Less than 20 years ago, patients complaining of fatigue were often given a "tonic shot" by their doctor. Many people claimed this worked like magic to improve their energy levels. What was this miracle tonic? A simple injection of vitamin B-12.
Although the practice of administering vitamin B-12 injections has fallen out of favor, modern medical science now understands why vitamin B-12 supplementation makes people feel better, and the reasons extend far beyond just the "placebo effect" of receiving a shot.
The Far-Reaching Effects of Vitamin B-12 Deficiency
Vitamin B-12, called "cobalamin" because it contains the mineral cobalt, is required for a staggering number of physical functions and chemical reactions. Best known for its participation in the manufacture of red blood cells, B-12 is also needed for production and maintenance of the myelin sheath that surrounds nerves and for production of DNA, the genetic material of all cells. And that's just the beginning.
The serious health consequences of vitamin B-12 deficiency can adversely affect nearly every system in the body.
Energy: Even minor deficiencies of vitamin B-12 can cause anemia, fatigue, shortness of breath and weakness.
The Nervous System: Deficiencies of B-12 can cause neurological changes including numbness and tingling in the hands and feet, balance problems, depression, confusion, poor memory and Alzheimer's-like symptoms. Long-term deficiencies of B-12 can result in permanent impairment of the nervous system.
The Gastro-Intestinal System: B-12 deficiency can cause decreased appetite, constipation, diarrhea or alternating constipation/diarrhea, weight loss and abdominal pain.
The Immune System: Vitamin B-12 is necessary for normal functioning of white blood cells. Studies show that B-12 helps regulate Natural-Killer T-cells and prevents chromosome damage.
The Cardiovascular System: Vitamin B-12 participates in the conversion of homocysteine to methionine. Elevated homocysteine levels are a known independent risk factor for heart attack, stroke and thrombosis. Without adequate B-12 levels, homocysteine levels typically rise.
Special Senses: Degenerative changes in the central nervous system caused by B-12 deficiency can also affect the optic nerve, resulting in blue-yellow color blindness.
Other symptoms of vitamin B-12 deficiency include sore mouth or tongue.
With so many physical functions at risk, it is easy to understand why knowledgeable clinicians and researchers consider B-12 supplementation beneficial.
Are You At Risk for a Vitamin B-12 Deficiency?
Medical science once believed that few people were vitamin B-12 deficient. This false assumption may stem from the fact that vitamin B-12 is produced in the body by a normal, healthy population of bowel bacteria.
Secondly, unlike other water-soluble vitamins, B-12 is stored in the liver, kidneys and other tissues. Deficiencies of B-12 often appear so slowly and subtly as to go unnoticed, and blood tests for vitamin B-12 levels miss early deficiency states at least 50% of the time.
So, who is at risk for vitamin B-12 deficiency? Recent research shows that a much larger segment of the population is likely deficient than previously thought.
Because assimilation of vitamin B-12 from food requires adequate stomach acid and intrinsic factor, and because stomach acid typically declines with age, people over 50 were once thought to be the biggest "at risk" population for B-12 deficiency. Previous studies showed 3% to 39% of seniors to be vitamin B-12 deficient, but newer studies suggest that number may be as high as 72% to 78%.
Vegetarians and vegans are another population believed to be at high risk for B-12 deficiency, in part because of low animal food intake of vitamin B-12 and also because many vegetable sources such as seaweed must be consumed in large amounts in order to provide adequate vitamin B-12.
Other high-risk groups for B-12 deficiency include:
• Those who use acid-blocking or neutralizing drugs (such as Prilosec, Prevacid, Nexium and others), or drugs which impair intestinal absorption (such as Metformin, Questron and Chloromycetin),
• People who have had gastric surgery,
• And people who have chronic illnesses such as ME/CFS and Fibromyalgia. (For an explanation of two complex models suggesting a connection between vitamin B-12 deficiency and ME/CFS - The Nitric Oxide Cycle and the Methylation Cycle - see "Deficiency in ME/CFS and FM May Provide Clues & Relief")
Bacterial overgrowth of the small intestine, which occurs frequently in people with low stomach acid, is a predisposing factor for B-12 deficiency because the bacteria themselves use vitamin B-12.
The most recent and disturbing studies suggest that vitamin B-12 deficiency is more prevalent in young adults than previously thought. One study found that vitamin B-12 deficiency was similar in three age groups (26-49 years, 50-64 years, and 65 years and older), but that early symptoms were simply less apparent in the young.
This study also found that those who did not take a vitamin B-12 containing supplement were twice as likely to be deficient as supplement users, regardless of age.
Four Forms of B-12 - Which One is Best?
Cobalamin is a collective term for four closely related forms of B-12 - cyanocobalamin, methylcobalamin, hydroxycobalamin, and adenosylcobalamin (dibencozide).
Cyanocobalamin, the most common form of B-12 found in nutritional supplements, has the lowest biological activity and must be converted in the liver to methylcobalamin or adenosylcobalamin before it can be utilized.
Because it can be converted to other forms of B-12, cyanocobalamin can be considered the "mother form" of B-12. However, this conversion is inefficient and some people may not benefit from cyanocobalamin due to lack of assimilation or conversion.
Methylcobalamin is considered by many researchers to be the most active form of vitamin B-12. It protects the nervous system by regulating glutamate-induced neuronal damage (common in aging) and promoting nerve cell regeneration.
Methylcobalamin is the only form of vitamin B-12 that participates in regulating circadian rhythms (sleep/wake cycles). It has been shown to improve sleep quality and refreshment from sleep, as well as increasing feelings of well-being, concentration and alertness.
Adenosylcobalamin (dibencozide), the second highly active form of vitamin B-12, is essential for energy metabolism. It is required for normal myelin sheath formation and nucleoprotein synthesis. Deficiencies are associated with nerve and spinal cord degeneration.
Hydroxocobalamin is a unique form of B-12 that participates in detoxification, especially cyanide detoxification. Cyanide levels are often elevated in smokers, people who eat cyanide-containing food (like cassava) and those with certain metabolic defects.
Excess cyanide in the tissues blocks conversion of cyanocobalamin to methylcobalamin or adenosylcobalamin. In such instances, hydroxocobalamin may be the vitamin B-12 of choice. Hydroxycobalamin is FDA-approved as a treatment for cyanide poisoning.
Oral Vs. Injectable: Which Delivery System is Preferred?
Although many people including some physicians still believe that injectable vitamin B-12 is the preferred route of administration, it is well-known and widely accepted that oral vitamin B-12 is equally as effective as injection in treating pernicious anemia and other B-12 deficient states.
Conclusions and Recommendations
• Vitamin B-12 deficiency is far more widespread than previously thought, with up to 30% of young people affected and possibly as many as 78% of the over 50 population suffering from deficiency.
• Those at special risk include:
- Vegetarians and vegans,
- People taking acid-neutralizing drugs or various other drugs, and
- Patients with cognitive impairment and/or chronic illnesses.
• The U.S. Institute of Medicine recommends that adults over 50 obtain their vitamin B-12 from supplements.
• Because symptoms of vitamin B-12 deficiency often manifest months or years before B-12 blood tests become abnormal, early deficiencies are often missed.
• Symptoms and side effects of B-12 deficiency are many and varied, can mimic other diseases such as Chronic Fatigue Syndrome, and can produce irreversible changes of the nervous system if not corrected early.
• Oral vitamin B-12 supplementation is extremely safe, as effective as injections, comparatively inexpensive, and more convenient than injections.
• Those at risk of vitamin B-12 deficiency or with symptoms suggestive of B-12 deficiency should consider adding this important nutrient to their supplement protocol.
- Herbert V. Vitamin B-12 in Present Knowledge in Nutrition. 17th ed. Washington, D.C.: International Life Sciences Institute Press,1996.
- Combs G. Vitamin B-12 in The Vitamins. New York: Academic Press, Inc, 1992.
- Healton EB, Savage DG, Brust JC, Garrett TF, Lindenbaum J. Neurological aspects of cobalamin deficiency. Medicine 1991;70:229-244.
- Herbert V and Das K. Vitamin B-12 in Modern Nutrition in health and disease. 8th ed. Baltimore: Williams & Wilkins, 1994.
- Zittoun J and Zittoun R. Modern clinical testing strategies in cobalamin and folate deficiency. Sem Hematol 1999;36:35-46.
- Bottiglieri T. Folate, vitamin B-12, and neuropsychiatric disorders. Nutr Rev 1996;54:382-90.
- Roze E, Gervais D, Demeret S, Ogier de Baulny H, Zittoun J, Benoist JF, Said G, Pierrot-Deseilligny C, Bolgert F.Neuropsychiatric disturbances in presumed late-onset cobalamin C disease.Arch Neurol. 2003 Oct;60(10):1457-62.
- Robertson JS, Hsia YE, Scully KJ.Defective leukocyte metabolism in human cobalamin defieciency: impaired propionate oxidation and serine biosynthesis reversible by cyanocobalamin therapy.J Lab Clin Med. 1976 Jan;87(1):89-97.
- Tamura J, Kubota K, Murakami H, Sawamura M, Matsushima T, Tamura T, Saitoh T, Kurabayshi H, Naruse T. Immunomodulation by vitamin B-12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B-12-deficient patients by methyl-B-12 treatment. Clin Exp Immunol. 1999 Apr;116(1):28-32.
- Fenech MF, Dreosti IE, Rinaldi JR.Folate, vitamin B-12, homocysteine status and chromosome damage rate in lymphocytes of older men. Carcinogenesis. 1997 Jul;18(7):1329-36.
- Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). NationalCholesterol Education Program, NationalHeart, Lung, and Blood Institute, National Institues of Health, September 2002. NIHPublication No. 02-5215.
- Selhub J, Jacques PF, Bostom AG, D'Agostino RB, Wilson PW,Belanger AJ, O'Leary DH, Wolf PA, Scaefer EJ, Rosenberg IH. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N Engl J Med 1995;332:286-91.
- Rimm EB, Willett WC, Hu FB, Sampson L, Colditz G A, Manson J E, Hennekens C, Stampfer M J. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. J Am Med Assoc 1998;279:359-64.
- Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med 1998;49:31-62.
- Boers GH. Hyperhomocysteinemia: A newly recognized risk factor for vascular disease. Neth J Med 1994;45:34-41.
- Selhub J, Jacques PF, Wilson PF, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. J Am Med Assoc 1993;270:2693-8.
- Malinow MR. Plasma homocyst(e)ine and arterial occlusive diseases: A mini-review. Clin Chem 1995;41:173-6.
- Flynn MA, Herbert V, Nolph GB, Krause G. Atherogenesis and the homocysteine-folate-cobalamin triad: do we need standardized analyses? J Am Coll Nutr 1997;16:258-67.
- Fortin LJ, Genest J, Jr. Measurement of homocyst(e)ine in the prediction of arteriosclerosis. Clin Biochem 1995;28:155-62.
- Siri PW, Verhoef P, Kok FJ. Vitamins B6, B-12, and folate: Association with plasma total homocysteine and risk of coronary atherosclerosis. J Am Coll Nutr 1998;17:435-41.
- Remacha AF, Souto JC, Rámila E, Perea G, Sarda MP, Fontcuberta J.Enhanced risk of thrombotic disease in patients with acquired vitamin B-12 and/or folate deficiency: role of hyperhomocysteinemia.Ann Hematol. 2002 Nov;81(11):616-21. Epub 2002 Nov 9.
- Beers, M.H., Berkow, R. et al. The Merck Manual of Diagnosis and Therapy, Seventeenth Edition, 1999 Merck and Co., Chapter 127 page 867.
- Monsen ALB and Ueland PM. Homocysteine and methylmalonic acid in diagnosis and risk assessment from infancy to adolescent. American Journal of Clinical Nutrition 2003; 78:7-21.
- Carmel R. Megaloblastic anemias. Curr Opin Hematol 1994;1:107-12.
- Oh R, Brown DL. Vitamin B-12 deficiency. Am Fam Physician. 2003 Mar 1;67(5):979-86.
- Pennypacker LC, Allen RH, Kelly JP, Matthews LM, Grigsby J, Kaye K, Lindenbaum J, Stabler SP.High prevalence of cobalamin deficiency in elderly outpatients.J Am Geriatr Soc. 1992 Dec;40(12):1197-204.
- Rajan S, Wallace JI, Brodkin KI, Beresford SA, Allen RH, Stabler SP.Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults.J Am Geriatr Soc. 2002 Nov;50(11):1789-95.
- Akaike A, Tamura Y, Sato Y, Yokota T. Protective effects of a vitamin B-12 analog, methylcobalamin, against glutamate cytotoxicity in cultured cortical neurons. Eur J Pharmacol. 1993 Sep 7;241(1):1-6.
- Kikuchi M, Kashii S, Honda Y, Tamura Y, Kaneda K, Akaike A.Protective effects of methylcobalamin, a vitamin B-12 analog, against glutamate-induced neurotoxicity in retinal cell culture. Invest Ophthalmol Vis Sci. 1997 Apr;38(5):848-54.
- Watanabe T, et al. 1994. Ultra-high dose methylcobalamin promotes nerve regeneration in experimental acrylamide neuropathy. J Neurol Sci 122:140-43.
- Mayer G.,Kroger M., Meier-Ewert K.Effects of vitamin B-12 on performance and circadian rhythm in normal subjects. Neuropsychopharmacology,1996, vol. 15, no5, pp. 456-464.
- Olle Selinus, B. J. Alloway. Essentials of Medical Geology. Academic Press, 2005,p.519.ISBN 0126363412.
- The Pharmacological Basis of Therapeutics, Goodman and Gillman, Tenth Edititon, Page-1503-1513.
- R.S.Satoskar & S.D. Bhanderkar. Pharmacology and Therapeutics, Revised 12th, Page No.424-425.
- Linnell JC, Matthews DM. Cobalamin metabolism and its clinical aspects. Clin Sci (Lond). 1984 Feb;66(2):113-21.
- Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 2000.
- Lederle FA. Oral cobalamin for pernicious anemia: back from the verge of extinction. J Am Geriatr Soc 1998;46:1125-7.
- Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood 1998;92: 1191-8.
- Lederle FA. Oral cobalamin for pernicious anemia. Medicine's best kept secret? JAMA 1991;265:94-5.
- Bolaman Z, Kadikoylu G, Yukselen V, Yavasoglu I, Barutca S, Senturk T.Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study.Clin Ther. 2003 Dec;25(12):3124-34.
- Swain R. An update of vitamin B-12 metabolism and deficiency states.J Fam Pract. 1995 Dec;41(6):595-600.
- Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B-12, pantothenic acid, biotin, and choline. National Academy Press. Washington, DC, 1998.
- van Goor L, Woiski MD, Lagaay AM, Meinders AE, Tak PP.Review: cobalamin deficiency and mental impairment in elderly people. Age Ageing. 1995 Nov;24(6):536-42.
- Martin DC, Francis J, Protetch J, Huff FJ. Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study. J Am Geriatr Soc. 1992 Feb;40(2):168-72.
45. National Institutes of Health Fact Sheet on vitamin B-12 http://ods.od.nih.gov/factsheets/vitaminB-12.asp
46. Louwman MW, van Dusseldorp M, van de Vijver FJ, Thomas CM, Schneede J, Ueland PM, Refsum H, van Staveren WA. Signs of impaired cognitive function in adolescents with marginal cobalamin status. Am J Clin Nutr. 2000 Sep;72(3):762-9.
- Nilsson-Ehle H. Age-related changes in cobalamin (vitamin B-12) handling. Implications for therapy. Drugs Aging. 1998 Apr;12(4):277-92.
- Garcia A, Paris-Pombo A, Evans L, Day A, Freedman M.Is low-dose oral cobalamin enough to normalize cobalamin function in older people?J Am Geriatr Soc. 2002 Aug;50(8):1401-4.
- Kwok T, Tang C, Woo J, Lai WK, Law LK, Pang CP.Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels.Int J Geriatr Psychiatry. 1998 Sep;13(9):611-6.
* Dr. Dana Myatt, NMD, is a practicing naturopathic family physician, educator, author, and speaker with a special interest in nutrition. She lectures widely to medical and lay audiences, and hosts a website (DrMyattsWellnessClub.com). Mark Ziemann, RN, Dr. Myatt's husband and collaborator, is also an educator, author, and speaker specializing in holistic nursing practice and patient education.
See also “B-12 Deficiency in ME/CFS and Fibromyalgia May Provide Clues & Relief,” another article by Myatt & Ziemann explaining the possible role of B-12 deficiency in chronic fatigue syndrome, fibromyalgia, and related illnesses.
Note: This information has not been evaluated by the FDA. It is generic and is not meant to prevent, diagnose, treat, or cure any condition, illness, or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.