Dropping by to share a review article just published in The Journal of Headache and Pain which adds to the growing body of research suggesting microbial dysbiosis is implicated in migraine pathogenesis. It found migraine patients have less diverse gut microbiomes with elevated bacteroidetes, proteobacteria and firmicutes as well as reduced faecalibacterium, a butyrate producer known for its anti-inflammatory effects. This imbalance may increase gut permeability resulting in neuroinflammation impacting migraine onset and severity. Probiotics and synbiotics reduced migraine frequency, severity, and painkiller use (excluding triptans) in five randomized trials, though results varied by strain and population.
Unravelling the gut-brain connection: a systematic review of migraine and the gut microbiome https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-025-02039-7
Could similar microbial mechanisms apply to CH? I suspect so. We know CH shares neuroinflammatory pathways with migraines and a couple of recent CH studies suggest there may be a systemic inflammatory component in CH as CH’ers, regardless of whether chronic or episodic (in or out of bout) were found to have elevated levels of oncostatin M and I believe it was the most recent paper that identified a distinct difference in inflammatory cytokine profiles between episodic and chronic CH sufferers.
Elevated cytokine levels in the central nervous system of cluster headache patients in bout and in remission https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-024-01829-9
Distinct Alterations of Inflammatory Biomarkers in Cluster Headache: A Case Control Study https://onlinelibrary.wiley.com/doi/10.1002/ana.27205
So what evidence is there that perhaps diet may be a key therapeutic target for CH? We have the 2018 Lorenzo study to refer, where 15 of 18 chronic CH patients had a therapeutic response with 11 of those achieving clinical remission on a ketogenic diet with the author stating “we observed for the first time that a 3-month ketogenesis ameliorates clinical features of CCH.” Is it reasonable then to ask might its efficacy lie in shifting the microbiome towards a less inflammatory profile?
Efficacy of Modified Atkins Ketogenic Diet in Chronic Cluster Headache: An Open-Label, Single-Arm, Clinical Trial https://pmc.ncbi.nlm.nih.gov/articles/PMC5816269/
If you read into the literature on vitamin D3, I think there is a strong case for the vitamin D3 regimens use as a preventative therapeutic option to have in the CH toolkit given it’s unique role in modulating the immune response – notably in a dose dependent manner, as shown in one of my all-time favourite vitamin D research papers, somewhat supporting the proposed 10,000iu per day dosage as per the regimen.
Disassociation of Vitamin D’s Calcemic Activity and Non-calcemic Genomic Activity and Individual Responsiveness: A Randomized Controlled Double-Blind Clinical Trial
https://www.nature.com/articles/s41598-019-53864-1
The above paper was written by Professor Michael Holick, regarded as one of the pioneering vitamin D3 researchers, alongside others like Wagner and Hollis etc. He also wrote another paper showing that vitamin D3 modulates the human microbiome, increasing beneficial bacteria and decreasing pathogenic bacteria.
The Effect of Various Doses of Oral Vitamin D3 Supplementation on Gut Microbiota in Healthy Adults: A Randomized, Double-blinded, Dose-response Study
https://pubmed.ncbi.nlm.nih.gov/31892611/
The emerging “psilocy-biome” research is nothing short of intriguing too. Psilocybin may alter gut microbiota, increasing beneficial bacteria and reducing inflammation. It could act via the gut-brain axis with microbes metabolizing psilocybin to influence serotonin pathways or dampen neuroinflammation though this needs more study there was a fantastic paper recently published exploring this subject. Further, if the anti-inflammatory effects of psilocybin are in part derived from the interaction with the microbiome, might this contribute to variation in therapeutic response to psilocybin for CH?
Mind over matter: the microbial mindscapes of psychedelics and the gut-brain axis https://www.sciencedirect.com/science/article/pii/S1043661824002834
From my humble perspective it is an exciting time to be following the research. It is interesting as a sufferer to hypothesize where all this may converge in the context of CH. It is also tempting to speculate that a patient led vitamin D3 regimen dated as early as 2011 aligns nicely with what recent research is suggesting in respect of the underlying inflammatory component now suspected in CH, particularly given my personal success with the regimen since 2015. As always, anyone considering the regimen is encouraged to doing it under the care of a physician and the regular monitoring of labs for calcium, PTH and 25(OH)D vitamin D.
Dropping by to share a review article just published in The Journal of Headache and Pain which adds to the growing body of research suggesting microbial dysbiosis is implicated in migraine pathogenesis. It found migraine patients have less diverse gut microbiomes with elevated bacteroidetes, proteobacteria and firmicutes as well as reduced faecalibacterium, a butyrate producer known for its anti-inflammatory effects. This imbalance may increase gut permeability resulting in neuroinflammation impacting migraine onset and severity. Probiotics and synbiotics reduced migraine frequency, severity, and painkiller use (excluding triptans) in five randomized trials, though results varied by strain and population. Unravelling the gut-brain connection: a systematic review of migraine and the gut microbiome https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-025-02039-7 Could similar microbial mechanisms apply to CH? I suspect so. We know CH shares neuroinflammatory pathways with migraines and a couple of recent CH studies suggest there may be a systemic inflammatory component in CH as CH’ers, regardless of whether chronic or episodic (in or out of bout) were found to have elevated levels of oncostatin M and I believe it was the most recent paper that identified a distinct difference in inflammatory cytokine profiles between episodic and chronic CH sufferers. Elevated cytokine levels in the central nervous system of cluster headache patients in bout and in remission https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-024-01829-9 Distinct Alterations of Inflammatory Biomarkers in Cluster Headache: A Case Control Study https://onlinelibrary.wiley.com/doi/10.1002/ana.27205 So what evidence is there that perhaps diet may be a key therapeutic target for CH? We have the 2018 Lorenzo study to refer, where 15 of 18 chronic CH patients had a therapeutic response with 11 of those achieving clinical remission on a ketogenic diet with the author stating “we observed for the first time that a 3-month ketogenesis ameliorates clinical features of CCH.” Is it reasonable then to ask might its efficacy lie in shifting the microbiome towards a less inflammatory profile? Efficacy of Modified Atkins Ketogenic Diet in Chronic Cluster Headache: An Open-Label, Single-Arm, Clinical Trial https://pmc.ncbi.nlm.nih.gov/articles/PMC5816269/ If you read into the literature on vitamin D3, I think there is a strong case for the vitamin D3 regimens use as a preventative therapeutic option to have in the CH toolkit given it’s unique role in modulating the immune response – notably in a dose dependent manner, as shown in one of my all-time favourite vitamin D research papers, somewhat supporting the proposed 10,000iu per day dosage as per the regimen. Disassociation of Vitamin D’s Calcemic Activity and Non-calcemic Genomic Activity and Individual Responsiveness: A Randomized Controlled Double-Blind Clinical Trial https://www.nature.com/articles/s41598-019-53864-1 The above paper was written by Professor Michael Holick, regarded as one of the pioneering vitamin D3 researchers, alongside others like Wagner and Hollis etc. He also wrote another paper showing that vitamin D3 modulates the human microbiome, increasing beneficial bacteria and decreasing pathogenic bacteria. The Effect of Various Doses of Oral Vitamin D3 Supplementation on Gut Microbiota in Healthy Adults: A Randomized, Double-blinded, Dose-response Study https://pubmed.ncbi.nlm.nih.gov/31892611/ The emerging “psilocy-biome” research is nothing short of intriguing too. Psilocybin may alter gut microbiota, increasing beneficial bacteria and reducing inflammation. It could act via the gut-brain axis with microbes metabolizing psilocybin to influence serotonin pathways or dampen neuroinflammation though this needs more study there was a fantastic paper recently published exploring this subject. Further, if the anti-inflammatory effects of psilocybin are in part derived from the interaction with the microbiome, might this contribute to variation in therapeutic response to psilocybin for CH? Mind over matter: the microbial mindscapes of psychedelics and the gut-brain axis https://www.sciencedirect.com/science/article/pii/S1043661824002834 From my humble perspective it is an exciting time to be following the research. It is interesting as a sufferer to hypothesize where all this may converge in the context of CH. It is also tempting to speculate that a patient led vitamin D3 regimen dated as early as 2011 aligns nicely with what recent research is suggesting in respect of the underlying inflammatory component now suspected in CH, particularly given my personal success with the regimen since 2015. As always, anyone considering the regimen is encouraged to doing it under the care of a physician and the regular monitoring of labs for calcium, PTH and 25(OH)D vitamin D.
