Alessandro Pinto; Alessio Bonucci; Elisa Maggi; Mariangela Corsi; Rita Businaro
Review: The few studies conducted on humans available so far are based on a pre/post design but without a reference control group and without randomization. Of particular interest were the RCTs that correlated the introduction of KD to an improvement of verbal receptive vocabulary and of reaction time in children affected by epilepsy, as well as an improvement in attention and memory in patients affected by multiple sclerosis. The results demonstrated causal evidence and stressed the need to increase the number of studies to demonstrate that 4:1 KD induces a cognitive improvement in neurological diseases
Maciej Gasior, Michael A. Rogawski, and Adam L. Hartman
The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. Moreover, there is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neuro-degenerative disorders including Alzheimer’s disease and Parkinson’s disease, and may also be protective in traumatic brain injury and stroke.
Hayden White and Balasubramanian Venkatesh
Although much feared by clinicians, the ability to produce ketones has allowed humans to withstand prolonged periods of starvation. At such times, ketones can supply up to 50% of basal energy requirements. More interesting, however, is the fact that ketones can provide as much as 70% of the brain’s energy needs, more efficiently than glucose.
LaManna JC, Salem N, Puchowicz M, Erokwu B, Koppaka S, Flask C, Lee Z.
The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as beta-hydroxybutyrate (beta HB) and acetoacetate (AcAc), as occurs with fasting, prolonged starvation or chronic feeding of a high fat/low carbohydrate diet (ketogenic diet). In this study, the local cerebral metabolic rate of glucose consumption (CMRglu; microM/min/100g) was calculated in the cortex and cerebellum of control and ketotic rats using Patlak analysis.
Zhang Y, Kuang Y, Xu K, Harris D, Lee Z, LaManna J, Puchowicz MA.
The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as β-hydroxybutyrate and acetoacetate, as occurs with fasting, starvation, or chronic feeding of a ketogenic diet. The relationship between changes in cerebral metabolic rates of glucose (CMRglc) and degree or duration of ketosis remains uncertain. To investigate if CMRglc decreases with chronic ketosis, 2-[(18)F]fluoro-2-deoxy-D-glucose in combination with positron emission tomography, was applied in anesthetized young adult rats fed 3 weeks of either standard or ketogenic diets.
Krikorian R, Shidler MD, Dangelo K, Couch SC, Benoit SC, Clegg DJ.
We randomly assigned 23 older adults with mild cognitive impairment to either a high carbohydrate or very low carbohydrate diet. Following the 6-week intervention period, we observed improved verbal memory performance for the low carbohydrate subjects (p = 0.01) as well as reductions in weight (p < 0.0001), waist circumference (p < 0.0001), fasting glucose (p = 0.009), and fasting insulin (p = 0.005).
Reger MA, Henderson ST, Hale C, Cholerton B, Baker LD, Watson GS, Hyde K, Chapman D, Craft S.
Glucose is the brain’s principal energy substrate. In Alzheimer’s disease (AD), there appears to be a pathological decrease in the brain’s ability to use glucose. Neurobiological evidence suggests that ketone bodies are an effective alternative energy substrate for the brain. Elevation of plasma ketone body levels through an oral dose of medium chain triglycerides (MCTs) may improve cognitive functioning in older adults with memory disorders.