Study Data Suggests Difficulties With Mediterranean-Ketogenic Dietary Intervention in Parkinson Disease

Silke Cresswell-Appel, MD

In an ongoing crossover study (NCT05469997) testing the effects of 2 dietary strategies on patients with Parkinson disease (PD), results showed that while participants embraced Mediterranean-style diets, there were several noted barriers to their combination with ketogenic-style interventions.¹

These interim data were presented at the 2024 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held September 27-October 1, in Philadelphia, Pennsylvania, by senior author Silke Cresswell-Appel, an associate professor at the University of British Columbia. In the trial, 50 participants were asked to follow two 8-week dietary interventions, separated by an 8-week washout: 1) a high-fat, low-carbohydrate Mediterranean diet (MEDI-KD) and 2) a standard Mediterranean diet supplemented with medium chain triglycerides.

Coming into the study, emerging evidence has suggested that both ketogenic and Mediterranean diets have beneficial and likely complementary effects in PD. Among the 50 participants, 48 attended first study visits, of which 45 (94%) started the first diet to which they were randomized. Throughout the study period, participant responses from interviews showed that patients took positively to the professional nutritional guidance, increased dietary mindfulness, and Mediterranean-style cuisine. In contrast, negative sentiments were focused on the restrictive nature and social impracticability of the ketogenic diet, as well as the gastrointestinal adverse effects of MCT oil.

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In the study, 5 (10%) participants withdrew, and 1 was lost to follow-up (2%), before completing the first intervention phase, while another 3 (6%) withdrew before completing the second phase. For the MEDI-KD, patients withdrew mainly because of social limitations (1/4), gastroparesis leading to increased OFF time (1/4), socioeconomic (1/4) and time (1/4) constraints. Reasons for withdrawing the MEDI-MCT included tremor exacerbation (1/4), diarrhea (1/4), time constraints (1/4), and a disabling injury (1/4).

Plasma ketone body levels in normal humans fluctuate between 0 and 0.25 mM, increasing to about 1 mM with prolonged exercise or 24h fast and further rising to 5–7 mM in prolonged fasting by 3 days or more, at which point production equilibrates with consumption. In the trial, the mean blood ketone level in the MEDI-KD and MEDI-MCT phases were 0.42 (SD, 0.28; n = 22) mM and 0.27 (SD, 0.18; n = 19) mM, respectively.

PD, the second most common neurodegenerative disease globally, escalates into impairments in motor and nonmotor functions, including tremors, rigidity, gait disturbances, anxiety, depression, cognitive deficits, and interference with activities of daily living. As a result of these symptoms, patients experience neuronal loss in the substantia nigra pars compacta with loss of striatal dopamine uptake. While traditional treatment for PD includes the application of levodopa, patients and medical providers are progressively interested in nonpharmacological, adjunct treatments like diets to help manage the significant adverse effects patients face.

A pilot study published earlier this year found that low-carbohydrate diets are a safe and potentially effective method in mitigating the symptoms of PD. The small-scale trial featured 7 patients with the disease who were on a 24-week ketogenic dietary intervention adjusted for body mass index that consisted of 1750 kcal per day, 152 g of fat, 75 g protein, and 16 g net of carbohydrates. After the 24-week treatment period, participants reported improved biomarkers, enhanced cognition, mood, motor and nonmotor symptoms, and reduced pain and anxiety. Qualitative interviews supported the quantitative findings, emphasizing the intervention's ease and family support.²

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REFERENCES
1. Tosefsky K, Wang Y, Kuan A, et al. Interim analysis of the feasibility of Mediterranean-ketogenic dietary interventions in Parkinson’s disease. Presented at: 2024 MDS Congress; September 27-October 1; Philadelphia, PA. ABSTRACT 501
2. Tidman MM, White DR, White TA. Impact of a keto diet on symptoms of Parkinson's disease, biomarkers, depression, anxiety and quality of life: a longitudinal study. Neurodegenerative Disease Management. Published online June 13, 2024. doi:10.1080/17582024.2024.2352394