How many mechanisms of ketogenic diet action can you name?
Mechanisms of action
The ketogenic diet involves many mechanisms of action.
- Lowers blood sugar and insulin levels
- Decreases leptin
- Produces ketone bodies, which are an alternate source of energy, instead of glucose
- Changes neurotransmitter systems, including GABA, glutamate, and adenosine, as well as changes in ion channel regulation
- Increases mitochondrial function and production
- Increases circulating PUFA’s – neuroprotective (PUFA’s are Polyunsaturated fatty acids that include Omega-3’s and Omega-6’s. )
- Decreases inflammation
- Up regulation of glutathione peroxidase (an antioxidant)
- Lowers levels of IL-1β and inflammatory cytokines
- Changes the gut microbiome
- Changes DNA methylation and gene expression
- Increases autophagy – removal of damaged cell parts
- Increases nicotinamide adenine dinucleotide (NAD+)
- Activates Sirtuin genes
Other ways the ketogenic diet affects human bodies
- Ketone bodies have anti-seizure effects
- Many foods are eliminated as part of the ketogenic diet (speculative hypothesis)
Some recent studies point to the gut microbiome connection in brain health.
- The role of gut microbes on brain health continues to strengthen. (1)
“In conclusion, our study identified 26 schizophrenia-associated bacterial species representing potential microbial targets for future treatment, as well as gut–brain modules, some of which may give rise to new microbial metabolites involved in the development of schizophrenia.”Feng Zhu Et al.
- The ketogenic diet improves lipid metabolism and blood pressure. “Ketone body receptor GPR43 regulates lipid metabolism under ketogenic conditions” (2)
- The gut microbiome plays a role in many illnesses, including metabolic disorders and mental health. Different foods and diets directly impact the bacteria living in our guts. Which foods are best for us? (3)
“A calorie is NOT a calorie. A sugar is NOT a sugar. And now we know a fiber is NOT a fiber. Different fibers feed different bacteria, likely promoting different health effects.”Robert Lustig, MD
- Exploring the gut microbiome, schizophrenia and bipolar disorder. (4)
Podcasts – hear Dr. Palmer in his own words
- Interviewed by David Gornoski.
- 28:00 The Ketogenic diet is doing at least 40 different things to the brain. Helping cells repair themselves helps the body heal. Alternate fuel for brain cells – switching from glucose to fat.
- 30:00 Is metabolism a simple fix?
- 35:20 Why just any healthy diet won’t do.
- Interviewed by Paul Saladino, MD. Mechanism discussion starts at 35:40. Neurotransmitters are mentioned at 19:00 & 25:00. Recommend listening from beginning, as Dr. Palmer builds a persuasive supportive arguments from the beginning
- Interviewed by Shawn Baker, MD & Zach Bitters. Gut microbiome discussion starts at 1:27:51. This podcast complements the one before and covers different aspects.
- Interviewed by Karl Goldcamp. Part 3: Episode 65. 25:16 Why understanding mechanisms of action is important. Increasing brain neurotransmitters GABA & Adenosine. Mitochondria repair. Activate anti-aging pathways.
- Interviewed by Jimmy Moore. 38:30 – Inflammation
The information above is based on Dr. Palmer’s 2019 presentation “The Ketogenic Diet in Psychiatry.” This link enables you to see him give this as a Grand Rounds, an overview presentation to fellow healthcare professionals. This article has been fact checked by Christie Barnett, APN.
Research on mechanisms of ketogenic diet action
Seminal research studies include:
- Bough, K. J., & Rho, J. M. (2007). Anticonvulsant Mechanisms of the Ketogenic Diet. Epilepsia, 48(1), 43–58. https://doi.org/10.1111/j.1528-1167.2007.00915.x
- Rho, J. M., & Sankar, R. (2008). The ketogenic diet in a pill: Is this possible? Epilepsia, 49 Suppl 8(Suppl 8), 127–133. https://doi.org/10.1111/j.1528-1167.2008.01857.x
- Masino, S. A., & Rho, J. M. (2012). Mechanisms of Ketogenic Diet Action. In J. L. Noebels, M. Avoli, M. A. Rogawski, R. W. Olsen, & A. V. Delgado-Escueta (Eds.), Jasper’s Basic Mechanisms of the Epilepsies (4th ed.). Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK98219/
Recent research footnotes
- Zhu, F., Ju, Y., Wang, W., Wang, Q., Guo, R., Ma, Q., … Ma, X. (2019). Identification of gut microbiome markers for schizophrenia delineates a potential role of Streptococcus. BioRxiv, 774265. https://doi.org/10.1101/774265
- Miyamoto, J., Ohue-Kitano, R., Mukouyama, H., Nishida, A., Watanabe, K., Igarashi, M., … Kimura, I. (2019). Ketone body receptor GPR43 regulates lipid metabolism under ketogenic conditions. Proceedings of the National Academy of Sciences, 201912573. https://doi.org/10.1073/pnas.1912573116
- Patnode, M. L., Beller, Z. W., Han, N. D., Cheng, J., Peters, S. L., Terrapon, N., … Gordon, J. I. (2019). Interspecies Competition Impacts Targeted Manipulation of Human Gut Bacteria by Fiber-Derived Glycans. Cell, 179(1), 59-73.e13. https://doi.org/10.1016/j.cell.2019.08.011
- Clay, H. B., Sillivan, S., & Konradi, C. (2011). Mitochondrial dysfunction and pathology in bipolar disorder and schizophrenia. International Journal of Developmental Neuroscience : The Official Journal of the International Society for Developmental Neuroscience, 29(3), 311–324. https://doi.org/10.1016/j.ijdevneu.2010.08.007
Citation library on Zotero.org
For a more extensive list of studies, visit Cecile’s citation library “Keto for Psych” on Zotero.org.
With permission, I’ve added most of the research cited on ChrisPalmerMD.com. However, Dr. Palmer was not involved in the choice and categorization of research for the library.