Vitamin B Group And The Immune System

Lorraine T Miller, Department of Nutrition and Food Management, Oregon State University, Corvallis, Oregon, USA

Copyright © 1998 Elsevier Ltd. All Rights Reserved.

The B-complex vitamins differ markedly in chemical structure and biological function. Pyridoxal phosphate (PLP), the predominant coenzyme form of vitamin B6, has a paramount role in the metabolism of amino acids and protein, including protein synthesis. Folate coenzymes function in the transport of single carbon moieties and are essential for the synthesis of DNA. Folate deficiency results in impaired cell division and altered protein synthesis, particularly of rapid growing tissues. Vitamin B12 is needed for the utilization of folate and the synthesis of DNA. Thiamin performs its coenzyme function as thiamin pyrophosphate in metabolism of 2-ketosugars and a-keto acids. Riboflavin and niacin are precursors of coenzymes involved in biological oxidations. Pantothenic acid functions in acyl-group activation reactions as a component of coenzyme A. Biotin is involved in biochemical reactions which add carboxyl groups to molecules.

Vitamin B6 deficiency produces profound changes in immune function in animals. The thymus is the lymphoid tissue most severely affected. Thymic hormone activity is decreased and lymphopenia is observed. Vitamin B6 deficiency impairs delayed cutaneous hypersensitivity responses, primary and secondary T cell-mediated cytotoxicity and rejection of skin grafts. Impaired humoral responses in vitamin Bft-deficient animals are indicated by poor antibody production after primary or booster immunization. Both B and T lymphocytes from vitamin B6-deficient animals have depressed proliferative responses to in vitro antigen or mitogen stimulation. Vitamin B6 deficiency, however, does not affect phagocytosis by macrophages or activity of natural killer (NK) cells. Increased amounts of vitamin Bft do not enhance immune function in mice that are not vitamin B6-deficient.

Humans depleted of vitamin B6 have fewer circulating lymphocytes. Vitamin B6 deficiency, produced by a vitamin B6 antagonist, mildly impaired humoral antibody responses to tetanus toxoid and typhoid vaccine. In patients with Hodgkin's disease or renal failure, in whom both biochemical vitamin B6 deficiency and impaired immune responses were observed, supplementary vitamin B6 normalized vitamin B6 status and improved results of various immunological tests. In elderly subjects who had no evidence of any underlying systemic disease, vitamin B6 supplementation improved in vitro lymphocyte blastogenesis in response to various mitogens. Lymphocyte blastogenesis after vitamin Bh supplementation was higher in subjects whose presupplcment vitamin B6 status was subnormal than in those whose presupplement vitamin Bh status was normal. Vitamin B6 supplementation in the elderly also resulted in increased proportions of CD3 1 and CD4" cells, but not CD8+ cells. A vitamin Bft intake slightly higher than the US recommended dietary allowance (RDA) improved in vitro lymphocyte proliferation and interleukin 2 (IL-2) production in young and elderly adults.

The biochemical lesion(s) underlying the detrimental effects of vitamin B6 deficiency on the immune system are not well understood. Early studies suggested that synthesis of DNA is diminished through a decrease in one-carbon pools resulting from the depressed PLP-dependent conversion of serine to glycine in vitamin B6 deficiency.

Folate and vitamin BJ2 deficiencies are associated with reduced host resistance and impaired lymphocyte function. Folate-deficient animals have a smaller thymus, a decrease in T cclls, as well as impaired cytotoxicity and in vitro lymphocyte response to mitogens. Additionally, folate deficiency results in reduced complement-fixing antibodies and impaired response to murine rotavirus. Patients with megaloblastic anemia due to folate deficiency had impaired neutrophil phagocytosis. Patients with low serum concentrations of vitamin B]2 also had impaired neutrophil function, which was corrected by vitamin B12. In animals, vitamin B]2 improves antibody function and mitogenic responses.

Pantothenic acid deficiency suppresses humoral antibody responsiveness to antigens in animals. In humans, when a combined deficiency of pantothenic acid and vitamin B6 was induced by antagonists of these vitamins, antibody responses to tetanus toxoid and typhoid antigen were almost completely inhibited and hypogammaglobulinemia developed. Antibody response, however, to polio vaccine immunization was normal.

Deficiencies in thiamin, biotin and riboflavin interfere moderately with immunologic function. Riboflavin deficiency decreases the ability to produce humoral antibodies in response to antigens. Rats deficient in thiamin, riboflavin or biotin had a reduced development of plaque-forming cells in response to immunization. Infants with multiple biotin-dependent carboxylase deficiencies showed delayed cutaneous hypersensitivity, impaired in vitro lymphocyte response to antigens and depressed antibody formation response to immunization.

Although isolated B-complex vitamin deficiencies have been found to have a detrimental effect on immune functions, the problem in reality is more complex. The metabolism of this group of vitamins along with other micron utrients is interconnected and multiple nutritional deficiencies occur in humans. Current research suggests that an intake of micronutrients, including the B-complex vitamins, two to three times higher than the US RDA, is necessary to obtain optimal immune function in healthy older adults. In placebo-controlled, double-blind studies in older adults a micronutrient supplement which included B-complex vitamins significantly enhanced NK cell cytotoxicity, lymphocyte proliferation and antibody titers to influenza vaccine, and reduced the number of sick days. Research is needed to determine the amounts of B-complex vitamins, as well as other micronutrients, needed for optimal immune function in humans and the mechanisms by which these micronutrients function in the immune system.

See also: Aging and the immune system; Humoral immunity; Lymphoma; Nutrition and the immune system; Thymic hormones and peptides.

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