Destroying Immune Homeostasis in Normal Adults With Antioxidant Supplements

V. Herbert. Destroying Immune Homeostasis in Normal Adults With Antioxidant Supplements. Amer. J. Clinical Nutrition,1997; 65:1901 (June).

Dear Sir:

Healthy adults are in homeostatic equilibrium. In fact, homeostatic equilibrium and health are essentially synonyms. Jeng et al. (1) present yet another study showing that supplementation with vitamins C and E mount an uncalled-for immunopotentiation, disturbing normal homeostatic immune equilibrium. Their paper ignores the issue that this may do more harm than good (2,3).

As reviewed recently by Chinnaiyan et al. (4), Drappa et al. (5), and Liu et al. (6), mononuclear cell (particularly T-lymphocyte) stimulation is a mixed blessing, helpful to some and harmful to others. Help or harm is dependent on each individualís genetic makeup, plus ingested and absorbed environmental factors (eg, nutrients, antigens, drugs), which induce expression and/or suppression of genetic predisposition (2-6).

ìLymphocytes are equipped to eradicate noxious agents (microbes, cancer cells, and grafts) that disturb the bodyís equilibrium, but when their cellular activity is excessive, the results are harmful^î(6). The same killer lymphocytes which are immunoprotective also are immunopathogenic (2-6). Which they are in each individual is decided to a significant extent by the orderliness or derangements of lymphocyte apoptosis, or programmed cell death, the physiologic process essential to normal cell development and homeostasis (4-6). In our gene codes is a ìdeath domainî of signals for production of a complex of intracellular signaling molecules for expression of apoptosis promoters and suppressors (4-6).

The three most recent publications I cite (4-6) focus particularly on FAS gene mediated lymphocyte apoptosis and the fact that mutations in FAS inhibit FAS-dependent apoptosis, causing lymphocytes which should have died to instead spew out a stream of antibodies generating and maintaining autoimmune disorders (eg, autoimmune hemolytic anemia, thrombocytopenia, rheumatoid arthritis, lupus erythrematosis, and multiple sclerosis) and a multitude of neoplasms (eg, malignant lymphoma and thyroid and epithelial cell cancers (2-6). Lymphocyte suppressor therapy (e.g., corticosteroids, methotrexate) (2-6) helps to variable degrees by suppressing and killing these semi-immortal lymphocytes. Unfortunately, they tend to rise again, producing one or another of the various autoimmune disorders and neoplasms of which they are capable (2-6).

Further research needs to be done to determine whether vitamin E, particularly dl-a-tocopherol (the dominant vitamin E in supplements) not only stimulates T-cell production, but also triggers inhibition of apoptosis of the T-cells it generates.

Excess a-tocopherol has just been found to be harmful by displacing g-tocopherol from plasma and tissues, the only tocopherol form that effectively traps electrophilic NO_x by nitrating it into g-tocopherol in the nucleophilic 5 position, which is blocked on a-tocopherol by a methyl group (7). Free NO_x both inhibits apoptosis and promotes cancer (7). This helps explain why Kushi et al (8) found food vitamin E (which is principally g-tocopherol rather than a-tocopherol) to be beneficial against all-cause mortality whereas supplemental vitamin E (which is all a-tocopherol (9) ) was not.

Although Christen et al (7) suggest that the solution to the problem is to add g-tocopherol to a-tocopherol supplements, I suggest that the solution to a harmful pill is not taking it in the first place, rather than adding its antidote. It is interesting that a primary harm from supplemental a-tocopherol is its displacement of food g-tocopherol, just as a primary harm from supplemental b-carotene is its competition with food carotenoids for absorption (9).

The lucrative vitamin C, vitamin E and other ìimmune enhancerî supplement industry harms millions by not labeling their products ìCAUTION: This productís immune enhancement may be bad for you.î

REFERENCES

1. Jeng K-CG, Yang C-S, Siu W-Y, et al. Supplementation with vitamins C and E enhances cytokine production by peripheral blood mononuclear cells in healthy adults. Am J Clin Nutr 1996;64:960-5.

2. Herbert V, Kasdan TS. Alfalfa, vitamin E, and autoimmune disorders. Am J Clin Nutr 1994:60, 639-640.

3. Herbert V. Alfalfa, vitamin E, and autoimmune disorders: Reply to J Whittam et al. Am J Clin Nutr 1995; 62:1026.

4. Chinnaiyan AM, OíRourke K, Yu G-L, et al. Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD 95. Science 1996; 274:990-992.

5. Drappa J, Vainshnaw AK, Sullivan KE, et al. Fas gene mutation in the Canale-Smith syndrome, an inherited lymphoproliferative disorder association with autoimmunity. N Engl J Med 1996; 335:1643-1649.

6. Lui CC, Young LHY, Young LD-E. Mechanisms of disease: Lymphocyte- mediated cytolysis and disease. N Engl J Med 1996; 335:1651-1659.

7. Christen S, Woodall AA, Shigenaga MK, et al. g-Tocopherol traps mutagenic electrophiles such as NO_x and complements a-tocopherol: physiological implications. Proc Natl Acad Sci 1997; 94: 3217-22.

8. Kushi HHL, Folsom AR, Prineas RH, et al. Dietary antioxidant vitamins and death from coronary heart disease. N Engl J Med 1996; 334: 1156-62.

9.Herbert V. The value of antioxidant supplements vs their natural counterparts. J Am Diet Assoc1997; 97: 375 (letter).