Sue Hughes
February 27, 2014

A high-calorie, carbohydrate-based diet was safe and appeared to be associated with improved survival in a small pilot study in patients with advanced amyotrophic lateral sclerosis (ALS).

The study, published online February 27 in The Lancet, was conducted by a group led by Anne-Marie Wills, MD, Massachusetts General Hospital, Harvard Medical School, Boston.

“Our primary aim was to look at safety and tolerability of hypercaloric enteric nutrition,” she commented to Medscape Medical News. “We did not expect to see an effect on survival or disease progression in such a small study, but we did actually find a benefit in the combined score for survival and disease progression with a high-calorie diet.”

She added: “These results provide preliminary evidence for a new, simple, low-cost, low-risk treatment for amyotrophic lateral sclerosis. The only approved therapy for ALS so far is riluzole, which is associated with a small improvement in survival. ALS clinicians are frustrated by the lack of treatments. I’m hopeful that nutrition will have a meaningful effect for these patients.”

Noting, however, that it is difficult to make any recommendations based on 1 phase 2 study, she added: “We need to do further studies in earlier disease, but for now, based on the findings so far, I would say that it is advisable for patients at least not to lose weight.”

In an accompanying editorial, Ammar Al-Chalabi, MD, King’s College London, United Kingdom, says the idea of a high-calorie diet in ALS is supported by good background evidence, but the current study is not large enough to be relied on for clinical decisions.

He writes: “I will not be changing my advice to patients on the basis of this study, but 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 potentially robust, non-pharmacological treatment for amyotrophic lateral sclerosis that is well tolerated and easy to administer, but the work that they have started must be finished before any solid conclusions can be drawn.”

No Guidelines

Dr. Wills explained that patients with ALS lose a lot of weight and often need feeding by tube. There are no nutritional guidelines on what type of diet they should receive; for example, should the aim be to maintain weight or give excess calories with the intent of weight gain?

“We have observed that ALS patients who are overweight tend to have better survival than those with normal or low body weight. Also, in a mouse of model of ALS, animals fed a high-calorie diet live longer,” she noted.

For the current study, 20 patients with ALS who were already receiving percutaneous enteral nutrition were randomly assigned to 4 months of normal replacement calories (control) or to high-calorie diets with a high-carbohydrate regimen or a high-fat regimen.

The primary outcomes were safety and tolerability. These showed that patients in the high-calorie, high-carbohydrate group had fewer adverse events than those in the control group. In addition, there were fewer deaths and better functional scores in the high-calorie, high-carbohydrate group.

“Half the patients in the control arm died versus none in the high calorie carbohydrate group. And the patients who survived in the control arm had a worse functional score than those in the high calorie carbohydrate arm,” Dr. Wills told Medscape Medical News.

Table. Adverse Events and Deaths on High-Calorie, High-Carbohydrate–Based Diet vs Control

The researchers report that the high-fat diet resulted in weight loss, despite participants consuming up to 174% of their estimated energy requirements. They suggest this might have been due to the lower tolerability and higher rate of gastrointestinal adverse effects seen with the high-fat diet compared with the high-carbohydrate diet.

Benefit on ALS Functional Rating Score?

The ALS Functional Rating Scale–Revised (ALSFRS-R) — a measure of physical functioning in patients with ALS, with a higher score indicating better function — declined more slowly in the high-carbohydrate group than in the other groups, but this difference was not statistically significant.

The ALSFRS-R analysis excluded participants who died during the study because only 1 follow-up assessment was completed, so the researchers also performed an exploratory post hoc combined assessment of function and survival analysis. This showed a significantly higher score in the high-calorie, high-carbohydrate group compared with the control group (14.8 vs 6.0; P = .01).

Dr. Wills noted that recruitment into this study was difficult. “It took twice as long as we had planned, with twice as many sites to complete the study. This is not a common disease, and only a small percentage of patients have a feeding tube. These patients are very ill and are often cared for at hospices, which do not participate in clinical trials. But we wanted to do the first study in tube-fed individuals as it is easier to define nutritional intake this way, and it is also easier to blind the study. This is the first clinical trial to be conducted in such advanced ALS patients,” she said.

The researchers are now planning a further study in patients at an earlier stage of disease. This would probably take the form of a cluster randomized trial, where each entire clinic is randomly assigned to the intervention or control. They are currently seeking funding for such a study.

Lancet. Published online February 28, 2014.

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