Anti-inflammatory effect of a ketogenic diet

If the immune response cannot be stopped at the right moment, the ongoing activity of the immune cells may result in damage to the body’s own tissue. The “weapons” immune cells use against end-ringers include reactive oxygen species (ROS), which are used almost like “bullets.” These ROS can just as easily damage our own cells.

If the complex mechanism for normal containment of the immune response fails, chronic disease can result. These include autoimmune diseases such as multiple sclerosis, rheumatoid arthritis or type 1 diabetes, but also chronic inflammatory bowel diseases such as Crohn’s disease or ulcerative colitis.

One often reads that sufferers of certain inflammatory diseases turn to a LCHF or ketogenic diet to achieve an anti-inflammatory effect.

In order to assess whether such a diet can have an effect on inflammation, the underlying mechanisms must be understood. These go down to the transcriptional level – the level of gene regulation. Transcription factors regulate which gene is read and which is not.

The transcription factor NF-κB (pronounced “NF-kappaB”) plays a central role in the inflammatory process. It regulates some genes responsible for the formation of enzymes and messenger substances of the immune response. Thus, NF-κB activity enhances the formation of interleukins (e.g., IL-6). These are messenger substances that stimulate immune cells.

By activating the formation of the enzyme cyclooxygenase, NF-κB promotes the formation of prostaglandin-E2, a messenger substance that causes, among other things, the swelling of tissues, increased pain sensation or fever.

Because of its proinflammatory effect, research is being conducted to determine how inhibition of the transcription factor can lead to a decrease in inflammation. Drugs are being developed to reduce NF-κB activation. These include so-called TNF inhibitors, which inhibit the so-called tumor necrosis factor (TNF) a few steps further up the signaling pathway. TNF activates NF-κB. If TNF is inhibited, NF-κB activity is also reduced. For example, the active medical ingredient adalimumab – a TNF inhibitor used for autoimmune diseases such as Crohn’s disease – exerts its effect.

As is already clear, the regulation of these signaling pathways is highly complex and occurs in several steps. A wide variety of receptors and messenger substances are involved, and at each individual point in the signaling pathway a component can be inhibited or activated.

Exciting in the context of ketogenic diets is the finding that calorie reduction can block the formation (expression) of NF-κB and thus reduce inflammatory^responses1,2. The ketogenic diet showed comparable effects with calorie reduction in various^studies3,4. At the biochemical level, both nutritional therapy approaches have similar mechanisms of action.

A 2017 University of California study examined the mechanisms of action by which calorie reduction and a ketogenic diet influence an immune response
⁵
. The study revealed that the energy metabolism of the cell plays a central role. Both ketogenic diets and caloric restriction are characterized by lower glucose intake and glucose metabolism. The absence of glucose altered energy metabolism in the cells of the rats studied such that the signaling pathway of NF-κB was inhibited, which suppressed the pro-inflammatory effects of NF-κB.

Conversely, when glucose availability is high, the pro-inflammatory pathway is activated. In short, glucose promotes inflammation, and the absence of glucose inhibits inflammatory processes.

Other studies, especially those investigating the influence of ketogenic diets on neurodegenerative diseases (including Alzheimer’s disease, multiple sclerosis), show other mechanisms of action of a ketogenic diet that may also be responsible for the anti-inflammatory effect.

For example, compared to glucose metabolism, ketone body metabolism produces fewer free radicals and reactive oxygen species (ROS)
⁶
.

The high fat intake on a ketogenic diet, when properly composed, also results in an increased amount of anti-inflammatory polyunsaturated fatty acids (omega-3). These can reduce inflammatory responses via binding to specific receptors (PPARs)
⁷
. This effect also appears to occur via an effect on NF-κB.

The complete mechanisms of action of the interaction of ketogenic diet and inflammation have not yet been elucidated, especially in human studies. However, the current state of studies, as well as reports from people affected by chronic inflammatory diseases, show an interesting potential. Since a ketogenic diet, properly composed, has other positive effects and is associated with low risks, this type of diet is a promising way for sufferers to alleviate symptoms.

In the linked article, I described the ketogenic diet, its composition, and how to get started. In addition, you can find more background articles on ketogenic nutrition on our blog. In the “Recipes” section you will find ketogenic recipes. Those who want more comprehensive guidance to get started can choose my book “Low Carb typgerecht” or have an individual diet plan created.