-mineral pills
  10. Vitamin B-12: plant sources, requirements, and assay
  11. Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements

Literature Reviews

  1. https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/
  2. http://lpi.oregonstate.edu/mic/vitamins/vitamin-B12
  3. https://chriskresser.com/why-b12-deficiency-is-significantly-underdiagnosed/
  4. http://my.chriskresser.com/wp-content/uploads/membership-files/ebooks/B12%20Deficiency.pdf?_ga=2.64622383.142105651.1510440224-1420409820.1507333193
  5. Everything You Need to Know About Vitamin B12 – Global Healing Center
  6. http://www.veganhealth.org/b12/plant
  7. Could It Be B12 – An Epidemic of Misdiagnoses
  8. http://www.veganhealth.org/b12/dig
  9. http://www.veganhealth.org/b12/vegansources#origin
  10. http://www.veganbodybuilding.com/forum/viewtopic.php?t=3032 – interesting but not supported by NIH
  11. https://www.health.harvard.edu/staying-healthy/vitamin-b12-deficiency
  12. Vitamin B12 in Vegetarian Diets

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