Objective: Assess the feasibility, safety and exploratory efficacy of two Mediterranean-ketogenic dietary interventions in individuals with Parkinson’s disease (PD).

Background: Both Mediterranean and ketogenic diets have been proposed as adjunct nutritional interventions in PD. Combining these two approaches may optimize benefits while minimizing risks and adherence barriers associated with standard ketogenic diets.

Method: In this phase II, random-order crossover study (NCT05469997), participants with PD followed 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 (MeDi-MCT).

Results: Of 52 randomized participants, 48 started one of the two interventions. Forty-one (79%) participants completed at least one intervention, and 33 (63%) completed both intervention phases. There were no intervention-related serious adverse events, nor any significant changes in plasma lipid profiles. A mean reduction in body mass of -2.63 (SD: 1.86) kg from baseline was observed at the 8-week follow-up for the MeDi-KD phase (p < 0.001), whereas body mass remained stable during the MeDi-MCT phase (mean change from baseline: 0.03 (SD: 1.74) kg; p = 0.6). Seventy-three percent and 92% of participants reported deviating from the MeDi-KD and MeDi-MCT no more than a few times per month, respectively. Moderate adherence to the Mediterranean diet was achieved with both interventions, with mean Mediterranean Diet Adherence Scores of 6.7 (SD: 1.6) during MeDi-KD and 7.2 (SD: 2.3) during the MeDi-MCT out of a maximum score of 14. At follow-up, 50% of participants in the MeDi-KD group were in nutritional ketosis (BHB > 0.5 mM), as compared with only 1 (3%) participant following the MeDi-MCT. A significant mean within-participant decrease in MDS-UPDRS Part II scores of -1.4 (SD: 4.3; p = 0.039) points and Part IV scores of -1.1 (SD: 3.0; p = 0.033) points was observed following the MeDi-MCT.

Conclusion: Mediterranean-ketogenic interventions appear safe and potentially beneficial in individuals with PD. Future phase III trials should optimize behavioural strategies to improve adherence.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/random-order-crossover-trial-assessing-the-safety-feasibility-and-exploratory-efficacy-of-two-mediterranean-ketogenic-nutritional-interventions-in-parkinsons-disease/