Among the 545,377 men and 510,169 women who formed the baseline population, 805 with ALS were identified during a follow-up period that ranged from 10 years to 18 years across the 5 cohorts. The proportion of participants taking vitamin E supplements at baseline, either in multivitamins or as a single supplement, ranged from 38% in NHS (1980) to 71% in NIH-AARP women (1995–1996) (). Median dietary vitamin E intake was lowest among women in NIH-AARP (8.8 IU/day) and highest among men in HPFS (14.6 IU/day).
Characteristics of the Cohorts Included in a Pooled Analysis of Vitamin E Intake and Amyotrophic Lateral Sclerosis Risk, 1976–2005
Overall, there was no significant association between supplemental vitamin E intake and ALS risk; among persons who consumed at least 400 IU per day, the multivariable-adjusted pooled relative risk was 1.18 (95% confidence interval (CI): 0.83, 1.67; P
= 0.35) compared with nonusers (). (See Web Table 1
) for sex-specific results.) The combined use of vitamin E and vitamin C supplements was also not associated with ALS; the multivariable-adjusted relative risk for persons using both vitamin E and vitamin C supplements compared with those who used neither was 1.03 (95% CI: 0.86, 1.22; P
= 0.79). In analyses restricted to the cohorts with information on duration of use (231 cases), there was an inverse trend between number of years vitamin E supplements were used and ALS (). Although the overall inverse trend was significant (P
-trend = 0.01), the numbers of cases were small in some categories (compared with nonusers at baseline, multivariable-adjusted relative risk (RR) = 1.05 (95% CI: 0.60, 1.84) among users for ≤1 year (12 cases), RR = 0.77 (95% CI: 0.33, 1.77) among users for 2–4 years (7 cases), and RR = 0.64 (95% CI: 0.39, 1.04; P
= 0.075) among users for ≥5 years (18 cases)).
Pooled Relative Risk of Amyotrophic Lateral Sclerosis by Total Supplemental Vitamin E Intake in Data From 5 Cohort Studies, 1976–2005
Figure 1. Pooled relative risk of amyotrophic lateral sclerosis by duration of vitamin E supplement use reported at baseline in data from 5 cohort studies (the Nurses’ Health Study (NHS; 1976–2004), the Health Professionals Follow-up Study (HPFS; (more ...)
Rates of ALS were lower among persons in the highest quartile of energy-adjusted dietary vitamin E intake compared with those in the lowest quartile (RR = 0.77, 95% CI: 0.59, 0.99; P
= 0.04) (). Multivariable adjustment did not materially change the results, although power was reduced and the P
value was no longer significant. In women, there was a clear inverse dose-response with increasing dietary vitamin E intake (compared with persons in the lowest quartile of energy-adjusted dietary vitamin E intake, multivariable RR = 0.88 (95% CI: 0.64, 1.21) for the second quartile, RR = 0.71 (95% CI: 0.51, 0.99) for the third quartile, and RR = 0.57 (95% CI: 0.40, 0.80) for the fourth quartile; P
-trend = 0.002) (Web Table 2
). In analyses of dietary vitamin E restricted to nonusers of supplemental vitamin E, results were similar to those found among all participants (), although statistical significance did not persist, particularly among the women (Web Table 3
Pooled Relative Risk of Amyotrophic Lateral Sclerosis by Dietary Vitamin E Intake in Data From 5 Cohort Studies, 1976–2005
Pooled Relative Risk of Amyotrophic Lateral Sclerosis by Dietary Vitamin E Intake Among Nonusers of Supplemental Vitamin E in Data From 5 Cohort Studies, 1976–2005
Results were similar when the first 4 years of follow-up were excluded. The pooled relative risks were 1.42 (95% CI: 0.75, 2.68; P = 0.29) comparing users of vitamin E supplements (≥400 IU/day) with never users and 0.80 (95% CI: 0.58, 1.10; P = 0.17) comparing persons in the highest quartile of dietary vitamin E intake with those in the lowest.
There was no evidence of effect modification by smoking, sex, or vitamin C intake (P > 0.05). Only in MEC was there some evidence that the association between dietary vitamin E and ALS was modified by age at baseline. Compared with persons in the lowest quartile of energy-adjusted dietary vitamin E intake, the multivariable adjusted relative risk of ALS among persons aged 65 years or above was 0.45 (95% CI: 0.22, 0.91; P = 0.03) for the second quartile, 0.32 (95% CI: 0.15, 0.67; P = 0.003) for the third quartile, and 0.21 (95% CI: 0.09, 0.48; P = 0.0002) for the fourth quartile. There was no association among persons under age 65 years (P for interaction = 0.002).