Vitamin B12 Deficiency, the Epidemic of Misdiagnosis
 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)
What Causes B12 Deficiency?
 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.
Itis important to discover B12 deficiency early, since nerve damage can be irreversible if not discovered right away.
Jeffrey Dach, M.D.
4700 Sheridan, Suite T.
Hollywood Florida, 33021
954 983 1443
References
(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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This Message was posted on the message board at: Forums.WrongDiagnosis.com
Originally Posted by Jeffrey Dach MD;
Sally, I found your book on B12 Misdiagnosis to be excellent, and have included it in my newsletter found at: https://www.truemedmd.com/B12_Jeffrey_Dach_DrDach.html
In addition, I have added urinary methyl malonic acid to my routine panel which is usually done either at LabCorp or Quest Lab which is a Mass Spec technique.
Thanks for performing a valuable service by putting all the B12 information into a highly readable and fascinating book containing many useful items of information about B12 diagnosis, testing and treatment which I learned from your book after being in practice 25 years.
regards, jeffrey dach
Here is Sally's Reply:
I am so pleased that you enjoyed our book and are offering the urinary methylmalonic acid test!
I enjoyed your website and will be referring patients to it.
In addition, I have had some people for whatever reason their MMA is normal, but their serum B12 is low, and they are symptomatic, therefore you still treat and give a trial of B12 injections. The reverse is also true where the serum B12 is normal and the MMA is elevated and the patient is symptomatic.
Therefore, if either the MMA or B12 is abnormal and the patient is symptomatic always treat. The MMA is very helpful but I don't think it is 100% for everyone as in all tests. That is why it is beneficial to run together. I enjoyed your B12 educational update on your website excellent job!
In the next month I will be doing an interview on Retirement Living TV regarding the epidemic of B12 deficiency in people over age 55. CN8-The Comcast Network (Mid-Atlantic & North East). Channel 5 in Denver , and DirecTV Channel 364.
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It's a very useful blog and is very informative...cheers,
Suma valluru vitamin-shoppe
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Dear Suma, Thanks very much for your kind words, Jeffrey Dach MD
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I read the above mentioned book on B12. I started the B12 injections with just the serum B12 test (level 259). I found it quite informative and plan on buying some more copies to share with two physicians I am currently seeing. I have been diagnosed with Peripheral Neuropathy (PN) and wondered how much you had looked into what helps with PN outside of the benefits of B12 can offer (possibly). I am a nurse so I am researching like crazy. I plan on going to a physician to start bio-identical hormones next month and hope that this too may help the PN... any thoughts?
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If you google B12 on the internet, the first thing for sale is a B12 transdermal patch. No one else offers this and I am skeptical that it can substitute for shots. Have you heard of it? Is it legit? I can't seem to get real info on it. What would you suggest to ask about it? Supposedly it has a patent pending, but I didn't get a clear answer about that from the company. Would appreciate your help.
Regards from Patricia in West Palm Beach
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Dear Patricia,
We use the B12 injections which are very inexpensive and work quite well. And we also use the serum B12 and urine methyl malonate to check on response to treatment.
There are many transdermal delivery systems. For example, fat soluble hormones such as estrogen, progesterone, DHEA and testosterone are commonly delivered transdermally. So, in theory transdermal delivery of B12 is possible for people who, for some reason, can not tolerate the SubQ B12 injections. However, I would like to see data showing serum B12 levels before and after use of the transdermal patch in a patient series. If the patch works, I would expect serum B12 levels to go up after use.
Since subQ injection of B12 is fairly painless with a tiny needle, there is very little reason to go to a transdermal system.
regards from Dr. Dach.
Warmest Regards from,
Jeffrey Dach, M.D.
Medical Director of TrueMedMD
4700 Sheridan, Suite T
Hollywood, Florida 33021
954 983 1443 office
954 983 1452 fax
954 559 0334 cell
www.TrueMedMD.com
www.drdach.com
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I really enjoy your website and the blog setup you have. It gets information out to the public and allows people to share their stories.
I just turned 21 not to long ago, and i have been from doctor to doctor over the past year....even the hospital. So many tests were run on me to find out what the problem was. I was experiencing heart palpitations, depression, weakness, tired eyes, shaking, dizziness, loss of appetite and lack of interest to even go out of the house. This was not me at all.
Beta Thalassemia minor runs in my family and if not taken care of with iron and folic acid daily can lead to anemia. Well, i am slightly anemic now which just adds more problems to my plate.
I started taking birth control in November 2006 because my menstrual cycle would be so painful i would be in bed. Finally i decided to go off of those pills because i had heard from prior birth control users that the side effects can be horrible.
After doing research over and over on the internet and talking to several doctor's, my hematologist discovered that my B12 level was extremely low.....actually 44 points lower then the normal level. I am now getting B12 shots every month and have come off the birth control to rid my body of any synthetic hormone. On top of that i take an iron pill and two folic acid pills daily.
This is my first week of recovery so wish me luck!
I knew there was something wrong with me when my body started feeling tired all the time. My primary care doctor didn't know what the heck he was doin when he perscribed to lexapro...i am not crazy!!! Mental illness does not run in my family at all and they is nothing in my life that has happened for me to be feeling the way i am. I like how you use natural vitamins instead of synthetics.
I couldn't agree with you more. I am not a doctor at all, but am a phlebotomist, so i do have some medical knowledge when it comes to medications. With your experience and practice...could you possibly see my side effects and the way i have been feeling part of the lack of B12 and side effects from birth control??
It's gotten so bad to where i was scared to leave the house to be in places other than my home. Scary. Ok doc..now that i have told you my life story thank you again for the wonderful blogs!!
Sincerely,
Ashley D. Springer
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Dear Ashly,
Thank you for your comment and your kind words. As you know from reading my articles, I am not a fan of synthetic hormones found in BCP's. Nor am I a fan of the SSRI class of antidepressants which have considerable adverse side effects. I hope you have a good response to the new changes you write about, and I wish you the very best of health in the future.
Regards from Jeffrey Dach MD
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I read your article about B12 deficiency with great interest.
I haven't felt well for about 7 years, worse the last two. I've been a vegetarian for 9 years. Blood tests have shown nothing and drs look at me as if I am exaggerating when the tests come back normal.
I mentioned my symptoms being consistent with B12 deficiency, so my doctor did a blood test and said no, my level was 400.
I am under the impression, especially after reading your article, that a simple B12 blood test is not conclusive because it does not show whether B12 is actually being absorbed.
Do you know of any Connecticut doctors who feel as you do, would take me seriously, and would run the right diagnostic test?
THANK YOU for any help you are able to offer. I can't stand to feel this way any longer, especially if it can be easily corrected with simple B12 injections.
Donna M, Watertown CT.
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Dear Donna,
Thanks for reading my blog article on Vitamin B12 deficiency.
Our routine lab panel includes both the B12 blood test as well as the MMA urine test, as mentioned in the book, "Could it Be B12, An Epidemic of MisDiagnoses?" by Sally M. Pacholok R.N. and Jeffrey J Stuart D.O.
The blood B12, of course indicates GI tract absorption into the blood stream, while the MMA test indicates whether the B12 is actually active in cellular metabolism. We have been finding many cases of B12 deficiency with the typical neurological symptoms which fortunately resolve with inexpensive B12 capsules and/or injections.
To find a doctor in your area, go to the ACAM or A4M doctor's directory page. Enter your zip code for the doctors in your area. Click here for the link to the page:
A4M Doctor's Directory
I wish you the very best of health in the future.
(disclaimer)
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Thanks.
Jill
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Dear Jill,
The latest USDA recommendations is that all people over 50 should supplement with B12.
Regards,
Jeffrey Dach MD
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I've had mild pain in my legs on and off for several years, which would usually go away after exercise. But in the last couple of weeks the pain became severe. I have started taking HRT for osteopenia a couple of months ago, with associated unpleasant side effects. I could not find, however, leg pain as a side effect. I was worried about PAD, of course, and heart problems.
I read, three days ago, about vitamin B12 deficiency associated with leg pain. I went and bought a B complex supplement, and have been taking it for three days. The reduction in pain in just three days is amazing! It's not gone, but it is tolerable. Maybe it will be gone after a couple of weeks. I have an appointment to see my doctor soon. You can bet she will hear about this.
Michelle
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My daughter, now 17, was first diagnosed with B12 deficiency when she was 14. She was referred to Children's Hospital in Vancouver but, unfortunately, they had never dealt with it. They did a full digestive tract scope and found nothing wrong. Their only answer was B12 shots because the Schilling test showed that she just didn't absorb it.
Is there ANY hope of doing something that will help so she doesn't have to take the shots every 3 weeks? (monthly isn't enough for her).
I'm trying a liquid that I will have her hold in her mouth for at least 30 seconds.
I am also investigating a patch that supposedly has an enhancer that helps absorption of larger molecules. After almost 4 years of this, we are desperate.
Thanks!
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