Strenuous Physical Activity Linked to ALS in Older Women

Pauline Anderson

January 26, 2016

New research has linked strenuous physical activity (PA) with amyotrophic lateral sclerosis (ALS) mortality in older women.

The study results showed that being a current or former smoker strengthened the link and that obesity and diabetes tended to protect against ALS mortality.

The results imply that some people may be more susceptible to the adverse effects of strenuous PA or combinations of environmental exposures when it comes to ALS risk, said lead author Yvonne L. Eaglehouse, PhD, an epidemiologist and postdoctoral scholar, Cancer Institute and School of Public Health, University of Pittsburgh, Pennsylvania.

Dr Yvonne L. Eaglehouse

"This study should not have any bearing on public health recommendations for being active; what it should do is get us thinking about these potential biomechanisms and gene-environment interactions that are contributing to this increased risk for ALS mortality that we're seeing in women who are doing strenuous activities," she told Medscape Medical News.

The study, published online January 19 in JAMA Neurology, used data from the Women's Health Initiative, which recruited over 161,000 women aged 50 to 79 years from 1993 to 1998.

At the time of enrollment, participants completed a personal health questionnaire that included items on PA, exercise, and lifestyle. PA was classified as mild, moderate (not exhausting), and strenuous (working up a sweat and heart beating fast).

Activity Intensity

Researchers also collected data on the frequency and duration (in 20-minute increments), and energy expenditure (calculated in metabolic equivalent task scores) for each PA intensity.

They had information on 165 deaths in which ALS was the underlying cause. The mean follow-up time to death or censor of these women was 9.59 years.

There were more deaths from ALS with increasing frequency of strenuous PA, with the percentage varying from 0.09% for 0 days per week to 0.16% for 4 days a week (P for trend = .06).

Age-adjusted ALS mortality rates varied from 7.4/100,000 person-years (95% confidence interval [CI], 5.5 - 9.9) for women who reported no strenuous PA to 10.6/100,000 person-years (95% CI, 5.6 - 20.0) for women who did strenuous PA on 3 or more days per week (P = .07).

There seemed to be a dose-response relationship: Women doing strenuous activity more times a week (3 or more) and for longer periods of time (more than 40 minutes) had the highest risk, commented Dr Eaglehouse.

There were no significant associations between frequency or duration of mild or moderate PA and ALS mortality.

About half of the women who eventually died of ALS reported that they had performed strenuous PA on 3 or more days per week at age 50 years, with a similar percentage at age 35 years and at age 18 years.

As for smoking, the study found that the age-adjusted ALS mortality rates were at least double among current and past smokers who exercised strenuously than in current or past smokers not exercising strenuously.

Inverse Associations

Body mass index (BMI) was inversely related to death from ALS. In stratified analyses, the age-adjusted hazard ratio was 2.47 (95% CI, 1.01 - 6.07) for ALS mortality with strenuous PA on 3 or more days per week compared with none among women with a BMI of 30.0 or higher.

Diabetes status was also inversely associated with AS mortality. Women reporting no diabetes had higher rates of ALS mortality.

But the study couldn't separate out the inter-relationships between diabetes, obesity, and PA, commented Dr Eaglehouse.

"People who are physically active tend to have a more normal body weight and are less likely to have diabetes and when they stop being active, they may gain weight," she said. "It may be a kind of chicken-and-egg thing."

Oxidative stress is among the possible mechanisms by which strenuous PA affects ALS risk, said Dr Eaglehouse. "Strenuous activity, as opposed to mild or more moderate activity, can increase reactive oxygen species and neuronal cell damage, and possibly has glutamate toxic effects."

But more research needs to be done to look at these potential mechanisms and how they interact with environmental or genetic factors, she said.

"Is there some type of effect of oxidative stress or oxidative damage from cigarette smoking in combination with strenuous activity, and is this occurring in a group of individuals who are already genetically susceptible?"

It would also be good to know if there's some sort of "threshold" of strenuous activity at which it has a negative effect for ALS risk, she added.

Dr Eaglehouse stressed that strenuous PA has many beneficial effects on health. For example, it helps prevent cardiovascular disease, diabetes, some forms of cancer, and possibly the onset of Alzheimer's disease, and has a positive effect on bones and joints.

The Women's Health Initiativeprogram is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services. Dr Eaglehouse is supported by a grant from the National Cancer Institute, National Institutes of Health. Dr Eaglehouse has disclosed no relevant financial relationships.

JAMA Neurol. Published online January 19, 2016. Abstract

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