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Chester Myers' Nutrition Series

HIV & Vitamin B12

Low intake of B vitamins is associated with faster progression of HIV disease. People with HIV should be able to get enough of most of these from supplements that are taken as pills. Vitamin B12, however, should be taken either by injection or under the tongue (sublingual form).

From the 1996 Vancouver AIDS Conference: data collected from 312 subjects, monitored since 1984, indicate that

    "median AIDS-free time was estimated to be four years shorter in subjects with low serum B12 levels (<120 pmol/L) compared to those with adequate B12 levels (|120 pmol/L). Low serum B12 levels were independently and significantly associated with an increased risk of progression to AIDS...."
    Tang et al, "The Role of Serum Micronutrient Levels in HIV-1 Disease Progression", abstract Mo.C.320 (from Johns Hopkins University).

    In the absence of supplementation, studies indicate that up to 95% of those with HIV may be deficient in B12. In this study, among those who had adequate levels of vitamin B12, there was an average of 4 years increase in AIDS-free time for the period from 1984 to 1996.

    Have people giving you nutritional advice alerted you to this information? If not, why not? Are you getting up-to-date information regarding HIV and nutrition? Make sure that people who give you advice regarding HIV are truly concerned with your life. More and more, the information indicates those who are aggressive about their micronutrient supplementation live longer. Of special importance are vitamin E, the B-complex vitamins, and vitamin A. Be careful of taking more than 8,000 IU of vitamin A as vitamin A can be toxic. A better way to get vitamin A is from carotenoids such as in vegetables and fruits that are coloured yellow-to-red (e.g., cooked carrots, cooked pumpkin, cooked squash, cooked yams, cooked sweet peppers, cantaloupe) or take supplemental mixed carotenoids that are from natural sources.

    Make sure you are already taking a good quality multivitamin with minerals, but do NOT rely on this for your vitamin B12. For people living with HIV, we should not rely on the stomach route for B12, and blood tests for it are unreliable. Weekly intramuscular injections or daily under the tongue (sublingual) varieties are likely best. Be wary of nutritional advice that places an emphasis on only getting more calories. This may be harmful in the absence of supplementation with vitamins and minerals. You need these tools (vitamins and minerals) in order to use the calories in your food. When you have HIV, supplementation is necessary. Food Alone is Not Enough.

    [The most common form of vitamin B12 that is available in Canada is called cyanocobalamin. However, the form called hydroxocobalamin has been shown to have antiviral activity in the test tube; the cyanocobalamin form does not have antiviral activity. In addition, the hydroxo-form is more active as vitamin B12. It would seem reasonable to use the hydroxo-form, but this seems more readily available in the US than in Canada. The nasal gel form of this vitamin is no longer sold.]

    Low vitamin B12 during HIV infection can be a source of
    • anaemia (low red blood cells),
    • anorexia (lack of appetite),
    • dementia (poor brain function),
    • diarrhea (the 'shits'),
    • fatigue (tiredness),
    • loss of feeling for vibrations of high frequency (with a tuning fork),
    • memory loss,
    • myelopathy (damaged nerve cells of the spinal column),
    • peripheral neuropathy (numbness or tingling in the feet, fingers, or other extremities),
    • skin hyperpigmentation (limited to people of colour),
    • sore tongue,
    • visual disorders, and
    • weight loss.
    When B12 is low in our body, this may cause an increase in the value of MCV, one of the numbers from our bloodwork. MCV stands for Mean Corpuscular (or Cell) Volume and refers to the size of the red blood cells. I have seen a disturbing number of people who have high values of MCV on their bloodwork sheets. It is considered too high if it is a value above about 95. One B12 specialist noted that values below 88 are best. AZT has been noted to cause high MCV values, but this is likely a secondary effect because AZT lowers vitamin B12 in the body (reported at the 1991 Florence International AIDS Conference). There are other factors such as low iron or low B6 which can also cause the MCV value to be high but I've usually seen the MCV value go down when B12 is taken often enough (see below). Vitamin B6, however, is an important part of our regular program of vitamin/mineral supplementation.

    MCV doesn't always get high when B12 is low, so a normal value doesn't necessarily mean our B12 levels are okay. In fact one study recommended that MCV values not be used as an indicator since they may be normal in spite of low B12. In general, it seems best not to take a chance, and routine B12 supplementation for everyone with HIV has been recommended.

    Dr. Kotler, a highly regarded doctor from New York, noted in Philadelphia (1995) that HIV+ people should get B12 either by injection, under the tongue, or with a form (no longer available) that we snuff up the nose. If for whatever reason someone is not getting B12 by one of these routes, then it is particularly important to watch out for a high MCV value. But remember that a normal MCV doesn't guarantee your B12 level is okay.

    Neurological symptoms often occur well before there is evidence of low B12 in the blood work even when B12 tests are working okay. Unfortunately, by the time neurological symptoms occur they may be not all reversible, even in the absence of HIV. Also, even in the absence of HIV, blood levels of vitamin B12 may remain normal when other parts of the body are low.

    Why not use other B12 tests?
    There are blood tests that can look directly at vitamin B12 levels in our bodies in the absence of HIV. There are other tests that look at the results of a possible deficiency. When we have HIV there is no single test that is reliable for looking at B12 directly. Especially unreliable is the commonly used RIA (radioimmune dilution assay) test. A test called the "homocysteine test" was once thought reliable, but is now considered unreliable in many cases. Homocysteine is a compound normally found in the body. It should become too high when B12 is too low, but many with HIV are unable to increase levels of this compound. This results from a general condition where the body is low in a class of compounds called thiols, i.e., sulfur-containing compounds.

    Thus, a B12 test that indicates a low value may underestimate the extent to which it is low.

    I agree entirely with the conclusion of a French group which stated at a 1995 meeting on HIV and nutrition that "no clinical or laboratory test abnormalities[are] reliable for detecting B12 [deficiency]".

    How many people with HIV are deficient in B12?
    Vitamin B12 becomes low in many people with HIV and it gets lower if the disease progresses. It's difficult to know how many people living with HIV are deficient in vitamin B12. Some studies have indicated 16% to 30% of HIV+ people to be low B12. At the Third International it was stated that at least 60% are low. An even more recent study found 95% to be low. One study noted that injections of B12 which should last for several months may last only a few days for many with HIV. Because of the problems with tests, it is likely that many more are low in this vitamin than indicated by these reports.

    Not only is B12 directly important for our bodies, but very recent data from a test tube study indicates the hydroxo-form of B12 may have direct antiviral activity. Thus not only is it important to make sure B12 is not deficient, but it may be worthwhile to keep higher than normal levels present in the body (this vitamin is generally considered to be non-toxic).

    How much B12?
    Many people take by injection 1 cc of vitamin B12 once or twice a week. At a 1993 pharmacy meeting I attended in San Diego, 3 injections per week were recommended. Under-the-tongue forms are usually taken twice a day, and it is important to keep it under the tongue until it is all dissolved. [Some people feel that the under-the-tongue method is not very effective since the tablet may be easily swallowed, or washed down the throat by saliva.]

    What else is important for vitamin B12?
    Low vitamin B12 can be a source of anaemia (low red blood cells) simply because B12 is needed in order for the body to make the blood cells. This in turn causes tiredness. The haemoglobin is part of the blood work that may be low in these cases. However, there are other causes of low haemoglobin. If a low haemoglobin does not come back to normal with B12, it may be necessary to get more iron or more magnesium. Iron may be particularly important for women who lose it during the menstrual period. Otherwise magnesium may be of concern. Get your doctor to check your serum magnesium level as part of your bloodwork.

    Vitamin B12 needs to be balanced with enough folic acid, which is another vitamin.
    As far as we know now, blood tests for folic acid are reliable. Watch the "RBC (or ERC) folate" number in your bloodwork reports and try to keep this value in the upper part of its normal range. You may need to ask to have this test done, if your doctor has not already included it.

    Remember that you should consider vitamin B12 separately from the other B vitamins, called the B-complex. Make sure your multivitamin contains these, or even take an extra B-complex on its own. Good supplementation programs have been described in a number of papers available from CATIE.

    References re Vitamin B12

    Analogues to B12 are produced in the body and may cause problems:
    Abjalla C, Benhayoun S, Nicolas JP, Gueant JL, Lambert, Existence of Vitamin-B12 Analogues in Biological Samples - A Reality, Journal of Nutritional Biochemistry 4:543-548 (1993).

    Carmel, 1983 (reference below).
    Carmel et al, 1988 (reference below).
    Cooper et al (reference below).

    Kolhouse JF, Kondo H, Allen NC, Podell E, Allen RH, Cobalamin Analogues are Present in Human Plasma and can Mask Cobalamin Deficiency because Current Radioisotope Dilution Assays are not Specific for True Cobalamin, The New England Journal of Medicine 299:785-792 (1978).

    Homocysteine test useful in absence of HIV:
    Hall CA, Chu RC, Serum homocysteine in routine evaluation of potential B12 and folate deficiency, European Journal of Haematology 45:143-149 (1990).

    Joosten E, Pelemans W, Devos P, Lesaffre E, Goossens W, Criel A, Verhaeghe R, Cobalamin Absorption and Serum Homocysteine and Methylmalonic Acid in Elderly Subjects with Low Serum Cobalamin, European Journal of Haematology 51:25-30 (1993).

    Homocysteine misleading in presence of HIV (!!):
    Genest JJ, McNamara JR, Salem DN, Wilson PWF, Schaefer EJ, Malinow MR, Plasma Homocyst(e)ine Levels in Men With Premature Coronary Artery Disease, Journal of the American College of Cardiology 16:1114-1119 (1990) (by deduction).

    Mansoor MA, Ueland PM, Svardal AM, Redox status and protein binding of plasma homocysteine and other aminothiols in patients with hyperhomocysteinemia due to cobalamin deficiency, American Journal of Clinical Nutrition 59:631-635 (1994) (by deduction).

    Baum et al, 1994 (reference below)

    Low B12 frequent in HIV disease:
    Burkes RL, Cohen H, Krailo M, Sinow RM, Carmel R, Low serum cobalamin levels occur frequently in the acquired immune deficiency syndrome and related disorders, European Journal of Haematology 38:141-147 (1987).

    Carmel R, Perezperez GI, Blaser MJ, Helicobacter Pylori Infection and Food-Cobalamin Malabsorption, Digestive Diseases and Sciences 39:309-314 (1994) (by deduction).

    Ehrenpreis ED, Carlson SJ, Boorstein HL, Craig RM, Malabsorption and deficiency of vitamin B-12 in HIV-infected patients with chronic diarrhea, Digestive Diseases and Sciences 39:2159-2162 (1994).

    Force G, Marguet F, Manicacci M, Prevalence of Vitamin B12 Deficiency with or without Clinical and Laboratory Test Abnormalities in Patients with Advanced AIDS", abstract P024, International Conference Nutrition and HIV Infection, Cannes, France, 1995.

    Harriman GR, Smith PD, Horne MK, Fox CH, Koenig S, Lack EE, Lane HC, Fauci AS, Vitamin B12 Malabsorption in Patients With Acquired Immunodeficiency Syndrome, Archives of Internal Medicine 149:2039-2041 (1989).

    Hansen M, Gimsing P, Ingeberg S, Jans H, Nexø H, Cobalamin binding proteins in patients with HIV infection, European Journal of Haematology 48:228-231 (1992).

    Harris PJ, Candeloro P, HIV-Infected Patients with Vitamin B-12 Deficiency and Autoantibodies to Intrinsic Factor, AIDS Patient Care June:125-128 (1991).

    Herbert V, B12 Defiency in AIDS, JAMA 260:2837 (1988).

    Kieburtz CD, Giang DW, Schiffer RB, Vakil N., Abnormal Vitamin B12 Metabolism in Human Immunodeficiency Virus Infection: Association with Neurologic Dysfunction", Archives in. Neurology 48:312-314 (1991).

    Kotler D, - reported in Philadelphia (1995) that at least 60% of those with HIV are likely deficient in vitamin B12.

    Paltiel O, Falutz J, Veilleux M, Rosenblatt DS, Gordon K, Clinical Correlates of Subnormal Vitamin B12 Levels in Patients Infected With the Human Immunodeficiency Virus, American Journal of Hematology 49:318-322 (1995).

    Remacha AF, Riera A, Cadafalch J, Gimferrer E, Vitamin B-12 abnormalities in HIV-infected Patients, European Journal of Haematology 47:60-64 (1991).

    Scholl U, Knechten H, Vitamine B12 in the Course of HIV-Infection in Man, International Conference Nutrition and HIV Infection, Cannes, France, 1995.

    Ullrich R, HIV Enteropathy, plenary session, International Conference Nutrition and HIV Infection, Cannes, France, 1995 (B12 deficiencies common and increase with disease progression).

    Florence '91 abstr. MB2306 - B12 even lower with AZT.

    MCV may be normal in some cases of low B12:
    Beach RS, Lefkowitz M, PAACNOTES 1, issue 6. Notes deficiencies of Zn, Se, Cu, pyridoxine, B12 even when asymptomatic and Mean Corpuscular Volume not a reliable indicator for B12 status.

    Burkes et al, 1987 (above)

    Neurological problems from low vitamin B12:
    Allen RH, Stabler SP, Savage DG, Lindenbaum J, Metabolic Abnormalities in Cobalamin (Vitamin-B12) and Folate Deficiency, FASEB Journal 7:1344-1353 (1993).

    Beach RS, Morgan R, Wilkie F, Mantero-Atienza E, Blaney N, Shor-Posner G, Lu Y, Eisdorfer C, Baum MK, Plasma Vitamin B12 Level as a Potential Cofactor in Studies of Human Immunodeficiency Virus Type 1-Related Cognitive Changes, Archives of Neurology 49:501-506 (1992).

    Carmel R, Megaloblastic Anemia: Vitamin B12 and Folate, Chapter 8 in Current Hematology 2:243-280 (1983).

    Carmel R, Karnaze DS, Weiner JM, Neurologic abnormalities in cobalamin deficiency are associated with higher cobalamin "analogue" values than are hematologic abnormalites, Journal of Laboratory and Clinical Medicine 111:57-62 (1988).

    Das KC, Herbert V, Vitamin B12-Folate Interrelations, Chapter 10 in Clinics in Haematology 5:697-725 (1976).

    Hall CA, Function of Vitamin B12 in the Central Nervous System as Revealed by Congenital Defects, American Journal of Hematology 34:121-127 (1990).

    Hansen et al, 1992 (reference above).
    Kieburtz et al, 1991 (reference above).

    Reynolds EH, Neurological Aspects of Folate and Vitamin B12 Metabolism, Chapter 9 in Clinics in Haematology 5:661-695 (1976).

    Neurological symptom often occur before problems in blood work:
    Herbert V, Don't Ignore Low Serum Cobalamin (Vitamin B12) Levels, Archives of Internal Medicine 148:1705-1707 (1988).

    Lindenbaum J, Healton EB, Savage DG, Brust JCM, Garrett TJ, Podell ER, Marcell PD, Stabler SP, Allen RH, Neuropsychiatric Disorders Caused by Cobalamin Deficiency in the Absence of Anemia or Macrocytosis, The New England Journal of Medicine 318:1720-1728 (1988).

    Problems with B12 tests:
    Allen RH, Stabler SP, Savage DG, Lindenbaum J, Diagnosis of Cobalamin Deficiency I: Usefulness of Serum Methylmalonic Acid and Total Homocysteine Concentrations, American Journal of Hematology 34:90-98 (1990).

    Baum et al, 1995 (reference below).
    Carmel, 1983 (reference above).

    Carmel R, Subtle and Atypical Cobalamin Deficiency States, American Journal of Hematology 34:108-114 (1990).

    Cohen KL, Donaldson RM, Unreliability of Radiodilution Assays as Screening Tests for Cobalamin (Vitamin B12) Deficiency, JAMA 244:1942-1945 (1980).

    Cooper BA, Whitehead VM, Evidence that some Patients with Pernicious Anemia are not Recognized by Radiodilution Assay for Cobalamin in Serum, The New England Journal of Medicine 299:816-818 (1978).

    Force et al, 1995 (reference above).
    Kolhouse et al, 1978 (above).

    Lindenbaum J, Savage DG, Stabler SP, Allen RH, Diagnosis of Cobalamin Deficiency: II. Relative Sensitivities of Serum Cobalamin, Methylmalonic Acid, and Total Homocysteine Concentrations, American Journal of Hematology 34:99-107 (1990).

    Matchar DB, McCrory DC, Millington DS, Feussner JR, Performance of the serum cobalamin assay for diagnosis of cobalamin deficiency, American Journal of the Medical Sciences 308:276-283 (1994).

    Mollin DL, Anderson BB, Burman JF, The Serum Vitamin B12 Level: Its Assay and Significance, Chapter 3 in Clinics in Haematology 5:521-546 (1976).

    Nexo E, Hansen M, Rasmussen K, Lindgren A, Grasbeck R, How to diagnose cobalamin deficiency, Scandinavian Journal of Clinical and Laboratory Investigation 54:Suppl. 219:61S-76S (1994).

    Reynolds EH, Bottiglieri T, Laundy M, Stern J, Payan J, Linnell J, Faludy J, Subacute Combined Degeneration with High Serum Vitamin-B12 Level and Abnormal Vitamin-B12 Binding Protein - New Cause of an Old Syndrome, Archives of Neurology 50:739-742 (1993).

    Savage DG, Lindenbaum J, Stabler SP, Allen RH, Sensitivity of Serum Methylmalonic Acid and Total Homocysteine Determinations for Diagnosing Cobalamin and Folate Deficiencies, The American Journal of Medicine 96:239-246 (1994).

    Thompson WG, Babitz L, Cassino C, Freedman M, Lipkin M, Evaluation of Current Criteria Used to Measure Vitamin B12 Levels, The American Journal of Medicine 82:291-294 (1987).

    Blood levels may be maintained at the expense of tissue levels:
    Beck WS, second-hand report.
    Mollin et al, 1976 (above)

    High vitamin C intake does not interfere with B12 in the body. It only interferes with certain tests:
    Hathcock JN, Rader JI, Micronutrient Safety in Micronutrients and Immune Functions: Cytokines and Metabolism, Annals of the New York Academy of Science. 587:257-266 (1990).

    Herbert V, Jacob E, Wong KTJ, Scott J, Pfeffer RD, Low serum vitamin B12 levels in patients receiving ascorbic acid in megadoses: studies concerning the effect of ascorbate on radioisotope vitamin B12 assay, The American Journal of Clinical Nutrition 31:253-258 (1978).

    Mollin et al, 1976 (above)

    Rivers JM, Safety of High-Level Vitamin C Ingestion, JM Rivers, 1987

    Vitamin B12 beneficial in HIV disease:
    Baum MK, Shor-Posner G, Lu Y, et al, Micronutrients and HIV-1 Disease Progression, AIDS 9:1051-1056 (1995) ("normalization of [serum] vitamin A, vitamin B12 and zinc was associated with higher CD4 cell counts").

    Baum MK, Cure N, Shor-Posner G, The B-complex Vitamins, Immune Regulation, Cognitive Function, and HIV-1 Infection, Chapter 8 in Nutrition and AIDS, ed. RR Watson, CRC Press, 1994.

    Coodley G, use of B12 to reverse dementia, Third International Symposium on Nutrition and HIV/AIDS, Philadelphia, 1994.

    Tang AM, Graham NMH, Semba RD et al,Tthe role of serum micronutrient levels in HIV-1 disease progression, abstract Mo.C.320, Vancouver International AIDS Conference, 1996.

    Weinberg JB, Sauls DL, Misukonis MA, Shugars DC, Inhibition of productive human immunodeficiency virus-1 infection by cobalamins, Blood 86:1281-1287 (1995) (in vitro).

    In this series:
    • HIV & Diet revisited
    • HIV & Dietary Supplements revisited
    • HIV & Nutrients revisited
    • HIV & Cysteine revisited
    • HIV & Copper and Zinc revisited
    • HIV & Carnitine
    • HIV & The Gut
    • HIV & Liquid Food Supplements
    • References for HIV & Nutrition
    Author, Chester Myers, holds both honours B.Sc. and M.Sc. (1969) degrees in physical chemistry from Dalhousie University, and a Ph.D. (1975) from the University of Toronto (biophysical chemistry) where he investigated the mechanism of action of one of the digestive enzymes. In addition to publishing in the scientific literature and having authored several patents, he has written extensively on topics regarding health and HIV. The latter include articles in The Positive Side, Canadian AIDS News, and monographs available from the AIDS Committee of Toronto (ACT), the Community AIDS Treatment Information Exchange (CATIE), and various other organizations.
      Disclaimer:
      The material in this publication is for information purposes only. It does not endorse any particular treatment program nor strategy; neither is it intended as medical advice nor as a replacement for medical advice.

      ©This document is copyrighted by Chester Myers. All materials may be reprinted and/or distributed without prior permission. However, reprints may not be edited.

      February 1997
      Last modified on: 09/15/2004

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