How many mechanisms of ketogenic diet action can you name?

Ketogenic diet mechanisms of action

Mechanisms of action

The ketogenic diet involves many mechanisms of action.

  1. Lowers blood sugar and insulin levels
  2. Decreases leptin
  3. Produces ketone bodies, which are an alternate source of energy, instead of glucose
  4. Changes neurotransmitter systems, including GABA, glutamate, and adenosine, as well as changes in ion channel regulation
  5. Increases mitochondrial function and production
  6. Increases circulating PUFA’s – neuroprotective (PUFA’s are Polyunsaturated fatty acids that include Omega-3’s and Omega-6’s. )
  7. Decreases inflammation
    • Up regulation of glutathione peroxidase (an antioxidant)
    • Lowers levels of IL-1β and inflammatory cytokines
  8. Changes the gut microbiome
  9. Changes DNA methylation and gene expression
  10. Increases autophagy – removal of damaged cell parts
  11. Increases nicotinamide adenine dinucleotide (NAD+)
  12. 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)

Emerging research

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

Sources:

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:

Questions? Join our own Chris Palmer, MD or Amy Berger of Tuit Nutrition to discuss mechanisms on twitter

Recent research footnotes

  1. 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
  2. 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
  3. 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
  4. 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.

We’d appreciate any help with tagging and adding research!  We’ve curated research for each disorder and the ketogenic diet and summarize research highlights in our site bibliography

Cecile Seth

Cecile Seth, MBA. Journalist. Co-Founder. Harvard Business School. Wellesley College. Bain & Company. Ms. Seth's award-winning blog, STEMshoots, helps her suburb with community planning and strengthening its schools.

1 Response

  1. Ingmunn B. Eiddkrem says:

    As always I yhink the research of Chris Palmer is interesting, not at least because I myself have experienced schizofrenia but now I am symptom free and don’t take any drugs. I have a question to Chris Palmer about his use of the concept of mechanisms. What do you mean by mechanisms in this connection? Which of the mechanisms you are mentioning can be defined as causal nechanisms and why. The concept of mchanism is often used in different sciences, also social sciences but this concept is very rarely clearly defined. The science philosopher Roy Bhaskar used the concept of mechanism exclusively in this sense a generative mechanism, i.e. a causal mechanism.
    At the same time, it is assumed to have a depth dimension that is not as observable.

    On a more basic level, therefore, Roy Bhaskar and the critical realists start out with the assumption that reality is structured in a certain way, and that it is primarily the structures of reality rather than the structures in our own minds (Kant) that makse knowledge of reality possible.

    This is expressed in three different ontological domains. These are constituted by the real domain, which consists of the objects of reality, characterized by specific internal structures and properties with certain causal (generative) potentials and / or propensities which, when activated, act as generative or causal mechanisms. Under given circumstances, the causal mechanisms may propel the next two levels of reality in the form of events at the ontological domain of the actual, and the subjects’ experiences and / or observation of these events at the level of the empirical domain (Bhaskar, 1998:). The causal mechanisms at the level of the real domain can be triggered and / or blocked, depending on the degree to which other counteracting or supportive mechanisms are simultaneously effective in a current context.
    The objects of reality and their causal mechanisms are also part of a differentiated, level-divided ontology. Reality is assumed to be hierarchically divided into different ontological levels (emergence) where the higher levels encompass the social reality with a focus on human-society interaction. Social reality is assumed to be at the top of the hierarchy, and this level therefore assumes the psychological, biological, chemical level, which in turn presupposes the physical level, the most basic level, at the bottom of the hierarchy. The consequence of this ontological hierarchy is, in short, that phenomena that emerge from the mechanisms of the higher levels can also be assumed to be influenced by mechanisms derived from the lower levels.

    This understanding that reality is hierarchically divided into different ontological levels also applies to the understanding of man. This means that man can be understood ontologically at the lowest level – the physical level, the biological-biochemical level, as a psychological-psychosocial being and a socio-economic being. With such an ontological approach, one also has the opportunity to implement measures for schizophrenics and others with mental disorders.

    This short introduction to Roy Bhakar’s critical realism may seem very abstract and even difficult to understand, but the most important implication will be that the attention in the research will be primarily aimed at discovering the causes of mental disorders and not just symptoms at the level of the actual and the empirical. This is e.g. the intention of functional medicine, but my question is whether those who participate in such research have been able to develop an ontological understanding that supports and underpins the intention of this research..

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