Numerous studies now show the detrimental effects of low-grade systemic inflammation. Inflammation is involved in a variety of conditions from neurological to degenerative conditions, and is considered a risk factor for cardiovascular disease.
Low-grade systemic inflammation can now be measured easily with the inflammatory marker highly sensitive C-reactive protein (hs-CRP). This is the same marker used as a cardiovascular risk factor, and is an inexpensive blood test. A less sensitive test for C-reactive protein is used in screenings for rheumatological conditions.
It is important to be able to produce an effective immune response when needed to eliminate pathogens. Chronic systemic inflammation is tissue-destructive, and cardiovascular tissue is no exception.
Men with the highest level of C-reactive protein (CRP) showed in a study to have three times the incidence of myocardial infarction and two times the incidence of ischemic stroke when compared with men having the lowest level.1
Women are not better off. When 28,000 postmenopausal women were studied, the women with the highest value of CRP had a greater than four-fold risk of experiencing a cardiac problem when compared to those with the lowest level.2 In another study in which the participants also were women, those with the highest level had a seven-fold increase in risk of myocardial infarction or stroke.3
Researchers at the National Center for Chronic Disease Prevention and Health Promotion concluded in an article that large numbers of U.S. women (approximately 26.6 million) have an increased concentration of CRP, indicating high risk for cardiovascular disease.4
Even children are starting to express signs of increased cardiovascular risk. Obese boys, average age 11.2 years, tend to have high CRP levels, elevated blood pressure and dyslipidemia.5
The eyes also are affected negatively by inflammation. CRP levels have been found to be significantly higher among patients with advanced age-related macular degeneration.6
What is triggering low-grade systemic inflammation?2 There can be many reasons for chronic inflammation. Chronic bacterial or viral infections can certainly be a source, as can chronic allergies. Gastrointestinal dysfunction caused by bacterial or parasitic infections, as well as food sensitivities and allergies, lead to increased intestinal permeability, triggering immune responses and inflammation.
While all these conditions can cause inflammation, a major source of low-grade chronic inflammation for a lot of people today is insulin resistance. Insulin resistance is a gradual process in which receptor sites on the cell membranes get less and less sensitive to insulin. The result is a decreased ability of insulin to transfer blood glucose into the cells, where it can be used for energy.
As the pancreas tries to compensate by producing more insulin to get glucose into the cells, the result is elevated blood glucose and blood insulin levels. Glucose will react with proteins and produce glycosylated protein, causing oxidative stress and tissue destruction. Elevated levels of insulin will trigger release of inflammatory cytokines. The result of insulin resistance is increased systemic inflammation, which can be measured with hs-CRP. It also increases the risk for developing type II diabetes.
While genetic predisposition can make someone more susceptible to insulin resistance, a high glycemic index diet and lack of exercise are major reasons for developing insulin resistance.
Researchers at Harvard Medical School stated in an article that glycemic load is significantly and positively associated with highly sensitive C-reactive protein (hs-CRP) in healthy middle-aged women.7 Another study showed an independent relationship of central fat accumulation and insulin resistance with CRP plasma levels.8 Insulin resistance is associated with a low chronic inflammatory state, and CRP concentrations are higher in people with central obesity and insulin resistance.9,10
In another interesting study, researchers concluded that fasting glucose is significantly and positively associated with plasma CRP in middle-aged subjects.11 They found that CRP levels increased continuously across the spectrum of fasting glucose, beginning in the lowest quartile of normal fasting glucose.
How do you recognize these patients? You can check glucose and insulin, but even better is a glucose tolerance test where insulin also is measured, since fasting glucose can sometimes be normal in these patients. Ideally, fasting glucose should be in the 80s per ml/dl. Even without a glucose tolerance test, there are signs and symptoms by which these patients can be recognized. The most common signs and symptoms are as follows:
fasting glucose over 100 ml/dl
elevated triglycerides and/or cholesterol
elevated blood pressure
elevated waist-to-hip ratio (accumulation of fat around the waist)
fatigue, especially after eating
A patient with glucose-insulin abnormalities may not experience all of these signs and symptoms, but they usually experience some of them.
What is the solution? A low glycemic index diet and more physical activity. As insulin resistance improves, systemic inflammation is reduced. This can be verified with a follow-up test for hs-CRP. Usually a very significant reduction is seen in only four weeks after implementing an effective program. Not only a reduction in hs-CRP can be seen, but also a significant reduction of total cholesterol, triglycerides and LDL (low density lipoprotein). An increase in HDL (high density lipoprotein) and a decrease in blood pressure also can be expected.
The dietary recommendations for the meals in an effective program have to include specific components. One of these components is fiber. Food containing a lot of fiber will slow down the absorption of glucose in the meal. Fiber intake is independently associated with serum CRP concentrations.12 A low glycemic index diet dose not have to be either very high in protein or extremely low in carbohydrates. The type of fat included in the diet also is of great importance. Whole grains - for example, oatmeal or other grains, which is often recommended - does not produce effective results in my experience. To go into detail about the different components of an effective diet is beyond the scope of this article.
An effective program to reduce insulin resistance and systemic inflammation is a great tool for improving a variety of conditions, since a lot of people today have less-than-optimal glucose-insulin metabolism. This approach makes it easier to treat many pathologies because it affects the patient on a cellular level, where chronic conditions have originate.
Ridker PM, et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. New England J Med 1997;336(14):973-9.
Ridker PM, et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. New England J Med 2000;342(12):836-42.
Ridker PM, Buring JE, Shih J, et al. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation Aug. 25, 1998;98(8):731-3.
Ford ES, Giles WH, Mokdad AH, et al. Distribution and correlates of C-reactive protein concentrations among adult U.S. women. Clin Chem Jan. 6, 2004.
Hiura M, Kikuchi T, Nagasaki K, Ulchiyama M. Elevation of serum C-reactive protein levels in associated with obesity in boys. Hypertens Res July 2003;26(7):541-6.
Seddon JM, Gensier G, Milton RC, Klein ML, Rifai N. Association between C-reactive protein and age-related macular degeneration. JAMA Feb. 11, 2004;291(6):704-10.
Liu S, Manson JE, Buring JE, et al. Relation between a diet with a high glycemic load and plasma concentrations of a high-sensitivity C-reactive protein in middle-aged women. Am J Clin Nutr March 2002;75(3):492-8.
Pannacciulli N, Canatore FP, Mimenna A, et al. C-reactive protein is independently associated with total body fat, central fat, and insulin resistance in adult women. Int J Obes Relat Metab Disord October 2001;25(10):1416-20.
Romano M, Guagnano MT, Pacini G, et al. Association of inflammation markers with impaired insulin sensitivity and coagulative activation in obese healthy women. J Clin Endocrinol Metab November 2003;88(11):5321-6.
Chambers JC, Eda S, Bassett P, et al. C-reactive protein, insulin resistance, central obesity, and coronary heart disease risk in Indian Asians from the United Kingdom compared with European whites. Circulation July 10, 2001;104(2):145-50.
Aronson D, Bartha P, et al. Association between fasting glucose and C-reactive protein in middle-aged subjects. Diabet Med January 2004;21(1):39-44.
Ajami UA, Ford ES, Mokad AH. Dietary fiber and C-reactive protein findings from national health and nutrition examination survey data. J Nutr May 2004;134(5):1181-5.