. Parkinson Disease and Ketogenic Diet

The pathogenesis of sporadic Parkinson disease (PD) remains unresolved, but numerous studies suggest that the primary cause is excitotoxic degeneration of dopaminergic neurons in the substantia nigra, leading to abnormalities of movement, and to an increasing extent in cognition and other cortical function disorders. It has been suggested that an impairment of mitochondrial function involving the substantia nigra plays an important contributory role in PD beginning and progression [94]. For example, Kashiwaya et al. used a heroin analogue 1-methyl-4-phenylpyridinium, MPP(+), that produces death of dopaminergic substantia nigra cells by inhibiting the mitochondrial NADH dehydrogenase multienzyme complex, producing a syndrome similar to Parkinson’s disease in cultured mesencephalic neurons. β-Hydroxybutyrate protected these neurons from MPP(+) toxicity neurodegeneration [74]. In animal models, 1-methyl-4-phenol-1,2,5,6-tetrahydropyridine (MPTP) is used to produce selective destruction of dopaminergic neurons in the substantia nigra that mimics human Parkinson’s disease-like syndrome. As for other, abovementioned, diseases the positive effects of KD on mitochondrial function could be a key factor in the utilization of such diet as ketones may bypass the defect in complex I activity implicated in PD. Infusion of β-hydroxybutyric acid in mouse protects from ageing the dopaminergic neurodegeneration and motor deficits induced by MPTP [49]. Moreover KD protected dopaminergic neurons of the substantia nigra against 6-hydroxydopamine neurotoxicity in a rat model of Parkinson disease [95]. VanItaille et al. [96] demonstrated that in humans, able to prepare a “hyperketogenic” diet at home and adhere to it for 28 days, the high level of KB was related to an improvement in the Unified Parkinson’s Disease Rating Scale scores.