How Does a Ketogenic Diet Affect YOU? Part 3: C-Reactive Protein: A Marker of Inflammation

by Katie Mark

The latest craze surrounding the ketogenic diet has us further investigating whether or not a high-fat/low-carbohydrate lifestyle might be an appropriate dietary approach for some people. In this 3-part series (click here for part 1 and part 2), we’re evaluating how the ketogenic diet affects biomarkers.

The ketogenic diet is a very low-carbohydrate (<10% of total calories), moderate protein and high-fat (>70% of total calories) diet. After at least two weeks of keto-adaptation, the body’s energy source switches from glucose to fat.

In part one of “How Does a Ketogenic Diet Affect YOU?” we found studies suggesting that nutritional ketosis lowers fasting glucose and insulin levels and possibly increases insulin sensitivity. In part two, we investigated the impact of ketosis on cortisol. We found that a high-fat, carbohydrate-restricted diet may increase certain forms of cortisol, but blood cortisol levels are only half the story. Further research is needed to clarify the relationship between ketosis and an increase in certain forms of cortisol: the active form (cortisol), the inactive form (cortisone) and metabolites of cortisol from enzymatic breakdown.

Now let’s evaluate how the ketogenic diet affects C-reactive protein (CRP).

Increased CRP: Is there a need to worry?

C-Reactive Protein

C-Reactive Protein Model

CRP is considered a marker of inflammation. The liver makes CRP when inflammation in the body is present. High levels of CRP are influenced by genetics, high stress, exposure to environmental toxins and a sedentary lifestyle. Diet can also impact CRP levels, especially diets high in refined and processed foods.

There are two blood tests to measure CRP. The non-specific test indicates acute CRP levels that result from general inflammation in the body. The more sensitive measure is the highly sensitive CRP (hs-CRP) test, which accurately measures basal levels of CRP by measuring inflammation in blood vessels. The hs-CRP test is the accepted measure to determine the risk for cardiovascular disease (CVD).

Higher CRP levels signify a higher risk for developing CVD and abdominal obesity. Weight loss is known to decrease markers of inflammation such as CRP.

It is believed that a high saturated fat and very low carbohydrate diet (VLCARB) increases the risk for CVD. A study published in Nutrition Metabolism (London) compared a VLCARB diet to two low saturated fat, high carbohydrate diets to determine their effect on body composition and CVD risk. The isocaloric (similar calorie composition) diets were: very low fat (CHO:fat:protein; %SF 70:10:20), high unsaturated fat (50:30:20; 6%) and VLCARB (4:61:35, 20%). The study concluded that weight loss resulted in a reduction of CRP regardless of the dietary macronutrient composition. Yet, it is uncertain whether or not the macronutrient composition of a diet influences inflammation.

A study published in The Journal of American College of Nutrition found an increase in CRP in overweight women who followed a short-term low carbohydrate, high-fat weight loss diet. The study reported that an increase in CRP might have resulted from the oxidative stress caused by this type of diet.

Another study published in Obesity (Silver Spring) looked into the inflammatory response caused by a high-fat, low-carbohydrate weight loss diet (HF) by randomly assigning 19 overweight men and women to either an antioxidant (AS) or placebo (P) supplement. The objective was to see if the antioxidants vitamins C and E could decrease the inflammation reported in a HF diet.

CRP decreased 32% in the AS group and increased 50% for the P group; however, this was statistically insignificant. The HF diet did not decrease CRP within the short-term 7-day study even though other markers of inflammation decreased.

The study could not confirm if oxidative stress was causing the inflammation. It was concluded that further research is needed to determine the different CRP responses over the long term, especially while using antioxidant supplements. This is important considering most fruits and vegetables, which are low in fat, contain antioxidants.

The Verdict

A ketogenic diet may increase CRP levels, but weight loss reduces CRP levels. The reason for the increase in CRP is unclear. One plausible explanation is that low intakes of magnesium, vitamin C and other nutrients while on a ketogenic diet may lead to this effect. When magnesium is low, CRP increases. It has been reported that increased vitamin C intake may reduce high CRP levels.

An imbalance between anti-inflammatory fats (omega-3 fatty acids) and pro-inflammatory fats (omega-6 fatty acids) is another possible explanation. Polyunsaturated vegetable oils primarily contain the pro-inflammatory omega-6 fatty acids. Eating less grain-fed meats and chicken and more grass-fed meats and free-range chicken is also important to consider. Grain-fed animals have higher omega-6s whereas grass-fed animals have higher omega-3s. Omega-3s are anti-inflammatory and important for normal body functions, including regulating blood clotting and building cell membranes in the brain. Omega-3s are also suggested to protect against heart disease.

An elevated CRP level is never a good thing. If you are opting for a ketogenic diet, increasing magnesium and vitamin C intake as well as choosing grass-fed products may reduce CRP levels.

Katie Mark is a first year Nutrition Communication/Master of Public Health student who enjoys road cycling and traveling.

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