3-week keto diet did not ease motor symptoms in small study

Illustration of various fruits, vegetables, beans and fish.

A three-week ketogenic diet, one low in carbohydrates and high in fat, supplemented with a specific type of fat — called medium chain triglycerides — showed no significant benefits in easing motor symptoms in a small group of people with Parkinson’s disease, a pilot trial has found.

Whether this diet may improve cognition or slow disease progression “requires further study,” researchers wrote in the study “A randomized feasibility trial of medium chain triglyceride-supplemented ketogenic diet in people with Parkinson’s disease,” which was published in the journal BMC Neurology.

Parkinson’s disease is mostly known for its motor difficulties, but patients can also experience nonmotor symptoms, such as cognitive impairment, depression, anxiety, and sleep disturbances.

Growing evidence supports the benefits of a ketogenic, or keto, diet for the treatment of neurodegenerative disorders, including Parkinson’s and Alzheimer’s disease. A keto diet is low in carbs and high in healthy fats with limited protein intake. It forces the body to use ketone bodies as fuel instead of sugar (glucose) which comes from carbohydrates such as grains. Ketone bodies are a type of fuel the liver produces from stored fat.

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Ketosis may be beneficial for aging and neurodegenerative diseases

The use of ketone bodies, a process called ketosis, leads to an array of metabolic adaptations by the body believed to be beneficial to slow aging and neurodegenerative diseases associated with an energy deficit, such as Parkinson’s. Previous studies have linked the diet to reduced motor symptoms and improved cognition in Parkinson’s patients.

However, despite these promising findings, not all patients can tolerate the keto diet, with dropout rates varying from 14% to 28%.

With this in mind, a team led by researchers at the National Institutes of Health (NIH), in Bethesda, Maryland, conducted a pilot Phase 1 clinical study (NCT04584346) to assess how Parkinson’s patients can tolerate a keto diet supplemented with a medium chain triglyceride (MCT) oil. MCTs are a type of fat found in coconut oil, palm kernel oil, and dairy products, and are an alternative source of fat for people who cannot tolerate other fat types.

A total of 16 Parkinson’s patients were randomly assigned to an MCT-keto diet (seven patients with a mean age of 67.3 years) or a standard diet (nine patients with a mean age of 67.1 years) for a seven-day inpatient admission at the NIH. After, all patients followed a two-week MCT-keto diet at home.

Besides tolerability (the trial’s main goal), the researchers also assessed changes in the Timed Up & Go (TUG) test after seven days to assess balance and functional mobility. The TUG test measures the time it takes for a participant sitting on a chair to stand up, walk for three meters, turn back, and attempt to sit on the chair. Longer times indicate poorer balance.

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Tests for disease severity/progression, nonmotor symptoms, working memory

Exploratory outcomes included disease severity and progression as evaluated with the Unified Parkinson’s Disease Rating Scale (UPDRS), nonmotor symptoms as assessed using the Non-Motor Symptom Scale (NMSS), and working memory.

Resting-state electroencephalography (rsEEG) was also analyzed, which refers to EEG signals recorded while a person is not engaged in any particular task. EEG measures the brain’s electrical activity in a non-invasive way.

Fifteen patients completed the study (one patient withdrew due to difficulties in following a keto diet at home).

According to a daily survey made at the beginning of the study, symptoms were similar in both groups. The only exception was a significantly higher percentage of daily off periods — times between medication doses when symptoms aren’t adequately controlled — in the standard diet group.

The majority of patients (12 out of 15) were “somewhat likely” to “very likely” to continue a similar keto diet in the future, according to a survey at the end of the study. The most commonly reported benefits were related to energy (six patients), better motor function (six patients), lower appetite (four patients), eased constipation (four patients), and less fatigue (four patients).

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Side effects of keto diet: fatigue, headache, urinary incontinence, gait freezing

The most common side effects of a keto diet were fatigue (five patients), headache/light-headedness (two patients), and possible Parkinson’s symptoms such as urinary incontinence and new episodes of gait freezing, a fairly common disease motor symptom.

No differences were seen in the TUG test after seven days between the groups. Nonmotor symptoms significantly decreased from the start of the study (baseline) in both groups after three weeks, but to a greater extent in the keto group, as shown by NMSS scores.

All other exploratory outcomes — UPDRS, working memory, and rsEEG — were not significantly different between the groups.

Blood ketosis, a state where the body produces high levels of ketone bodies in the blood as an alternative energy source, was detected by day four in the keto group when compared with the other group, with a further increase by week three.

An increasing trend in levodopa metabolites 3,4-dihydroxyphenylacetic acid and dopamine was seen after three days in the keto group, but this didn’t reach statistical significance when compared with the other group. Levodopa metabolites are the substances produced when levodopa, a medication commonly used in Parkinson’s, is broken down or transformed within the body.

Elevated levels of these metabolites could suggest increased activity of levodopa decarboxylase, the enzyme that converts levodopa into dopamine, which is the chemical messenger that is missing in people with Parkinson’s disease.

Overall, an MCT-supplemented keto diet “is feasible and acceptable” for Parkinson’s patients “but requires further study to understand its effects on symptoms and disease,” the researchers concluded.

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