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HIV-Related Vitamin B12 Deficiency
By Sharon Ann Meyer, AS, AA, DTR
During the past 20 years we have learned a great deal about the effect of HIV and AIDS on nutritional status. Investigators have found numerous vitamin and mineral deficiencies in people with chronic HIV infection.1,2,3 Early studies noted that hard to detect vitamin B12 deficiency occurs in about half of all HIV-positive individuals,4 and supplementation may be warranted in those patients with advanced HIV infection.5 We now know that cobalamin deficiency is common in all stages of HIV disease and may play a more crucial role in HIV/AIDS than was previously thought.6,7,8
Vitamin B12 helps us in many ways. Because of its role in DNA synthesis, adequate amounts of this important vitamin are necessary for the formation of DNA. Vitamin B12 functions especially in the gastrointestinal tract, the nervous system, and in the bone marrow. It may also help to maintain blood and tissue GSH (reduced glutathione) and ascorbic acid in their reduced state.7 Cobalamin has a role in maintaining the sheath that surrounds and protects nerve fibers and helps to promote their normal growth.8 A deficiency may interfere with both carbohydrate and fatty acid metabolism and effects could manifest themselves in tissues of the central nervous system. Of particular importance to people living with HIV infection, vitamin B12 deficiency could be an important and treatable cause of neurological dysfunction.8
B12 Deficiency in HIV Disease
There are numerous causes of vitamin B12 deficiency, including: (1) malabsorption due to enteropathy; (2) malabsorption due to decreased secretion of stomach acid (hypochlorhydria) and intrinsic factor; and (3) malnutrition due to appetite suppression during cachexia.6,7,8 Intestinal infections causing chronic diarrhea and recreational drugs such as alcohol, ÒpoppersÓ (butyl nitrite), and marijuana,7 in addition to inadequate dietary intake, are also involved in the development of cobalamin deficiency. Conditions associated with decreased vitamin B12 absorption, such as hypochlorhydria and abnormalities of cobalamin transport or metabolism, occur in people living with HIV. Also, below normal levels of cobalamin are highly prevalent in HIV-challenged people who have chronic diarrhea.9
The amount of vitamin B12 absorption depends on dietary intake and is regulated to about 2.5 to 3.0 micrograms (µg) per day by intrinsic factor, which is secreted from cells in the stomach.10 Cobalamin must be bound to the intrinsic factor before mucosal epithelial cells (microvilli) absorb it.7,8 Low intrinsic factor secretion contributes to vitamin B12 malabsorption, and decreased parietal cell secretion of intrinsic factor and acid may occur independently in HIV-associated gastric secretory failure.5 Also, several drugs, such as methotrexate, pentamidine, and trimethoprim, can interfere with the absorption of vitamin B12.
Elyse Singer notes that cobalamin is relevant in cognition disorders because vitamin B12 deficiencies may play a role in demyelination.11 Both folate and vitamin B12 deficiency may cause similar neurological and psychiatric disturbances including depression, dementia, myelopathy, and peripheral neuropathy.12 According to Swain, the fifth stage of the vitamin B12 deficiency syndrome results in irreversible neuropsychiatric manifestations.13 There are various symptoms of cobalamin deficiency.6,7,8,14 Balt recently found significant relationships between vitamin B12 deficiency and weight loss and diarrhea.15
SYMPTOMS OF VITAMIN B12 DEFICIENCY
"Abdominal discomfort
"Anorexia
"Confusion
"Dementia
"Dyspnea
"Glossitis
"Loss of vibration sensation
"Mental depression
"Neurologic disturbances
"Pallor
"Prolonged bleeding time
"Soreness of mouth/tongue
"Weight loss
Diagnosing B12 Deficiency
Vitamin B12 absorption tests, such as the Schilling test, are considered to be of limited use for diagnosing cobalamin deficiencies.16 Elevated serum homocysteine may also not adequately reveal a subtle vitamin B12 deficiency associated with HIV.7 Furthermore, a deficiency may exist despite normal total serum B12, normal serum homocysteine, and a normal Schilling test.4,17 In this instance, Herbert and others found that low holotranscobalamin II (a cobalamin-binding protein) is the earliest serum marker of subnormal vitamin B12 absorption in AIDS.4 Sensitive assays such as those for serum methylmalonic acid (MMA) and total homocysteine may be necessary to demonstrate the existence of a hard to detect (by conventional methods) B12 deficiency.7
Increasing Cobalamin
Mainly, bacteria that live in the intestinal tract produce vitamin B12.10 A normal liver can store enough cobalamin to take care of body needs for 3 to 5 years. The vitamin B12 Recommended Dietary AllowanceÑthe average daily dietary intake level that is enough to meet the nutrient requirements of most healthy individualsÑ is 2.4 µg for adults ages 19 and above. Women who are pregnant need at least 2.6 µg per day.
Vitamin B12 has a very low potential for toxicity.18 The Institute of Medicine recommends vitamin B12 supplements or fortified food for adults over 50 years of age because of the increased risk of impaired vitamin B12 absorption. Although there are no standard dietary supplement guidelines for people living with HIV, many clinicians recommend a vitamin B12 complex supplement and fortified food for HIV-positive people as well. Increasing cobalamin intake results in decreased absorption, but absorption is greater if the vitamin is present in several meals instead of in a single meal. The best food sources of vitamin B12 are foods of animal origin; seafood such as salmon, tuna and crab; fortified breakfast cereals; and dairy products. Eating more fortified cereals and dairy products can help to improve vitamin B12 status.14
Screening HIV-positive individuals for cobalamin deficiency sometimes allows for early detection of a negative vitamin B12 balance. Cobalamin deficiency screening may also help the healthcare provider to plan the best possible care.15 Normalization of serum B12 is correlated with increased CD4 T-cell counts, and low serum B12 is associated with accelerated disease progression.2,3 Also, supplementation with vitamin B12 may be an effective means of improving the intracellular redox balance and/or facilitating the proper metabolism of antioxidants in HIV infection.7
Treatments
For people without conditions associated with deficiency who have adequate vitamin B12 levels, consuming foods high in vitamin B12 will help to lessen the occurrence of a deficiency. Treatments for cobalamin deficiency include oral supplements, intranasal gel or spray, and B12 injections. John Babish, PhD, recommends 1,000 mg®¢1,500 µg of oral vitamin B12. This amount allows for bioavailability of 30 mg®¢100 µg even in people with poor absorption.19 In other cases, B12 by injection may be necessary. The usual dose of intramuscular vitamin B12 is 1,000 µg monthly. Regardless of the method of supplementation, vitamin B12 levels should be followed to ensure adequacy of treatment. Some researchers (Thomas F. Brennan, PhD and William Sarill, MA at <>) are investigating an enhanced uptake formulation of vitamin B12 called Cobamaxª (generic name, cyanocobalamin aminolate).
It seems prudent to investigate the vitamin B12 status of people living with HIV. Fine and Soria have noted that we should not withhold vitamin B12 therapy from people with borderline B12 levels because the consequence of allowing myelopathy, neuropathy, dementia, and mental disorders to worsen clearly outweighs any disadvantages of therapy.17
Author's Note: This article is an edited version of references 7 and 8, which are available in their complete form at http://www.hivresources. com/NewsView.html. Contact the author by e-mail at or at HIV ReSources, Inc., PO Box 39385, Ft. Lauderdale, FL 3 if you would like a complete list of this article's references.
Sharon Ann Meyer is the President of HIV ReSources, Inc. http://www.hivresources.com in Fort Lauderdale, Florida. She is the Editor-in-Chief of the HIV ReSource Review, HIV Nutrition Update and the free HIV Nutrition News Update http://www.hivresources.com/Archive1.html. Sharon is also co-author of HIV Medications Food Interactions (And So Much More) http://www.foodmedinteractions.com.
References
1. Baum M, Cassetti L, Bonvehi P, Shor®¢Posner G, et al. Inadequate dietary intake and altered nutrition status in early HIV-1 infection. Nutrition. 1994;10(1):16®¢20.
2. Baum MK, Shor®¢Posner G, Lu Y, et al. Micronutrients and HIV-1 disease progression. AIDS. 1995;9(9):1051®¢1056.
3. Tang AM, Graham NMH, Chandra RK, Saah AJ. Low serum vitamin B12 concentrations are associated with faster human immunodeficiency virus type I (HIV-1) disease progression. J Nutr. 1997;127(2):345®¢3451.
4. Herbert V, Fong W, Gulle V, Stopler T. Low holotranscobalamin II is the earliest serum marker for subnormal vitamin B12 (cobalamin) absorption in patients with AIDS. Am J Hematol. 1990;34(2):132®¢139.
5. Herzlich BC, Schiano TD, Moussa Z, Zimbalist E, et al. Decreased intrinsic factor secretion in AIDS: Relation to parietal cell acid secretory capacity and vitamin B12 malabsorption. Am J Gastroenterol. 1992;87(12):1781®¢1788.
6. Patrick L. Nutrients and HIV: Part TwoÑVitamins A and E, zinc, B-vitamins, and magnesium. Altern Med Rev. 2000 Feb;5(1):39®¢51. Available online at: http://www.thorne.com/ altmedrev/.fulltext/5/1/39.html (accessed 17 Jan 2001).
7. Sarill WJ, Brennan TF. Vitamin B12 revisited: Old wine in new bottles. HIV ReSource Review. 1999;4(3):1, 4, 6®¢8, 14®¢20.
8. Meyer SA. B12: Dementia and cognition. A review of HIV-related vitamin B12 deficiency, cognition, and dementia. HIV ReSource Review. 1996;1(3):1, 4, 6®¢8, 10®¢12.
9. Ehrenpreis ED, Carlson SJ, Boorstein HL, Craig RM. Malabsorption and deficiency of vitamin B12 in HIV-infected patients with chronic diarrhea. Dig Dis Sci. 1994;39(10):2159®¢2162.
10. Robinson CH, Lawler MR. The water soluble vitamins: The vitamin B complex: vitamin B12. In: Beck JJ, ed. Normal and Therapeutic Nutrition, 16th Edition. New York, New York: Macmillan Publishing Company, Inc.; 1982:233®¢236.
11. Smith D. Understanding dementia and neurologic disorders: Interview with Elyse Singer, MD. AIDS Treatment News. No. 171, March 19, 1993.
12. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S®¢adeno®¢sylmethionine) in neurological disorders. Drugs. 1994;48(2):137®¢152.
13. Swain R. An update of vitamin B12 metabolism and deficiency states. J Fam Pract. 1995;41(6):595®¢600.
14. Tucker KL, Rich S, Rosenberg I, Jacques P, et al. Plasma vitamin B12 concentrations relate to intake source in the Framingham Offspring study. Am J Clin Nutr. 2000;71(2):514®¢522.
15. Balt CA. An investigation of the relationship between vitamin B12 deficiency and HIV infection. J Assoc Nurses AIDS Care. 2000;11(1):24®¢8, 31®¢5.
16. Nexo E, Hansen M, Rasmussen K, et al. How to diagnose cobalamin deficiency. Scand J Clin Lab Invest Suppl. 1994;219:61®¢76.
17. Fine EJ, Soria ED. Myths about vitamin B12 deficiency. South Med J. 1991;84(12):1475®¢1481.
18. Vitamin B12 Fact Sheet. Bethesda, MD: National Institutes of Health (NIH); Updated 1/2001. Available online at: <http://www.cc.nih.gov/ ccc/supplements/vitb12.html> (accessed 17 Jan 2001).
19. Lee A. Conference report: AIDS wasting in the forefront. Positive Communication. Summer 2000;5(2):1®¢5.
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