the Epidemic of Misdiagnosis
by Jeffrey Dach MD
A good friend of ours, otherwise healthy, had the sudden onset of 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. Left Image Courtesy Wikepedia
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)
B12 is a huge molecule and absorption depends on many cofactors, so that it is quite possible to take adequate amounts of B12 in the diet, and still have a B12 deficiency. 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 antacid drug 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. 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)Above image B12 Chemical Structure, Note Cobalt at center of ring, surrounded by four nitrogen molecules, courtesy of wikipedia.
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.
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, Miller has identified genetic defects in which transport proteins are absent or deficient causing B12 deficiency (11).
Symptoms Which Might Indicate a B12 Deficiency
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. The physical signs and symptoms can often mimic other diseases and the diagnosis is frequently missed. An excellent book on the topic is: Could it Be B12? An Epidemic of Misdiagnosis by Sally M. Pacholok, R.N. and Jeffrey J Stuart, D.O. (1) B12 deficiency damages the myelin sheath around the nerve fibers, this is a soft fatty insulating material which is also damaged in demyelinating diseases such as multiple sclerosis.
Mental Changes:
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:
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, TIAs, CVA, heart attack, heart failure, claudication, all associated with elevated homocysteine levels caused by B12 deficiency.
Megaloblastic Anemia (enlarged red blood cells with anemia)
In this type of anemia, the red blood cells are fewer in number, yet they are larger in diameter (this large size is called megaloblastic and is measured on the CBC with the mean corpscular volume, MCV). The anemia can cause fatigue, and weakess.
Increased Cancer Risk from B12 Deficiency
Cervical Dysplasia and increased risk for other dysplasias and cancers is associated with B12 deficiency. B12 supplementation is part of our cancer prevention program.
Testing for the Diagnosis of B12 Deficiency
Most doctors do not test for B12, and even they do a blood test, they do the standard serum B12 which is unreliable.(12) A more accurate screening test called the methyl malonate test has been devised.(13)(15)(16) This is the best test and the one that we do routinely in the office. The substance, Methyl Malonate is elevated in the urine and serum in patients with B12 deficiency. We have added this test to our standard panel, so everyone will be routinely screened with the most advanced and accurate test for B12 deficiency. Should the B12 level be low in spite of oral or sublingual B12 supplements, then inexpensive B12 injections can be taken at home. Recent work by Kuzminski showed that daily 2 mg. oral B12 serves as well as monthly 1 mg intramuscular B12 injections.(14) We also test for Serum Homocysteine which is elevated in B12 deficiency, and of course the standard serum B12 test is aso included in our panel.
It is important to discover B12 deficiency early, since nerve damage can be irreversible if not discovered right away.
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(1) http://www.amazon.com/Could-Be-B12-Epidemic-Misdiagnoses/dp/1884956467
Could It Be B12?: An Epidemic of Misdiagnoses (Paperback) by Sally M. Pacholok, Jeffrey J. Stuart
(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)
(doi:10.1146/annurev.nutr.19.1.357) 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) http://www.aafp.org/afp/20040115/letters.html
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) http://forums.wrongdiagnosis.com/showthread.php?t=9948
Sally Pacholok, R.N. Health Forum Message Board where you can read her messages and post your own message.
(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
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