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May 7, 1997, Vol 277, No. 17 >
ARTICLE | May 7, 1997

Vitamin E Supplementation and In Vivo Immune Response in Healthy Elderly Subjects: Title and subTitle BreakA Randomized Controlled Trial FREE

Simin Nikbin Meydani, DVM, PhD; Mohsen Meydani, DVM, PhD; Jeffrey B. Blumberg, PhD; Lynette S. Leka; George Siber, MD; Robert Loszewski; Claudette Thompson; Marcos C. Pedrosa, MD; Richard D. Diamond, MD; B. David Stollar, MD
[+] Author Affiliations

The contents of this publication do not necessarily reflect the views or policies of the US Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.

Reprints: Simin Nikbin Meydani, DVM, PhD, Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St, Boston, MA 02111 (e-mail: S_Meydani_IM@HNRC.TUFTS.EDU).


JAMA. 1997;277(17):1380-1386. doi:10.1001/jama.1997.03540410058031
Text Size: A A A
Published online
Article
References

Objective.  —To determine whether long-term supplementation with vitamin E enhances in vivo, clinically relevant measures of cell-mediated immunity in healthy elderly subjects.

Design.  —Randomized, double-blind, placebo-controlled intervention study.

Setting and Participants.  —A total of 88 free-living, healthy subjects at least 65 years of age.

Intervention.  —Subjects were randomly assigned to a placebo group or to groups consuming 60, 200, or 800 mg/d of vitamin E for 235 days.

Main Outcome Measures.  —Delayed-type hypersensitivity skin response (DTH); antibody response to hepatitis B, tetanus and diphtheria, and pneumococcal vaccines; and autoantibodies to DNA and thyroglobulin were assessed before and after supplementation.

Results.  —Supplementation with vitamin E for 4 months improved certain clinically relevant indexes of cell-mediated immunity in healthy elderly. Subjects consuming 200 mg/d of vitamin E had a 65% increase in DTH and a 6-fold increase in antibody titer to hepatitis B compared with placebo (17% and 3-fold, respectively), 60-mg/d (41% and 3-fold, respectively), and 800-mg/d (49% and 2.5-fold, respectively) groups. The 200-mg/d group also had a significant increase in antibody titer to tetanus vaccine. Subjects in the upper tertile of serum α-tocopherol (vitamin E) concentration (>48.4 μmol/L [2.08 mg/dL]) after supplementation had higher antibody response to hepatitis B and DTH. Vitamin E supplementation had no effect on antibody titer to diphtheria and did not affect immunoglobulin levels or levels of T and B cells. No significant effect of vitamin E supplementation on autoantibody levels was observed.

Conclusions.  —Our results indicate that a level of vitamin E greater than currently recommended enhances certain clinically relevant in vivo indexes of T-cell-mediated function in healthy elderly persons. No adverse effects were observed with vitamin E supplementation.

REFERENCES

1 +
Siskind GW.  Immunological aspects of aging: an overview . In: Schimke RT, ed. Biological Mechanism in Aging . Bethesda, Md: US Dept of Agriculture, National Institutes of Health; 1980;:455-467.
2 +
Rodysill KJ, Hansen L, O'Leary JJ.  Cutaneous-delayed hypersensitivity in nursing home and geriatric clinic patients: implications for the tuberculin test . J Am Geriatr Soc . 1989;;37:435-443.
3 +
Roberts-Thomson IC, Whittingham S, Youngchaiyud U, Mackay IR.  Ageing, immune response, and mortality . Lancet . 1974;;2:368-370.
4 +
Wayne SJ, Rhyne RL, Garry PJ, Goodwin JS.  Cell-mediated immunity as a predictor of morbidity and mortality in the aged . J Gerontol Ser A Biol Sci Med Sci . 1990;;45:M45-M48.
5 +
Cohn JR, Hohl CA, Buckley CE.  The relationship between cutaneous cellular immune responsiveness and mortality in a nursing home population . J Am Geriatr Soc . 1983;;31:808-809.
6 +
Christou NV, Tellado-Rodriguez J, Chartrand L, et al.  Estimating mortality risk in preoperative patients using immunologic, nutritional, and acute-phase response variables . Ann Surg . 1989;;210:69-77.
7 +
Makinodan T.  Patterns of age-related immunologic changes . Nutr Rev . 1995;;53:S27-S31.
8 +
Whittingham S, Buckley JD, MacKay IR.  Factors influencing the secondary Ab response to flagellin in man . Clin Exp Immunol . 1978;;34:170-178.
9 +
Burns EA, Lum LG, L'Hommedieu G, Goodwin JS.  Specific humoral immunity in the elderly: in vivo and in vitro response to vaccination . J Gerontol . 1993;;48:B231-B236.
10 +
Ershler WB, Moore AL, Socinski MA.  Influenza and aging: age-related changes and the effect of thymosin on the Ab response to influenza vaccine . J Clin Immunol . 1985;;4:445-454.
11 +
Kishimoto S, Tomino S, Mitsuya H, Fujiwara H.  Age-related decline in the in vitro and in vivo synthesis of anti-TT antibody in humans . J Immunol . 1980;;1980:2347-2352.
12 +
Howells CHL, Vesselinova-Jenkins CK, Evans AD, James J.  Influenza vaccination and mortality from bronchopneumonia in the elderly . Lancet . 1975;; 1:381-383.
13 +
Ruben FL, Uhrin M.  Specific immunoglobulin-class antibody responses in the elderly before and after 14-valent pneumococcal vaccine . J Infect Dis . 1985;;151:845-848.
14 +
Fujiwara M, Kishimoto S.  IgE antibody formation and aging, I: age-related changes in IgE antibody formation and avidity for the DNP-determinant in mice . J Immunol . 1979;;123:263-268.
15 +
Rowley MJ, Buchanan H, Mackay IR.  Reciprocal change with age in antibody to extrinsic and intrinsic antigens . Lancet . 1968;;2:24-26.
16 +
Meydani SN, Meydani M, Verdon CP, Shapiro AC, Blumberg JB, Hayes KC.  Vitamin E supplementation suppresses prostaglandin E2 synthesis and enhances the immune response of aged mice . Mech Ageing Dev . 1986;;34:191-201.
17 +
Bartocci A, Maggi FM, Welker RD, Veronese F.  Age-related immunosuppression: putative role of prostaglandins . In: Backman RS, Honn XV, Ramwell P, eds. Prostaglandins and Cancer . New York, NY: Alan R. Liss; 1982;:725-730.
18 +
Hayek MG, Meydani SN, Meydani M, Blumberg JB.  Age differences in eicosanoid production of mouse splenocytes: effects on mitogen-induced T-cell proliferation . J Gerontol . 1994;;49:B197-B207.
19 +
Beharka AA, Wu D, Han S-N, Meydani SN.  Macrophage prostaglandin production contributes to the age-associated decrease in T cell function which is reversed by the dietary antioxidant vitamin E . Mech Ageing Dev . 1997;;94:157-165.
20 +
Anderson GD, Hauser SD, McGarity KL, Bremer ME, Isakson PC, Gregory SA.  Selective inhibition of cyclooxygenase (Cox)-2 reverses inflammation and expression of Cox 2 and interleukin 6 in rat adjuvant arthritis . J Clin Invest . 1996;;97:2672-2679.
21 +
Goodwin JS.  Prostaglandins and host defense in cancer . Med Clin North Am . 1981;;65:829-844.
22 +
Sano H, Kawahito Y, Wilder RL, et al.  Expression of cyclooxygenase-1 and -2 in human colorectal cancer . Cancer Res . 1995;;55:3785-3789.
23 +
Kargman SL, O'Neill GP, Vickers PJ, Evans JF, Mancini JA, Jothy S.  Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer . Cancer Res . 1995;;55:2556-2559.
24 +
Chandra RK.  Effect of vitamin and trace-element supplementation on immune responses and infectious disease in elderly subjects . Lancet . 1992;;340:1124-1127.
25 +
Bogden JD, Bendich A, Kemp FW, et al.  Daily micronutrient supplements enhance delayed-hypersensitivity skin test responses in older people . Am J Clin Nutr . 1994;;60:437-447.
26 +
Meydani M, Blumberg JB. Vitamin E. In: Hartz SC, Russell RM, Rosenberg IH, eds. Nutrition in the Elderly: The Boston Nutritional Status Survey . London, England: Smith-Gordon & Co Ltd; 1992;:103-109.
27 +
Meydani SN, Meydani M, Rall L, Morrow F, Blumberg JB.  Assessment of the safety of high-dose, short-term supplementation with vitamin E in healthy older adults . Am J Clin Nutr . 1994;;60:704-709.
28 +
Meydani SN, Lichtenstein AH, Cornwall S, et al.  Immunologic effects of National Cholesterol Education Panel (NCEP) Step-2 diets with and without fish-derived n-3 fatty acid enrichment . J Clin Invest . 1993;;92:105-113.
29 +
Shahid NS, Steinhof MC, Hoque SS, Begum T, Thompson C, Siber G.  Serum, breast milk, and infant antibody after maternal immunization with pneumococcal vaccine . Lancet . 1995;;346:1252-1257.
30 +
Siber GR, Santosham M, Reid GR, et al.  Impaired antibody response to Haemophilus influenzae type B polysaccharide and low IgG2 and IgG4 in Apache children . N Engl J Med . 1990;;323:1387-1392.
31 +
Zouali M, Stollar BD.  A rapid ELISA for measurement of antibodies to nucleic acid antigens using YV-related polystyrene microplates . J Immunol Methods . 1986;;90:105-110.
32 +
Bieri JG, Tolliver TJ, Catignani GL.  Simultaneous determination of alpha-tocopherol and retinol in plasma or red cells by high-pressure liquid chromatography . Am J Clin Nutr . 1979;;32:2143-2149.
33 +
Meydani M, Natiello F, Goldin B, et al.  Effect of long-term fish oil supplementation on vitamin E status and lipid peroxidation in women . J Nutr . 1991;;121:484-491.
34 +
GRAND [database online]. Grand Forks, ND: US Dept of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center; 1990.
35 +
Diamond RD, Lyman CA, Wysong DR.  Disparate effects of interferon-gamma and tumor necrosis factor-alpha on early neutrophil respiratory burst and fungicidal responses to Candida albicans hyphae in vitro . J Clin Invest . 1991;;87:711-720.
36 +
Meydani SN, Barklund PM, Liu S, et al.  Effect of vitamin E supplementation on immune responsiveness of healthy elderly subjects . Am J Clin Nutr . 1990;;52:557-563.
37 +
Chavance M, Brubacher G, Herbert B, et al.  Immunological nutritional status among the elderly . In: Chandra RK, ed. Nutritional Immunity and Illness in the Elderly . Elmsford, NY: Pergamon Press Inc; 1985;:137-142.
38 +
Chavance M, Herbeth B, Fournier C, Janot C, Vernhes G.  Vitamin status, immunity, and infections in an elderly population . Eur J Clin Nutr . 1989;;43:827-835.
39 +
Tengerdy RP, Heinzerling RH, Mathias MM.  Effect of vitamin E on disease resistance and immune response . In: de Duve C, Hayaishi O, eds. Tocopherol, Oxygen, and Biomembranes . New York, NY: Elsevier Science Inc; 1978;:191-200.
40 +
Julseth DR. Evaluation of Vitamin E and Disease Stress on Turkey Performance . Fort Collins: Colorado State University; 1984;.
41 +
Ellis RP, Vorhies MW.  Effect of supplemental dietary vitamin E on the serologic response of swine to an Escherichia coli bacteria . J Am Vet Med Assoc . 1986;;168:231-232.
42 +
Heinzerling RH, Tengerdy RP, Wick LL, Lueker DC.  Vitamin E protects mice against Diplococcus pneumonia type I infection . Infect Immun . 1974;;10:1292-1295.
43 +
Hayek MG, Taylor SF, Bender BS, et al. Vitamin E supplementation decreases lung viral titer in mice infected with influenza. J Infect Dis. In press.
44 +
Wang Y, Hwang DS, Licing B, Watson RR.  Nutritional status and immune responses in mice with murine AIDS are normalized by vitamin E supplementation . J Nutr . 1994;;124:2024-2032.
45 +
Reddy PG, Morrill JL, Minocha HC, Morrill MB, Dayton AB, Frey RA.  Effects of supplemental vitamin E on the immune system of calves . J Dairy Sci . 1985;;69:164-171.
46 +
Teige J, Tollersrud S, Lund A, Larsen HJ.  Swine dysentery: the influence of dietary vitamin E and selenium on the clinical and pathological effect of Treponema hyodysenteriae infection in pigs . Res Vet Sci . 1982;;32:95-160.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Siskind GW.  Immunological aspects of aging: an overview . In: Schimke RT, ed. Biological Mechanism in Aging . Bethesda, Md: US Dept of Agriculture, National Institutes of Health; 1980;:455-467.
2 +
Rodysill KJ, Hansen L, O'Leary JJ.  Cutaneous-delayed hypersensitivity in nursing home and geriatric clinic patients: implications for the tuberculin test . J Am Geriatr Soc . 1989;;37:435-443.
3 +
Roberts-Thomson IC, Whittingham S, Youngchaiyud U, Mackay IR.  Ageing, immune response, and mortality . Lancet . 1974;;2:368-370.
4 +
Wayne SJ, Rhyne RL, Garry PJ, Goodwin JS.  Cell-mediated immunity as a predictor of morbidity and mortality in the aged . J Gerontol Ser A Biol Sci Med Sci . 1990;;45:M45-M48.
5 +
Cohn JR, Hohl CA, Buckley CE.  The relationship between cutaneous cellular immune responsiveness and mortality in a nursing home population . J Am Geriatr Soc . 1983;;31:808-809.
6 +
Christou NV, Tellado-Rodriguez J, Chartrand L, et al.  Estimating mortality risk in preoperative patients using immunologic, nutritional, and acute-phase response variables . Ann Surg . 1989;;210:69-77.
7 +
Makinodan T.  Patterns of age-related immunologic changes . Nutr Rev . 1995;;53:S27-S31.
8 +
Whittingham S, Buckley JD, MacKay IR.  Factors influencing the secondary Ab response to flagellin in man . Clin Exp Immunol . 1978;;34:170-178.
9 +
Burns EA, Lum LG, L'Hommedieu G, Goodwin JS.  Specific humoral immunity in the elderly: in vivo and in vitro response to vaccination . J Gerontol . 1993;;48:B231-B236.
10 +
Ershler WB, Moore AL, Socinski MA.  Influenza and aging: age-related changes and the effect of thymosin on the Ab response to influenza vaccine . J Clin Immunol . 1985;;4:445-454.
11 +
Kishimoto S, Tomino S, Mitsuya H, Fujiwara H.  Age-related decline in the in vitro and in vivo synthesis of anti-TT antibody in humans . J Immunol . 1980;;1980:2347-2352.
12 +
Howells CHL, Vesselinova-Jenkins CK, Evans AD, James J.  Influenza vaccination and mortality from bronchopneumonia in the elderly . Lancet . 1975;; 1:381-383.
13 +
Ruben FL, Uhrin M.  Specific immunoglobulin-class antibody responses in the elderly before and after 14-valent pneumococcal vaccine . J Infect Dis . 1985;;151:845-848.
14 +
Fujiwara M, Kishimoto S.  IgE antibody formation and aging, I: age-related changes in IgE antibody formation and avidity for the DNP-determinant in mice . J Immunol . 1979;;123:263-268.
15 +
Rowley MJ, Buchanan H, Mackay IR.  Reciprocal change with age in antibody to extrinsic and intrinsic antigens . Lancet . 1968;;2:24-26.
16 +
Meydani SN, Meydani M, Verdon CP, Shapiro AC, Blumberg JB, Hayes KC.  Vitamin E supplementation suppresses prostaglandin E2 synthesis and enhances the immune response of aged mice . Mech Ageing Dev . 1986;;34:191-201.
17 +
Bartocci A, Maggi FM, Welker RD, Veronese F.  Age-related immunosuppression: putative role of prostaglandins . In: Backman RS, Honn XV, Ramwell P, eds. Prostaglandins and Cancer . New York, NY: Alan R. Liss; 1982;:725-730.
18 +
Hayek MG, Meydani SN, Meydani M, Blumberg JB.  Age differences in eicosanoid production of mouse splenocytes: effects on mitogen-induced T-cell proliferation . J Gerontol . 1994;;49:B197-B207.
19 +
Beharka AA, Wu D, Han S-N, Meydani SN.  Macrophage prostaglandin production contributes to the age-associated decrease in T cell function which is reversed by the dietary antioxidant vitamin E . Mech Ageing Dev . 1997;;94:157-165.
20 +
Anderson GD, Hauser SD, McGarity KL, Bremer ME, Isakson PC, Gregory SA.  Selective inhibition of cyclooxygenase (Cox)-2 reverses inflammation and expression of Cox 2 and interleukin 6 in rat adjuvant arthritis . J Clin Invest . 1996;;97:2672-2679.
21 +
Goodwin JS.  Prostaglandins and host defense in cancer . Med Clin North Am . 1981;;65:829-844.
22 +
Sano H, Kawahito Y, Wilder RL, et al.  Expression of cyclooxygenase-1 and -2 in human colorectal cancer . Cancer Res . 1995;;55:3785-3789.
23 +
Kargman SL, O'Neill GP, Vickers PJ, Evans JF, Mancini JA, Jothy S.  Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer . Cancer Res . 1995;;55:2556-2559.
24 +
Chandra RK.  Effect of vitamin and trace-element supplementation on immune responses and infectious disease in elderly subjects . Lancet . 1992;;340:1124-1127.
25 +
Bogden JD, Bendich A, Kemp FW, et al.  Daily micronutrient supplements enhance delayed-hypersensitivity skin test responses in older people . Am J Clin Nutr . 1994;;60:437-447.
26 +
Meydani M, Blumberg JB. Vitamin E. In: Hartz SC, Russell RM, Rosenberg IH, eds. Nutrition in the Elderly: The Boston Nutritional Status Survey . London, England: Smith-Gordon & Co Ltd; 1992;:103-109.
27 +
Meydani SN, Meydani M, Rall L, Morrow F, Blumberg JB.  Assessment of the safety of high-dose, short-term supplementation with vitamin E in healthy older adults . Am J Clin Nutr . 1994;;60:704-709.
28 +
Meydani SN, Lichtenstein AH, Cornwall S, et al.  Immunologic effects of National Cholesterol Education Panel (NCEP) Step-2 diets with and without fish-derived n-3 fatty acid enrichment . J Clin Invest . 1993;;92:105-113.
29 +
Shahid NS, Steinhof MC, Hoque SS, Begum T, Thompson C, Siber G.  Serum, breast milk, and infant antibody after maternal immunization with pneumococcal vaccine . Lancet . 1995;;346:1252-1257.
30 +
Siber GR, Santosham M, Reid GR, et al.  Impaired antibody response to Haemophilus influenzae type B polysaccharide and low IgG2 and IgG4 in Apache children . N Engl J Med . 1990;;323:1387-1392.
31 +
Zouali M, Stollar BD.  A rapid ELISA for measurement of antibodies to nucleic acid antigens using YV-related polystyrene microplates . J Immunol Methods . 1986;;90:105-110.
32 +
Bieri JG, Tolliver TJ, Catignani GL.  Simultaneous determination of alpha-tocopherol and retinol in plasma or red cells by high-pressure liquid chromatography . Am J Clin Nutr . 1979;;32:2143-2149.
33 +
Meydani M, Natiello F, Goldin B, et al.  Effect of long-term fish oil supplementation on vitamin E status and lipid peroxidation in women . J Nutr . 1991;;121:484-491.
34 +
GRAND [database online]. Grand Forks, ND: US Dept of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center; 1990.
35 +
Diamond RD, Lyman CA, Wysong DR.  Disparate effects of interferon-gamma and tumor necrosis factor-alpha on early neutrophil respiratory burst and fungicidal responses to Candida albicans hyphae in vitro . J Clin Invest . 1991;;87:711-720.
36 +
Meydani SN, Barklund PM, Liu S, et al.  Effect of vitamin E supplementation on immune responsiveness of healthy elderly subjects . Am J Clin Nutr . 1990;;52:557-563.
37 +
Chavance M, Brubacher G, Herbert B, et al.  Immunological nutritional status among the elderly . In: Chandra RK, ed. Nutritional Immunity and Illness in the Elderly . Elmsford, NY: Pergamon Press Inc; 1985;:137-142.
38 +
Chavance M, Herbeth B, Fournier C, Janot C, Vernhes G.  Vitamin status, immunity, and infections in an elderly population . Eur J Clin Nutr . 1989;;43:827-835.
39 +
Tengerdy RP, Heinzerling RH, Mathias MM.  Effect of vitamin E on disease resistance and immune response . In: de Duve C, Hayaishi O, eds. Tocopherol, Oxygen, and Biomembranes . New York, NY: Elsevier Science Inc; 1978;:191-200.
40 +
Julseth DR. Evaluation of Vitamin E and Disease Stress on Turkey Performance . Fort Collins: Colorado State University; 1984;.
41 +
Ellis RP, Vorhies MW.  Effect of supplemental dietary vitamin E on the serologic response of swine to an Escherichia coli bacteria . J Am Vet Med Assoc . 1986;;168:231-232.
42 +
Heinzerling RH, Tengerdy RP, Wick LL, Lueker DC.  Vitamin E protects mice against Diplococcus pneumonia type I infection . Infect Immun . 1974;;10:1292-1295.
43 +
Hayek MG, Taylor SF, Bender BS, et al. Vitamin E supplementation decreases lung viral titer in mice infected with influenza. J Infect Dis. In press.
44 +
Wang Y, Hwang DS, Licing B, Watson RR.  Nutritional status and immune responses in mice with murine AIDS are normalized by vitamin E supplementation . J Nutr . 1994;;124:2024-2032.
45 +
Reddy PG, Morrill JL, Minocha HC, Morrill MB, Dayton AB, Frey RA.  Effects of supplemental vitamin E on the immune system of calves . J Dairy Sci . 1985;;69:164-171.
46 +
Teige J, Tollersrud S, Lund A, Larsen HJ.  Swine dysentery: the influence of dietary vitamin E and selenium on the clinical and pathological effect of Treponema hyodysenteriae infection in pigs . Res Vet Sci . 1982;;32:95-160.

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