Vitamin E May Affect the Life Expectancy of Men
Vitamin E May Affect the Life Expectancy of Men
Background: antioxidants might protect against oxidative stress, which has been suggested as a cause of aging.
Methods: the Alpha-Tocopherol-Beta-Carotene (ATBC) Study recruited males aged 50–69 years who smoked at least five cigarettes per day at the baseline. The current study was restricted to participants who were followed up past the age of 65. Deaths were identified in the National Death Registry (1,445 deaths). We constructed Kaplan–Meier survival curves for all participants, and for four subgroups defined by dietary vitamin C intake and level of smoking. We also constructed Cox regression models allowing a different vitamin E effect for low and high age ranges.
Results: among all 10,837 participants, vitamin E had no effect on those who were 65–70 years old, but reduced mortality by 24% when participants were 71 or older. Among 2,284 men with dietary vitamin C intakes above the median who smoked less than a pack of cigarettes per day, vitamin E extended lifespan by 2 years at the upper limit of the follow-up age span. In this subgroup, the survival curves of vitamin E and no-vitamin E participants diverged at 71 years. In the other three subgroups covering 80% of the participants, vitamin E did not affect mortality.
Conclusions: this is the first study to strongly indicate that protection against oxidative stress can increase the life expectancy of some initially healthy population groups. Nevertheless, the lack of effect in 80% of this male cohort shows that vitamin E is no panacea for extending life expectancy.
Half a century ago, Harman proposed that endogenous free radicals might cause aging. There is evidence that the level of oxidative stress increases during aging, suggesting that its importance may be particularly great in the later phases of life. Yet, the role of oxidative stress in the aging of humans is not well understood.
A corollary of the oxidative stress theory is that antioxidants might increase lifespan because they protect against oxidants. Administration of antioxidants and overexpression of antioxidative enzymes, such as superoxide dismutase (SOD), catalase and glutathione reductase, have in some cases increased the lifespan of animals, but not uniformly. In Drosophila, overexpression of SOD increased lifespan in strains in which it was initially short, but not in strains in which lifespan was initially long. Vitamin E administration and overexpression of glutathione reductase extended the lifespan of Drosphila during hyperoxia, but not while the oxygen level was normal. Administration of low levels of vitamin C and vitamin E increased lifespan of Drosophila, but high levels did not, indicating the importance of dosage. Finally, overexpression of SOD and catalase together extended the lifespan of Drosophila, whereas each alone had only a minor effect. Heterogeneity in these findings seems to be particularly important since it indicates that antioxidant levels might be limiting factors under some conditions, although they are not a panacea for extending lifespan universally.
Vitamin E supplementation increased lifespan in some mice studies, but not in all; however, high levels of vitamin E reduced lifespan. Furthermore, vitamin C administration and overexpression of catalase increased the lifespan of mice in some studies, but vitamin C was ineffective in one study. These studies indicate that protection against oxidative stress may increase the lifespan of mammals under some conditions.
Several large randomised trials of humans found that vitamin E supplementation does not reduce mortality. These negative findings have often been interpreted as evidence that vitamin E does not protect against oxidative stress in humans.
The Alpha-Tocopherol-Beta-Carotene (ATBC) Study was a large randomised trial, which examined the effect of 50 mg/day of vitamin E on the risk of lung cancer in male smokers. In our previous analyses of the ATBC Study data, we found that age, smoking and dietary vitamin C intake significantly modified the vitamin E supplementation effect on the incidence of the common cold, pneumonia and tuberculosis. This heterogeneity motivated us to test whether the effect on mortality might also be heterogeneous. We found significant modification of the supplementation effect in that vitamin E decreased mortality by 41% among those who were 66 or older at baseline and consumed vitamin C at a level above the median.
A large trial can accurately estimate the overall effect of vitamin E on mortality. However, if vitamin E influences the lifespan, it is possible that a benefit on the oldest participants might be camouflaged by the large middle-aged majority of study participants. In this study, we analyse the effect of vitamin E by the age of the participant at the follow-up. This allows us to accurately examine the age-dependency of vitamin E effect on the old ATBC Study participants. Since our focus is on the oldest participants, we restrict this analysis to the follow-up period when the participants were 65 and over.
Abstract and Introduction
Abstract
Background: antioxidants might protect against oxidative stress, which has been suggested as a cause of aging.
Methods: the Alpha-Tocopherol-Beta-Carotene (ATBC) Study recruited males aged 50–69 years who smoked at least five cigarettes per day at the baseline. The current study was restricted to participants who were followed up past the age of 65. Deaths were identified in the National Death Registry (1,445 deaths). We constructed Kaplan–Meier survival curves for all participants, and for four subgroups defined by dietary vitamin C intake and level of smoking. We also constructed Cox regression models allowing a different vitamin E effect for low and high age ranges.
Results: among all 10,837 participants, vitamin E had no effect on those who were 65–70 years old, but reduced mortality by 24% when participants were 71 or older. Among 2,284 men with dietary vitamin C intakes above the median who smoked less than a pack of cigarettes per day, vitamin E extended lifespan by 2 years at the upper limit of the follow-up age span. In this subgroup, the survival curves of vitamin E and no-vitamin E participants diverged at 71 years. In the other three subgroups covering 80% of the participants, vitamin E did not affect mortality.
Conclusions: this is the first study to strongly indicate that protection against oxidative stress can increase the life expectancy of some initially healthy population groups. Nevertheless, the lack of effect in 80% of this male cohort shows that vitamin E is no panacea for extending life expectancy.
Introduction
Half a century ago, Harman proposed that endogenous free radicals might cause aging. There is evidence that the level of oxidative stress increases during aging, suggesting that its importance may be particularly great in the later phases of life. Yet, the role of oxidative stress in the aging of humans is not well understood.
A corollary of the oxidative stress theory is that antioxidants might increase lifespan because they protect against oxidants. Administration of antioxidants and overexpression of antioxidative enzymes, such as superoxide dismutase (SOD), catalase and glutathione reductase, have in some cases increased the lifespan of animals, but not uniformly. In Drosophila, overexpression of SOD increased lifespan in strains in which it was initially short, but not in strains in which lifespan was initially long. Vitamin E administration and overexpression of glutathione reductase extended the lifespan of Drosphila during hyperoxia, but not while the oxygen level was normal. Administration of low levels of vitamin C and vitamin E increased lifespan of Drosophila, but high levels did not, indicating the importance of dosage. Finally, overexpression of SOD and catalase together extended the lifespan of Drosophila, whereas each alone had only a minor effect. Heterogeneity in these findings seems to be particularly important since it indicates that antioxidant levels might be limiting factors under some conditions, although they are not a panacea for extending lifespan universally.
Vitamin E supplementation increased lifespan in some mice studies, but not in all; however, high levels of vitamin E reduced lifespan. Furthermore, vitamin C administration and overexpression of catalase increased the lifespan of mice in some studies, but vitamin C was ineffective in one study. These studies indicate that protection against oxidative stress may increase the lifespan of mammals under some conditions.
Several large randomised trials of humans found that vitamin E supplementation does not reduce mortality. These negative findings have often been interpreted as evidence that vitamin E does not protect against oxidative stress in humans.
The Alpha-Tocopherol-Beta-Carotene (ATBC) Study was a large randomised trial, which examined the effect of 50 mg/day of vitamin E on the risk of lung cancer in male smokers. In our previous analyses of the ATBC Study data, we found that age, smoking and dietary vitamin C intake significantly modified the vitamin E supplementation effect on the incidence of the common cold, pneumonia and tuberculosis. This heterogeneity motivated us to test whether the effect on mortality might also be heterogeneous. We found significant modification of the supplementation effect in that vitamin E decreased mortality by 41% among those who were 66 or older at baseline and consumed vitamin C at a level above the median.
A large trial can accurately estimate the overall effect of vitamin E on mortality. However, if vitamin E influences the lifespan, it is possible that a benefit on the oldest participants might be camouflaged by the large middle-aged majority of study participants. In this study, we analyse the effect of vitamin E by the age of the participant at the follow-up. This allows us to accurately examine the age-dependency of vitamin E effect on the old ATBC Study participants. Since our focus is on the oldest participants, we restrict this analysis to the follow-up period when the participants were 65 and over.
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