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High-calorie diet could slow progression of motor neuron disease (ALS)


ALS is a rapidly progressive, fatal neurodegenerative disorder affecting the nerve cells that control muscle movement (motor neurons). Patients gradually lose the ability to control the body's muscles, including the muscles which control breathing. This leads to respiratory failure and death on average about 3 years after patients are diagnosed.

Loss of weight, both muscle and fat, is common as ALS progresses, and patients experience more difficulties eating, swallowing, and maintaining their bodyweight. Recent work suggests that these problems might also contribute to the course of the disease: patients who are mildly obese are more likely to live longer, and mice carrying a gene which causes ALS lived longer when they were fed a calorie-rich diet high in fat.

The new study, funded by the Muscular Dystrophy Association, was performed at 12 ALS centres [1] and led by Dr Anne-Marie Wills at the Massachusetts General Hospital, in Boston, USA. To participate in the study, patients with advanced ALS had to already have a feeding tube (known as PEG tubes, or percutaneous endoscopic gastrostomy tubes), which allows food to be delivered directly into the stomach. Twenty patients were split into three groups, each with a different diet plan - a control group (to maintain weight) and two high-calorie (hypercaloric) groups: one high in carbohydrates, the other high in fat. The diets lasted for 4 months, and data on safety and survival were collected from the beginning of the study for a total of 5 months.

This study was primarily intended to assess safety and tolerability of the diets for ALS patients: patients given the high-carbohydrate/high-calorie diet experienced fewer adverse events (23 vs 42), and significantly fewer serious adverse events (0 vs 9) including deaths from respiratory failure than the control group.

Patients given the high-carbohydrate/high-calorie diet also gained slightly more weight than the other groups (an average of 0•39kg [about 0•86lbs] gained per month, compared to an average gain of 0•11kg [0•24lbs] per month in the control group, and an average weight loss of 0•46kg [1•01lbs] in the high-fat high-calorie diet group).

According to Dr Wills, "There is good epidemiological evidence that, in ALS, survival is determined by nutritional status. This pilot study demonstrates the safety of a novel, simple, low-cost treatment for a devastating disease where currently, very few treatment options are available. The adverse outcomes that we feared might result from weight gain, such as diabetes or heart disease, were not observed in our study period of five months."*

Nonetheless, the authors point out that the findings should be interpreted "with caution", and call for larger trials, with similar nutritional interventions tested at an earlier stage in the disease for ALS patients.

"Although the sample size was small, we are optimistic about these results, because they are consistent with previous studies in ALS mouse models that showed that hypercaloric diets improve survival,"* says Dr Wills. "Not only could this type of nutritional intervention be a novel way to treat and slow down the progression of ALS, it might also be useful in other neurological diseases."*

Writing in a linked Comment, Dr Ammar Al-Chalabi, of King's College London, UK, states that, "I will not be changing my advice to patients on the basis of this study, but I am eager to see the results of a large Phase 3 trial. Wills and colleagues have taken the first steps needed to provide evidence for a robust, non-pharmacological treatment that is well tolerated and easy to administer. We must finish the work they have started."



This study was funded by The Muscular Dystrophy Association with additional support from the National Center for Research Resources, the National Institutes of Health, and the Harvard NeuroDiscovery Center.

[1] The 12 Centres were within the Northeast ALS Consortium, a network of 100 academic ALS centres across North America, Ireland, and Israel.

*Quotes direct from authors and cannot be found in text of Article.

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