Metabolic Therapies for Neurological Diseases
Based on the work of Matthew Phillips, a neurologist and researcher
Dr. Matthew Phillips is a neurologist and researcher in New Zealand who investigates metabolic therapies for neurological diseases. He describes his approach as examining neurological disorders through the lens of metabolism and mitochondrial biology.
This article focuses on his clinical research using ketogenic diets in Alzheimer’s and Parkinson’s disease. These small, short-term trials have reported improvements in some measures of daily functioning, quality of life, and symptoms, while leaving important questions unanswered.
A companion article, “Brain Energy & Neurological Health,” explores the scientific rationale for studying ketones as an alternative brain fuel.
Metabolic Neurology
Dr. Phillips views many neurological diseases through the lens of metabolism and mitochondrial function. The brain requires enormous amounts of energy, and disturbances in the way brain cells produce and use energy may contribute to neurodegenerative disease.
Ketogenic diets and fasting change the body’s metabolism, reducing reliance on glucose and increasing the production of ketones. Ketones can provide the brain with an alternative source of energy.
Phillips is investigating whether these metabolic changes can improve brain function and potentially influence the course of neurological diseases.
The Alzheimer’s Clinical Trial
Dr. Phillips and his colleagues conducted a randomized crossover trial involving 26 people with clinically confirmed Alzheimer’s disease. Each participant was assigned to follow a modified ketogenic diet and a usual diet supplemented with low-fat healthy-eating guidance, in separate 12-week periods with a 10-week washout between them. Twenty-one participants completed the ketogenic-diet period.
Compared with the control diet, the ketogenic diet produced statistically significant improvements in measures of daily functioning and quality of life. Cognitive scores were numerically higher, but the difference was not statistically significant.
The study supports further investigation, but its small size and short duration limit what it can establish about lasting benefits or disease progression.
Parkinson’s Disease
Dr. Phillips and his colleagues conducted an eight-week pilot randomized trial comparing a ketogenic diet with a low-fat, high-carbohydrate diet in people with Parkinson’s disease. Forty-seven participants were randomized, 44 started their assigned diets, and 38 completed the study.
Both groups improved on symptom scales. The ketogenic group showed greater improvement in nonmotor symptoms, including fatigue, daytime sleepiness, urinary problems, pain, and reported cognitive difficulties. There was no significant between-group difference on the other measured sections, which included motor symptoms and motor complications.
Some participants in the ketogenic group experienced intermittent worsening of tremor or rigidity. This small, short-term study supports further research, but it does not establish that a ketogenic diet slows Parkinson’s disease progression.
Ketogenic Diets and Fasting
A ketogenic diet substantially reduces carbohydrate intake, causing the liver to produce ketones from fat. These ketones can provide an alternative source of energy for the brain.
Fasting can produce a similar metabolic shift. Phillips is interested in how both dietary ketosis and periods of fasting may influence cellular energy metabolism, mitochondrial function, and the brain’s resilience to disease.
Ketogenic diets have a long-established role in treating some forms of epilepsy, and their use in Alzheimer’s, Parkinson’s, and other neurological diseases remains an active area of research.
The clinical trials summarized here tested ketogenic diets. They should not be treated as evidence that fasting produces the same benefits.
What the Research Shows
Phillips’s work is valuable because it tests metabolic approaches in human clinical trials, rather than relying only on laboratory findings or proposed mechanisms.
The studies discussed here reported benefits on some measures of daily functioning, quality of life, and Parkinson’s nonmotor symptoms. However, the Alzheimer’s trial did not demonstrate a statistically significant cognitive benefit, and the Parkinson’s trial did not show a between-group advantage on its motor measures.pubmed.ncbi.nlm.nih+1
These findings justify larger and longer trials. They do not establish that ketogenic diets prevent, stop, or reverse Alzheimer’s or Parkinson’s disease, or that fasting produces equivalent results.
A Note of Caution
These approaches remain under investigation for Alzheimer’s and Parkinson’s disease. Anyone considering a ketogenic diet or fasting for a neurological condition should discuss it with their treating clinician and a qualified dietitian. Dietary changes should not replace prescribed treatment, and medications should not be adjusted without professional supervision.
Learn More
Website
Dr. Matthew Phillips’s website on metabolic therapies for neurological diseases.
Research
Randomized Crossover Trial of a Modified Ketogenic Diet in Alzheimer’s Disease
Alzheimer’s Research & Therapy, 2021
Alzheimer’s Research & Therapy, 2021
A randomized crossover trial found that a modified ketogenic diet was feasible and produced improvements in daily function and quality of life in people with Alzheimer’s disease, although the study was small and short-term.
Movement Disorders, 2018
A small randomized controlled trial found that both low-fat and ketogenic diets were feasible in people with Parkinson’s disease, with the ketogenic group showing greater improvement in several nonmotor symptoms.
Videos
Dr. Phillips discusses his Alzheimer’s trial, which reported improvements in daily functioning and quality of life, but not a statistically significant improvement in cognition.
Phillips explains why fasting and ketogenic diets are being studied for dementia and how ketones may provide an alternative source of energy when the brain has difficulty using glucose.
Dr. Phillips explains his view that neurodegenerative diseases may develop from underlying metabolic dysfunction long before symptoms appear and discusses the potential for metabolic therapies to intervene earlier.
Phillips explains how ketosis changes the brain’s energy metabolism and discusses why ketogenic diets and fasting are being studied for Alzheimer’s, Parkinson’s, and other neurological diseases.
Dr. Phillips explains how fasting, exercise, and ketosis may create beneficial metabolic stress that strengthens mitochondria and could potentially improve resilience in Parkinson’s disease.
Phillips discusses a striking individual case of neurological improvement and explores whether ketogenic diets and other metabolic stresses that stimulate mitohormesis could contribute to recovery. Of course, an individual case cannot establish that the intervention caused the improvement or that similar results would occur in other patients.