Role of Ketogenic Diets in Neurodegenerative Diseases (Alzheimer’s Disease and Parkinson’s Disease)

Abstract

The goal of this review was to assess the effectiveness of ketogenic diets on the therapy of neurodegenerative diseases. The ketogenic diet is a low-carbohydrate and fat-rich diet. Its implementation has a fasting-like effect, which brings the body into a state of ketosis. The ketogenic diet has, for almost 100 years, been used in the therapy of drug-resistant epilepsy, but current studies indicate possible neuroprotective effects. Thus far, only a few studies have evaluated the role of the ketogenic diet in the prevention of Parkinson’s disease (PD) and Alzheimer’s disease (AD). Single studies with human participants have demonstrated a reduction of disease symptoms after application. The application of the ketogenic diet to elderly people, however, raises certain concerns. Persons with neurodegenerative diseases are at risk of malnutrition, while food intake reduction is associated with disease symptoms. In turn, the ketogenic diet leads to a reduced appetite; it is not attractive from an organoleptic point of view, and may be accompanied by side effects of the gastrointestinal system. All this may lead to further lowering of consumed food portions by elderly persons with neurodegenerative diseases and, in consequence, to further reduction in the supply of nutrients provided by the diet. Neither data on the long-term application of the ketogenic diet in patients with neurodegenerative disease or data on its effects on disease symptoms are available. Further research is needed to evaluate the suitability of the ketogenic diet in the therapy of AD- or PD-affected persons.

Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration

“…The ketogenic diet has shown to have neuroprotective effects in the context of several neurodegenerative diseases, such as Alzheimer's, and Parkinson's disease [70]. The neuroprotective effect of the ketogenic diet has been hypothesized to be a result of the biochemical changes resulting from glycolytic inhibition, increased acetyl-CoA production, and formation of ketone bodies in the cell [71].…”

“…We have previously shown that different anatomical regions of the human retina are susceptible to oxidative stress, highlighting the importance of antioxidant availability in the retina [13]. Ketone bodies increase mitochondrial respiration via increased ATP production and reduce ROS formation by increasing NADH oxidation, thereby improving the efficiency of the mitochondrial respiratory chain complex [70]. Targeting the TCA cycle and fatty acid synthase pathway by acetyl-CoA production via the ketogenic diet led to increased global retinal visual function compared to controls by one month of age.…”

Ketogenic diets and protective mechanisms in epilepsy, metabolic disorders, cancer, neuronal loss, and muscle and nerve degeneration

“…Neurodegeneration associates with abnormal glycolysis and attenuated glucose uptake and metabolism, and KD inhibits these changes via altered metabolic activity (Figure ) (Wlodarek, ). Ketone bodies provide neuroprotection via ATP generation and regulate NADPH/NADP ratio, GSH activity, mitochondrial permeability, and reduced glycolytic flux, apoptosis, and neuroinflammation, resulting in normal synaptic neurotransmission (Wlodarek, ). β‐hydroxybutyrate treatment and dietary restrain in calorie intake also reduce oxidative stress, neuronal apoptosis, and neuroinflammation and enhance generation of neurotrophins, such as BDNF, and neurotrophin‐3 and glial cell line‐derived neurotrophic factor that significantly relate with altered neuronal functions, particularly in the aging brain (Wlodarek, ).…”

“…β-hydroxybutyrate treatment and dietary restrain in calorie intake also reduce oxidative stress, neuronal apoptosis, and neuroinflammation and enhance generation of neurotrophins, such as BDNF, and neurotrophin-3 and glial cell line-derived neurotrophic factor that significantly relate with altered neuronal functions, particularly in the aging brain (Wlodarek, 2019).…”

“…Ketone bodies also inhibited rotenone-induced abnormal functioning of the respiratory mitochondrial chain, via re- However, ketosis augmented the systemic adiponetin levels and dysregulated the normal GABA and AMPK activities and ROS levels, which appeared detrimental for aged AD and PD patients. KD also emerged as a cause for malnourishment in neurodegenerative patients, and hence a balanced composition in KD appears essential for optimum benefits with minimum adverse effects (Wlodarek, 2019).…”