K. Tosefsky, JS. Lam, YN. Wang, S. Keymanesh, AJ. Kuan, A. Metcalfe-Roach, MS. Cirstea, MA. Sacheli, B. Brett Finlay, TR. Cohen, et al. (2026). A randomized safety and feasibility crossover trial of two Mediterranean-ketogenic interventions in individuals with Parkinson's disease. Journal of Parkinson's disease, 16(2), 332-350. https://doi.org/10.1177/1877718X261418986

PubMed 41637153

[Abstract]
BackgroundBoth Mediterranean and ketogenic diets have been proposed as nutritional interventions in Parkinson's disease (PD). Combined approaches may offer maximal benefits.ObjectiveAssess the feasibility, safety and exploratory efficacy of two ketogenic interventions, using a Mediterranean diet base, in individuals with PD (PwP).MethodsIn this Phase II, random-order crossover study, PwP 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).ResultsOf 52 participants randomized, 48 started the trial. Forty-one (79%) participants completed at least one, whereas only 33 (63%) completed both intervention phases. There were no intervention-related serious adverse events, nor any significant changes in plasma lipid profiles. 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 Mediterranean Diet Adherence Screener scores of 6.7 (SD: 1.6) and 7.2 (SD: 2.3) were achieved during the MeDi-KD and MeDi-MCT, respectively, out of a maximum of 14. Fifty percent of participants were in nutritional ketosis ([beta-hydroxybutyrate] ([BHB]) > 0.5 mM) at follow-up for the MeDi-KD, as compared with only 1 (3%) participant following the MeDi-MCT. MDS-UPDRS Part II and IV scores decreased by a mean of -1.4 (SD: 4.2; p = 0.039) and -1.0 (SD: 3.0; p = 0.044) points, respectively, following the MeDi-MCT.ConclusionsWhile both Mediterranean-ketogenic interventions appear safe in the short-term in PwP, their feasibility is called into question by a high study dropout rate (37%) and modest adherence. Preliminary benefits observed in patient-reported motor experiences were paradoxically limited to the MCT-supplemented MeDi, in which ketosis was not reliably achieved. Together, our findings indicate the need to refine behavioral strategies to optimize dietary awareness and adherence in future trials.Trial RegistrationThe trial was registered on ClinicalTrials.gov: NCT05469997.