Dietary Factors Linked to Better -- or Worse -- Function in ALS

Pauline Anderson

November 10, 2016

Among patients recently diagnosed with amyotrophic lateral sclerosis (ALS), those who consume foods high in antioxidant nutrients and carotenoids have better function than those with a poorer diet, according to a new study.

"Foods high in antioxidants and carotenes, which are really fruits and vegetables, as well as high-fiber grains, fish, and poultry, all seem to make the disease a bit less severe," said lead study author, Jeri W Nieves, PhD, associate professor of clinical epidemiology, Mailman School of Public Health, Columbia University, New York City, New York.

But contrary to other recent research, the ALS Multicenter Cohort Study of Oxidative Stress (ALSCOSMOS) showed that milk-derived foods appear to have a negative effect on ALS.

The analysis was published online October 24 in JAMA Neurology.

There's a growing interest in the role of nutrients in ALS, the researchers note. Recent evidence suggests that the ALS risk increases with higher intake of carbohydrates, glutamate, and fat and with lower intake of fruits, vegetables, vitamin E, carotenoids and certain polyunsaturated fatty acids.

Research also suggests that oxidative stress is associated with the pathogenesis of ALS and that dietary factors may increase or decrease oxidative stress.

The current analysis included 302 patients, median age 63.2 years, diagnosed with ALS less than 18 months after symptom onset at 16 centers across the United States. This group had a median symptom duration of 0.94 years and a median body mass index (BMI) of 26. At baseline, about half of the patients reported eating problems early in the course of the disease and occasional choking.

Functional Performance

To assess functional performance, investigators used the ALS Functional Rating Scale-Revised (ALSFRS-R), which is the most widely used clinical outcome in ALS clinical trials and has been extensively validated. At baseline, the median ALSFRS-R score was 37, reflecting modestly severe ALS (higher scores indicate better function).

Investigators used forced vital capacity (FVC) to measure respiratory function. At baseline, the median FVC was 82%, or low normal respiratory function. (A higher FVC percentage indicates better function.)

To assess diet, researchers used a shortened version of a previously validated food frequency questionnaire (FFQ). The questionnaire focused on foods and nutrients considered to be antioxidants; vitamins A, C, and E; β-carotene; calcium; iron; zinc; and selenium. There were also questions on supplement intake.

Nutrient Indexes

Using a standard reference nutrient database, researchers converted information from the FFQ into estimates of average daily nutrient intake. They developed a carotene index, and, given that antioxidants may be particularly important, they devised a separate antioxidant index.

If nutrients had antioxidant properties or were reported to be associated with reduced risk for ALS, investigators considered them to be "good." If nutrients were associated with oxidative stress or were previously reported to be associated with increased risk for ALS, investigators classified these as "bad."

Researchers used weighted quartile sum regression, which allows for analyses of combinations of nutrients and food groups. Essentially, said Dr Nieves, she and her colleagues took all the carotene that patients got from different foods (foods high in carotene include orange foods, such as carrots and squash) and summed them together into an index; they did the same to develop the antioxidant index.

After adjustment for age, sex, BMI, duration of symptoms, and calorie intake, the antioxidant index and the carotene index were positively associated with ALSFRS-R score and with percentage FVC.

The two most highly weighted micronutrients associated with the ALSFRS-R score were those believed to be strong antioxidants: lutein and zeaxanthin (15%) and omega-3 fatty acids (18%).

The dominant components associated with percentage FVC were omega-3 fatty acids (19%), omega-6 fatty acids (23%), and fiber from grains (9%) and from vegetables and fruits (14%).

"Good" foods, such as fish, poultry, nuts and seeds, and some oils, many of which are rich sources of antioxidants, were positively associated with ALSFRS-R score and percentage of FVC. There "was not really a signal" for foods like beef, pork, and cheese, said Dr Nieves.

On the other hand, cured lunch meats (32%) and, to a greater extent, milk (50%) were highly weighted in a negative association with ALSFRS-R score.

It's difficult to say why milk might have such a negative impact, but its high animal fat content could be a factor, said Dr Nieves. "One of the theories we are looking at with ALS and diet is whether oxidative stress is involved. Some fats may promote oxidative stress, so that would be one potential mechanism."

At the same time, though, milk has some of the "good" micronutrients. "So it's hard to pull out exactly what that means," said Dr Nieves.

Supplement Use

The finding about milk could be important because patients and caregivers often use a milk-based supplement in the expectation that it will improve nutrition. Milk is "packed with protein and a lot of nutrients," and milk replacements such as Ensure may offer a "quick and easy" supplement, especially when swallowing issues are involved, said Dr Nieves.

"When you're trying to make sure someone gets better nutritional care, one of the first things you look to is some kind of supplement, and many are milk-based."

A previous study showed that milk-based supplements led to weight gain, improved biochemistry, and a slower decline in ALSFRS-R score. Although that study followed patients forward in time, "which was a better design than ours," it was a 4-month study of only 16 patients with ALS, said Dr Nieves.

"It's hard to put a lot of weight on a short-term study. I still think we need to look at this more deeply and figure out what is the best product to be giving ALS patients."

Dr Nieves said she doesn't want to put too much emphasis on these study findings. "It's important because it was the first study that ever showed a relationship between diet and severity of ALS at time of diagnosis, but, that said, there were issues with the study design and we need confirmation of the findings."

The researchers will be following study patients forward to see whether any of the dietary factors they looked at, including milk products, relate to how quickly the disease progresses.

Until then, Dr Nieves recommends that patients with newly diagnosed ALS follow a diet "high in fruits and vegetables, lean protein and fiber," which is "potentially beneficial not only for ALS patients, but may well help prevent many diseases," she said, and is in line with the Dietary Guidelines for Americans.  

As for milk, Dr Nieves said she's not yet ready to recommend avoiding it because its negative association with ALS "is unique to our one study and does not agree with typical dietary guidelines."

Tempting Recommendation

Whether or not "good food," as defined by this study, should be recommended in the management of ALS "is uncertain and needs further research — but it will be tempting to institute the recommendation," Michael Swash, MD, Royal London Hospital, Barts and the London School of Medicine, Queen Mary University of London, United Kingdom, writes in an accompanying editorial.

In any case, this and other recent studies on dietary factors "represent a new direction in ALS research," says Dr Swash.

Previous epidemiologic studies, including those on diet, exercise, manual labor, and mechanical trauma, "are subject to various forms of bias, especially recall bias and the effect of previously held opinion," writes Dr Swash. "All these confounding issues are difficult to control and require new approaches to data collection, but constitute a promising line of investigation."

Medscape Medical News invited Alberto Ascherio, MD, DrPH, professor of epidemiology and nutrition, Harvard T.H. Chan School of Public Health, and professor of medicine, Harvard Medical School, Boston, Massachusetts, to add his comments. He was the senior author of previous longitudinal studies suggesting a protective role of carotenoids and omega-3 on risk for ALS.

Because of its cross-sectional design, this new study only provides correlations that don't imply causation, said Dr Ascherio. "For example, the healthier diet could have been a consequence rather than the cause of the lower disease severity."

Nevertheless, he said, it is "notable" that the results match those of previous longitudinal investigations that suggested that individuals with higher intakes of carotenoids and omega-3 fatty acids have a lower risk for ALS. 

"This convergence suggests that further research on the potential effects of diet on the course of ALS could be worth pursuing," he concluded.

The study was supported by a grant from the National Institute of Environmental Health Sciences, National Institutes of Health. The Muscular Dystrophy Association funded an earlier study that was incorporated into the Amyotrophic Lateral Sclerosis Multicenter Cohort Study of Oxidative Stress. Muscular Dystrophy Association Wings Over Wall Street, The Judith and Jean Pape Adams Charitable Foundation, and Ride for Life also supported part of the study. Dr Nieves and Dr Swash have disclosed no relevant financial relationships.

JAMA Neurol. Published online October 24, 2016. Abstract, Editorial

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