Pathophysiological Abnormalities in Migraine Ameliorated by Ketosis: A Proof-of-Concept Review

Abstract

Migraine is a prevalent heterogeneous neurological disorder, enumerated as the eighth most disabling neurological disorder by the World Health Organization. The growing advancement in technology and investigation of various facets of cerebral metabolism in migraine has shed light to metabolic mechanisms in migraine pathophysiology. A growing number of clinical research postulates migraine as a reaction to oxidative stress levels that go beyond antioxidant capacity or cerebral energy deficiency. This has become an extremely attractive subject area and over the past years there has also been a sustained research activity in using ketone bodies (KB) as a novel potential migraine prophylaxis. Not much epidemiological research has been conducted to exhibit the efficacy of ketone bodies in abnormal metabolism in migraine pathophysiology. Therefore, a better understanding of ketone bodies in metabolic migraine may provide novel therapeutic opportunities. The goal of this review is to assess present understanding on potential migraine triggers, as well as how ketogenic interventions support metabolic disability in migraines and address the therapeutic importance of ketones in migraine treatment, accenting clinical studies (including neuroimaging and therapeutic studies). This review is intended to demonstrate existing literature on the effects of ketone bodies on metabolic migraine traits to guide the readership through current concepts and foster a perspective for future research.

Energy metabolism disorders in migraine: triggers, pathways, and therapeutic repurposing

“…KD plays an important role in reducing the frequency and severity of migraine attacks in both adolescents and adults ( 115 ), and it has also been shown to improve sleep disorders ( 116 ). As a result, KB supplementation may represent a potential prophylactic treatment strategy for migraine ( 117 ). A randomized controlled trial is currently investigating the safety and efficacy of exogenous KB salts, specifically 3-hydroxybutyric acid, for migraine prophylaxis ( 118 ).…”

Energy metabolism disorders in migraine: triggers, pathways, and therapeutic repurposing

“…KD plays an important role in reducing the frequency and severity of migraine attacks in both adolescents and adults ( 115 ), and it has also been shown to improve sleep disorders ( 116 ). As a result, KB supplementation may represent a potential prophylactic treatment strategy for migraine ( 117 ). A randomized controlled trial is currently investigating the safety and efficacy of exogenous KB salts, specifically 3-hydroxybutyric acid, for migraine prophylaxis ( 118 ).…”

The Hypometabolic State of the Migraine Brain: Is a Ketogenic Diet the Answer?

“…The KD acts on many pathways that were previously discussed including increasing mitochondrial function, reducing inflammation, reducing cortical spreading depression, and normalizing cortical hyperexcitability (Di Lorenzo et al 2021;Murakami and Tognini 2022;Huynh and Calabrese 2022). Ketone bodies can supply more ATP than glucose which better counteracts the energy deficit seen in migraine (Di Lorenzo et al 2021).…”

Ketogenic Diet Applied in Weight Reduction of Overweight and Obese Individuals with Progress Prediction by Use of the Modified Wishnofsky Equation

“…Studies show that different diet patterns influence diet changes and maintain reduced body weight [ 2 , 15 ], and one of them is the ketogenic diet, which is characterized by a significant reduced intake of carbohydrates (<30 g/day) and standard protein intake (1.2–1.5 g/kg of ideal body weight or 1.0–1.2 g/kg of fat free mass) [ 16 ]. This diet is also often used in diet therapy of obesity, type 2 diabetes mellitus, migraines, polycystic ovary syndrome, and even epilepsy [ 17 , 18 , 19 , 20 , 21 , 22 ]. There are several types of eating patterns within the keto diet.…”

Energy metabolism disorders in migraine: triggers, pathways, and therapeutic repurposing

“…KD plays an important role in reducing the frequency and severity of migraine attacks in both adolescents and adults ( 115 ), and it has also been shown to improve sleep disorders ( 116 ). As a result, KB supplementation may represent a potential prophylactic treatment strategy for migraine ( 117 ). A randomized controlled trial is currently investigating the safety and efficacy of exogenous KB salts, specifically 3-hydroxybutyric acid, for migraine prophylaxis ( 118 ).…”

The Hypometabolic State of the Migraine Brain: Is a Ketogenic Diet the Answer?

“…The KD acts on many pathways that were previously discussed including increasing mitochondrial function, reducing inflammation, reducing cortical spreading depression, and normalizing cortical hyperexcitability (Di Lorenzo et al 2021;Murakami and Tognini 2022;Huynh and Calabrese 2022). Ketone bodies can supply more ATP than glucose which better counteracts the energy deficit seen in migraine (Di Lorenzo et al 2021).…”

Ketogenic Diet Applied in Weight Reduction of Overweight and Obese Individuals with Progress Prediction by Use of the Modified Wishnofsky Equation

“…Studies show that different diet patterns influence diet changes and maintain reduced body weight [ 2 , 15 ], and one of them is the ketogenic diet, which is characterized by a significant reduced intake of carbohydrates (<30 g/day) and standard protein intake (1.2–1.5 g/kg of ideal body weight or 1.0–1.2 g/kg of fat free mass) [ 16 ]. This diet is also often used in diet therapy of obesity, type 2 diabetes mellitus, migraines, polycystic ovary syndrome, and even epilepsy [ 17 , 18 , 19 , 20 , 21 , 22 ]. There are several types of eating patterns within the keto diet.…”

Energy metabolism disorders in migraine: triggers, pathways, and therapeutic repurposing

“…KD plays an important role in reducing the frequency and severity of migraine attacks in both adolescents and adults ( 115 ), and it has also been shown to improve sleep disorders ( 116 ). As a result, KB supplementation may represent a potential prophylactic treatment strategy for migraine ( 117 ). A randomized controlled trial is currently investigating the safety and efficacy of exogenous KB salts, specifically 3-hydroxybutyric acid, for migraine prophylaxis ( 118 ).…”

The Hypometabolic State of the Migraine Brain: Is a Ketogenic Diet the Answer?

“…The KD acts on many pathways that were previously discussed including increasing mitochondrial function, reducing inflammation, reducing cortical spreading depression, and normalizing cortical hyperexcitability (Di Lorenzo et al 2021;Murakami and Tognini 2022;Huynh and Calabrese 2022). Ketone bodies can supply more ATP than glucose which better counteracts the energy deficit seen in migraine (Di Lorenzo et al 2021).…”

Ketogenic Diet Applied in Weight Reduction of Overweight and Obese Individuals with Progress Prediction by Use of the Modified Wishnofsky Equation

“…Studies show that different diet patterns influence diet changes and maintain reduced body weight [ 2 , 15 ], and one of them is the ketogenic diet, which is characterized by a significant reduced intake of carbohydrates (<30 g/day) and standard protein intake (1.2–1.5 g/kg of ideal body weight or 1.0–1.2 g/kg of fat free mass) [ 16 ]. This diet is also often used in diet therapy of obesity, type 2 diabetes mellitus, migraines, polycystic ovary syndrome, and even epilepsy [ 17 , 18 , 19 , 20 , 21 , 22 ]. There are several types of eating patterns within the keto diet.…”