Ketogenic therapy for Parkinson's disease: A systematic review and synthesis without meta-analysis of animal and human trials. (September 2022)

• Record Type: Journal Article
• Authors: Grammatikopoulou, Maria G.; Tousinas, Georgios; Balodimou, Chrysanthi; Anastasilakis, Dimitrios A.; Gkiouras, Konstantinos; Dardiotis, Efthimios; Evangeliou, Athanasios E.; Bogdanos, Dimitrios P.; Goulis, Dimitrios G.
• Is Part Of: Maturitas. Volume 163(2022)
• Page Start: 46
• Page End: 61
• Publication Date: 2022-09
• Subjects: Levodopa -- Low-carbohydrate diet -- Neurodegenerative disease -- Dopamine -- beta-hydroxybutyrate -- Tremor -- Motor deficit -- Octanoic acid -- 3, 4-dihydroxyphenylacetic acid (DOPAC) -- 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydro-pyridine (MPTP); Climacteric -- Periodicals; Menopause -- Periodicals; Climacteric -- Periodicals; Geriatrics -- Periodicals; Menopause -- Periodicals; Middle Aged -- Periodicals; Climatère -- Périodiques; Ménopause -- Périodiques; Climacterium; Climacteric; Menopause; Electronic journals; Periodicals; 612.66
• DOI: 10.1016/j.maturitas.2022.06.001
• Languages: English
• ISSNs: 0378-5122

Abstract

Highlights: In patients with Parkinson's disease (PD), nutrition is used as a complementary therapy for optimizing levodopa administration and treating long-term, medication-induced adverse events and comorbidities. The ketogenic diet (KD) and the administration of ketogenic agents is a promising therapeutic regime for several neurological disorders. Randomized controlled trials (RCTs) examining the effect of ketogenic therapy for PD are highly heterogenous, often lacking key outcomes of the PD Outcomes Consensus. Animal research is more promising regarding the effects of ketogenic therapy, but animal models and toxin models for the induction of PD entail several caveats. Abstract: Objective: The aim of the present systematic review was to assess the efficacy of ketogenic therapy in Parkinson's disease (PD), using all available data from randomized controlled trials (RCTs) on humans and animal studies with PD models. Design: Systematic review of in vivo studies. Methods: Studies related to the research question were identified through searches in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, clinicaltrials.gov and the gray literature, from inception until November 2021. Rayyan was employed to screen and identify all studies fulfilling the inclusion criteria. Cochrane's revised Risk of Bias 2.0 and SYRCLE tools evaluated bias in RCTs and animal studies, respectively. An effect direction plot was developed to synthesize the evidence of the RCTs. Results: Twelve studies were identified and included in the qualitative synthesis (4 RCTs and 8 animal trials). Interventions included ketogenic diets (KDs), supplementation with medium-chain triglyceride (MCT) oil, caprylic acid administration and ketone ester drinks. The animal research used zebrafish and rodents, and PD was toxin-induced. Based on the available RCTs, ketogenic therapy does not improve motor coordination and functioning, cognitive impairment, anthropometrics, blood lipids and glycemic control, exercise performance or voice disorders in patients with PD. The evidence is scattered and heterogenous, with single trials assessing different outcomes; thus, a synthesis of the evidence cannot be conclusive regarding the efficacy of ketogenic therapy. On the other hand, animal studies tend to demonstrate more promising results, with marked improvements in locomotor activity, dopaminergic activity, redox status, and inflammatory markers. Conclusions: Although animal studies indicate promising results, research on the effect of ketogenic therapy in PD is still in its infancy, with RCTs conducted on humans being heterogeneous and lacking PD-specific outcomes. More studies are required to recommend or refute the use of ketogenic therapy in PD.