Chronic Inflammation:
The Silent Enemy Burning Within Anyone who has cut, sprained or burned themselves has experienced pain, heat, redness and swelling—the sure signs of acute inflammation, or what the ancient Greeks described as “the internal fire.” In the aftermath of an injury, the body ignites with an inflammatory response to ward off infection and jumpstart tissue repair. This reaction is a lifesaver, as white blood cells rush to the scene of the trauma to fight the deadly bacteria that can quickly spread. However, in some people, the inflammatory response is triggered inappropriately or never fully shuts off, potentially resulting in a state of chronic inflammation. Blood tests have detected low levels of inflammation in people diagnosed with a wide variety of illnesses. For example, the “silent” inflammation of cardiovascular blood vessels is now widely believed to be a key part of atherosclerosis. We now know that chronic inflammation continually drains energy from the body as it persistently tries to put out the internal fire, weakening our immune system, making it vulnerable to attack, and even triggering other conditions.
“Research indicates that the effects of this chronic, lowgrade, invisible inflammation are at the basis of aging and age-related diseases such as cardiovascular disease, diabetes, certain forms of cancer, Parkinson’s, Alzheimer’s, and autoimmune disorders,” says Nicholas V. Perricone, MD. In this way, chronic inflammation can lurk like a silent enemy with a hidden burning ember, who persistently steals life forces from the body, while also igniting a variety of other common ailments, such as asthma, arthritis and multiple sclerosis. Dr. Perricone is among a growing number of researchers who believe that chronic inflammation results from a combination of genetics, diet and lifestyle choices that hamper the body’s ability to squelch the internal fire of the inflammatory response.
Causes of Chronic Inflammation Exactly how biochemical processes cause chronic inflammation is not yet understood, but we do know that women and older people suffer more inflammatory illnesses. “Inflammation is a particular issue for women during and after menopause,” notes Marcelle Pick, a Nurse Practitioner at Women To Women, in Portland, ME. “Somehow—and we’re not sure yet how—this hormonal transition stokes the fire. Inflammation caused by hormonal imbalance could be a key reason why women suffer 75% of all auto-immune disease.” In his book, The Inflammation Syndrome, Jack Challem proposes that diet is primarily to blame for an increase in inflammatory illness. “The typical Western diet now contains at least thirty
“Inflammation caused by hormonal imbalance could be a key reason why women suffer 75% of all autoimmune disease.” Continued on Page 2
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times more of pro-inflammatory nutrients than just a century ago,” he says. “As a result, people have become nutritionally and biochemically primed for powerful, out-of-control inflammatory reactions.”
Mr. Challem suggests that “If you are a weekend-warrior athlete who frequently gets injured, it might be a good idea to take up a more moderate and regular physical activity, such as swimming or walking.”
Once your body is primed for inflammation, any number of triggers can provide the spark. Common triggers include frequent infections, environmental stresses such as tobacco smoke, allergies and food sensitivities. Avoiding situations that trigger inflammation is necessary for giving your immune system time to “cool off” and dial down the inflammatory response.
Additional triggers include hypertension, hyperglycemia, and dietary imbalances, such as an imbalance of essential fatty acids and/or inadequate antioxidant intake. In particular, obesity has been pegged as a central part of the vicious cycle that can perpetuate an inflammatory state. “Excess weight contributes to inflammation because fat cells secrete chemicals, such as C-reactive protein and interleukin-6, that promote inflammation. If you are overweight you have a greater risk of developing adult-onset diabetes, which also has a strong inflammatory component,” points out Mr. Challem. “In a nutshell, each inflammatory disorder has an additive effect, increasing the body’s overall level of inflammation and the risk of very serious diseases.”
Injuries, especially among an aging population, can also lead to chronic inflammation as a result of the natural decline in the cell renewal process. In the July 2012 issue of Ray Peat’s Newsletter, Dr. Peat notes that the structure of aging tissue changes over time, and as cells die off, the void is increasingly filled with collagen, producing scar tissue. Repeated damage to imperfectly repaired tissue can contribute to more generalized inflammation.
In The Anti-Inflammation Zone, Barry Sears, PhD, concurs that
“In a nutshell, each inflammatory disorder has an additive effect, increasing the body’s overall level of inflammation and the risk of very serious diseases.”
underlying hormonal changes occur when inflammation persists in the body, and that these changes then perpetuate the body’s inflammatory response. Dr. Sears says that eating the wrong type of fats and too many carbohydrates causes overproduction of two hormones: pro-inflammatory eicosanoids and insulin. High levels of these hormones then cause the body to produce more cortisol (the “stress hormone”), which furthers inflammation.
Testing Your Inflam mation Levels In an attempt to curtail the compounding effects of the silent enemy, practitioners are increasingly using blood tests to detect inflammation. The most common test used to detect levels of inflammation in the bloodstream measures a substance called C-reactive protein (CRP). The body makes CRP from the pro-inflammatory cytokine interleukin-6 (IL-6), produced chiefly by the liver. An infection or injury can cause CRP levels to spike. This simple and inexpensive blood test has been used for more than 70 years to measure changes in the body’s overall inflammation levels, which helps practitioners track treatment success. Over the past decade, an improved test, the highly sensitive CRP (hs-CRP) test, became available—just as research began to show a link between low levels of chronic inflammation and cardiovascular disease. Mild elevations of CRP can be Continued on Page 3
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Symptoms of Silent Inflammation Blood tests for markers such as C-reactive protein (CRP) are a means to determining your degree of silent inflammation. Should you get tested? If you answer “yes” to more than three of the following questions, you could benefit from a CRP blood test. 99 Do you smoke? 99 Do you have diabetes? 99 Do you have gum disease? 99 Are you overweight? 99 Are you always craving carbohydrates? 99 Are you constantly hungry? 99 Are you tired, especially after exercise? 99 Are your fingernails brittle? 99 Are you constipated? 99 Are you groggy upon waking? 99 Do you have difficulty concentrating? 99 Do you have headaches?
detected when chronic inflammation occurs. In his book, C-Reactive Protein, cardiologist Scott J. Deron, DO, says that he and other doctors now typically include the hs-CRP test as one of several assessments (including measures of cholesterol and triglycerides) used to build a cardiovascular risk profile. “Studies indicate that increased levels of CRP can be present many years before heart disease sets in,” says Dr. Deron.
In his own practice, Dr. Deron says that CRP results have successfully motivated his patients to make lifestyle changes. “Normal, healthy people don’t have high levels of CRP in the blood,” he tells them. “So if your CRP levels begin to increase, something is amiss.” An alternative to the CRP test is the “sedimentation rate” test, which measures how fast red blood cells settle and form a sediment. It is considered less sensitive than the hs-CRP test, but can be useful for some patients. Both tests, however, have a serious drawback: they are non-specific; that is, they simply detect inflammation from all sources, including medications or injuries. For this reason, they cannot always be used to measure “silent inflammation.” For a list of symptoms commonly associated with chronic inflammation, see the box to the left on this page. It is best to discuss these symptoms with your healthcare practitioner to determine if testing is appropriate for you.
Implications for Disease For years, high levels of lowdensity lipoprotein (LDL) cholesterol were thought to be the best marker for future cardiovascular disease. However, a ground-breaking 2002 study, part of the Women’s Health Initiative, showed that people with high CRP levels were 4.5 times more likely to have a heart attack; this is much more predictive than LDL cholesterol or
any other known measurement. In this study, which followed nearly 28,000 women for eight years, patients with the greatest risk of heart attack were those with high levels of both CRP and LDL cholesterol. Women with the highest levels of CRP were almost 16 times more likely to develop diabetes. In addition to predicting the onset of heart disease, elevated CRP levels correspond to a lower survival rate once these problems occur, according to Dr. Deron. High CRP levels exist in people who suffer recurrent heart attacks or angina. In his book, Dr. Deron notes that CRP may not just be a marker for inflammation, it might be a cause. He cites a study that showed that CRP inflames arteries by triggering the formation of clots and plaque. Other studies have found “silent inflammation” to be a significant risk factor for stroke and Alzheimer’s disease. In one study, those with the highest CRP levels were three times more likely to develop Alzhei mer’s disease over a 20-year period. In patients with many forms of cancer, high levels of CRP correspond to a lower survival rate. Gum disease and rheumatoid arthritis are among the inflammatory conditions that raise your risk of heart disease. Experts now believe inflammation may be the underlying reason. “Bear in mind that other wellestablished heart disease risk factors, such as obesity, lack of exercise, smoking, and high blood pressure, are all known Continued on Page 4
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to increase inflammation and CRP levels,” reminds Dr. Deron. As mentioned earlier, obesity is also commonly associated with inflammatory conditions. In his article on how to lose weight by reducing inflammation, Dr. Perricone reports that scientists now regard body fat as an active endocrine organ. He explains that body fat produces hormones, including those that control our immune system and how much fat we store. Too much of certain hormones, such as cortisol or insulin, can put our bodies in a chronic state of insulin resistance—and low-level inflammation.
Hormones and Inflammation Research into the interplay between inflammation and hormones is still in its infancy. In particular, the sex hormones such as estrogens and progesterone appear to have important, but complex effects on the body’s inflammatory response. For example, many observers have wondered if the increase in inflammatory diseases that coincide with menopause, such as arthritis, might be related to shifts in the balance of progesterone and estrogens. The complexity of hormonal effects on inflammation is evident in the scientific literature. For example, a literature review examining the role of
estrogens in inflammation concluded that estrogens can either inflame or dampen inflammation, depending on a variety of factors, including the amount and composition of estrogens, the type of immune stimulus, the types of cells becoming inflamed, the presence of other hormones, and the presence of hormone receptors. A 2007 article published in Endocrine Reviews concurs that estrogens have both anti-inflammatory and pro-inflammatory roles, and that estrogens do not function in the same manner in all inflammatory diseases, due to “the enormous variable responses of immune and repair systems.” A 2003 study published in the Journal of the American College of Cardiology suggested two possible keys to this puzzle regarding estrogens’ effects on inflammation: n the type of estrogen n the route of administration. This study of 26 women, which compared the administration of two different types of estrogen, showed that oral conjugated equine estrogen pills (Premarin®) doubled CRP levels and lowered levels of an antiinflammatory growth factor (insulin-like growth factor-1 or IGF-1). Conversely, estradiol (Climara®) delivered via a transdermal patch did not increase markers for inflammation. “Because CRP is a powerful predictor of an adverse prognosis in otherwise
healthy postmenopausal women,” the authors concluded, “the route of administration may be an important consideration in minimizing the adverse effects of ET [estrogen therapy] on cardiovascular outcomes.” A depletion of cortisol, the “stress” hormone, is also often implicated in furthering a pro-inflammatory state. Like insulin, cortisol is required for energy metabolism. It is also produced in large amounts in response to an acute short-term stress, such as an infection. Thus, cortisol response must be adequate to handle short-term inflammation. After the stress and inflammation passes, the body’s “fight or flight” hormones quickly return to normal. The problem with cortisol occurs when inflammation doesn’t stop. “Constant stress means constant secretion of cortisol,” Dr. Sears says. “As your body adapts to chronic stress, you become hyperinsulinemic, thereby creating more visceral fat. This fuels a new round of cortisol secretion, and the end result is you get fatter and wind up with chronic silent inflammation.” Unfortunately, the body’s hormonal balance favors excess cortisol as we age, and counterbalancing levels of estrogens and testosterone drop. The resulting chronically high cortisol levels take a heavy toll on the body, Continued on Page 5
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from insulin resistance to reduced immune system function. Excess cortisol is also associated with a low level of thyroid hormone, which typically results in difficulty losing weight, chronic infections, fatigue, and a wide variety of other conditions that may further compound the effects of inflammation. Future research may unlock a clinical role for the adrenal hormone pregnenolone, the precursor to all steroid hormones in the body. Prior to the use of prescription cortisone in the 1950s, pregnenolone was used to treat arthritis after it was shown to be effective against joint swelling and inflammation. A study done in 1951 noted that those who responded to pregnenolone found the greatest benefit in recent lesions with the most visible inflammation. In his book, Pregnenolone: Nature’s Feel Good Hormone, Ray Sahelian, MD, wrote, “It remains to be seen how Preg[nenolone] can be effectively used in combination with other prescribed medicines and to alleviate
... diet is key to putting out the burning ember within.
the pain and other symptoms of rheumatoid arthritis.” He also noted that positive findings would permit lowering doses of non-steroidal anti-inflammatory drugs (NSAIDS), which cause serious side effects.
The Fix: Putting Out the Fire For many people, the quick fix for their health concerns is over-the-counter or prescription medications. However, commonly used anti-inflammatory drugs such as NSAIDS and synthetic corticosteroids can have serious side effects. And, while a class of drugs called statins has demonstrated effectiveness in lowering both cholesterol and CRP levels, they also introduce the risk of serious side effects. In search of better ways to “cool off” the body’s proinflammatory responses, many patients and practitioners are now looking beyond the medicine cabinet to the kitchen and the gym. Many practitioners now recommend that patients seeking to lower chronic inflammation start with a healthier lifestyle, specifically quitting smoking, and reforming their diet and workout habits. As a cardiologist, Dr. Deron promotes reducing inflammation as one way to prevent heart disease. His usual advice? Eating right, getting exercise, losing weight and reducing stress.
Others concur that diet is key to putting out the burning ember within. For example, to counter the effects of triggers that are difficult to avoid, such as environmental allergies, Mr. Challem recommends dietary changes and nutritional supplements to help squelch the body’s inflammatory response and normalize the body’s immune response. Dr. Sears provides a diet and exercise plan devised to stop the overproduction of hormones that fuel chronic inflammation. He recommends “anti-inflammatory” foods, while stressing the need for moderation in the intake of protein, carbohydrates and dietary fats. A typical “anti-inflammatory” diet seeks to amplify the body’s own anti-inflammatory substances. One such diet, espoused by Mr. Challem, separates foods into “hot” and “cold” groups. “Hot foods,” he says, set the stage for inflammation. They include: n most vegetable oils and food fried in them n margarine and most salad dressings n baked goods n many packaged foods n fast food meals n sugared beverages. Conversely, “cold” foods help douse inflammation, Mr. Challem says. He recommends consuming more: n olive oil Continued on Page 6
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n The Inflammation Syndrome: The Complete Nutritional Program to Prevent and Reverse Heart Disease, Arthritis, Diabetes, Allergies, and Asthma by Jack Challem; John Wiley & Sons; Hoboken, NJ; 2003.
n fish, particularly cold water species n fresh vegetables n low-sugar fruits n free-range beef and chicken and game n mineral water.
n The Anti-Inflammation Zone by Barry Sears, PhD; Harper Collins Publishers; New York, NY; 2005.
By replacing “hot” foods with “cold” ones, we boost our levels of anti-inflammatory vitamins, minerals, proteins, and omega-3 fatty acids, while reducing our levels of pro-inflammatory fats, says Mr. Challem. Moreover, an anti-inflammatory diet also reduces body fat and helps to curtail excess insulin levels, providing additional health benefits.
n C-Reactive Protein by Scott J. Deron, D.O., FACC; McGraw-Hill; New York, NY; 2004. n “The Complex Role of Estrogens in Inflammation” by Rainer H. Straub, MD; Endocrine Reviews, Volume 28: 521-574, 2007.
References
n “Differential Effects of Oral Versus Transdermal Estrogen Replacement Therapy on C-Reactive Protein in Postmenopausal Women” by Wanpen Vongpatanasin, MD, et. al.; Journal of the American College of Cardiology, Volume 41: 1358-1363, 2003.
n “The Perricone Weight Loss Program” by Nicholas V. Perricone, MD; Life Extension, November 2005. n “Inflammation—the key to chronic disease?” by Marcelle Pick, NP OB/GYN, on womentowomen.com.
n Pregnenolone: Nature’s Feel Good Hormone by Ray Sahelian, MD; Avery Publishing Group, Inc.; Garden City Park, NY; 1997.
n “When Energy Fails: Edema, Hypertension, Heart Failure, Sarcopenia, Cramps, etc.” by Ray Peat, PhD, in Ray Peat’s Newsletter, July 2012.
n “C-Reactive Protein Levels and Outcomes after Statin Therapy” by Paul M. Ridker, MD, et al.; The New England Journal of Medicine, Volume 352:20-28, Jan. 6, 2005.
Connections is a publication of Women’s International Pharmacy, which is dedicated to the education and management of PMS, menopause, infertility, postpartum depression, and other hormone-related conditions and therapies.
This publication is distributed with the understanding that it does not constitute medical advice for individual problems. Although material is intended to be accurate, please seek proper medical advice from a competent healthcare professional. Publisher: Constance Kindschi Hegerfeld, Executive VP, Women’s International Pharmacy Co-Editors: Julie Johnson and Carol Petersen, RPh, CNP; Women’s International Pharmacy Writer: Kathleen McCormick, McCormick Communications Copyright © August 2012, Women’s International Pharmacy. This newsletter may not be reproduced or distributed without the permission of Women’s International Pharmacy. ® For more information, please visit www.womensinternational.com or call (800) 279-5708.
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