Rajan S, Wallace JI, Beresford SA, et al. Screening for cobalamin deficiency in geriatric outpatients: prevalence and influence of synthetic cobalamin intake. J Am Geriatr Soc, 2002;50:624630.

B₁₂ deficiency is commonly related to:

• Food.   Cobalamin malabsorption syndrome (MOST COMMON REASON) –  occurs when the stomach lining loses the ability to produce intrinsic factor, a protein that binds to B12 to enable its absorption whenit reaches the lower end of the small intestine;
  • You can be consuming B₁₂ in animal products and still not be absorbing enough of it
  • Those over the age of 50 have limited ability to absorb B₁₂
• Pernicious Anemia.   Progressive automimmune destruction of stomach lining cells:

(1) Reduces secretion of B₁₂– releasing gastric acid and enzymes

AND

(2) Antibodies bind to intrinsic factor preventing formation of B₁₂– IF complex and consequently B₁₂ absorption.

Intramuscular B₁₂ shots are a common treatment, although high dose oral B₁₂ delivers similar amounts (E.g. 1000mg supplies 1 mg B₁₂ by passive absorption) .

Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998;92(4):11911198. (PubMed)

Lederle FA. Oral cobalamin for pernicious anemia. Medicine’s best kept secret? JAMA. 1991;265(1):94-95.

Hathcock JN, Troendle GJ. Oral cobalamin for treatment of pernicious anemia? JAMA. 1991;265(1):96-97.

•  Food-bound vitamin B₁₂ malabsorption.   More common in those over 60 commonly resulting from atrophic gastritis, in which atrophy of stomach glands results in stomach inflammation (possibly associated with H. Pylori)and decreased stomach acid production, and thus nonrelease of B₁₂ from food. This is different to pernicious anemia because intrinsic factor is still available, which means that crystalline-form B₁₂ in supplements or fortified food, which is not bound to protein, can still be absorbed.

•  Aging.   Typically because of dietary insufficiency or malabsorption. Hydrochloric acid (HCl) is needed to release B₁₂ from food, but HCl production decreases with age and HCl levels are decreased by long-term use of antacids or anti-ulcer drugs.

20- 50% of those over 50 are unable to absorb natural (protein-bound) B₁₂

Institute of Medicine. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B₁₂, pantothenic acid, biotin and choline. Washington, DC: National Academy Press 1998.

•  AIDS.   Increases risk of B₁₂ deficiency, possibly due to failure of IF-B₁₂ receptors to take up IF-B₁₂ complex

Shane B. Folic acid, vitamin B₁₂, and vitamin B6. In: Stipanuk M, ed. Biochemical and Physiological Aspects of Human Nutrition. Philadelphia: W.B. Saunders Co.; 2000:483518.

•  Vegan diet.   Animal products are the prime B₁₂ source; predominantly vegetarian cultures (E.g. India) have high B₁₂ deficiency rates.
•  Surgical resection of ileal intestine containing IF- B₁₂ receptors
•  Pancreatic insufficiencies of enzymes or calcium
•  Those taking Metformin.   May interfere with absorption of calcium, required for small intestine receptors to take up B₁₂

Herbert V. Vitamin B₁₂. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. 7th ed. Washington D.C.: ILSI Press; 1996:191205.

Symptoms of B₁₂ deficiency include:

•  Megaloblastic anemia.    Diminished folate production, even in the presence of folate; a symptom of pernicious anemia; produces large, immature, hemoglobin-poor RBCs
•  Neurological.    Numbness/tingling in arms, or legs, difficulty walking, memory loss, disorientation, dementia, possibly due to megaloblastic anemia or nerve sheath damage
•  GI-related symptoms – sore tongue, loss of appetite, constipation

Some diseases associated with B₁₂ deficiency

Reference: Linus Pauling Institute

•  Cardiovascular Disease (CVD) related to elevated homocysteine levels
•  Cancer related to deficiency of folate and its connection to DNA synthesis
•  Neural tube defects – possibly connected to folates role in reducing homocysteine, since increased risk of NTD is associated with elevated levels of homocysteine
•  Alzheimer’s disease / Dementia – possibly connected to B₁₂‘s role in myelin sheath integrity
•  Depression

RDA for adult men and women is 2.4 mcg B₁₂ / day

Absorption or retention rate is related to the dose provided

Institute of Medicine. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid,biotin and choline. Washington, DC: National Academy Press 1998.

Natural B₁₂ Sources

Only bacteria can make B₁₂ –  such that B₁₂ is naturally present bound to protein in fish, animals and their products, but not significantly in plants (unless they still have dirt on them). In this form, B₁₂ must first be cleaved from protein via stomach acidand pepsin to be available for absorption.

*There’s a reason for the high B₁₂ values in shellfish i.e. a high bacterial load!

Who needs to supplement B₁₂?

Non-vegan diet for healthy people should provide sufficient B_12.    However, the following persons should definitely supplement B₁₂

• Strict vegetarians
• Women intending to get pregnant

It is prudent for those with conditions related to B12 malabsorption to empirically supplement B12 (especially given the lack of reliable diagnostic tests together with the low risk of B12supplementation)

• The “Over 50’s”
• Those who have had:
  •  Bariactric surgery
  •  Ileal resection of >20cm
  •  Partial or total gastrectomy may damage/remove parietal cells responsible for gastric acid production
• Those with:
  • Low stomach acid.   Usually due to atrophic gastritis caused by H. Pylori infection, common in over 50’s).    Need B12 in supplemental (non-protein bound) form since they can not depend on hydrochloric acid to cleave B12 from food.
  •  Pernicious anema.   Due to lack of gastric acid and intrinsic factor; those with pernicious anemia need a high dose B12 supplement that relies on the 1% B12 absorption by passive diffusion at the terminal ileum (where the small intestine meets the colon). E.g. Crohn’s disease, Celiac’s disease
  • People with chronic alcoholism.    Due to atrophy of the villi in the small intestines. Lambert D, Benhayoun S, Adjalla C, et al. Alcoholic cirrhosis and cobalamin metabolism. Digestion, 1997;58:64-  71.
  • Whipples Disease.   Causes malabsorption
  •  Chronic pancreatitis.    Insufficient pancreatic secretions impedes cleavage of B₁₂ from B₁₂Rprotein complex, and therefore formation of the B₁₂IF complex. Andres E, VidalAlaball J, Federici L, et al. Clinical aspects of cobalamin deficiency in elderly patients. Epidemiology, causes,clinical manifestations, and treatment with special focus on oral cobalamin therapy. Eur J Intern Med, 2007;18:456- 462.
  • Small intestine bacterial overgrowth.   Bacteria bind B₁₂ for their own use; at risk are those with hypochlorhydria, intestinal dysmotility, intestinal obstructions or adhesions, intestinal diverticuli, blind loops of bowel due to past surgery, and those without an intact ileocecal valve.
• People taking meds that interfere with B₁₂ absorption:
  •  Gastric acid suppressive agents.   i.e. proton pump inhibitors (E.g. omeprazole, lansoprazole), H2inhibitor antagonists (E.g. Tagamet, Pepsid, Zantac);
  •  Cholestyramine (anti-cholesterol)
  •  Neomycin (antibiotic)
  •  Colchine (anti- gout)
  •  Metformin (diabetic med) (ties up needed calcium)
  •  Nitrous oxide (laughing gas) (anaesthetic) inhibits B₁₂-dependent enzymes
• Also those with cirrhosis.    Diminishes liver’s storage capacity of B₁₂; Paradoxically, a degrading liver causes high serum B₁₂ as it releases its stores, although despite raised serum levels, the tissues remain depleted.   Ermens AAM, Vlasveld LT. Significance of elevated cobalamin (vitamin B₁₂) levels in blood. Clin Biochem, 2003;36:585590.