Inflammation, Nutritional Ketosis, Type 2 Diabetes and Keto-Immune Modulation

Nutritional ketosis has anti-inflammatory and immune-modulating effects that are as potent as the most powerful drugs. This explains how a well-formulated ketogenic diet reverses type 2 diabetes, pre-diabetes, and metabolic syndrome.

Inflammation enables our bodies to recognize and respond to infection and injury. Having too weak of an inflammatory response leaves us prone to infection or impaired healing. But having too great of a response, or one that remains over-active for too long, puts us at risk for a form of chronic injury that underlies type 2 diabetes, coronary heart disease, many common cancers, and Alzheimer’s disease.

This balance between too little and too much inflammation is regulated by a number of circumstances including our genetic inheritance, toxins in the environment, and by many components of our diet.

Currently, we have a host of different drug classes designed to modulate inflammation, but safely managing their dose and duration of use requires professional vigilance to avoid dangerous side effects.

In the past decade, nutritional ketosis has emerged as a potent modulator of inflammation. And, unlike drugs that typically target just one aspect of the body’s immune response, keto-immuno-modulation (KIM) seems to work evenly to balance the anti-inflammatory effect in a safe, sustainable and surprisingly potent way without the serious side effects that characterize most pharmaceuticals.

Measuring Inflammation Levels

High-normal white blood cell count (WBC) levels as well as another test reflective of inflammation in the body called C-reactive protein (CRP) have been shown to also predict the development of type 2 diabetes, many common forms of cancer, and probably Alzheimer’s.

Complexity of Inflammation at a Glance

When there is too much inflammation a class of disorders called auto-immune disease can occur and the body’s activated defenses attack some of its own organs, causing conditions like rheumatoid arthritis, lupus, psoriasis, and type 1 diabetes. These immune disorders can result in an increased risk of heart disease, as are people with type 2 diabetes.

Drugs that Reduce Inflammation

Older, established drugs, like aspirin, tend to have more general modes of action and a broader spectrum of side effects. Recent pharmaceutical research has moved to target specific enzymes, bioactive molecules, or white blood cell types involved in inflammation to try to reduce side effects, but by focusing on just one single step in the complex cascade of the inflammation/immune system, there is a strong tendency to distort this system rather than reduce the inflammatory effect in a balanced manner.

The risks associated with chronic use of a variety of anti-inflammatory drugs often outweigh the desired benefits.

One example, when aspirin is used routinely in people without known heart disease (primary prevention), fatal hemorrhage is significantly increased.

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Dietary Anti-inflammatory Treatments

A natural form of vitamin E – gamma-tocopherol (rather than alpha-tocopherol) has potent anti-inflammatory and oxidative stress lowering properties when used alone or in combination with the omega-3 fatty acid DHA.

Weight loss itself has been shown to reduce inflammation, and it appears that the greater the weight loss the larger the anti-inflammatory effect. This could be attributable to a reduction in the amount of very inflammatory belly fat, and/or a result of some patients being in nutritional ketosis.

Beta-hydroxybutyrate has potent regulatory effects on inflammation

Among the many ‘nutritional factors’ with potential anti-inflammatory properties, the ketone beta-hydroxybutyrate (BOHB) is emerging as both highly potent and uniquely safe as a long-term treatment for inflammation. When in the physiologically normal range that is seen with nutritional ketosis, BOHB activates a number of different genes that protect our cells from oxidative stress and inflammation.

Reactive oxygen species (ROS), aka ‘free radicals’ appear to be connected to inflammation. NSAIDs can’t block them. BOHB prevents this whole class of pro-inflammatory compounds from being created in the first place.

Please see the original Virta Post for the diagramof the contrasting effects of diets containing carbohydrate-plus-protein totals above 30% (thus suppressing ketogenesis) and a ketogenic diet on down-stream inflammatory pathways regulated by BOHB.

Upon starting a well-formulated ketogenic diet, the fatty acid most commonly attacked by ROS, called arachidonic acid, promptly increases. Much less AA is being destroyed by ROS when the body is in nutritional ketosis, therefore less needs to be made in order to maintain optimum membrane levels of this important essential fatty acid.

The level of AA in muscle membrane is strongly correlated with insulin sensitivity thus offering an explanation for the prompt improvement in insulin sensitivity upon initiation of a ketogenic diet.

Clinical Studies Demonstrating Reduced Inflammation

In a randomized trial comparing two weight loss diets – one ketogenic and the other low fat, high carbohydrate – the ketogenic diet demonstrated much greater anti-inflammatory effects after 12 weeks. Additionally, in our Virta/IUH study of patients with type 2 diabetes, both WBC count and C-reactive protein (CRP) were dramatically reduced in the ketogenic diet group compared to the usual care group at 1 and 2-year follow-up. In particular, the reduction in CRP in the ketogenic diet group at 1 year was comparable in magnitude (35-40%) to what is seen with the most potent statin drug.But unlike the statin, which appears to be primarily focused on CRP and has no effect on WBC count, nutritional ketosis addresses both, providing a more balanced effect on the network of interacting bioactive components influencing inflammation.

Perhaps, nutritional ketosis should be considered the new metabolic normal for people with diseases associated with or caused by chronic inflammation.

This Post has been condensed from Inflammation, Nutritional Ketosis, Type 2 Diabetes and Keto-Immune Modulation by Stephen Phinney, MD, PhD, Bailey, Ph.D., Jeff Volek, PhD, RD January 3, 2019 scientific information and Citations of the supporting studies are included in the Virta post.

Not sure what the Ketogenic diet is? Please read, What is the Ketogenic Diet? , in my Blog

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