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What is Vitamin B12 and Why is it Important?

The science of nutrition is fascinating, practical, and progressive. As new discoveries regarding specific issues, diets, and nutrients are made, nutrition professionals gain better understanding and sometimes revise existing recommendations. Vitamin B12 is a good example. Findings made in the last few years challenged many assumptions regarding this nutrient and forced scientists to rethink important aspects regarding vitamin B12 needs and recommendations, and deficiency criteria, prevention, and treatment. The information in this article highlights a few of these new discoveries.

Vitamin B12, called cobalamin, is unique for more than one reason. Its chemical structure is more complex than any other vitamin. In addition, cobalamin contains a unique chemical structure that incorporates a mineral: cobalt. Vitamin B12 is made only by microorganisms, such as bacteria. This nutrient is essential for the synthesis of nucleic acids (DNA), which means that its role is critical for growth and development, such as in pregnancy and/or childhood, for example. Vitamin B12 is also essential for the synthesis of myelin, a specific type of nerve coating. Therefore, a deficiency of vitamin B12 may result in the malfunction of both the peripheral and central nervous systems. If untreated, symptoms (which can include tremors, tingling, and feeling pins and needles) can progress to paralysis and spinal cord compression, and could potentially become irreversible. Cobalamin is also essential for the synthesis of all blood cells, including red blood cells. Thus, a deficiency of vitamin B12 may result in anemia and associated symptoms.

Vitamin B12 deficiency is common and happens mainly for three reasons: inadequate intake, malabsorption, or a specific genetic defect called MTHFR mutation. Inadequate intake is often the reason for vitamin B12 deficiency among vegetarians, especially vegans. This is because this vitamin is not naturally found in foods of plant origin. The highest risk for deficiency among vegetarians include those with special physiological needs, such as pregnant and lactating women, infants, and the elderly.

Malabsorption of vitamin B12 occurs among people who have gastrointestinal surgery, those with health conditions affecting the GI tract (such as Celiac disease and Crohn’s disease), and among people who take medication that impacts vitamin B12 absorption and status. For example, individuals taking metformin, aspirin, and/or antacids have an elevated risk of deficiency.

How common is vitamin B12 deficiency among vegetarians?

Vitamin B12 deficiency among vegetarians depends mainly on the type of vegetarian diet individuals adhere to. Vegan individuals have the highest risk and deficiency prevalence, while deficiency among vegetarians, although also wide-spread, is less prevalent. Virtually all studies that have been conducted among vegetarians show a high proportion of participating vegetarians having biochemical vitamin B12 deficiency. In fact, this nutrient deficiency is often seen in more than 50% of the participating individuals, and much higher prevalence—reaching over 70%, 80% and 90%—has been reported. The illustration below shows the prevalence of elevated homocysteine among selected individuals from the Adventist Health Study II (homocysteine is a marker of vitamin B12 status. Among vegetarians, elevated homocysteine indicates vitamin B12 deficiency).

Prevalence of elevated homocysteine among selected participants of the Adventist Health Study II.

Individuals with vitamin B12 deficiency often are misdiagnosed. Some of the common misdiagnoses include dementia, multiple sclerosis, diabetes-related neuropathy, rare neurodegenerative health conditions, autism, or Wilson’s disease. In such cases, progression in manifestation of symptoms continues and may result in disability or death.

Symptoms of vitamin B12 deficiency can be divided into several categories including neurological, psychiatric, oral (manifestation in the oral cavity), dermatological, hematological, and rare manifestations. Selected symptoms for each of the above mentioned categories are listed in the table below. In addition, symptoms related to fertility and pregnancy outcomes (congenital malformations) are common. They may include hypospadias, neural tube defects, spina bifida and anencephaly.

Table 1. Selected symptoms of vitamin B12 deficiency.

Category

Symptoms

Neurological

Deterioration of the myelin, cognitive decline (e.g. memory loss), speech impairment (slurring), difficulty walking, inability to feel the ground, tingling, difficulty concentrating, numbness in both legs, mood alteration/swings, muscle cramps, paralysis, electric shock sensations, jerking movements of abdominal muscles, anxiety, depression, clumsiness, visual impairment

Psychiatric

Disorientation, hyperactivity, decreased need for sleep, reckless and agitated behavior, social withdrawal, decreased interest, apathy, difficulty with falling asleep and concentrating, suspiciousness, hearing voices, hallucinations

Oral

Glossitis, pain and burning sensation in tongue, gradually progressive hoarseness, difficulty eating, red stains on inside of cheeks and tongue, oral epithelial dysplasia

Dermatological

Hyperpigmentation (blackish discoloration of the skin on knuckles, darkening of hands, feet, and tongue), skin lesions on feet, neck, and upper and lower limbs

Hematological

Pancytopenia (low count of all blood cell types), macrocytic anemia, hyperhomocysteinemia

Rare

Anorexia, exercise intolerance, urinary incontinence, persistent watery diarrhea

Although many people with vitamin B12 deficiency do not have overt manifestations of symptoms (for this reason, some scientists call it asymptomatic biochemical deficiency), it does not mean that symptoms are not present. Not all symptoms are manifested in a way that is detectable to individuals with a deficiency. For example, vitamin B12 deficiency is a risk factor for low bone mineral density and increased risk of bone fractures. Similarly, a deficiency is associated with hearing loss. Also, this nutrient deficiency is associated with increased risk of cardiovascular disease, especially stroke, brain atrophy and cognitive decline. Among pregnant women, a deficiency of this vitamin may cause inability to carry a live pregnancy to term.

Of most concern are cases of vitamin B12 deficiency among infants and toddlers. A number of case reports of vitamin B12-related complications among these children born to vegetarian, especially vegan, mothers and/or fed with vegetarian or vegan diets have been published. Infants and toddlers who develop vitamin B12 deficiency are often diagnosed with developmental delays and neurological damages. These children have such profound developmental delays that at age 1, 1.5, or 2 years they may often not be able to sit up properly, eat or even smile, and may have severe deficient weight, height, and head circumference. Unfortunately, even mortalities among infants born to and breastfed by vegetarian and vegan women deficient in vitamin B12 have been reported.

Before more severe symptoms develop, individuals with vitamin B12 deficiency may experience mild and nonspecific symptoms. These symptoms include fatigue, irritability, feeling sleepy, inability to concentrate, feeling pins and needles in legs, tremors, and depression. Anyone with any of the above-listed symptoms should be checked for vitamin B12 deficiency. It is important to realize that vitamin B12 deficiency develops in stages. These stages include 1) inadequate intake, 2) cell vitamin B12 depletion, 3) abnormal biomarkers of vitamin B12 (e.g., low serum vitamin B12 or elevated homocysteine), 4) development of mild symptoms such as fatigue and irritability, and 5) development of severe symptoms including neurological impairments.

When overt symptoms of vitamin B12 are detected, a person may have been deficient for months or even years. Symptoms of vitamin B12 deficiency are progressive and if untreated, some symptoms, especially neurological manifestations, are irreversible. It is equally important to know that in many infants and children diagnosed with vitamin B12 deficiency the diagnosis was made months after the first symptoms of deficiency were manifested (severity of symptoms progressed during this time). These facts underscore the importance of taking preventive measures (described below) to avoid developing a deficiency. The table below summarizes pediatric symptoms of vitamin B12 deficiency.

There are several vitamin B12 assessment techniques. They include serum or plasma B12 concentration, holotranscobalamin II, homocysteine, serum or urinary methylmalonic acid, and mean corpuscular volume (MCV). Holotranscobalamin II and methymalonic acid are the most accurate assessment methods while serum or plasma B12 and MCV are believed to be unreliable. Unfortunately, physicians often check for either of the two least reliable measurements and often rule out vitamin B12 deficiency as a cause of symptoms based on the outcomes of these assessments. Another unfortunate practice is the range of serum vitamin B12 used as normal. Symptoms of vitamin B12 deficiency have been described among individuals with serum vitamin B12 lower than 300 pmol/L (and in some cases even with higher serum B12 values). “Normal” range of vitamin B12 is often given as one between 148 to 780 pmol/L. Also, if homocysteine concentration was assessed, a value of less than 15 μmol/L is often used a normal homocysteine concentration. However, much lower homocysteine concentrations have been associated with vitamin B12 deficiency symptoms, such as increased risk of arterial stenosis. To correctly assess vitamin B12 status, it is recommended that assessment is done using at least two different measurements (e.g. serum vitamin B12 and homocysteine). The table below includes normal values for the different vitamin B12 assessment methods.

Table 2. Reference values for vitamin B12 biomarkers.

Meat and animal products naturally contain vitamin B12. However, because of their detrimental effect on the risk of developing several chronic health conditions, including heart disease, cancer, diabetes, and Alzheimer’s disease, it is best to avoid consuming these products. Some plant foods are fortified with vitamin B12. They include some soymilks, tofu, and some cereal products. However, it is unlikely that the amount of vitamin B12 in these products is sufficient to maintain a high enough serum vitamin B12 concentration. Thus, the most reliable way to prevent vitamin B12 deficiency among individuals at risk of vitamin B12 deficiency is to take vitamin B12 supplements. A dose of 250 μg per day is adequate for most adults. Elderly individuals should consider taking a higher dose (e.g. 500 μg). Children should be taking smaller amounts, between 5 to 25 μg, depending on age. For deficient individuals, high dose supplements or vitamin B12 injections are recommended. Physicians should be consulted in making such decisions.

 

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Notes & References:

1. Watanabe F. Vitamin B12 Sources and Bioavailability. Exp Biol Med 2007;232:1266–1274.

2. Koury MJ & Ponka P. New insight into erythropoiesis: The Roles of Folate, Vitamin B12, and Iron. Annu Rev Nutr, 2004;24:105-131.

3. Yetley EA, Pfeiffer CM, Phinney KW, Bailey RL, Blackmore S, Bock JL, Brody LC, Carmel R, Curtin RL, Durazo-Arvizu RL, Eckfeldt JH, Green R, Gregory JF, Hoofnagle AN, Jacobsen DW, Jacques PF, Lacher DA, Molloy AM, Massaro J, Mills JL, Nexo E, Rader JI, Selhub J, Sempos C, Shane B, Stabler S, Stover P, Tamura T, Tedstone A, Thorpe SJ, Coates PM, Johnson CL, Picciano MF. Biomarkers of vitamin B-12 status in NHANES: a roundtable summary. Am J Clin Nutr, 2011;94(suppl):313S–321S.

4. Allen LH. How common is vitamin B12 deficiency? Am J Clin Nutr, 2009;89(suppl):693S–696S.

5. Stabler SP. & Allen RH. Vitamin B12 deficiency as a world-wide problem. Annu Rev Nutr, 2004;24:299–326.

6. Johnson MA, Hawthorne NA, Brackett WR, Fischer JG, Gunter EW, Allen RH, Stabler SP. Hyperhomocysteinemia and vitamin B12 deficiency in elderly using Title IIIc nutrition services. Am J Clin Nutr, 2003;77:211-220.

7. Anthony A. Vegetarianism and vitamin B-12 (cobalamin) deficiency. Am J Clin Nutr, 2003;78:3–6.

8. Pfeiffer CM, Caudill SP, Gunter EW, Osterloh J, and Sampson EJ. Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999–2000 Am J Clin Nutr, August 2005;82:442-450.

9. Allen LH,Rosenberg IH,Oakley GP,Omenn GS. Considering the case for vitamin B12 fortification of flour. Food and Nutrition Bulletin, 2010;31;S36-S46.

10. Carmel R. Efficacy and safety of fortification and supplementation with vitamin B12: Biochemical and physiological effects. Food and Nutrition Bulletin, 2008;28(2):S177-S187.

11. Pawlak, R., Parrott, SJ., Raj, S., Cullum-Dugan, D., & Lucus, D. (2012). How prevalent is vitamin B12 among vegetarians? Nutrition Reviews, 2013;71(2):110-117.

12. Pawlak, R., Parrott, SJ., Raj. S., Cullum-Dugan, D., Lucus, D. (2012). Understanding vitamin B12. American Journal of Lifestyle Medicine, 7(1):59-65.

13. Rusher, DR., & Pawlak, R. (2013). A Review of 89 Published Case Studies of Vitamin B12 Deficiency. J Hum Nutr Food Sci 1(2): 1008.

14. Pawlak R. Jestem mama jestem wegetarianka (I am a mother, I am a vegetarian). 1st edition. ISBN 078-83-52103-65-2.

15. Pawlak R. “Zatrzymac mlodosc. Jak opoznic proces starzenia sie i zyc bez chorob.” 1st edition. ISBN 978-83-62103-47-8

16. Pawlak R. W obronie wegetarianizmu (In defense of vegetarianism). Nowe Spojrzenia. 2nd edition. 2012 ISBN-978-83-61640-27-1.

17. Krivosikova S, Krajcovicova-Kudlackova M, Spustova V, Stefikova K, Valachovicova M, Blazicek P, Nemcova T. The association between high plasma homocysteine levels and lower bone mineral density in Slovak women: the impact of vegetarian diet. Eur J Nutr. 2010;49(3):147–153

18. Kwok T, Chook P, Qiao M, Tam L, Poon YK, Ahuja AT, Woo J, Celermajer DS, Woo KS. Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status. J Nutr Health Aging. 2012;16(6):569-573.

19. Waldmann A, Koschizke JW, Leitzmann C, Hahn A. German vegan study: Diet, life-style factors, and cardiovascular risk profile. Ann Nutr Metab. 2005;49(6):366–372.

20. Elmadfa I, Singer I. Vitamin B-12 and homocysteine status among vegetarians: a global perspective. Am J Clin Nutr. 2009;89(5)(suppl):1693S–1698S.

 

Roman Pawlak, Ph.D, RD is Associate Professor of Nutrition in the Department of Nutrition Science at East Carolina University.

Photo by Nyana Stoica on Unsplash

 

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