- A study receiving MDA support and conducted in part through the MDA ALS Clinical Research Network has shown that a high-carbohydrate, high-calorie tube feeding formula was safe and well-tolerated in a small number of ALS patients at a late stage of the disease.
- Those in the high-carbohydrate, high-calorie group gained more weight and experienced fewer adverse events, including deaths, than those on tube feedings designed to replace expended calories and maintain weight (control group) or those on a high-fat, high-calorie formula, which may not have been well absorbed.
- The study suggests that increasing calories is safe and may be beneficial in ALS, and that larger, longer studies should be conducted to further test this hypothesis.
A study supported in part by MDA has found that a high-calorie, high-carbohydrate diet is safe and well-tolerated in late-stage amyotrophic lateral sclerosis (ALS), that it leads to moderate weight gain, and that it may slow disease progression.
Neurologist Anne-Marie Wills, an MDA research grantee at Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues, published their findings Feb. 28, 2014, in the journal The Lancet.
The results, while intriguing, are based on small numbers and a short time period. However, the investigators say the findings support larger and longer studies of nutritional intervention in ALS, perhaps at an earlier stage of the disorder.
The investigators say they believe the results "provide preliminary evidence for a novel, simple, low-cost, low-risk treatment for this devastating disease." They also say the findings "support growing interest in the use of dietary interventions to treat neurological diseases."
Valerie Cwik, M.D., MDA's chief medical and scientific officer, said, "In recent years there has been increasing evidence about the benefits of nutrition and maintaining weight on disease course in ALS, although specific dietary recommendations are lacking. The results from this small study suggest that diet composition, not simply caloric intake, may be important, and provide support for a larger study of nutritional interventions in ALS."
About the nutrition in ALS study
The study was conducted at 12 ALS centers, five of which are part of the MDA ALS Clinical Research Network. It included only ALS patients who were already receiving tube feedings, thereby including only those who were relatively far advanced in their disease course.
Twenty-four participants were randomly assigned to receive one of three tube feeding formulas: a "control" formula supplying enough calories to replace energy expenditure with a standard percentage of carbohydrates, calories and protein; a high-fat, high-calorie formula; or a high-carbohydrate, high-calorie formula. Twenty people completed the study, after four left before starting the diet because of the perceived burden of study participation.
Some participants were still able to consume food by mouth, and they were allowed to continue doing so in addition to receiving tube feedings.
Participants were assigned to the diets for four months and were followed for five months. The study was primarily designed to measure safety and tolerability of the diets, but it also looked at weight gain and measures of disease progression.
For details of this completed study, see High Fat/High Calorie Trial in Amyotrophic Lateral Sclerosis; or enter NCT00983983 in the search box at ClinicalTrials.gov.
High-carbohydrate, high-calorie group fared best
Participants on the high-carbohydrate, high-calorie formula experienced 23 adverse events compared to 42 for those on the control diet (although the difference was not statistically significant) and significantly fewer serious adverse events (none versus nine, which was statistically significant), including deaths from respiratory failure, compared to the control group. The high-fat group did no better than the controls.
On average, participants on the control formula gained an average of 0.11 kilograms (0.24 pounds) per month. Those on the high-carbohydrate, high-calorie formula gained an average of 0.39 kilograms (0.86 pounds) per month, while those on the high-fat, high-calorie formula actually lost 0.46 kilograms (1 pound) per month.
These results were somewhat surprising, as the researchers had originally hypothesized that the high-fat, high-calorie formula would cause the greatest weight gain. They say the high-fat, high-calorie diet may not have been absorbed well across the intestinal wall.
On a combined assessment of function and survival, the high-carbohydrate, high-calorie group fared better than either the control group or the high-fat, high-calorie group, with the latter two showing similar results. The difference was statistically significant.
"Our results ... support the concept that ALS is a multi-organ, systemic disease, characterized by metabolic dysfunction," the authors write. "We believe that, given the promising results of this pilot study and lack of treatment options for ALS, nutritional interventions should be studied in larger, randomized, controlled trials at earlier stages of the disease."
Ammar Al-Chalabi, a professor of neurology and complex disease genetics at King's College London, wrote an accompanying editorial, also published in The Lancet on Feb. 28, 2014, where it can be read online without charge. In it, he said, "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."