Seizures and the Ketogenic Diet: Does the Gut Bacteria Hold the Answer?

I have long been a proponent of the ketogenic diet (KD) for kids with seizures. I have seen miracles with my own eyes:  children with intractable seizures improving immeasurably, even coming off seizure meds.  In fact, one of my old nutrition clients, a little boy down in Australia, made such a remarkable recovery that his case was documented and studied by the hospital where he’d been treated for several years.

The ketogenic diet consists of a very high ratio of fat to carbohydrate and protein.  The human brain can only use two substances to feed its cells:  ketones and glucose.   The lack of glucose in the diet forces the body into a state of ketosis, wherein the liver products ketones to keep the brain fed. Diets like Atkins use ketosis for rapid weight loss:   once in a state of ketosis, the body will rapidly metabolize its fat stores for energy.  To prevent unwanted weight loss in children, extremely high amounts of fat are consumed.

I have read studies over the last years postulating that the diet worked not only because ketones are highly anti-inflammatory for the brain, but also because the diet itself causes an alteration of gut flora, as you might imagine.  You are completely changing what you are feeding your microbiome. One study, published last year, looked at the microbiome in children on the ketogenic diet compared to healthy infants.[i]  The diet dramatically worked, “After being on KD treatment for a week, 64% of epileptic infants showed an obvious improvement, with a 50% decrease in seizure frequency,” and yes, the microbiome was radically different between the two groups.  They conclude that indeed, these alterations could well be a major factor in the diet’s efficacy.

Last week, a remarkable study was published in Cell, further exploring this link.[ii]  The UCLA researchers noted that in less than 4 days, mice on the diet had radical changes to their gut bacteria – and way fewer seizures.  They looked at two other groups of mice as well:  one which had been reared in a germ-free environment and a group that was treated with antibiotics.  “’In both cases, we found the ketogenic diet was no longer effective in protecting against seizures,’ said lead author Christine Olson, a UCLA graduate student in Hsiao’s laboratory. ‘This suggests that the gut microbiota is required for the diet to effectively reduce seizures.’”

The researchers were actually able to zero in on two kinds of bacteria that were elevated by the ketogenic diet and were playing a role in affording the protection from seizures:  Akkermansia muciniphila and Parabacteroides.  They then gave these two species to the germ-free mice and were able to restore the protection from seizures.  What’s even more amazing is that both species needed to be given together for it to work.  Alone, each did nothing.  HOLY COW…how amazing is that?!

But wait, there’s more.  They also found that these bacteria altered levels of GABA in the brain.  GABA is the neurotransmitter that quiets the neurons of the brain, and many drugs given for seizures also boost it in relation to glutamate, which activates neurons.

That is just a remarkable piece of research.  And really exciting.  Imagine a future where seizures can be treated with just a probiotic!

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[i] Xie, G, et. all.  Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy. World Journal of Gastroenterology.  2017. 23(33): 6164-6171.  DOI:10.3748/wjg.v23.i33.6164

[ii] https://www.eurekalert.org/pub_releases/2018-05/uoc–gbp052118.php