Inflammation and the Ketogenic Diet

Inflammation and the Ketogenic Diet

Inflammation is the body’s natural response to protect against disease and environmental toxins, but chronic inflammation can lead to various health problems. The ketogenic diet, often referred to as keto, is a very low-carb, high-fat diet that has been studied for its effects on inflammation.

Inflammation and blood glucose are intricately connected through a variety of mechanisms. High blood glucose levels can lead to inflammation. Conversely, lowering blood glucose levels can help reduce inflammation. One mechanism by which the reduction of inflammation is achieved is the reduced production of free radicals. When blood sugar levels are high, the production of free radicals increases. 

Free radicals are unstable atoms or molecules with unpaired electrons in their outermost shell. They can be a normal by-product of various metabolic processes. Still, they can also be generated through exposure to environmental toxins such as radiation, tobacco smoke, and pollution. The unpaired electron in a free radical makes it want to find another electron to pair with to become stable. It will interact with other molecules to take an electron, setting off a reaction known as oxidative stress. The molecule that has lost the electron becomes another free radical and will take an electron from a different molecule. When free radicals interact with critical cellular components—like DNA, proteins, or cell membranes—they can cause damage that accumulates over time and is believed to contribute to the aging process and the development of various diseases, including cancer, cardiovascular disease, and neurodegenerative disorders.

High glucose levels in the blood can also lead to the formation of Advanced Glycation End Products (AGEs), harmful compounds formed when protein or fat combines with glucose in the bloodstream. AGEs can be absorbed through the diet. Foods high in protein and fat, such as meat, cheese, and egg yolk, are rich in AGEs. Foods high in carbohydrates have the lowest amount of AGEs. AGEs lead to inflammation and cell damage. They can also bind to receptors called RAGE (receptor for AGEs), further perpetuating inflammation and oxidative stress. AGES are implicated in microvascular disease in diabetes mellitus.

High blood sugar levels can activate other inflammatory pathways, including stimulating proinflammatory cytokines, signaling molecules that promote inflammation. Finally, high glucose levels can damage blood vessels, leading to inflammation and dysfunction. Since the ketogenic diet is low in carbohydrates, it can help regulate blood sugar levels, indirectly reducing inflammation.

Obesity is also linked to chronic inflammation, so losing weight through the keto diet can have additional anti-inflammatory effects. Obesity creates a proinflammatory endocrinologic environment that alters cellular signaling between adipocytes, immunologic cells, and epithelial cells. This results in the over-activation of adipose tissue macrophages and the upregulation of compounds associated with carcinogenesis. Obesity is associated with a deficiency in numerous immunologic cells, including dendritic cells, natural killer cells, and T cells. This can be partly attributed to a recent finding of leptin receptor expression on these immune cells and the upregulation of leptin signaling in the obese state. Several clinical trials have demonstrated the feasibility of a high-fat, low-carbohydrate diet as an adjuvant treatment for cancer, and current trials are investigating the impact of this intervention on disease outcomes. Preclinical trials have demonstrated that a ketogenic diet can impede tumor growth in various cancers through anti-angiogenic, anti-inflammatory, and proapoptotic mechanisms.

The ketogenic diet causes the body to produce ketone bodies as an energy source instead of glucose. One of these ketone bodies, beta-hydroxybutyrate (BHB), has been found to have anti-inflammatory effects. BHB can inhibit the NLRP3 inflammasome, a protein complex that activates inflammatory processes.

Keto diets often include foods high in omega-3 fatty acids, such as fatty fish, flaxseeds, and chia seeds, which are known for their anti-inflammatory effects. These effects can be beneficial in any diet, including a ketogenic diet. Omega-3 fatty acids may decrease inflammation in several ways. After consumption, omega-3 fatty acids can be converted into compounds called resolvins and protectins, both of which have powerful anti-inflammatory properties. These compounds help resolve inflammation and promote the healing process. Omega-3 fatty acids can inhibit the production of molecules and substances that promote inflammation, such as cytokines and eicosanoids. Omega-3 fatty acids become a part of cell membranes throughout the body, and they can help improve cell function and reduce inflammation at the cellular level. They can also influence the expression of specific genes involved in inflammatory responses by downregulating the expression of proinflammatory genes.

Omega-3 fatty acids have anti-inflammatory effects but should be balanced with omega-6 fatty acids in the diet. In the modern Western diet, the ratio of omega-6 to omega-3 fatty acids tends to be too high, which may promote inflammation. Consuming more omega-3-rich foods or taking supplements can help improve this ratio.

Current therapeutic uses of the ketogenic diet include the treatment of refractory epilepsy in children and treating specific glycogen storage diseases. Research suggests that ketogenesis benefits neurodegenerative disorders, nonalcoholic fatty liver disease, and complications of diabetes, including retinopathy and progression of microvascular disease.

People with certain health conditions, such as pancreatitis, liver failure, disorders of fat metabolism, certain mitochondrial disorders, gallbladder disease, or those who are pregnant or breastfeeding, should avoid a ketogenic diet.

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