Vitamin E Intake and Risk of Amyotrophic Lateral Sclerosis
The authors investigated whether vitamin E intake was associated with amyotrophic lateral sclerosis (ALS) in the Nurses' Health Study (1976–2004), the Health Professionals Follow-up Study (1986–2004), the Cancer Prevention Study II Nutrition Cohort (1992–2004), the Multiethnic Cohort Study (1993–2005), and the National Institutes of Health-AARP Diet and Health Study (1995–2005). ALS deaths were identified through the National Death Index. In the Nurses' Health Study and the Health Professionals Follow-up Study, confirmed nonfatal ALS cases were also included. Cohort-specific results were estimated using Cox proportional hazards models and pooled using random-effects models. Among 1,055,546 participants, 805 developed ALS. Overall, using vitamin E supplements was not associated with ALS. However, within cohorts with information on duration of vitamin E supplement use (231 cases), ALS rates declined with increasing years of use (P-trend = 0.01). Compared with nonusers, the multivariable-adjusted relative risk was 1.05 (95% confidence interval (CI): 0.60, 1.84) among users for ≤1 year (12 cases), 0.77 (95% CI: 0.33, 1.77) among users for 2–4 years (7 cases), and 0.64 (95% CI: 0.39, 1.04) among users for ≥5 years (18 cases). For dietary vitamin E intake, the multivariable-adjusted relative risk comparing the highest quartile with the lowest was 0.79 (95% CI: 0.61, 1.03); an inverse dose-response was evident in women (P-trend = 0.002) but not in men (P-trend = 0.71). In this large, pooled prospective study, long-term vitamin E supplement use was associated with lower ALS rates. A possible protective effect of vitamin E deserves further consideration.
A role for oxidative stress in the pathogenesis of amyotrophic lateral sclerosis (ALS) is supported by the presence of biomarkers of oxidative damage in sporadic ALS patients and by the occurrence of familial ALS among carriers of several distinct mutations in the copper/zinc superoxide dismutase gene (SOD1), a critical component of cellular antioxidant defense mechanisms. Vitamin E is an important cellular antioxidant that has been shown to delay the onset of clinical disease in transgenic mice expressing mutant copies of the gene coding for superoxide dismutase, an animal model of ALS. Although promising at the time, vitamin E supplementation was found to be ineffective in randomized trials of patients with ALS. However, it remains possible that high vitamin E intake in apparently healthy persons could reduce disease risk or delay its onset.
The results of previous epidemiologic studies on vitamin E and ALS risk have been inconsistent. No association was found in 2 early case-control studies (including 107 and 161 ALS patients). A significantly decreased risk of ALS was reported in a more recent case-control study in the Netherlands (including 132 ALS patients) among persons with higher dietary vitamin E intake and in a prospective study in the United States (including 525 ALS deaths) among long-term users of vitamin E supplements. Therefore, we conducted a larger prospective study to examine whether supplemental and dietary vitamin E were related to risk of ALS using data from 5 large ongoing cohort studies: the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), the Cancer Prevention Study II Nutrition Cohort (CPS-II Nutrition), the Multiethnic Cohort Study (MEC), and the National Institutes of Health-AARP Diet and Health Study (NIH-AARP). Together these cohorts comprise over 1 million men and women, 805 of whom developed ALS during follow-up.
Abstract and Introduction
Abstract
The authors investigated whether vitamin E intake was associated with amyotrophic lateral sclerosis (ALS) in the Nurses' Health Study (1976–2004), the Health Professionals Follow-up Study (1986–2004), the Cancer Prevention Study II Nutrition Cohort (1992–2004), the Multiethnic Cohort Study (1993–2005), and the National Institutes of Health-AARP Diet and Health Study (1995–2005). ALS deaths were identified through the National Death Index. In the Nurses' Health Study and the Health Professionals Follow-up Study, confirmed nonfatal ALS cases were also included. Cohort-specific results were estimated using Cox proportional hazards models and pooled using random-effects models. Among 1,055,546 participants, 805 developed ALS. Overall, using vitamin E supplements was not associated with ALS. However, within cohorts with information on duration of vitamin E supplement use (231 cases), ALS rates declined with increasing years of use (P-trend = 0.01). Compared with nonusers, the multivariable-adjusted relative risk was 1.05 (95% confidence interval (CI): 0.60, 1.84) among users for ≤1 year (12 cases), 0.77 (95% CI: 0.33, 1.77) among users for 2–4 years (7 cases), and 0.64 (95% CI: 0.39, 1.04) among users for ≥5 years (18 cases). For dietary vitamin E intake, the multivariable-adjusted relative risk comparing the highest quartile with the lowest was 0.79 (95% CI: 0.61, 1.03); an inverse dose-response was evident in women (P-trend = 0.002) but not in men (P-trend = 0.71). In this large, pooled prospective study, long-term vitamin E supplement use was associated with lower ALS rates. A possible protective effect of vitamin E deserves further consideration.
Introduction
A role for oxidative stress in the pathogenesis of amyotrophic lateral sclerosis (ALS) is supported by the presence of biomarkers of oxidative damage in sporadic ALS patients and by the occurrence of familial ALS among carriers of several distinct mutations in the copper/zinc superoxide dismutase gene (SOD1), a critical component of cellular antioxidant defense mechanisms. Vitamin E is an important cellular antioxidant that has been shown to delay the onset of clinical disease in transgenic mice expressing mutant copies of the gene coding for superoxide dismutase, an animal model of ALS. Although promising at the time, vitamin E supplementation was found to be ineffective in randomized trials of patients with ALS. However, it remains possible that high vitamin E intake in apparently healthy persons could reduce disease risk or delay its onset.
The results of previous epidemiologic studies on vitamin E and ALS risk have been inconsistent. No association was found in 2 early case-control studies (including 107 and 161 ALS patients). A significantly decreased risk of ALS was reported in a more recent case-control study in the Netherlands (including 132 ALS patients) among persons with higher dietary vitamin E intake and in a prospective study in the United States (including 525 ALS deaths) among long-term users of vitamin E supplements. Therefore, we conducted a larger prospective study to examine whether supplemental and dietary vitamin E were related to risk of ALS using data from 5 large ongoing cohort studies: the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), the Cancer Prevention Study II Nutrition Cohort (CPS-II Nutrition), the Multiethnic Cohort Study (MEC), and the National Institutes of Health-AARP Diet and Health Study (NIH-AARP). Together these cohorts comprise over 1 million men and women, 805 of whom developed ALS during follow-up.
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