Vitamin B12

Vitamin B12 is from the group of Vitamin B complex. It contains mineral Cobalt and it is also known as cobalamin ⁽¹⁾. It is a water soluble vitamin which can’t be prepared by humans body itself so to meet the requirement you have to consume it through animal foods or supplements.

Function:

• Vitamin B12 is essential for human body as it plays an important role in various cellular functions.
• Vitamin B12 acts as cofactor for enzymes which are essential for DNA synthesis, fatty acid and protein metabolism ⁽²⁾
• It is involved in energy production which is required for human body to function properly.
• Vitamin B12 is required for proper functioning of brain and central nervous system
• It is required in the normal formation of red blood cells. RBCs transport oxygen and in their absence body can’t make enough oxygen.

 Dietary Sources: 

It is an essential nutrient that your body can’t make on its own, so you need to get it from foods or supplementation.

• It is naturally present in animal source foods like dairy products, meat, fish, eggs and shell fish. These contain Vitamin B12 in concentration of 1-10ug/100g wet weight ⁽³⁾.
• Rich sources of Vitamin B12 include:
• Beef
• Pork
• Poultry
• Lamb
• Fish most commonly haddock and tuna
• Dairy products: milk, cheese, and yogurt
• Few nutritional yeast products
• Eggs
• It is not found in plant foods so fortified foods are available for vegetarians. Soy milk and breakfast cereals are fortified with Vitamin B12.

Recommended Dietary Allowance:  The recommended intake for Vitamin B12 is ⁽³⁾. In pregnancy it is 2.6mcg and in lactation 2.8mcg.

 

Age	RDA
0-6months	0.4mcg
7-12months	0.5mcg
1-3years	0.9mcg
4-8years	1.2mcg
9-13years	1.8mcg
14+years	2.4mcg

 High Levels of Vitamin B12:  High levels of Vitamin B12 ranging from 350-1,200 pmol/l indicate that there is some disorder of liver and blood associated with malignancy ⁽⁴⁾

 Vitamin B12 Deficiency: Vitamin B12 deficiency is common and can be assessed by various signs and symptoms. It is mostly associated with poor absorption of vitamin B12 from food ⁽⁴⁾

• Serum Vitamin B12 <150 pmol/L (<200 pg/mL) indicates deficiency
• Serum vitamin B12: 150–221 pmol/L (200–300 pg/mL) indicates depletion.

Fig: Clinical Features of Vitamin B12 Deficiency ⁵

Sign & Symptoms: 

• It leads to damage to brain and nervous system. Patient may experience Nervousness, memory problems, depression and fatigue.
• Other symptoms include numbness and tingling in hands and feet, poor balance and loss of coordination.
• Gastrointestinal symptoms include constipation, weight loss and loss of appetite
• Insufficient vitamin B12 leads to anemia which has symptoms of shortness of breath, paleness, fatigue, diarrhea and sore mouth. .

Diagnosis: 

Missing and late diagnosis results in severe complications including of brain, spinal cord and blood cells. Early diagnosis leads to appropriate management. No gold standard test is available and diagnosis is made based on patient’s condition and laboratory investigations.

 Laboratory Investigations
Blood tests are carried out to assess the deficiency of Vitamin B12. These tests evaluate

• if patient has low level of hemoglobin
• low red blood cells or size of red blood cells larger than normal
• level of vitamin B12 in your blood
• level of folic acid

These tests do not give the accurate assessment so patient symptoms are taken into account to make a final diagnosis and test for pernicious anemia is also carried out. It is the autoimmune condition in which body cannot absorb Vitamin B12 from food leading to deficiency.

Risk factors:

Following individuals are at high risk of developing Vitamin B12 deficiency ⁽⁴⁾

• Old age > 65years
• History of gastric surgery
• Vegan diet
• Chronic gastrointestinal condition (celiac or Chron’s disease)
• Chronic bowel inflammatory condition, parasitic or bacterial infection ⁽²⁾
• Use of medicines as proton-pump inhibitors, H2 receptor antagonists, metformin, anticonvulsants can result in reduction of serum Vitamin B12 levels by inhibiting the absorption ^(6).

 Silent Vitamin B12 deficiency:  It is known as Subclinical Deficiency as there are no clinical signs and symptoms and is found to be more common than symptomatic Vitamin B12 deficiency. Patients with Vitamin B12 levels of 110–148 pmol/l should be re-evaluated in 1–2 months ⁽⁴⁾ and patients with risk factors are also to be assessed periodically.

Toxicity: No toxic effects have been determined with Vitamin B12 even when taken in large amounts. ^(3).

Vitamin B12 deficiency and Health: Vitamin B12 is essential to maintain a good health. Its deficiency whatever the cause is; may lead to various health disorders.

• Neural Tube Defects: These are the birth defects of brain and spinal cord and low levels leads to greater risk. ⁽²⁾
• Cardiovascular Disease: Low levels of Vitamin B12 may lead to higher risk of developing heart conditions. The Study has shown that fortification of food with folic acid along with Vitamin B12 has significantly reduced the risk of cardiovascular disease ⁽⁷⁾
• Cognitive Dysfunction: Vitamin B 12 status is linked with cognitive functioning in older adults. Decreased vitamin B12 levels reflect cognitive impairment and can be corrected by supplementing with Vitamin B12 ⁽⁸⁾. Alzheimer’s disease can also be delayed following supplementation with folate, vitamins B6 and B12 ⁽⁹⁾

 Treatment:

Patient is referred to a specialist depending upon the cause

• A specialist in blood conditions (Hematologist) is to be seen, if you are pregnant or has anemia or symptoms suggest that your nervous system has been affected
• A gastroenterologist is to be seen if your body is not absorbing enough vitamin B12.
• A dietitian is consulted if you are deficient due to poor diet  or a vegetarian

Intramuscular injections are considered the main treatment approach but oral therapy is also effective in most of the cases ⁽³⁾.

IM injection of Vitamin B12 is recommended for 3times a week for 2 weeks if you don’t have any complications of nervous system. Otherwise, injection is given every other day for at least 3 weeks or until any improvement is seen ^(10).

Oral Vitamin B12 therapy with 1 mg is found to be accurate to modify the vitamin B12 levels and cure any clinical manifestation of related to deficiency. It is an effective alternative for IM treatment as it avoids the discomfort, cost and contraindications associated with IM therapy ⁽¹¹⁾

Prevention: Deficiency of Vitamin B12 can be prevented by proper counselling and prior assessment.

• Older Patients are unable to sufficiently absorb Dietary vitamin B12 so they should intake food fortified with Vitamin B12 to avoid any deficiency associated complication
• Patients taking medications like proton pump inhibitors or H2 blockers for more than 12 months and metformin for more than 4 months should be screened for vitamin B12 deficiency.
• Vegetarians should be counseled to take supplements or fortified food.
• Patients who have undergone gastric surgery should take 1mg Oral vitamin B12 per day.

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References

1. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press, 1998. https://www.nal.usda.gov/sites/default/files/fnic_uploads/thiamin_full_report.pdf. Accessed 16.06.2019.
2. O’Leary, F., & Samman, S. (2010). Vitamin B12 in health and disease. Nutrients, 2(3), 299–316. doi:10.3390/nu2030299
3. Allen LH (2012), Vitamin B-12, Advances in Nutrition, Volume 3, Issue 1, Pages 54–55, https://doi.org/10.3945/an.111.001370
4. Michael J Shipton, and Jecko Thachil (2015); Vitamin B12 deficiency – A 21st century perspective; doi: 10.7861/clinmedicine.15-2-145; Clin Med; vol. 15 no. 2 145-150
5. Hunt A, Harrington D, Robinson S (2014); Vitamin B12 deficiency; BMJ;349:g5226. doi: 10.1136/bmj.g5226
6. Miller JW (2018); Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications. Adv Nutr;9(4):511S-518S. doi: 10.1093/advances/nmy023.
7. Quinlivan EP, McPartlin J, McNulty H, Ward M, Strain JJ, Weir DG, Scott JM (2002); Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease. Lancet;359(9302):227-8.
8. Lewis MS, Miller LS, Johnson MA, Dolce EB, Allen RH, Stabler SP (2005).Elevated methylmalonic acid is related to cognitive impairement in older adults enrolled in an elderly nutrition program. J Nutr Elder : 24(3):47-65.
9. Van Dam F1, Van Gool WA (2009); Hyperhomocysteinemia and Alzheimer’s disease: A systematic review. Arch Gerontol Geriatr;48(3): 425-30. doi: 10.1016/j.archger.2008.03.009.
10. LANGAN RC and GOODBRED AJ(2017), Vitamin B12 Deficiency: Recognition and Management; Am Fam Physician; 96(6): 384-389.
11. Andrès, E.; Zulfiqar, A.-A.; Serraj, K.; Vogel, T.; Kaltenbach, G (2018). Systematic Review and Pragmatic Clinical Approach to Oral and Nasal Vitamin B12 (Cobalamin) Treatment in Patients with Vitamin B12 Deficiency Related to Gastrointestinal Disorders.  Clin. Med., 7, 304.