Doctors perform lab testing to provide valuable additional information to a careful history and examination, in order to better assess a patient’s condition. It is of little value to perform a test unless the doctor has a thorough understanding of the meaning of a positive result. Unfortunately, very few doctors bother to test for C- Reactive Protein (C-RP), and fewer still have an in-depth knowledge of the significance of an elevated lab value. If one does have a full comprehension of the root cause interpretation of high C-RP levels (as you will have once you have finished this article), then one would probably agree with me when I say that it is probably the single most valuable test I perform. So let’s learn what C-RP is, and why it is so important.
C-RP is produced by the liver in response to chemicals released by white blood cells of the innate immune system called neutrophils, macrophages and dendritic cells; white blood cells of the adaptive immune system immune T-cells; and fat cells (adipocytes). It is called an acute phase protein, which means that it’s levels increase in response to inflammation. With acute inflammation, such as injury, surgery and especially infection, it’s levels rise rapidly to very high levels, and then decrease back to normal when the infection or injury resolves. It’s job is to bind to a lipid called lysophosphatidyl choline found on the surface of dead or dying cells (and some types of bacteria). In turn, this activates part of the innate immune system called the complement system, whose job is it to remove dying cells and bacteria in a process called phagocytosis. In a feedback loop, the complement system also releases chemicals that stimulate the production of C-RP.
Chemicals called cytokines and interleukins released by the above cells stimulate the production of C-RP. Interleukin-1, (IL-1), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-a) and NF-KappaBeta are all chemicals released during an inflammatory process that stimulate production of C-RP. Healthy levels of C-RP in someone without acute or chronic inflammation is less than 1mg. per liter of serum. Anything above 3mg/L is considered high. With acute infection it is normal to see a very rapid increase to extremely high levels, up to 500mg/L within 3-4 days of onset of an infection. C-RP is short-lived, with a half-life of only 19 hours, so once the stimulus stops, so does production. Levels then fall back to normal rapidly. The only major reason C-RP stays above it’s normal level of 1mg/L is that there is a constant inflammatory process stimulating its production. CRP concentrations between 3 to 20 mg/L are considered as metabolic inflammation (e.g. arteriosclerosis, type II diabetes mellitus, obesity, chronic gastro-intestinal inflammation, and inflammation from the liver/gall bladder to name a few causes).
Absent acute inflammation/infection, C-RP becomes a very useful laboratory test for chronic inflammation, which is a hallmark of virtually all chronic diseases. If C-RP is elevated one may be at increased risk for developing any one or more of the conditions discussed below. Similarly, when C-RP decreases in response to a variety of nutritional therapies, it may indicate, along with other lab tests (also called markers), that your risk is reduced and your chronic condition is improving. Here are a few of the chronic conditions in which C-RP may be elevated:
Studies have shown a relationship between C-RP levels and the risk of developing cardiovascular disease. People with levels below 1.0mg/L have the lowest risk; between 1-3mg/L have and average risk; and those with the highest risk have levels above 3mg/L. Arterial damage results from white blood cell invasion and inflammation within the artery wall. Levels above 2.4 mg/L have been associated with a doubling of risk for coronary event compared to levels below 1 mg/L. A study of over 8,000 older Chinese concluded that elevated C-RP levels are associated with a high risk of developing carotid artery plaque (arteriosclerosis).
Poor blood sugar control is associated with the development of macrovascular complications of diabetes. Studies have indicated that C-RP is an important risk factor for cardiovascular disease. In a study of diabetics, CRP increased with increasing HbA1c levels. These findings suggest an association between glycemic control and systemic inflammation in people with diabetes. Another 5-year study of over 2,000 diabetics showed that the higher the C-RP, the lower the survival rates.
Another large study looked at a number of variables as the cause of elevated C-RP levels. They concluded that obesity was the major determining factor in high C-RP, after correcting for many other potential reasons why C-RP would be high. Another study showed that obese women who work to lose weight, successfully decreased their C-RP levels.
It is extremely common (at least 30-40% of the USA population) for overweight people to have a condition called Non-Alcoholic Fatty Liver Disease. In my opinion, use of the word “Disease” is a misnomer. It would be more appropriate to call it a condition, since it is potentially totally reversible with weight loss. A highly accurate predictor as to whether you have this condition (absent having a liver biopsy performed), is simply to measure your abdomen at the level of the belly button and divide this number by your height. If that number is >.50, then it is highly likely that you have NAFLD. In a study of people with NAFLD it was concluded that C-RP can be used as a non-invasive marker for NAFLD, as it was found to be a strong predictor of NAFLD when elevated. Yet another study correlated NAFLD with an increased risk of cardiovascular disease, especially in people with high C-RP.
C-RP was found to be increased in the bile and serum of patients with gall bladder disease in the presence of bacteria in the gall bladder. High C-RP is also seen in the presence of gallstones.
C-RP is elevated in a group of diseases called Irritable Bowel Disease. These include Celiac and Crohn’s diseases, and Ulcerative Colitis. The most common diagnosis for digestive issues is Irritable Bowel Syndrome. It has been found that C-RP is also elevated in people with this condition. Overgrowth of unfriendly bacteria, called dysbiosis; and Leaky Gut Syndrome, in which the lining of the GI tract is damaged, thereby allowing various partially digested foods and bacterial dead cell wall particles to enter your bloodstream, are also conditions in which C-RP can increase.
The bottom line is this: an elevated C-RP is caused by certain chemicals that are produced by cells of the immune system. These chemicals (cytokines and interleukins) should not be present in the absence of infection. Their presence means that there is a chronic activation of the immune system, which in turn means that there is a chronic inflammatory process present. Chronic inflammation is the root cause of ALL chronic conditions, including all the ones discussed above. A chronically activated and imbalanced immune response is also the underlying cause of autoimmune disorders, which affect over 50 million Americans.
C-RP is an inexpensive lab test that will tell you if you have chronic inflammation, and therefore a higher risk of developing one or more chronic conditions that may shorten your lifespan, or reduce your quality of life. Weight loss; normalization of blood sugar; improvement of digestion, liver and gall bladder function; and intervention with Nutriceuticals known to combat inflammation, can all greatly reduce C-RP levels. Repeat testing will validate the success of treatment.
Isn’t it time you get tested?
About the Author: Dr. Douglas L. Weed
Dr. Weed practices Functional Nutrition, Chiropractic care, and offers weight loss solutions in Napa, CA at Heun Chiropractic, Inc. He has a doctorate in Chiropractic care and he has received certifications in physical rehabilitation and as a Qualified Medical Examiner. With a post-graduate certification in Functional Medicine, focusing on functional endocrinology, digestive disorders and Peripheral Neuropathy, he is committed to lifelong education and helping patience transform their health.