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High-calorie diet may slow progression of motor neuron disease

By Nathan Gray+

05-Mar-2014
Last updated on 05-Mar-2014 at 11:27 GMT

High-calorie diet may slow progression of motor neuron disease

Increasing caloric intake could be a relatively simple method for people with motor neurone disease to extend their life expectancy, according to new research.

The data from a small phase 2 clinical trial in the US suggests that patients receiving a high-calorie, high-carbohydrate tube-feeding formula lived longer with fewer adverse events than participants who received a standard formula designed maintain their weight.

Led by Dr Anne-Marie Wills from Massachusetts General Hospital, and funded by the Muscular Dystrophy Association, the team noted that more than 15 years ago it was observed that malnutrition was associated with shorter survival in people with motor neurone disease (also known as amyotrophic lateral sclerosis, or ALS) patients, with many subsequent studies confirming that patients who weigh more appear to live longer and have slower disease progression.

"We are particularly excited because these results provide the first preliminary evidence that a dietary intervention may improve life expectancy in ALS, and they are strongly supported by epidemiological and animal data," said Wills. "This strategy has never been tested before in ALS, and we are optimistic that it may provide a new, effective and inexpensive therapy for this devastating illness."

Writing in The Lancet, Wills and her colleagues reveal the findings of their clinical trial which compared the effects of a two high-calorie diets (either based on increased fat or carbohydrate intakes) with a control diet. They showed that those consuming the carbohydrate-based high-calorie diet had fewer adverse events, had put on more weight, had slower reduction functional scores, and perhaps most importantly had a better chance of living longer.

"While it's not possible to make clinical recommendations based on this single, small study, I think the results support the importance of avoiding weight loss in this disease," explained Wills.

"We're hoping to obtain funding for a large study of whether nutrition counselling to encourage weight gain … can help slow the progression of ALS, and I'm optimistic that interventions designed to maintain or increase weight could be even more effective if started before patients have lost a significant amount of weight."

Study details

The new study was performed at 12 ALS centres in the US, with Wills and her team recruiting 24 patients with advanced ALS who had lost a significant percentage of their original body weight and were receiving nutrition via tube feeding.

Two groups received formulas designed to provide 125% of the calories needed to maintain their weight – one high in fats and the other high in carbohydrates. A third group were given a control diet aimed at maintaining body weight.

During the four-month intervention period, participants recorded their tube feeding intake, along with anything they were able to consume by mouth and weekly measures of weight. At monthly study visits, measurements were taken of participants' fat and lean body mass; blood levels of cholesterol, insulin and other factors that could be affected by nutrition; and functions typically compromised by ALS.

At the end of the intervention period, none of the eight participants receiving the high-carbohydrate formula had withdrawn because of adverse events, while one of the six on the high-fat formula and three of the six in the control group discontinued participation because of adverse events, revealed the team.

Those on the high-carbohydrate formula also gained a modest amount of weight, while control group participants maintained their weight, they said – noting that those receiving the high-fat formula actually lost weight, even though they had taken in more than 150% of the calories estimated to maintain their weight.

After a five-month follow-up period Wills and her colleagues also found that no participants in the high-carbohydrate group died, while one in the high-fat group and three in the control group died.

Those receiving the high-carbohydrate diet also had a slower drop in their functional scores than the control group, although the difference was not statistically significant, said the team.

"There is good epidemiological evidence that, in ALS, survival is determined by nutritional status,” commented Wills. “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,” she added.

Source: The Lancet
Published online ahead of print, doi: 10.1016/S0140-6736(14)60222-1
“Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled phase 2 trial”
Authors: Anne-Marie Wills, Jane Hubbard, et al

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