"We know that ketone bodies are not only metabolized, they're also signaling molecules. First of all, they're a more efficient fuel than glucose. Per molecule, they produce a lot more ATP [adenosine triphosphate] than a molecule of glucose," she said. "They also induce mitochondrial biogenesis, [and] they're very potent reactive oxygen species inhibitors.
Further, they produce less oxidative stress per molecule burned and reduce brain excitability, she added. "They shift the equilibrium between glutamate and GABA [γ-aminobutyric acid] in the direction of GABA, and they also have an influence on glutamate transport itself."
She went on to note that supplying more KBs increases ketone body transporter mechanisms, they are anti-inflammatory, and they reduce blood glucose levels. "So they have a variety of potential migraine-relevant mechanisms in addition to being a more effective fuel" than glucose.
She and her colleagues have started enrolling patients with migraine in a double-blind, randomized, placebo-controlled trial (NCT03132233) to test the bHB supplement in a crossover design over 3 months in a group of 90 participants.
The impetus for this work was the fact that Gross developed migraines in her mid-teens, and she said she wants something that will work for her and for many other patients with migraine. The side effects of currently approved prophylactic drugs are "intolerable for most patients," she said, and avoiding food and lifestyle triggers of migraines severely limits ones activities and life.