Various conclusions or opinions are circulating about the ketogenic diet. Often contradictory, it is difficult to know what to think. This article will take stock of one specific aspect: the impact of this diet on inflammation. Let’s compare studies from major scientific journals, but with different opinions.

One meal is one too many?

According to some studies, the ketogenic diet increases inflammation. In 2019, González and colleagues published a study showing a significant increase in inflammation in participants who ate a single high-fat meal. You read correctly! After only one meal. It should be noted that several other similar studies had demonstrated the same conclusion, including that of Lemay and collaborators.

The question to ask here is: can we say that after a single high-fat meal this type of diet is harmful to health? Well, no! It should be understood that the ketogenic diet is not just about eating one meal that is high in fat and that this lifestyle is not all about eating a zero-fat diet. As stated in one of my previous articles, the basic principle is actually to induce a change in metabolism by favoring lipids (the sources of fat) as a fuel source at the expense of carbohydrates. You don’t see the results after just one meal, but rather once the body has adapted to this diet. In the end, the results reported after a single meal are not sufficient to reach conclusions that reflect all aspects of this type of diet.

What about rodent studies?

Rodent testing is quite common, but is it relevant in this case? I do not believe so. Here are some of the differences between humans and rodents:

  • The metabolism of humans and rodents are completely different.
  • Rodent food is not very specific. In general, the outlines of the formulas are vague (e.g.: high fat food made from palm oil). Since this is not precise, it is difficult to know exactly what we are comparing. Moreover, this food is not equivalent to what humans consume.
  • With the ketogenic diet, rats and mice can gain weight. This can even cause a fatty liver (steatosis) in mice which does not happen in humans just because of point #1 on this list.

Long-term clinical studies

It is with longer clinical studies that we observe an anti-inflammatory effect associated with the ketogenic diet. We’re talking about studies that last at least a few weeks.

After a period of 6 months, a clinical study demonstrated decreased inflammation as well as weight loss in participants who were all initially obese. A second clinical study focused on C-reactive protein (CRP; a marker of inflammation). During the first 3 weeks, participants adopted the ketogenic diet. The following 3 weeks, they resumed a so-called “standard” diet and then restarted the ketogenic diet during the last 3 weeks of the study. From the first 3 weeks, the researchers noted a significant reduction in CRP as when resuming this diet during the last 3 weeks.

Ketone Studies

Based on animal studies, ketones have been observed to act directly on the inflammation pathways. The mechanism of action of ketones therefore makes it possible to slow down inflammation by NLRP3 inflammasomes, to reduce certain interleukins (groups of cytokines; IL1 beta) and to decrease oxidative stress by activating the Nrf2 metabolic pathway as well as inhibiting inflammatory pathways (NF-κB).

Let’s sum it all up!

The ketogenic diet is a complex process. It is therefore important to make sure of the following points before making any assertions:

  • Know what we are talking about,
  • Check that the subjects used during the study have a metabolism similar to that of humans,
  • Cite studies of sufficient duration, and
  • Seek to have an overview.

Also, if the mechanisms of action have been demonstrated, this is a plus!

To get a result that reflects reality, it is not enough to rely on a single detail. For example, based on studies that meet all of the criteria listed above, it can be concluded that the ketogenic diet has an anti-inflammatory impact in humans.

If you want to see more detailed results from my own personal experience, I invite you to read my following 3 articles: Three Days With the Ketogenic Diet…, Ketogenic Diet: Changes in Just 3 months!, and Ketogenic Diet: Reaching the Suggested 6 Months!

 

 

References:

  • Bian H, Hakkarainen A, Lundbom N, Yki-Järvinen H. Effects of dietary interventions on liver volume in humans. Obesity (Silver Spring). 2014;22(4):989‐ doi:10.1002/oby.20623. https://onlinelibrary.wiley.com/doi/full/10.1002/oby.20623
  • de Luis D, Domingo JC, Izaola O, Casanueva FF, Bellido D, Sajoux I. Effect of DHA supplementation in a very low-calorie ketogenic diet in the treatment of obesity: a randomized clinical trial. Endocrine. 2016;54(1):111‐ doi:10.1007/s12020-016-0964-z https://pubmed.ncbi.nlm.nih.gov/27117144/
  • Dupuis N, Curatolo N, Benoist JF, Auvin S. Ketogenic diet exhibits anti-inflammatory properties. Epilepsia. 2015;56(7):e95‐e98. doi:10.1111/epi.13038 https://onlinelibrary.wiley.com/doi/full/10.1111/epi.13038
  • Ellenbroek JH, van Dijck L, Töns HA, et al. Long-term ketogenic diet causes glucose intolerance and reduced β- and α-cell mass but no weight loss in mice. Am J Physiol Endocrinol Metab. 2014;306(5):E552‐ doi:10.1152/ajpendo.00453.2013. https://journals.physiology.org/doi/full/10.1152/ajpendo.00453.2013
  • González F, Considine RV, Abdelhadi OA, Acton AJ. Saturated Fat Ingestion Promotes Lipopolysaccharide-Mediated Inflammation and Insulin Resistance in Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2019;104(3):934‐ doi:10.1210/jc.2018-01143 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364509/
  • Jornayvaz FR, Jurczak MJ, Lee HY, et al. A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite increasing energy expenditure and preventing weight gain. Am J Physiol Endocrinol Metab. 2010;299(5):E808‐ doi:10.1152/ajpendo.00361.2010. https://journals.physiology.org/doi/full/10.1152/ajpendo.00361.2010
  • Kübeck R, Bonet-Ripoll C, Hoffmann C, et al. Dietary fat and gut microbiota interactions determine diet-induced obesity in mice. Mol Metab. 2016;5(12):1162‐ Published 2016 Oct 13. doi:10.1016/j.molmet.2016.10.001 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123202/
  • Lemay DG, Huang S, Huang L, et al. Temporal changes in postprandial blood transcriptomes reveal subject-specific pattern of expression of innate immunity genes after a high-fat meal. J Nutr Biochem. 2019;72:108209. doi:10.1016/j.jnutbio.2019.06.007. https://pubmed.ncbi.nlm.nih.gov/31473510/
  • Lu Y, Yang YY, Zhou MW, et al. Ketogenic diet attenuates oxidative stress and inflammation after spinal cord injury by activating Nrf2 and suppressing the NF-κB signaling pathways. Neurosci Lett. 2018;683:13‐18. doi:10.1016/j.neulet.2018.06.016 https://pubmed.ncbi.nlm.nih.gov/29894768/
  • Merra G, Gratteri S, De Lorenzo A, et al. Effects of very-low-calorie diet on body composition, metabolic state, and genes expression: a randomized double-blind placebo-controlled trial. Eur Rev Med Pharmacol Sci. 2017;21(2):329‐345. https://www.europeanreview.org/article/12103
  • Youm YH, Nguyen KY, Grant RW, et al. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med. 2015;21(3):263‐269. doi:10.1038/nm.3804 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352123/