Vitamin B12 Deficiency, the Epidemic of Misdiagnosis

by Jeffrey Dach MD

this article is part one of a series, for part two click here.

A good friend of ours, otherwise healthy, had severe leg pain which baffled her doctors who could not explain it. After many months of suffering and no relief from many different medications and treatments, she tried inexpensive vitamin B12 injections, which gave her complete relief. Occasionally the pain returns and reminds her that it is time for another B12 injection. The injections are simple to do, with a syringe and tiny needle, the B12 is injected under the skin twice a week. Above Left Image B12 sign Courtesy Wikipedia.

I found this B12 story interesting, and there are many more B12 stories of misdiagnosis in this book, Could It Be B12?: An Epidemic of Misdiagnoses?” by Sally M. Pacholok R.N. and Jeffrey J Stuart D.O. (1).

How Common is B12 Deficiency?

Vitamin B12 deficiency is estimated to affect 10%-15% of individuals over the age of 60 (2). A recent study in Israel of elderly hospitalized patients found 40% had low or borderline serum B12 levels. (3). Vegetarians are another group with inadequate dietary B12 intake since much of our B12 comes from meat consumption. A recent study showed 50% of long term vegetarians have B12 deficiency, with decreased serum B12 levels and elevated homocysteine levels. (4) (5)

What Causes B12 Deficiency?

B12 is a large molecule (see diagram at left), and Gastrointestinal absorption depends on many Co-factors, so that it is quite possible to take adequate amounts of B12 in the diet, yet have a B12 deficiency from malabsorption.

Left image B12 Chemical Structure, Note Cobalt at center of ring, surrounded by four nitrogen molecules, courtesy of Wikipedia.

Low Gastric Acid-Acid Blocking Drugs

Absorption of B12 requires gastric acid, so anything which reduces gastric acid production such as gastric surgery, atrophic gastritis, or antacid drugs could produce B12 deficiency. The very popular class of antacid drugs called PPI’s (proton pump inhibitors) such as Prilosec (omeprazole) has been clearly shown to decrease B12 absorption. (6)(7). Other antacid pills such as Prevacid, Protonix, Zantac, Nexium, Aciphex, Zantec, Tagamet, Pepcid, Maalox, Mylanta, reduce gastric acid, inhibit B12 absorption, and may produce B12 deficiency.

Diabetes Drugs and Others



Drugs such as Metformin and other diabetes drugs can cause B12 deficiency. The anesthetic agent, Nitrous Oxide, or “laughing gas”, used in dental or surgical procedures causes B12 deficiency. (8)(9)(10)

Pernicious Anemia

Pernicious anemia is the second most common cause of B12 deficiency. This is an autoimmune disease with loss of Intrinsic Factor, in which antibodies damage the stomach lining interrupting the B12 absorption mechanism. The diagnosis is made with blood test positive for anti-parietal cell antibodies.

Vegetarians

Other people at risk for B12 deficiency include vegetarians, people with eating disorders such as bulemia and anorexia, inflammatory bowel disease with malabsorption (crohn’s). Auto-immune diseases such as Hashimoto’s thyroiditis may be associated with B12 deficiency(pernicious anemia). In addition,

Defective B12 Transport Proteins-Genetic Functional B12 Deficiency

Miller has identified genetic defects in which transport proteins are absent or deficient causing B12 deficiency (11). Diagnosis can be difficult. By running the urinary methyl malonate and the serum B12 test together, one can detect genetic transport protein defect. The serum B12 will be normal in the face of a very elevated urinary methylmalonate. This diagnosis will be missed by conventional doctors who order only a serum B12 and do not run a urinary methyl malonate. These patients have a severe functional B12 deficiency, sometimes symptomatic for many years, which responds well to B12 injections.

Symptoms Which Might Indicate a B12 Deficiency

Neurological Symptoms

Vitamin B12 deficiency can cause unusual neurological symptoms such as tremor, gait disturbance, severe pain, and can mimic MS (multiple sclerosis) or even Parkinson’s Syndrome. B12 deficiency damages the the fatty insulating material surrounding the nerve fibers called myelin sheath. This myelin sheath is also similarly damaged in demyelinating diseases such as multiple sclerosis.

Mental Changes:

B12 deficiency may cause Irritability, apathy, sleepiness, paranoia, personality changes, depression (including post-partum depression), memory loss, dementia, cognitive dysfunction or deterioration, fuzzy thinking, psychosis, dementia, hallucinations, violent behavior, in children; autistic behavior, developmental delay.

Neurological Signs and Symptoms:

B12 deficiency may cause abnormal sensations (pain, tingling, and/or numbness of legs, arms trunk or anywhere),diminished sense of touch, pain or temperature (may mimic diabetic neuropathy Charcot foot), loss of position sense, weakness, clumsiness, tremor, any symptoms which may mimic parkinson’s or multiple sclerosis, spasticity of muscles, incontinence, paralysis, vision changes, damage to optic nerve (optic neuritis).

Vascular Problems:

Atherosclerotic vascular disease is increased by B12 deficiency including; Coronary artery disease, Transient Ischemic Attack (TIA), Cerebrovascular accident, stroke (CVA), heart attack, heart failure, claudication, are all associated with elevated homocysteine levels caused by B12 deficiency.

Megaloblastic Anemia (enlarged red blood cells with anemia)

Large Read Blood Cells.

B12 deficiency may be associated with a peculiar type of anemia, the red blood cells are fewer in number, yet larger in diameter (called megaloblastic) and is measured on the CBC with the mean corpuscular volume, MCV). The anemia can cause fatigue, and weakness. (left image: Red blood cells courtesy of wikimedia commons)

Increased Cancer Risk from B12 Deficiency

Cervical Dysplasia and increased risk for other dysplasias and cancers are associated with B12 deficiency. B12 supplementation is part of our cancer prevention program.

Testing for the Diagnosis of B12 Deficiency

Most doctors ignore B12 testing, and even they do a blood test, they do the standard serum B12 only.(12) A more accurate screening method is to run both serum B12 and the urinary methyl malonate test.(13)(15)(16) This is our office routine. It is important to discover B12 deficiency early, since nerve damage can be irreversible if diagnosis is delayed/

B12 Treatment

B12 comes in various forms. For the more severe cases, genetic transport protein defect and B12 deficiency associated with neurological symptoms, B12 injections with hydroxycobalamin 1,000 mg weekly is standard. This is ordered from the compounding pharmacy and shipped to the patient’s home for self injection at home. The corner drug store version is the Cyano-Cobalmine injectable which in my opinion is an inferior form of B12, and no longer preferred. For the finicky patient who declines the B12 injectable, there is another option called Nascobal, a Nasal Spray form of Cyanocobalamin, one nostril once a week.

Most people prefer the B12 sublingual tablets. We use the 5 mg SL tabs from Source Naturals MethylCobalamin Vitamin B-12, These are Cherry Flavored sublingual tablets. In addition, Methylcobalamin oral capsules are widely available. Kuzminski showed that daily 2 mg. oral B12 serves as well as monthly 1 mg intramuscular B12 injections.(14)

Book: Could It Be B12?: An Epidemic of Misdiagnoses ?” by Sally M. Pacholok R.N. and Jeffrey J Stuart D.O. (1).

Articles with Related Content:

B12 Deficiency and Neuro-Psychiatric Disorders

Antacids Associated With B12 Deficiency

Multiple Sclerosis, B12 and Vitamin D

The Lady in Grey Hair Loss from Low Gastric Acid

Jeffrey Dach MD

7450 Griffin Road Suite 190

Davie, Fl 33314

954-792-4663

1) Could It Be B12?: An Epidemic of Misdiagnoses ?” by Sally M. Pacholok R.N. and Jeffrey J Stuart D.O.

(2) http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.nutr.19.1.357

Annual Review of Nutrition Vol. 19: 357-377 (Volume publication date July 1999) VITAMIN B12 DEFICIENCY IN THE ELDERLY , H.W. Baik and ­ R.M. Russell ­USDA Human Nutrition Research Center on Aging at Tufts University

(3) http://www.ncbi.nlm.nih.gov/pubmed/11426294

J Nutr Health Aging. 2001;5(2):124-7.High prevalence and impact of subnormal serum vitamin B12 levels in Israeli elders admitted to a geriatric hospital. Shahar A, Feiglin L, Shahar DR, Levy S, Seligsohn U.

(4) http://www.ajcn.org/cgi/content/full/70/3/626S#SEC4

Cobalamin studies on 2 total vegetarian (vegan) families. Milton G Crane, UD Register, and Richard Lukens. Weimar Institute, Weimar, CA, and the Department of Medicine and School of Public Health, Loma Linda University, CA. Funded by Donald and Barbara Cox and the Callicott-Register fund.

(5) http://www.ncbi.nlm.nih.gov/pubmed/12011576?dopt=Abstract

Ann Nutr Metab. 2002;46(2):73-9.Effect of vegetarian diet on homocysteine levels.Bissoli L, Di Francesco V, Ballarin A, Mandragona R, Trespidi R, Brocco G, Caruso B, Bosello O, Zamboni M.

(6) http://www.ncbi.nlm.nih.gov/pubmed/10369631

Ann Pharmacother. 1999 May;33(5):641-3.Omeprazole and vitamin B12 deficiency. Bradford GS, Taylor CT. Birmingham Baptist Medical Center

(7) http://www.ucpress.edu/books/pages/10083/10083.ch08.php

Merrill Goozner The $800 Million Pill The Truth behind the Cost of New Drugs Chapter 8, Me Too, Story of the Drug Industry in America 1930 to 2000, Prolosic, Nexium. H Pulori, etc. Patents for living things 1980- oil eating bacteria Merrill Goozner is former Chief Economics Correspondent at the Chicago Tribune.

(8) http://www.ncbi.nlm.nih.gov/pubmed/3949064

Int J Biochem. 1986;18(2):199-202.Nitrous oxide induced vitamin B12 deficiency: measurement of methylation reactions in the fruit bat (Rousettus aegyptiacus).McLoughlin JL, Cantrill RC.

(9) Letters to the Editor Use of Metformin Is a Cause of Vitamin B12 Deficiency DAVID R. BUVAT, M.D. January 15, 2004 AAFP

(10) http://www.aafp.org/afp/20030301/979.pdf

Vitamin B12 Deficiency Robert C. OH DAVID L. BROWN, AAFP MARCH 1, 2003 VOLUME 67, NUMBER 5

(11) http://bloodjournal.hematologylibrary.org/cgi/reprint/100/2/718.pdf

Transcobalamin II 775GC polymorphism and indices of vitamin B12 status in healthy older adults Blood 2002 100: 718-720 Joshua W. Miller, Marisa I. Ramos, Marjorie G. Garrod, Margaret A. Flynn, and Ralph Green

(12) http://www.clinchem.org/cgi/content/abstract/52/2/278

Measurement of Total Vitamin B12 and Holotranscobalamin, Singly and in Combination, in Screening for Metabolic Vitamin B12 Deficiency . Joshua W. Miller, Marjorie G. Garrod, Alan L. Rockwood, Mark M. Kushnir, Lindsay H. Allen3, Mary N. Haan4 and Ralph Green Clinical Chemistry. 2006;52:278-285.

(13) http://www.ajcn.org/cgi/reprint/20/6/573.pdf

Vitamin B12 Deficiency with Emphasis on Methylmalonic Acid as a Diagnostic Aid. LEWIS A. BARNESS, M.D. AMERICAN JOURNAL OF CLINICAL NUTRITION (Vol 20, No. 6, June, 1967, III). p 573

(14) http://bloodjournal.hematologylibrary.org/cgi/content/full/92/4/1191

Blood, Vol. 92 No. 4 (August 15), 1998: pp. 1191-1198 Effective Treatment of Cobalamin Deficiency With Oral Cobalamin By Antoinette M. Kuzminski, Eric J. Del Giacco, Robert H. Allen, Sally P. Stabler, and John Lindenbaum

(15) http://www.b12.com/

The Norman Clinical Laboratory,an excellent web site devoted to B12 and Methyl Malonic Acid testing with many references. Dr. Norman is the medical pioneer credited with doing all the original methyl malonate work.

(16) http://www.clinchem.org/cgi/content/full/50/8/1482

Urinary Methylmalonic Acid Test May Have Greater Value than the Total Homocysteine Assay for Screening Elderly Individuals for Cobalamin Deficiency. Clinical Chemistry. 2004;50:1482-1483. Letter to the Editor, Eric J. Norman Norman Clinical Laboratory, Inc., 1044 Sunwood Ct., Cincinnati, OH 45231

(17) http://lpi.oregonstate.edu/infocenter/vitamins/vitaminB12/

B12 information page at the Linus Pauling Institute, with excellent list of references with links.

(18) http://www.westonaprice.org/basicnutrition/vitaminb12.html

Vitamin B12: Vital Nutrient for Good Health By Sally Fallon and Mary G. Enig, PhD. At Weston Price Foundation

(19) deleted

(20) http://www.postgradmed.com/issues/2001/07_01/dharmarajan.shtml

Approaches to vitamin B12 deficiency, Early treatment may prevent devastating complications. T. S. Dharmarajan, MD; Edward P. Norkus, PhD. VOL 110 NO 1 JULY 2001 POSTGRADUATE MEDICINE

(21) http://www.ajcn.org/cgi/content/full/84/6/1259

American Journal of Clinical Nutrition, Vol. 84, No. 6, 1259-1260, December 2006. Assessing the association between vitamin B-12 status and cognitive function in older adults. Joshua W Miller.

(22) http://adc.bmj.com/cgi/content/abstract/77/2/137

Arch Dis Child 1997;77:137-139 ( August ) Persistence of neurological damage induced by dietary vitamin B-12 deficiency in infancy, Ursula von Schenck, Christine Bender-Götze, Berthold Koletzko

Update 2015: article on B12 deficiency from Just Naturally Healthy

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