Vitamin B12 is involved in many functions within the human body. For example it helps make DNA and red blood cells. Additionally, it is needed for the metabolism of fats, proteins and carbohydrates as well as having a role in the brain and nervous system, proper homocysteine metabolism for cardiovascular health and immune system function. It is important to note that this vitamin is essential, meaning it must be consumed through food as the body cannot make its own supply. Foods that contain B12 include mainly animal based foods. Animal sources include dairy products, eggs, fish, meat, and poultry, therefore vegans and vegetarians may wish to supplement their diets to ensure they have an adequate supply, in terms of supplements there are many options. B12 supplementation and intake through food should be on a regular occurrence as vitamin B12 is a water soluble vitamin and therefore is only stored in the body for short amounts of times.
Absorption and Other Functions:
B12 Specific Benefits:
Red Blood Cell Formation and Anemia Prevention:
Inadequate vitamin B12 levels cause a reduction in red blood cell formation and prevent them from developing properly. This is known as megaloblastic anaemia which is characterised by the development of large, immature red blood cells, which do not function very well in terms of oxygen transportation. In cases of anaemia, whereby the body does not have enough red blood cells to transport oxygen to your vital organs, symptoms like fatigue and weakness can occur [i].
One of the most common early signs of vitamin B12 deficiency is fatigue or lack of energy as B12 is valuable for cellular energy production [ii].
Skin and Nails:
Low vitamin B12 levels can cause various symptoms involving the skin; including hyperpigmentation, nail discoloration, vitiligo (the loss of skin colour in patches) and angular stomatitis (inflamed and cracked mouth corners) [iii] [iv].
Bone Health and Prevention of Osteoporosis:
More than 2,500 adults in one study showed that people with a vitamin B12 deficiency also had a suboptimal bone mineral density [v]. Similar studies have also shown a correlation between low vitamin B12 levels and poor bone health and osteoporosis, especially in females [vi] [vii].
Prevention of Birth Defects:
Neural tube defects are very common in cases of nutrient depletion or insufficiency during pregnancy. Furthermore, maternal vitamin B12 deficiency may contribute to premature birth or miscarriage. One study found that women with vitamin B12 levels lower than 250 mg/dL were three times more likely to give birth to a child with birth defects, when compared to those with adequate levels [viii].
Homocysteine and Heart Health Promotion:
Randomised clinical trials have shown that oral supplementation with the combination of folic acid, Vitamin B6, and B12 lowers circulating homocysteine levels [ix]. Homocysteine has been associated with the development of cardiovascular disease [x].
Depression and Mood:
It is thought vitamin B12 plays a critical role in the synthesis and use of serotonin, a brain chemical responsible for regulating mood. A study in people being treated for depression and low vitamin B12 levels found that those who received both antidepressants and vitamin B12 saw improvement in their depressive symptoms, compared to those solely treated with antidepressants [xi].
Methylcobalamin has been noted for its role in neuroprotection; the protection from a decline in neuronal health which can lead to neurodegenerative disease including dementia. This form of (B12) cobalamin supports the restoration of myelin sheath surrounding neurons (nerve cells) which results in improved signalling in the nervous system. Furthermore, there are ongoing investigations into its application in nerve injury models [xii]. One study in people with early-stage dementia showed that a combination of vitamin B12 and omega 3 fatty acid supplements slowed mental decline [xiii].
Asides from inadequate intakes from food, such as vegan and vegetarian diets left un-supplemented, other common causes of deficiency include:
Deficiency is also more common in individuals aged 60 and over [xv] .
Common signs of deficiency/ insufficiency [xvi]:
Insufficient B12 in the body can damage the myelin sheath that surrounds and protect nerve cells. Without this protection, nerves cease to function properly and conditions such as peripheral neuropathy occur. B12 deficiency that is relatively mild may also affect the nervous system and the proper functioning of the brain. Some case studies show evidence that this damage can be recovered from [xvii]. However, it is amongst popular opinion that this damage to the nervous system may be irreversible depending on the extent of the damage [xviii].
Types of Vitamin B12:
Methylcobalamin, adenosylcobalamin and hydroxycobalamin are the forms most readily available on the supplement market. Studies have found these forms to be superior in terms of safety and bioavailability (the amount of substance which successfully enters the bloodstream, and can therefore implement its actions on the body tissues) [xix]. Cyanocobalamin has a longer history of use as a supplemental form, it otherwise occurs only in trace amounts in human tissues as a result of cyanide intake from smoking or other sources. Interestingly, hydroxocobalamin is commonly used as an antidote in cases of cyanide poisoning [xx]. All of the aforementioned B12 forms have been shown in clinical studies to improve vitamin B12 status [xxi]. However, the cyanocobalamin form needs to be broken down to cobalamin and cyanide to be converted to the active forms of B12 in humans. Moreover, one study showed that cyanocobalamin urinary excretion that was 3 times higher than that of methylcobalamin. Thus highlighting that methylcobalamin may be more readily available to body tissues than cyanocobalamin. It was also found in this study that methylcobalamin supplementation caused 13% more cobalamin to be stored in the liver than did cyanocobalamin supplementation [xxii].
[i] Hariz, A. & Bhattacharya, P.T. (2021) ‘Megaloblastic Anemia’. [Updated 2021 Oct 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/b...
[ii] O'Leary, F. & Samman, S. (2010). 'Vitamin B12 in health and disease’. Nutrients, 2(3), 299–316.
[iii] O'Leary, F. & Samman, S. (2010). 'Vitamin B12 in health and disease’. Nutrients, 2(3), 299–316.
[iv] Basavaraj, K. H. Seemanthini, C. & Rashmi, R. (2010). ‘Diet in dermatology: present perspectives’. Indian journal of dermatology, 55(3), 205–210.
[v] Tucker, K.L, Hannan, M.T. Qiao, N,. et al. (2005) ‘Low plasma vitamin B12 is associated with lower BMD: the Framingham Osteoporosis Study’. Journal of Bone Mineral Research. 20(1):152-8.
[vi] Stone, K.L. Bauer, D.C. Sellmeyer, D. et al. (2004) ‘Low serum vitamin B-12 levels are associated with increased hip bone loss in older women: a prospective study.’ Journal of Clinical Endocrinology and Metabolism. 89(3):1217-21.
[vii] Bozkurt, N. Erdem, M. Yilmaz, E. et al. (2009) ‘The relationship of homocyteine, B12 and folic acid with the bone mineral density of the femur and lumbar spine in Turkish postmenopausal women’. Archives of Gynecology and Obstetrics. 280(3):381-7.
[viii] Molloy, A. M. Kirke, P. N. Troendle, J. F. et al. (2009). ‘Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic Acid fortification’. Pediatrics, 123(3), 917–923.
[ix] Maron, B. A., & Loscalzo, J. (2009). T’he treatment of hyperhomocysteinemia’. Annual review of medicine, 60, 39–54.
[x] Ganguly, P. & Alam, S. F. (2015). ‘Role of homocysteine in the development of cardiovascular disease’. Nutrition journal, 14, 6.
[xi] Syed, E. U. Wasay, M. & Awan, S. (2013). ‘Vitamin B12 supplementation in treating major depressive disorder: a randomized controlled trial’. The open neurology journal, 7, 44–48.
[xii] Spence, J.D. (2015) ‘Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke’, Nutrition Research, 36(2);09-116.
[xiii] Oulhaj, A., Jernerén, F., Refsum, H., Smith, A. D., & de Jager, C. A. (2016). Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment. Journal of Alzheimer's disease : JAD, 50(2), 547–557.
[xv] Allen, L.H. (2009) ‘How common is vitamin B-12 deficiency?’ American Journal of Clinical Nutrition. 89(2):693S-6S.
[xvii] Sakly, G. Hellara, O. Trabelsi, A. (2005) ‘Neuropathie périphérique réversible liée au déficit en vitamine B12 [Reversible peripheral neuropathy induced by vitamin B12 deficiency]’. Neurophysiol Clin.;35(5-6):149-53.
[xviii] H. Qiu, R. Green, M. Chen, Chapter 39 - Hematological Disorders Following Bariatric Surgery, Editor(s): Rajkumar Rajendram, Colin R. Martin, Victor R. Preedy, Metabolism and Pathophysiology of Bariatric Surgery, Academic Press, 2017, Pages 351-360.
[xix] Paul, C., & Brady, D. M. (2017). ‘Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms’. Integrative medicine (Encinitas, Calif.), 16(1), 42–49.
[xx] Thompson, J.P. & Marrs, T.C. (2012) ‘Hydroxocobalamin in cyanide poisoning’, Clinical Toxicology, 50(10); 875-885
[xxi] Obeid, R. Fedosov, S.N. Nexo, E. (2015) ‘Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency’. Molecular Nutrition and Food Research. 2015;59(7):1364–1372.
[xxii] Okuda, K. Yashima, K. Kitazaki, T. et al. (1973) ‘Intestinal absorption and concurrent chemical changes of methylcobalamin’. Journal of Laboratory and Clinical Medicine. 81(4):557–567.
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