Metabolic markers of short and long-term exogenous DL-beta-hydroxybutyrate supplementation in episodic migraine patients: an exploratory analysis of a randomized-controlled-trial.

Autor:	Putananickal N; Division of Neuropaediatrics, University of Basel Children's Hospital, University of Basel, Basel, Switzerland., Gross EC; Division of Neuropaediatrics, University of Basel Children's Hospital, University of Basel, Basel, Switzerland., Orsini AL; Neurology, University of Basel Hospital, University of Basel, Basel, Switzerland., Schmidt S; Division of Neuropaediatrics, University of Basel Children's Hospital, University of Basel, Basel, Switzerland., Hafner P; Division of Neuropaediatrics, University of Basel Children's Hospital, University of Basel, Basel, Switzerland., Gocheva V; Division of Neuropaediatrics, University of Basel Children's Hospital, University of Basel, Basel, Switzerland., Nagy S; Neurology, University of Basel Hospital, University of Basel, Basel, Switzerland., Henzi BC; Division of Neuropaediatrics, University of Basel Children's Hospital, University of Basel, Basel, Switzerland., Rubino D; Division of Neuropaediatrics, University of Basel Children's Hospital, University of Basel, Basel, Switzerland., Schädelin S; Department of Clinical Research, Clinical Trial Unit, University of Basel Hospital, University of Basel, Basel, Switzerland., Sandor P; RehaClinic, Bad Zurzach, Switzerland., Fischer D; Division of Neuropaediatrics, University of Basel Children's Hospital, University of Basel, Basel, Switzerland.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2023 May 04; Vol. 14, pp. 1172483. Date of Electronic Publication: 2023 May 04 (Print Publication: 2023).
DOI:	10.3389/fphar.2023.1172483
Abstrakt:	Background: Emerging findings propose that the pathophysiology of migraine may be associated with dysfunctional metabolic mechanisms. Recent findings suggest that migraine attacks are a response to the cerebral energy deficit, and ingestion of ketone bodies stabilizes the generation of a migraine attack. Based on these findings, ketone body supplementation is postulated as a prophylactic treatment approach to restore cerebral metabolism deficiency. Metabolic markers are unexplored after exogenous ketone body supplementation in episodic migraineurs. Therefore, the present single-arm uncontrolled explorative analysis evaluated blood ketone body and glucose concentration after short and long-term 6 g exogenous DL-Mg-Ca-beta-hydroxybutyrate (DL-βHB) supplementation. Methods: The presented data are part of the MigraKet randomized-control cross-over clinical trial of 41 episodic migraineurs (Number NCT03132233). Patients were given a single dose of 6 g DL-βHB. Ketone body and glucose blood concentration were assessed before intake, 20, and 40 min after DL-βHB intake. Ketone body, glucose concentration and glycated hemoglobin values were evaluated after 12 weeks of 18 g DL-βHB ingestion (total dose), taken three times daily (6g/dose; 3x/day). Linear models explored the association between the ketone body and glucose levels. Results: Ketone body concentration increased within-group to a mean of 0.46 (0.30) mmol/L after 40 min post- DL-βHB supplementation [estimate = 0.24 mmol/L, CI = (0.20.0.27), p < 0.01]. This within-group increase of ketone body concentration did not change after repeated daily intake of DL-βHB supplementation over 12 weeks [estimate = 0.00 mmol/L, CI = (-0.03.0.04), p = 0.794]. DL-βHB intake significantly reduced blood glucose concentration within-group from a mean baseline of 4.91 (0.42) mmol/L to 4.75 (0.47) mmol/L 40 min post-DL-βHB supplementation [estimate = -0.16 mmol/L, CI = (-0.15, 0.03), p < 0.01]. Repeated DL-βHB supplementation for 12 weeks showed no change within-group in acute ketone bodies concentration [estimate = 0.00 mmol/L, CI = (-0.03.0.04), p = 0.794] and in the HbA1c value [estimate = 0.02, CI = (-0.07.0.11), p = 0.69]. Conclusion: A single dose of 6 g DL-βHB significantly elevated blood ketone bodies and decreased blood glucose concentration within-group in episodic migraineurs. Long-term DL-βHB supplementation for 12 weeks showed no effect within-group on acute ketone body concentration and had not impact on HbA1c. The elevation of the ketone body concentration was moderate, indicating that nutritional ketosis was not reached. Therefore, a dose higher than 6 g of DL-βHB is required to reach the nutritional level of ketosis. ClinicalTrials.gov Identifier: NCT03132233. Competing Interests: EG and DF are the inventors of the patent WO 2018/115158 Al held by the UKBB and University of Basel on the use of beta-hydroxybutyrate in migraine prevention. EG is the founder and CEO of KetoSwiss AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Putananickal, Gross, Orsini, Schmidt, Hafner, Gocheva, Nagy, Henzi, Rubino, Schädelin, Sandor and Fischer.)
Databáze:	MEDLINE
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