Ketogenic diet in migraine: rationale, findings and perspectives

DOI: https://doi.org/10.1007/s10072-017-2889-6

Abstract-Summary Clinical data on KD in migraine—obtained from 150 patients investigated in case reports and prospective studies—suggest that KD may be a rapid onset effective prophylaxis for episodic and chronic migraine.

Randomized controlled studies are needed to confirm the usefulness of KD in migraine and to investigate its optimal duration, repeatability, feasibility in normal weight subjects, efficacy in pediatric population and association to conventional migraine prophylaxis.

Extended: This review outlines rationale, findings and perspectives of KD in

migraine treatment.

Introduction Ketogenic diet (KD) is a therapeutic tool for epilepsy and a fascinating treatment opportunity for other neurological disorders [537].

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Several evidence suggests that KD may be helpful in the preventive treatment of migraine, a disorder characterized by recurrent neurovascular pain attacks triggered by a hyperexcitable and hypometabolic brain [538].

This review outlines rationale, findings and perspectives of KD in migraine

treatment.

What is KD? KD is a very-low-carbohydrate diet based on a dramatic reduction in carbohydrate intake (usually <50 mg/day) coupled to a relative increase in protein and fat propor- tion which forces the metabolism to obtain its energy needs from lipids by free fatty acids mitochondrial beta-oxidation [537].

During KD, in absence of exogenous glucose as energy source, fatty acids are mobilized from adipose tissue depots and subsequently transported to the liver for conversion to ketone bodies (KB, i.e. acetoacetate, β-hydroxybutyric acid and ace- tone), a phenomenon naturally occurring during fasting.

KB are then distributed to metabolically active tissues, i.e. skeletal muscle, brain and heart, where they represent an important energy source since they are converted to acetyl-CoA, the substrate of Krebs cycle [537].

KD in Neurological Disorders KD is being considered “the most notable example of a dietary treatment with proven efficacy against a neurological condition” [539].

Human clinical evidence hints KD beneficial effects in diverse neurological dis- orders: Epilepsy Used to reduce seizures frequency since 1920s, KD is now a rec- ognized treatment for children with medically refractory epilepsy [540].

Parkinson’s disease A small feasibility study on diet induced hyperketonemia showed an improvement in Unified Parkinson’s Disease Rating Scale scores in all the 5 subjects studied [541].

Autism A pilot study showed an improvement of Childhood Autism Rating Scale

in 60% of children with autistic behavior adherent to KD for 6 months [542].

KD in Migraine De Lorenzo et al. described a marked migraine frequency reduction (from 15–16 days/month to headache disappearance) 3 days after KD was started or resumed in two female twins treated for weight-loss purpose.

Migraineurs treated with KD showed a significant improvement in attack fre- quency, headache days and analgesic use during the first month (corresponding to VLCKD), followed by a modest worsening—despite being improved compared with baseline—during TD1, and TD2 and subsequent SD period, whereas those treated with SD had a slower migraine improvement (significant reduction in head- ache days and analgesic intake at month 3 and in attack frequency at month 6).

Migraine worsening (following the initial improvement) when patients were shifted from KD to TD1 (at the end of the first treatment month) indicates that keto- genesis is helpful in migraine treatment independently from weight loss.

Conclusions and Perspectives We identified seven studies on the effects of KD in headache including 150 patients: 3 case reports (5 pts) [543–545], 2 case series (31 pts) [546, 547] and 2 prospective studies (114 pts) [548, 549].

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In almost all cases, KD started to be effective in a few days. Given these limitations, the aforementioned data suggest that KD is a promising

therapeutic tool for migraine prevention.

Future researches should specify what is the optimal KD duration, establish cri- teria for repeating KD cycles, verify KD effects duration and identify migraine endophenotypes more sensitive to KD.

Studies are also awaited to elucidate the unexpected very rapid KD onset of action in migraine which markedly contrasts with the delayed prophylactic effect of preventative migraine drugs.

Acknowledgement A machine generated summary based on the work of Barbanti, Piero; Fofi, Luisa; Aurilia, Cinzia; Egeo, Gabriella; Caprio, Massimiliano. 2017  in Neurological Sciences.

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