Vitamin B12


Vitamin B12 (cobalamin) is a water-soluble vitamin, which cannot be synthesised by either animals or plants. It is made only by bacteria, making B12 an essential molecule for humans. First identified in 1948, cobalamin is a red compound, containing a corrinoid ring (four pyrrole rings) with an atom of cobalt at its centre. It has the largest molecule of the vitamins, with a molecular weight of 1355. In 1964, Dorothy Hodgkin was awarded the Nobel Prize in Chemistry, for her efforts in elucidating the structure of vitamin B12 by x-ray crystallography. The cobalt atom accepts different ligands on the upper surface (hydroxyl, deoxyadenosine, methyl, cyanide), with methylcobalamin (Me-Cbl) and deoxyadenosylcobalamin (Ado-Cbl) being the active forms of the vitamin, functioning as coenzymes within the cell.


Requirements


A dietary reference intake (DRI) of 2.4mcg/day is a common value chosen for adults. Some researchers suggest that current recommended intake levels may be insufficient for adequate daily intake, given the physiological reductions in absorptive capacity accompanied by aging.


In western countries, the intake of cobalamin in the general population appears to be above the estimated requirements (average intake of B12 in the US is 3.4mcg per day). Despite this, it is not uncommon to see a moderate deficiency among omnivores.

During pregnancy and lactation requirements are increased due to the expansion of tissues and delivery to the foetus or the new-born. The recommended daily allowance (RDA) has been determined at 2.6mcg/day and 2.8mcg/day for pregnant and lactating women, respectively.


A recent report by the European Food Safety Authority (EFSA) panel established an Adequate Intake (AI) of 4mcg/day for adults. The EFSA settled on a safer amount of AI at 4.5mcg/day and 5mcg/day for pregnant and breastfeeding women, respectively.




Sources


The vitamin B12 is found in substantial quantities only in animal products. When the consumption of animal products is low or absent, its scarce presence in plant foods makes introduction in the form of fortified foods or supplements essential. Accounting for the losses during cooking and specific absorption rates, the quantities present in dairy and eggs are not enough to ensure the daily recommended intake in a balanced diet.

Some plant foods seem to represent a significant source of B12, though to date, data in the literature is insufficient to determine if these sources provide B12 in the active form, and whether regular consumption of these foods can be sustainable.


Vegetables like broccoli, asparagus and bean sprouts contain only traces of B12. Tea leaves contains some B12, though not an adequate amount to deem tea a reliable source for daily intake. Shiitake mushrooms can contain a significant amount, though with great variability. Whilst 50g of shiitake mushrooms could satisfy the daily requirement, it is unlikely to be eaten every day. The widely used edible seaweed nori contains relevant amounts of B12. Though currently, there is not enough data to suggest the use of seaweed as a favourable source. Some fermented vegetable foods such as sauerkraut, natto and tempeh can contain significant amounts of B12, though it is unlikely that their daily use in western countries represents a stable source.


The presence of B12 in these foods depends on environmental bacteria randomly present in the fermentative microorganism pool. Meaning it is challenging to standardise the content from one product to another. Supplementation is often avoided due to the preconceptions and aversions to products which are thought to be artificial, or due to the myth that the shortage will manifest itself only in rare cases after many years of ceased intake, a false idea, supported by some researchers.


Cyanocobalamin is the most economical, and historically the most used form in supplements, making it suitable for safe daily use. As the crystalline form of B12 used in supplements is not bound to food proteins, the bioavailability in supplements is equal, if not superior to food sources. There are no apparent substantial differences between the absorption of sublingual and oral forms. The institute of medicine (IOM) considers that naturally occurring B12 in food is absorbed by 50% in healthy adults.


Using multivitamins can be inefficient and counterproductive for the supplementation of B12. The B12 can be degraded in the presence of vitamin C and copper with the formation of inactive by-products. As a water-soluble vitamin with a specific transport system which is easily saturated, accumulation of a harmful amount of B12 is unlikely; you don’t need to worry about taking too much.



Role


Cobalamin is a cofactor in one-carbon transfers through methylation and molecular rearrangement. These processes take place in fatty acid, amino acid and nucleic acid metabolic pathways. As such, vitamin B12 is crucial for neurological function, red blood cell production and DNA synthesis. It is also a cofactor for three major reactions. The conversion of: methylmalonic acid to succinyl coenzyme A, homocysteine to methionine and 5-methyltetrahydrofolate to tetrahydrofolate.


Only two B12 dependent enzymes have been identified in humans. The first, methylmalonyl CoA mutase (requires Ado-Cbl) operates within the mitochondria, in the metabolism of branched-chain amino acids and fatty acids with an odd number of carbon atoms. A shortage of Ado-Cbl leads to an accumulation of methylmalonic acid (MMA). A deficiency of this vitamin form leads to neurological effects. The myelin sheaths of neurons are highly dependent on fatty acid metabolism and the low bioavailability of Ado-Cbl in neurons leads to the depletion of the myelin layer and dysfunctional nerve transmission.


The second, methionine synthase (requires Me-Cbl), participating in the metabolic homocysteine pathway, which is processed into methionine with the involvement of B6 and folate. This pathway is critical in the regeneration of the methyl donor S-adenosylmethionine and its dysfunction creates a shortage, affecting DNA synthesis and the physiological processes that require intense cell replication, such as the hematopoietic process of the erythrocytes.


Cobalamin displays other functions, not strictly metabolic, that could be lacking when deficient. A vitamin B12 deficiency could be related to oxidative stress markers like plasma glutathione, malondialdehyde and serum total antioxidant capacity, which could contribute to a neurophysiological disturbance. Furthermore, B12, can act as a detoxifying agent, removing potentially dangerous molecules from the body. The liver is the main reservoir with a capacity of 1-1.5mg.



Deficiency


Vitamin B12 deficiency is a common condition which can present with non-specific clinical features, and in severe cases with neurological or haematological abnormalities. Classically caused by pernicious anaemia, most cases are now caused due to food-bound cobalamin malabsorption.


Deficiencies are common in the elderly, resulting from secondary hypochlorhydria due to drug treatment or a physiological alteration of the gastrointestinal mucosa itself. The malabsorption can take place in cases of gastric or ileal restrictions, inflammatory bowel disease or for genetic defects in transport and cellular trafficking proteins. Deficiency has been documented in 11-90% of elderly, 63% of pregnant women, 25-86% of children and 21-41% of adolescents.


Deficiency manifests in the blood and central nervous system where B12 plays a key role in cell replication and fatty acid metabolism. Lower cobalamin blood concentrations can promote haematological shortages, resulting in increased mean corpuscular red blood cell volume (MCV) and anaemia through the alteration of erythropoiesis.


Cobalamins key role in neuronal health, and a severe deficiency would inhibit the formation of the myelin sheath, altering correct nerve transmission. Neurological symptoms are caused by progressive demyelination and can include peripheral neuropathy, involuntary movements of the upper extremities, acute onset of dizziness, ataxia, vomiting, mildly impaired cognitive functions, disorientation in time and short-term memory loss. Chronic deficiency can produce a dementia-like state, including episodes of psychosis. Neurological manifestations of vitamin deficiency can also occur in the absence of anaemia. If repletion comes late, the myelin degeneration caused by deficiency can also be irreversible.



Conclusions


A plant-based diet can be sustainable at all stages of life and in all physiological conditions, including infancy, pregnancy, lactation, senescence. Compared to non-vegetarians, vegetarians have reduced body mass index (BMI), serum cholesterol, serum glucose and blood pressure with a lower mortality rate due to ischemic heart disease. However, underestimating the correct supplementation of B12 can cancel out these benefits.

Some seaweed, mushrooms and fermented foods can be a useful source of B12, though content can vary broadly. The standardization of B12 -rich plant foods may be useful in preventing vitamin deficiency, overcoming the frequent ideological barriers on supplementation.

In the general population, vitamin B12 insufficiency is a relatively common finding, with an increased incidence with age. Most cases result in mild symptoms and are due to food bound malabsorption, with pernicious anaemia being much rarer, though often much more severe. A great obstacle in this area is knowing what ‘normal’ vitamin B12 levels should be. The safest, cheapest and most reliable source of vitamin B12 is an oral supplement.

References

Gille, D., & Schmid, A. (2015). Vitamin B12 in meat and dairy products. Nutr Rev, 73(2), 106-115. doi:10.1093/nutrit/nuu011


Langan, R. C., & Goodbred, A. J. (2017). Vitamin B12 Deficiency: Recognition and Management. Am Fam Physician, 96(6), 384-389.

Mann, J. & Truswell, S. (2017). Essentials of human nutrition. (5th ed.). London, United Kingdom: Oxford University Press.


Rizzo, G., Laganà, A. S., Rapisarda, A. M., La Ferrera, G. M., Buscema, M., Rossetti, P., . . . Vitale, S. G. (2016). Vitamin B12 among Vegetarians: Status, Assessment and Supplementation. Nutrients, 8(12). doi:10.3390/nu8120767


Romain, M., Sviri, S., Linton, D. M., Stav, I., & van Heerden, P. V. (2016). The role of Vitamin B12 in the critically ill--a review. Anaesth Intensive Care, 44(4), 447-452. doi:10.1177/0310057X1604400410


Shipton, M. J., & Thachil, J. (2015). Vitamin B12 deficiency - A 21st century perspective. Clin Med (Lond), 15(2), 145-150. doi:10.7861/clinmedicine.15-2-145

  • Instagram
  • Facebook
  • Twitter
  • YouTube