Increase in vitamin B-12 during highly active antiretroviral therapy

Institute of Medical Chemistry and Biochemistry
University of Innsbruck
Fritz Pregl Strasse 3
A-6020 Innsbruck
Austria
E-mail:dietmar.fuchs{at}uibk.ac.at

Robert Zangerle

Department of Dermatology and Venerology
University of Innsbruck
A-6020 Innsbruck
Austria

Dear Sir:

With great interest, we read the article by Remacha et al (1) in which they discussed a role for homocysteine as a marker for vitamin B-12 status in HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Compared with patients not receiving such therapy, patients receiving HAART not only had higher CD4⁺ and CD8⁺ cell counts and leukocyte counts, they also had higher hemoglobin and vitamin B-12 concentrations and mean corpuscular volumes but lower homocysteine concentrations. With regard to cell counts and vitamin B-12, we obtained similar results in patients with HIV infection (2). In addition, antiretroviral therapy decreased concentrations of the immune system activation markers neopterin and soluble 75-kDa tumor necrosis factor receptor. Thus, treatment of patients with HAART not only improves blood cell counts and vitamin B-12 status, it also slows down immune system activation. Amelioration of hyperhomocysteinemia might be a consequence of this latter effect.

Low vitamin B-12 concentrations are often seen in HIV-infected persons, sometimes even despite vitamin supplementation. Data indicate that such patients have an increased demand for vitamins. Immune system activation leading to increased formation of reactive oxygen species could deplete antioxidants including oxidation-sensitive B vitamins (3). In particular, both vitamin B-12 and methyltetrahydrofolate, which are essential cofactors in homocysteine-methionine metabolism, are easily oxidized (3, 4). In line with this assumption, the coincidence of increased concentrations of immune system activation markers and of homocysteine has been observed in several diseases (3, 5). By decreasing virus load, HAART may down-regulate an overactivated immune system in patients, and antioxidant status may improve. Thus, vitamin B-12 might also increase, even without supplementation. In conclusion, elevated homocysteine concentrations characterize patients with decreased vitamin B-12 concentrations. However, these decreased vitamin B-12 concentrations are not necessarily due to insufficient dietary intake of B vitamins; they could also be a consequence of the oxidative stress associated with immune system activation.

REFERENCES

1. Remacha AF, Cadafalch J, Sardà P, Barceló M, Fuster M. Vitamin B-12 metabolism in HIV-infected patients in the age of highly active antiretroviral therapy: role of homocysteine in assessing vitamin B-12 status. Am J Clin Nutr 2003;77:420-4.
2. Sarcletti M, Quirchmair G, Weiss G, Fuchs D, Zangerle R. Increase of haemoglobin levels by anti-retroviral therapy is associated with a decrease in immune activation. Eur J Haematol 2003;70:17-25.
3. Fuchs D, Jaeger M, Widner B, Wirleitner B, Artner-Dworzak E, Leblhuber F. Is hyperhomocysteinemia due to the oxidative depletion of folate rather than to insufficient dietary intake? Clin Chem Lab Med 2001;39:691-4.
4. McCaddon A, Regland B, Hudson P, Davies G. Functional vitamin B(12) deficiency and Alzheimer disease. Neurology 2002;58:1395-9.
5. Widner B, Leblhuber F, Frick B, Laich A, Artner-Dworzak E, Fuchs D. Moderate hyperhomocysteinaemia and immune activation in Parkinson's disease. J Neural Transm 2002;109:1445-52.