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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Nutritional Ketosis, Treating Type 2 Diabetes

Nutritional ketosis is a natural metabolic state in which your body adapts to burning fat rather than carbohydrates. It is clinically proven to directly reduce blood sugar (HbA1c), improve insulin sensitivity (HOMA-IR) and reduce inflammation (as measured by white blood cell count and CRP).

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Dr. Phinney answers viewer’s questions:

Q: I am interested in reversing type 2 diabetes – is a ketogenic diet recommended?? Thx! —Susie T.

Dr. Phinney’s Answer: Insulin resistance is the hallmark of type 2 diabetes and manifests as carbohydrate intolerance. Like other food intolerances, the most logical and effective approach to managing carbohydrate intolerance is to restrict sugars and starches to within the individual’s metabolic tolerance. A well-formulated ketogenic diet can not only prevent and slow down progression of type 2 diabetes, it can actually resolve all the signs and symptoms in many patients, in effect reversing the disease as long as the carbohydrate restriction is maintained.

For complete answers to this and the other questions please copy and paste this link into your address bar

Q: Appreciated your article on the concerns about prolonged fasting. Could you comment on the utility and safety of shorter durations of fasting (i.e. 16 hrs of fasting/8 hrs of eating or 20 hrs of fasting/4 hrs of eating over a period of 1 day)? —Anonymous

Q: Can you achieve this on a vegetarian diet too? A lot of people I know from India, including my wife, are vegetarian and prediabetic or T2D. I am a T1 and now on keto diet, but I am not able to convince the vegetarians to eat meat. —Anonymous

Q: Does the amount of fat I eat in a ketogenic diet interfere with my ability to burn body fat? —Marcos C.

Q: Why are blood ketone values lower in the morning than in the afternoon/evening? —Nikola S.

Q: When I started my cholesterol was fine. Now my glucose has dropped 40%, but my cholesterol is 241. Should I be worried? —Kerry J.

 Q: Since families often (and should!) eat together, is there any concern about children who are eating high fat diets at breakfast and dinner with their ketogenic parents, but higher carb foods at lunch/snacks at school? —Tera N.

 Q: What are your inflammation biomarkers? —Tekla B.

 Q: Can long-term keto diet contribute to hypothyroidism? —Sonia Z.

 Q: Why some people’s LDL goes sky high on keto diet? —Sonia Z.

Dr. Phinney: The changes we see in total and LDL cholesterol levels are much less predictable than the changes in triglycerides and HDL cholesterol. For the full answer click the link below.

Q: There is a lot of concern about protein intake and gluconeogenesis kicking people out of ketosis. As stated in your book, moderate protein is .6-1 gram/pound of lean body mass. As long as you stay within that protein range is GNG something to be concerned about? —James F.

 Q: Does Diazoxide helps in the ketone production? Thanks a lot for sharing your knowledge. Your influence is bigger than you think. —Salomon J.

 Q: Does athlete fat oxidation rate vary continuously with carb intake? Or is keto the only way to get it above 0.5g/min?—Norman T.

 Q: My daughter has high uric acid on KD, we don’t know if she did before KD, have you seen this before?—Justine L.

 Dr. Phinney: Yes, blood levels of uric acid usually double in the first week of a ketogenic diet or with fasting. This is because there is a competition between ketones and uric acid for excretion by the kidneys early in adaptation. As the adaptation process proceeds over a few months, the uric acid level comes down to normal levels even as nutritional ketosis continues, Thus this is a process of clearance (i.e., excretion), not over-production from dietary protein, and this temporary elevation in uric acid is usually harmless unless one is prone to gout. That said, the precursors of uric acid are pretty high in organ meats like liver and kidney, so if these are part of one’s diet, they should be eaten in moderation. You can learn more about keto-adaptation here.

Q: Thoughts on patients suffering from depression and/or hypothyroidism and keto diets? Also, interested in your thoughts on “The Fast Metabolism Diet” by Haylie Pomroy, which encourages a 5x/day eating plan, which includes a couple days of a keto-like diet after some carb and protein-heavy days each week over the course of a month. Thank you for what you do, sir. Appreciate your work. —Tyler S. 

Q: Love your and Dr. Volek’s low carb performance book – amongst the ‘good’ fats you talk about high-oleic safflower being acceptable (better PUFA ratio). Are high-oleic SUNflower oils OK and can you cook with them? —Chris B.

 Q: Could blood ketones, along with blood sugars, be used to fine-tune insulin dosing? Too little insulin with someone with type 1 and we get DKA. With too little insulin ketones disappear. Could we use ketone levels are consistently below 0.3mmol/L as a signal that we have too much basal insulin? —Marty K.

 Q: Does Virta know the benefit of whey protein for diabetes? Not sure in the context specifically of DM, but it is a very high quality protein source – BCAA, immunoglobulins —Salomon J.

 Q: Why NOT eat certain oils, such as safflower and sunflower oil? Do these oils impact ketosis or is it for other reasons? —India K.

Q: Can you please explain hair loss on Keto? —Jessy G.

Q: Thanks for all you do!! There are groups that advocate the potassium to sodium ratio at 4 grams to 1 gram per day. Does that fit into your view of those two. Also, is 400 milligrams of Magnesium appropriate? Thank you! My ketone level ranges from .3 to 1.2. —Mark K.

 Q: Are you looking at Cardiac Calcium Score? —Lincoln C.

 Q: Hi Dr. Phinney. I have chronic pain and take a lot of medications. Also have controlled type 2 diabetes. Do you think taking 4400mg of gabapentin a day could be why I am not losing weight that easily. I am eating under 30 grams of carbs a day and I don’t eat a lot of fat. I eat just twice a day, and only around 950-975 calories. Thank You! —Teresa R.

 Q: While someone pursuing a therapeutic ketogenic diet for the management of cancer, epilepsy, Alzheimer’s or dementia may want to reduce protein to achieve elevated ketone levels, do you think someone trying to manage diabetes or lose weight needs to consciously worry about “too much protein” or can they just follow their appetite when it comes to protein intake? —Marty K.

 Q: If you are trying to reduce saturated fat but maintain ketosis, what fat sources do you recommend? —Gail K.

For answers to the questions above please copy and paste this link into your address bar

For more information please refer to the book that Dr. Phinney and Dr. Volek co-authored the New York Times Best Selling “The New Atkins for a New You” published in March 2010. Available at

Disclaimer: The content of this email or Post is not intended for the treatment or prevention of disease, nor as a substitute for medical treatment, nor as an alternative to medical advice. Use of recommendations is at the choice and risk of the reader.

If you are interested in following my postings, please click the Follow button to receive an email when the next posting is available. Hint: You may have to click the Accept and Close button before follow is available.

If you wish to contact me by Email, please email using this form.

As always, I am interested in your thoughts on these topics.

May you Live Long Healthy.

Yours truly,

Lydia Polstra


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