Effect of fasting and a high fat, low carbohydrate diet on MND symptoms

Amyotrophic Lateral Sclerosis (ALS) / Motor Neurone Disease (MND) causes ongoing deterioration and death of nerve cells controlling muscle movement. This leads to muscle weakness and difficulties with walking, eating, and breathing.

In ALS, the body’s ability to produce energy from food, (metabolism), becomes less efficient, mainly due to the reduced function of the cell’s energy generators, called mitochondria.

Ordinarily, our cells use glucose, (sugar), as fuel to produce energy. Glucose is generated from carbohydrates – nutrients found in sugary and starchy foods in our diet. When carbohydrate supply is low, (e.g. after long periods without eating, or when a low-carbohydrate diet is followed), the body switches to an alternative energy generation system, called ketosis. Ketosis uses fats, instead of carbohydrates, to produce chemicals called ketones, which act as an alternative fuel for the body and brain.

Research in healthy people has shown that not eating for extended periods of time, (fasting) and/or following a low-carbohydrate, high-fat, (ketogenic), diet, can improve mitochondrial and metabolic function. These are the functions known to be impaired in ALS.

This study observed the effects of combining both fasting and a ketogenic diet, over 18 months, in a patient with ALS. Fasting was achieved by restricting eating to 2 one-hour mealtimes in each 24 hour period, outside of which only drinks were consumed. During the permitted mealtimes, the patient ate from a specific low-carbohydrate, high-fat, ketogenic diet. The study recorded changes in his movement, breathing, physical and mental health, to see whether a combination of fasting and a ketogenic diet was associated with any changes in his ALS symptoms.

Why is the study important?

There is no cure for ALS, and no treatment which slows the rapid decline in patients’ ability to function independently. Studies using genetically engineered mice have previously found that diet-based approaches may help to manage ALS symptoms and progression.

What did the authors do and how did they do it?

• A 64 year old man with ALS followed a fasted ketogenic diet for 18 months.
• The patient fasted for a total of 22 hours in each 24 hour period, eating only during 2 one-hour mealtimes per day.
• At each mealtime, he followed a diet comprised of 60% fat, 30% protein, 5% fibre and 5% carbohydrate, and ate until he was full.
• No other lifestyle changes were made during the trial.
• The patient was assessed across a range of functional measures before starting the diet, and at 6, 12 and 18 months from trial start.

Daily blood tests showed that whilst on the diet, the patient’s cells generated energy primarily from ketosis, rather than from glucose metabolism.

The majority of the measured ALS symptoms stabilised or improved during the trial, including a 7% improvement in functional ability, 17% and 13% improvement in breathing tests, 19% improvement in quality of life measures and 23% improvement in fatigue scores.  Swallowing ability and mental processes stayed stable, depression and stress scores improved, and weight loss slowed significantly.  Only physical function and two breathing measures showed decline.  The patient reported higher energy, better sleep, and reduction in chronic pain, stating the greatest benefits were to his mood, energy levels and quality of life. 45 months from the start of symptoms, he remains functionally independent and committed to the diet.

What do the findings mean going forward for people with the disease?

Symptoms most closely associated with ALS progression and shorter survival include faster functional decline, weight loss, reduced ability to exhale forcefully, and difficulty swallowing.  As each of these symptoms improved or stabilised in the case study, it is reasonable to suggest that the fasted ketogenic diet may be involved in slowing symptom progression and increasing survival in ALS patients.

Typically, the functional ability of those with ALS declines on a monthly basis.  However, 18 months after starting the diet trial, the patient’s functional ability scores had improved beyond his original pre-diet scores. 

Limitations: This is a single case study on one individual only.  Firm conclusions or wider generalisations cannot therefore be made about the effect of the fasting and ketogenic diet, or the biological processes that may be involved in any slowing of symptoms, until these findings have been reproduced in future studies.

However, it is suggested that using fasting and a high fat, low carbohydrate diet to force the body to use ketones, rather than glucose, as its cellular energy source, may provide ALS patients with a way to increase both the amount of cellular energy generated and the efficiency with which it gets to the cells that control the muscles.  These mechanisms together may have a protective effect on overall functional ability.

The study aligns with the evidence seen in earlier related mouse studies and can be considered to be an encouraging ‘proof of concept’ on which to base future studies investigating similar dietary strategies.

This study can be found at
Frontiers | Time-restricted ketogenic diet in amyotrophic lateral sclerosis: a case study (frontiersin.org)

Paper title
Time-restricted ketogenic diet in amyotrophic lateral sclerosis: a case study

Lead author
Matthew C. L. Phillips and Rognvald J. Dick

Publication details including date of publication
Published in Frontiers in Neurology, 2023, Volume 14, page 1329541.  Available at https://doi.org/10.3389/fneur.2023.1329541