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Ketogenic Diet Helps Nonmotor Symptoms in Parkinson's

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Hong Kong — A high fat, low carbohydrate ketogenic diet benefited people with Parkinson’s disease (PD), but so did a low fat, high carbohydrate diet, in a new pilot trial.

Both diets led to improvements in motor and nonmotor symptoms, but the patients who consumed the ketogenic diet showed greater improvements in nonmotor symptoms compared with the patients who were given the low fat diet.

Ketogenic diets have been tested in patients with various conditions, such as seizure disorders, and a small pilot study has shown benefits for migraineurs using supplements containing ketones. Preliminary evidence has suggested that manipulating the diet could have an effect on symptoms of PD, but studies have conflicted on the best fat-to-carbohydrate ratio.

Matthew Phillips, MSc, Waikato Hospital, Hamilton, New Zealand, and colleagues therefore carried out a randomized, controlled, pilot trial that compared a ketogenic diet with a low fat diet among PD patients in a hospital clinic. He described the diet plans as simple, affordable, and palatable.

He presented the results of the study during a poster tour here at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2018.

The primary outcomes measures were the within- and between-group changes in Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts 1-4 over 8 weeks.

Both groups showed improvements in their nonmotor symptoms. “The greatest between-group improvements were seen in urinary problems, pain, fatigue, daytime sleepiness, and cognitive impairment,” Phillips said. “Notably, these represent some of the more disabling, less levodopa-responsive nonmotor symptoms in Parkinson’s.”

PD patients (n = 47) were randomly allocated about equally to consume the low fat or the ketogenic diet. Twenty patients in the former group and 18 in the latter completed the study. At baseline, patients in the ketogenic group were slightly older (mean age, 64.29 years, vs 61.48 years) and had a slightly higher mean Hoehn and Yahr score (2.13 vs 1.78) as well as slightly higher scores on the MDS-UPDRS Parts 1-4.

The groups were well matched regarding sex and other variables. Throughout the study, all patients were assessed by the same neurologist on the same weekday at the same time of day. The neurologist who conducted the assessments was blinded to the randomization.

Total calories of the diets were kept the same. The amount of protein consumed by each group was also kept the same, “which is essential because protein interferes with levodopa absorption,” Phillips noted.

As expected, bedtime blood glucose levels were higher in the patients who consumed the low fat, high carbohydrate diet than in the patients who consumed the ketogenic diet. For the patients who were given the ketogenic diet, blood ketone levels were higher, averaging 1.2 mmol/L. “That is well within the range of physiological ketosis, a state in which neurons are obtaining energy from both glucose and ketones, so the neurons are sort of running like hybrid engines,” he said.

For both groups, UPDRS scores were significantly decreased, but for the patients who consumed ketogenic diet, there was a greater decrease in scores on Part 1 (nonmotor daily living experiences) than was seen in the patients who consumed the low fat diet, at -4.58 ± 2.17 points (41% improvement) vs 0.99 ± 3.63 points (11% improvement) (P < .001).

“Every single patient, in fact, in the keto group improved in their nonmotor symptoms. Not one got worse or stayed the same,” Phillips said.

He explained the thinking behind the two forms of diet for use in PD. A low fat, high carbohydrate diet could act to increase brain dopamine levels. On the other hand, evidence suggests that a high fat, low carbohydrate (ketogenic) diet may help to alleviate the dysfunctional mitochondrial energy metabolism that is seen in PD by supplying ketones as an alternative to glucose as a source of energy.

Both groups showed improvements; the magnitude of decrease in MDS-UPDRS scores for Parts 2, 3, or 4 (motor daily living experiences, motor examination, or motor complications, respectively) did not differ between the two groups.

The most common adverse effect was excessive hunger in the group that consumed the low fat diet; the group that consumed the ketogenic diet experienced unexpected and intermittent but transient exacerbations in PD tremor and/or rigidity.

The study showed that maintaining a low fat or ketogenic diet for 8 weeks was both plausible and safe. Both groups lost weight over the course of the study. The observed effects on MDS-UPDRS scores were not the result of weight loss, because the amount of weight loss was equivalent for both groups.

Two limitations of the study are the low number of patients and short duration, so the findings should be considered preliminary. Phillips said the findings suggest that a ketogenic diet may be a good complement to levodopa therapy for PD, pending results of longer randomized trials.

Poster tour moderator Tim Anderson, MD, FRACP, of the New Zealand Brain Research Institute in Christchurch and the University of Otago in Dunedin, commented to Medscape Medical News that ketogenic diets have “become a big thing in all sorts of ways.” Although he found the study interesting, he said, “It’s come out of left field. The magnitude of effect seems rather large to me, larger than I would have expected.”

He expressed concern about the short duration of the trial as well as the possibility of a placebo effect.

“There was no real control group who were maintained on normal diet,” he said. He said that although the participants could not be blinded to their assigned intervention, he still thinks a trial with such a control group is needed “because of the huge placebo effect in Parkinson’s disease. Just going into a trial in itself usually means that people’s Parkinson’s, as measured by various motor scales and so forth, is going to improve.” In addition, he said he would like to see a much longer trial to gauge the duration of effect.

Anderson said a ketogenic diet has been shown to be safe, having been used in many trials. In comparison with the ketogenic diets used in past decades for children with epilepsy, today’s ketogenic diets have been modified and are more palatable, so people may be able to be maintained on them longer. But longer trials need to be done to see how long people will stay on them, he said.

There was no commercial funding for the study. Matthew Phillips and Dr Anderson have disclosed no relevant financial relationships.

International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2018. Abstract 12, presented October 6, 2018.

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