To follow up Do broccoli sprouts treat migraines? which used a PubMed “sulforaphane migraine” search, a PubMed “diindolylmethane” search came across a 2020 Czech human cell study Antimigraine Drug Avitriptan Is a Ligand and Agonist of Human Aryl Hydrocarbon Receptor that Induces CYP1A1 in Hepatic and Intestinal Cells that had this informative Introduction:

“The aryl hydrocarbon receptor (AhR) transcriptionally controls a wide array of genes. AhR is a critical player in human physiology (e.g., hematopoiesis) and also in many pathophysiological processes such as diabetes, carcinogenesis, inflammation, infection or cardiovascular diseases.

Suitable candidates for off-targeting AhR could be the antimigraine drugs of triptan class, which have an indole core in their structure. Indole-based compounds were demonstrated as ligands of AhR, including dietary indoles (e.g., indole-3-carbinol and diindolylmethane).”

Adding AhR to the search showed:

• A 2020 US human cell / rodent study Serotonin Modulates AhR Activation by Interfering with CYP1A1-Mediated Clearance of AhR Ligands which clarified:
  

  “Most vegetables contain high levels of a TRP [tryptophan] derivative called glucobrassicin, which is cleaved into the weak AhR ligand indole-3-carbinol (I3C) during mastication by plant-derived myrosinase enzymes. I3C is converted to high affinity AhR ligands including 3, 3’-diindolylmethane (DIM) and indole [3, 2-b]carbazole (ICZ) as a result of exposure to the acidic environment of the stomach.”

• A 2019 Korean rodent study 3,3′-Diindolylmethane Promotes BDNF and Antioxidant Enzyme Formation via TrkB/Akt Pathway Activation for Neuroprotection against Oxidative Stress-Induced Apoptosis in Hippocampal Neuronal Cells directly tested DIM and found:
  

  “DIM attenuated memory impairment by protecting hippocampal neuronal cells against oxidative damage. DIM exerted neuroprotective and antioxidant actions through the activation of both BDNF production and antioxidant enzyme formation.”

Changing the PubMed search to “icz migraine” pulled up a 2013 review Biomedical Importance of Indoles that described sumatriptan as an indole, and:

“Since DIM accumulates in the cell nucleus, it likely contributes to cell nuclear events that have been ascribed to I3C.”

Widening the search to “i3c ahr” added:

• A 2020 Germany / Japan rodent study Dietary AhR Ligands Regulate AhRR Expression in Intestinal Immune Cells and Intestinal Microbiota Composition:
  

  “Dietary I3C supplementation restores AhR activation in the intestinal mucosa under conditions of malnutrition and deprivation of natural AhR ligands. It should be taken into consideration that the commonly used HFD [high fat diet] products and matching control diets can lead to an impairment of AhR signaling in intestinal immune cells and epithelial cells.”

• A 2017 German rodent study Indole-3-carbinol, a plant nutrient and AhR-Ligand precursor, supports oral tolerance against OVA and improves peanut allergy symptoms in mice:
  

  “I3C feeding robustly induced the AhR-target gene CYP4501A1 in the intestine; I3C feeding also induced the aldh1 gene, whose product catalyzes the formation of retinoic acid, an inducer of regulatory T cells. I3C feeding attenuated symptoms of peanut allergy.”

• A 2015 US review Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation:
  

  “Of these glucobrassicin-derived compounds, ICZ exhibits the highest affinity and activation potential for AHR and thus probably represents a physiologically relevant glucobrassicin-derived AHR ligand.”

Changing the search to “i3c migraine” picked up a 2011 UK human study Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial:

“In the study reported here, there was no statistically significant difference in serious adverse events between groups; in fact a higher proportion of women in the placebo group reported a serious adverse event. Although this study did not have sufficient power to study migraines, we did find a non-significant increase in reported headaches (18% on DIM, 12% on placebo, P=0.12).”

Returning to the original PubMed “sulforaphane migraine” search, Bioavailability of Sulforaphane Following Ingestion of Glucoraphanin-Rich Broccoli Sprout and Seed Extracts with Active Myrosinase: A Pilot Study of the Effects of Proton Pump Inhibitor Administration included one subject who took migraine medication. They weren’t a study outlier, however.

Although indole chemistry indicates a broccoli sprouts – migraine connection, I haven’t found relevant research. Maybe the known properties and actions of broccoli sprout compounds provide enough to affect causes of migraines?

See Part 3 to follow up.