Ketogenic Diet and Inflammation

According to the Journal of Child Neurology many types of pain and painful or progressive conditions involve chronic inflammation. Several mechanistic threads support the hypothesis that a ketogenic diet will reduce inflammation. 

Compared to glucose metabolism, ketone metabolism produces fewer reactive oxygen species - which are known to contribute to inflammation. A ketolytic metabolism produces fewer free radicals and reactive oxygen species through affecting the mitochondrial co-enzyme Q couple and the cytoplasmic glutathione couple.²⁷ Exogenously applied ketones reduce reactive oxygen species in vitro^28-32 and in vivo.³³ Therefore the ketone-based metabolism of a ketogenic diet should guard against inflammation.

Data suggesting positive effects of a ketogenic diet itself on inflammation or associated inflammatory processes have been accumulating recently. In rodents, ketogenic diets reduce reactive oxygen species in the brain³⁴ and reduce central inflammation and reactive oxygen species in a model of multiple sclerosis.³⁵

Two clinical papers have found that ketogenic diet feeding of 12 weeks to 6 months reduced signs of liver inflammation in obese patients with nonalcoholic fatty liver disease (in addition to improving various other physiological and biochemical variables).^{36, 37} Unfortunately, basic research into non-alcoholic fatty liver disease has been hampered by species differences between mice and humans in their hepatic reaction to ketogenic diets.³⁸

Beyond the effects of ketones and ketone metabolism, the high fat content of ketogenic diets will elevate fatty acid levels in the body, including long-chain polyunsaturated fatty acids that bind to peroxisome proliferator-activated receptors. When activated, these nuclear receptors induce transcriptional changes that culminate in enhanced lipid metabolism.³⁹ Synthetic peroxisome proliferator-activated receptor agonists reduce experimentally-induced inflammation,^40-42 and genetic knockout of a major peroxisome proliferator-activated receptor augments inflammatory reactions.⁴³ This effect appears to involve inhibition of pro-inflammatory pathways involving Nuclear Factor κB, Signal Transduction And Transcription-1, and Nuclear Factor of Activated T-cells.⁴⁴

An additional mechanism with anti-inflammatory potential is adenosine. As noted above evidence is mounting that a ketolytic metabolism elevates levels of the neuromodulator adenosine,^{17, 19} and adenosine has long been known to be anti-inflammatory,^{45, 46} acting via receptors at multiple sites including leukocytes,⁴⁷ endothelia,⁴⁸ and neurons.⁴⁹ Thus, the ketogenic diet might have anti-inflammatory effects through increased adenosine production.

Read the full discussion about the effects a ketogenic diet has on inflammation and pain here:  Ketogenic Diets and Pain

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