Antioxidant Response to Exercise-induced Oxidative Stress and Protection by Vitamin E M. MEYDANI, W. EVANS, G. HANDELMAN, R. A. FIELDING, S. N. MEYDANI, M. A. FIATARONE, J. B. BLUMBERG, AND J . G. CANNON USDA Human Nutrition Research Center on Aging at Tufts University Boston, Massachusetts 02111
There is an increased generation of free radicals and lipid peroxides associated with strenuous and exhaustive exercise. I In vitamin E-deficient animals, exercise increases susceptibility to free radical damage and results in premature exhaustion, greater fragility of lysosomal membranes, and marked depression of muscle mitochondrial respiratory control. The few human studies conducted to date indicate that vitamin E supplementation reduces oxidative stress and lipid peroxidation events following exercise and suggest that vitamin E requirements may increase with e ~ e r c i s e . ~ , ~ In order to investigate the potential for aprotective role of vitamin E supplementation against exercise-induced oxidative stress, 9 young (22-29 yr) and 12 older (55-74 yr) healthy men were studied following daily supplementation with 800 IU vitamin E or placebo for 48 days. Volunteers then engaged in a bout of eccentric exercise by running downhill on a treadmill at 75% of their maximum heart rate for 45 minutes. After 48 days, the concentration of plasma a-tocopherol increased6 (56% in young, 70% in older subjects) and y-tocopherol decreased (99% in young, 60% in older subjects). A protective effect of vitamin E was substantiated by measuring 24 h urinary thiobarbituric acid (TBA) adducts as an index of whole body response to oxidative stress. The protective effect of vitamin E extended up to 12 days postexercise, at which time muscle protein injury and remodeling was evident by urinary excretion of 3-methylhistidine.' Analysis of variance showed a significant (p < 0.01) effect of exercise on 24 h urinary TBA-adduct excretion. Both young and older placebo groups showed a marked increase in urinary TBA-adduct excretion that reached statistical significance by 12 d post-exercise (TABLE I). By contrast, vitamin E-supplemented groups showed no change in TBA-adduct excretion in 24 h urine samples. Significant decreases in both a- and y-tocopherol concentration and a concomitant increase of lipid conjugated dienes (intermediate products of lipid peroxidation) were found in biopsies obtained from vastus lateralis muscle before and immediately after exercise. In addition, muscle levels of linoleic and arachidonic acids in supplemented men were higher (p < 0.05) post-exercise than in those receiving placebo. These alterations in whole body lipid peroxide status following a bout of eccentric exercise are consistent with the hypothesis that vitamin E provides protection against exercise-induced oxidative injury. 363
ANNALS NEW YORK ACADEMY OF SCIENCES
364
Mean Differences in Percent Increase of 24-Hour Urinary TBA-Adduct Excretion between Placebo and Vitamin E-Supplemented Groups after Eccentric Exercise
TABLk: 1.
~
~~~
Day of exercise 12 Days post-exercise ~
Young
Older
14.5% 26.0%*
2.6% 59.9%**
~~
* p . 0.05 from day of exercise. ** p < 0.001 from day of exercise. REFERENCES 1.
2. 3. 4. 5. 6.
7.
GOHII.,K . , L. PACKER, B. D E L U M E NG., A. BROOKS& G. E. TERBLANCHE. 1986. J. Appl. Physiol. 60: 1986-1991. DAVIES. K . J. A . , A. T. QUINTANILHA. G . A. BROOKS& L. PACKER.1982. Biochem. Hiophys. Res. Commun. 107: 1198-1205. QC'INTANILHA,A. T., L. PACKER, J . M. s. DAVIES, T. L. RACANELLI & K . J. A. DAVIES. 1982. Ann. N.Y. Acad. Sci. 393: 32-47. R. BOUCHEZ,L. MASSAUX & R. PINCEMAIL, J., c. DEBY,G . CAMUS,F. PIRNAY, GOUTIER.1988. Eur. J. Appl. Physiol. 57: 189-191. SIMON-SCHNASS, I. & H. PABST.1988. J . Vitam. Nutr. Res. 58: 49-54. CANNON, J . G., s. F. ORENCOLE. R. A. FIELDING, M. MEYDANI, S. N . MEYDANI, M. A. F I A T A R O N E , J. B . BLUMBERG & W. J. EVANS.1990. Am. J. Physiol. 259: K 12 14-R I2 19. C A N N O NJ ., G., S . N . MEYDANI, R. A. FIELDING, M. A. FIATARONE, M. MEYDANI, M. FARHANGMEHR, S . F. ORENCOLE, J . B. BLUMBERG & W. EVANS.1991. Am. J. Physiol. 29: R1235-RI240.
There is an increased generation of free radicals and lipid peroxides associated with strenuous and exhaustive exercise. I In vitamin E-deficient animals, exercise increases susceptibility to free radical damage and results in premature exhaustion, greater fragility of lysosomal membranes, and marked depression of muscle mitochondrial respiratory control. The few human studies conducted to date indicate that vitamin E supplementation reduces oxidative stress and lipid peroxidation events following exercise and suggest that vitamin E requirements may increase with e ~ e r c i s e . ~ , ~ In order to investigate the potential for aprotective role of vitamin E supplementation against exercise-induced oxidative stress, 9 young (22-29 yr) and 12 older (55-74 yr) healthy men were studied following daily supplementation with 800 IU vitamin E or placebo for 48 days. Volunteers then engaged in a bout of eccentric exercise by running downhill on a treadmill at 75% of their maximum heart rate for 45 minutes. After 48 days, the concentration of plasma a-tocopherol increased6 (56% in young, 70% in older subjects) and y-tocopherol decreased (99% in young, 60% in older subjects). A protective effect of vitamin E was substantiated by measuring 24 h urinary thiobarbituric acid (TBA) adducts as an index of whole body response to oxidative stress. The protective effect of vitamin E extended up to 12 days postexercise, at which time muscle protein injury and remodeling was evident by urinary excretion of 3-methylhistidine.' Analysis of variance showed a significant (p < 0.01) effect of exercise on 24 h urinary TBA-adduct excretion. Both young and older placebo groups showed a marked increase in urinary TBA-adduct excretion that reached statistical significance by 12 d post-exercise (TABLE I). By contrast, vitamin E-supplemented groups showed no change in TBA-adduct excretion in 24 h urine samples. Significant decreases in both a- and y-tocopherol concentration and a concomitant increase of lipid conjugated dienes (intermediate products of lipid peroxidation) were found in biopsies obtained from vastus lateralis muscle before and immediately after exercise. In addition, muscle levels of linoleic and arachidonic acids in supplemented men were higher (p < 0.05) post-exercise than in those receiving placebo. These alterations in whole body lipid peroxide status following a bout of eccentric exercise are consistent with the hypothesis that vitamin E provides protection against exercise-induced oxidative injury. 363
ANNALS NEW YORK ACADEMY OF SCIENCES
364
Mean Differences in Percent Increase of 24-Hour Urinary TBA-Adduct Excretion between Placebo and Vitamin E-Supplemented Groups after Eccentric Exercise
TABLk: 1.
~
~~~
Day of exercise 12 Days post-exercise ~
Young
Older
14.5% 26.0%*
2.6% 59.9%**
~~
* p . 0.05 from day of exercise. ** p < 0.001 from day of exercise. REFERENCES 1.
2. 3. 4. 5. 6.
7.
GOHII.,K . , L. PACKER, B. D E L U M E NG., A. BROOKS& G. E. TERBLANCHE. 1986. J. Appl. Physiol. 60: 1986-1991. DAVIES. K . J. A . , A. T. QUINTANILHA. G . A. BROOKS& L. PACKER.1982. Biochem. Hiophys. Res. Commun. 107: 1198-1205. QC'INTANILHA,A. T., L. PACKER, J . M. s. DAVIES, T. L. RACANELLI & K . J. A. DAVIES. 1982. Ann. N.Y. Acad. Sci. 393: 32-47. R. BOUCHEZ,L. MASSAUX & R. PINCEMAIL, J., c. DEBY,G . CAMUS,F. PIRNAY, GOUTIER.1988. Eur. J. Appl. Physiol. 57: 189-191. SIMON-SCHNASS, I. & H. PABST.1988. J . Vitam. Nutr. Res. 58: 49-54. CANNON, J . G., s. F. ORENCOLE. R. A. FIELDING, M. MEYDANI, S. N . MEYDANI, M. A. F I A T A R O N E , J. B . BLUMBERG & W. J. EVANS.1990. Am. J. Physiol. 259: K 12 14-R I2 19. C A N N O NJ ., G., S . N . MEYDANI, R. A. FIELDING, M. A. FIATARONE, M. MEYDANI, M. FARHANGMEHR, S . F. ORENCOLE, J . B. BLUMBERG & W. EVANS.1991. Am. J. Physiol. 29: R1235-RI240.
