Excerpted from : The Experts Speak. October 1997; 7(10);132-134

        Clinical Pearls News
   A Health Letter on Current Research in NUTRITION and PREVENTIVE MEDICINE
        
        
        Vitamin B12 - Limits Too Low
        An Interview With
        Mark Goodman, Ph.D., M.A.
        Behavioral Medicine
        (973) 731-4521 (Phone, Voice Mail, FAX)

         This interview is based upon Dr. Goodman's original published research article:
    "Are U.S. Lower Normal B12 Limits Too Low?"
        Journal of The American Geriatric Society, October, 1996;44(10):1274-1275. #25957

Kirk Hamilton: Could you please share with me your educational background and current position?

: Could you please share with me your educational background and current position?

MG: I am one of approximately 12 individuals in the United States who have earned an accredited Ph.D. in Behavioral Medicine (with a specialization in clinical neuropsychology) from the University of Maryland School of Medicine, Baltimore. Behavioral Medicine is a new interdisciplinary specialty combining cross-training in behavioral psychology, neurosciences, physiology and medicine. My clinical externship and internship residencies were completed at Johns Hopkins and the Union Memorial Hospitals in Baltimore, Maryland. At the time of data collection on this B12 study, I was Attending Clinician and Faculty Preceptor on the Neurology / Psychiatry rotation for internal medicine and family practice residents with consultation- liaison assignments to Cardiology, Geriatrics, C.C.U., and general medicine services. I was also Principal Investigator conducting grant-funded clinical cardiac research. Currently, I am consulting and continuing clinically relevant research temporarily in New Jersey.

KH: Why do you suspect that the limits for vitamin B12 assessment are too low? Why do you suspect that the limits for vitamin B12 assessment are too low?

MG: I initially suspected vitamin B12 limits were too low when I encountered on consultation, geriatrics patients admitted with Alzheimer's diagnosis whose frontal lobe functioning was obviously intact. This is inconsistent with Alzheimer's diagnosis. They were exhibiting other global neuropsychological deficits with a systematic/metabolic profile. They were all following cardiac lipid-lowering diets.

KH: Have you encountered multiple patients who have normal or low normal vitamin B12 levels yet respond to vitamin B12 infections with a resolution of some of their neurologic deficit? Have you encountered multiple patients who have normal or low normal vitamin B12 levels yet respond to vitamin B12 infections with a resolution of some of their neurologic deficit?

MG: At the time of submission/acceptance of this paper, I had 5 cases identified as "B12 deficiency dementia" reversed with I.M. B12 where the presenting B12 levels were 250-400 pg/ml. Currently, I have encountered 19 additional cases with similar outcomes.

KH: Do you believe that there are many elderly who are subclinically vitamin B12 deficient, but their blood levels are in the normal range? Do you believe that there are many elderly who are subclinically vitamin B12 deficient, but their blood levels are in the normal range?

MG: Absolutely. We know that neurological changes precede hematologic changes in B12 deficiency by as much as 2 years. To those unskilled in geriatric neuropsychological assessment, this reported slow insidious mental status decline may be suggestive of a "terminal" Alzheimer's diagnosis. The Alzheimer's diagnosis is one which I obsess over and never confer cavalierly.

KH: Do you believe in the functional tests of methylmalonic acid and homocysteine to evaluate vitamin B12 levels? Do you believe in the functional tests of methylmalonic acid and homocysteine to evaluate vitamin B12 levels?

MG: Yes, I believe in methylmalonic acid and homocysteine tests to evaluate B12 levels. However, these tests are costly. This is why I prefer an empirical/therapeutic trial utilizing I.M. B12 1000 meg for 4-7 consecutive days (dependent on baseline values) during the first week, then once weekly for a one month period. If symptomatic improvement occurs, then this should be continued once monthly for life. I prefer recommending an empirical I.M. B12 trial because I do not wish to withhold such harmless intervention with a patient faced with the Alzheimer's diagnosis. I may be the final clinician equipped to doubt the diagnosis.

KH: Do you know of any harm or toxic side effects to vitamin B12? For example, if you gave it daily for two weeks at 1,000 meg/d?

Do you know of any harm or toxic side effects to vitamin B12? For example, if you gave it daily for two weeks at 1,000 meg/d?

MG: After having consulted with several of my former residents who are now board certified in internal medicine (one a GI/hepatology fellow at the University of Miami and another a hematology/oncology fellow in Texas), we all agree there are no major or toxic side effects to B12. B12 hypervitaminosis is extremely rare clinically and in the literature. Mostly anecdotal reports exist suggesting reversible symptoms of diarrhea, cutaneous rash, polycythemia and possibly peripheral vascular thrombosis. In response to your dosing question (1000 mcg daily for 2 weeks), Professor Robert F. Schilling, M.D., of the University of Wisconsin Medical School has recommended a more "reasonable schedule for initial replacement of 1000 mcg I.M. on 3 to 4 alternate days followed by one at 2 weeks, then at 4 weeks, then a month (Schilling, Hospital Practice, July 15, 1995, p. 49)."

KH: If you were giving an empirical injection, would it not be reasonable to give folic acid with vitamin B12 so as not to make a pernicious anemia since both are very low toxicity nutrients? If you were giving an empirical injection, would it not be reasonable to give folic acid with vitamin B12 so as not to make a pernicious anemia since both are very low toxicity nutrients?

MG: I have not recommended giving folic acid with B12 for 2 reasons. First, folic acid levels (and thiamine and magnesium levels) are always drawn with B12 levels during the dementia work-up's I perform. Folic acid levels were well within the normal limits in these patients. Second, I wanted to know I was treating only a low B12 level. This was done for the purpose of clinical research although I think it is reasonable to give folate with vitamin B12 if the attending clinician chooses.

KH: Do you know of any differences between hydroxocobalamin and cyanocobalamin as far as therapeutic efficacy? Do you know of any differences between hydroxocobalamin and cyanocobalamin as far as therapeutic efficacy?

MG: I can only address the therapeutic efficacy of cyanocobalamin since I have no experience with hydroxocobalamin.

KH: What would be the normal vitamin B12 range if you could arbitrarily assign it with the evidence you have available at present? What would be the normal vitamin B12 range if you could arbitrarily assign it with the evidence you have available at present?

MG: Based on my findings, I would like to see a lower normal parameter of serum B12 limit of about 450 pg/ml. I have several hypotheses under investigation which may explain the risk-factor and mechanism for this condition.

KH: How would you define true tissue vitamin B12 deficiency? How would you define true tissue vitamin B12 deficiency?

MG: Clinically, the absence of vibratory sensation recognition especially in the lower extremities. If frontal lobe executive function/mental abstraction is intact this rules out an Alzheimer's dementia diagnosis. However, short-term recall memory may be globally impaired. Also, I take a good diet history. If it is very high starch diet such as occurs in many convalescent facilities, then there is a high suspicion of vitamin B12 depletion and deficiency.

KH: Dr. Goodman could you please elaborate on why a high starch diet increases the risk to vitamin B12 deficiency? Dr. Goodman could you please elaborate on why a high starch diet increases the risk to vitamin B12 deficiency?

MG: In the convalescent facility diet there is little red meat due to expense and the desire to have residents on a lipid lowering regime. Also, there is a normal increase in gastric atrophy in the elderly which reduces vitamin B12 absorption. Thirdly, there is a down-regulation of the enzymes required for the formation and the manufacture of vitamin B12 when less vitamin B12 is consumed.