Of the ten leading causes of mortality in the United States, chronic, low-level inflammation contributes to the pathogenesis of at least seven. These include heart disease, cancer, chronic lower respiratory disease, stroke, Alzheimer’s disease, diabetes, and nephritis (Centers for Disease Control and Prevention 2011; Bastard et al. 2006; Cao 2011, Jha et al. 2009; Ferrucci et al. 2010; Glorieux et al. 2009; Kundu et al. 2008; Murphy 2012; Singh et al. 2011).

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Inflammation has classically been viewed as an acute (short term) response to tissue injury that produces characteristic symptoms and usually resolves spontaneously. More contemporary revelations show chronic inflammation to be a major factor in the development of degenerative disease and loss of youthful functions.

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Chronic inflammation can be triggered by cellular stress and dysfunction, such as that caused by excessive calorie consumption, elevated blood sugar levels, and oxidative stress. It is now clear that the destructive capacity of chronic inflammation is unprecedented among physiologic processes (Karin et al. 2006).

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The danger of chronic, low-level inflammation is that its silent nature belies its destructive power.

In fact, stress-induced inflammation, once triggered, can persist undetected for years, or even decades, propagating cell death throughout the body. Due to the fact that it contributes so greatly to deterioration associated with the aging process, this silent state of chronic inflammation has been coined “inflammaging”.

Chronic low-level inflammation may be threatening your health at this very moment, without you realizing it. In this protocol you will learn about low-cost blood tests that can assess the inflammatory state within your body. You’ll also discover novel approaches that combat chronic inflammation to help avoid age-related health decline.

The Inflammatory Process

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The Acute Inflammatory Response

Inflammation, the adaptive immune response to tissue injury or infection, plays a central role in metabolism in a variety of organisms (Medzhitov 2008).

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At its most basic level, an acute inflammatory response is triggered by 1) tissue injury (trauma, exposure to heat or chemicals); or 2) infection by viruses, bacteria, parasites, or fungi. The classic manifestation of acute inflammation is characterized by four cardinal signs: Redness and heat result from the increased blood flow to the site of injury. Swelling results from the accumulation of fluid at the injury site, a consequence of the increased blood flow. Finally, swelling can compress nerve endings near the injury, causing the characteristic pain associated with inflammation. Pain is also important to make the organism aware of the tissue damage. Additionally, inflammation in a joint usually results in a fifth sign (impairment of function), which has the effect of limiting movement and forcing rest of the injured joint to aid in healing.

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A well-controlled acute inflammatory response has several protective roles:

• It prevents the spread of infectious agents and damage to nearby tissues;

• helps to remove damaged tissue and pathogens, and;

• assists the body’s repair processes

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However, a third type of stimuli, cellular stress and malfunction, triggers chronic inflammation, which, rather than benefiting health, contributes to disease and age-related deterioration via numerous mechanisms.

Cellular Stress & Chronic, Low-Level Inflammation

Mitochondria – cellular organelles responsible for generating biochemical energy in the form of adenosine triphosphate (ATP) – are a fundamentally necessary component of life in higher organisms. In fact, in the case of sophisticated multicellular life forms, organismal viability depends upon optimal mitochondrial function. Paradoxically, mitochondrial processes can also bring about a tissue-destroying inflammatory mediator known as the inflammasome; this phenomenon is provoked by damaged and dysfunctional mitochondria(Green 2011).

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Mitochondrial dysfunction arises consequent of exposure to exogenous (e.g. environmental toxins, tobacco smoke) and endogenous (e.g. reactive oxygen species) stressors, and as a result of the aging process itself. For example, a byproduct of mitochondrial energy generation is the creation of free radical molecules. Free radicals can damage cellular structures and initiate a cascade of proinflammatory genetic signals that ultimately results in cell death (apoptosis), or worse, uncontrolled cell growth - the hallmark of cancer.

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Aging is associated with declining mitochondrial efficiency and increased production of free radical molecules. Recent research identifies this age-associated aberration of mitochondrial function as a principle actuator of chronic inflammation (Dinarello 2011). Specifically, mitochondrial dysfunction brings about inflammation as follows:

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1. Accumulation of free radicals induces mitochondrial membrane permeability;

2. Molecular components normally contained within the mitochondria leak into the cytoplasm (intracellular fluid in which cellular organelles are suspended);

3. Cytoplasmic pattern recognition receptors (PRR’s), which detect and initiate an immune response against intracellular pathogens, recognize the leaked mitochondrial molecules as potential threats;

4. Upon detection of the potential threat, PRR’s form a complex called the inflammasome that activates the inflammatory cytokine interleukin-1β, which then recruits components of the immune system to destroy the “infected” cell (Tschopp 2011).

 

These four steps represent a simplified scheme of mitochondrial dysfunction leading to cellular destruction; however, intracellular free radicals are not the only inducers of inflammatory cell death.

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Circulating sugars, primarily glucose and fructose, are culprits as well. When these “blood sugars” come in contact with proteins and lipids a damaging reaction occurs forming compounds called advanced glycation end products (AGEs). AGEs bind to the cell-surface receptor called receptor for advanced glycation end products, or RAGE. Upon activation, RAGE triggers the movement of the inflammatory mediator nuclear factor kappa-B (NF-kB) to the nucleus, where it activates numerous inflammatory genes (Mosquera 2010). Advanced glycation end products are primarily formed in vivo, and glycation is exacerbated by elevated blood sugar levels. However, dietary AGEs also contribute to inflammation; they are abundant in foods cooked at high temperatures, especially red meat (Witko-Sarsat et al. 1998; Vlassara et al. 2002).

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Additional biochemical inducers of a chronic inflammatory response include:

• Uric acid (urate) crystals, which can be deposited in joints during gouty arthritis; elevated levels are a risk factor for kidney disease, hypertension, and metabolic syndrome (Martinon et al. 2006, Alvarez-Lario et al. 2011);

• Oxidized lipoproteins (such as LDL), a significant contributor to atherosclerotic plaques (Nguyen Khoa et al. 1999); and

• Homocysteine, a non-protein-forming amino acid that is a marker and risk factor for cardiovascular disease, and may increase bone fracture risk (Au-Yeung et al. 2006).

 

Together, these proinflammatory instigators promote a perpetual low-level chronic inflammatory state called para-inflammation (Medzhitov 2008).

Although it progresses silently, para-inflammation presents a major threat to the health and longevity of all aging humans. Chronic, low-level inflammation is associated with common diseases including cancer, type II diabetes, osteoporosis, cardiovascular diseases, and others. Thus, by targeting the myriad physiological variables that can inaugurate an inflammatory response, one can effectively temper chronic inflammation and reduce their risk for inflammatory diseases.

Markers and Mediators of Inflammation

Following is a list of some of the most prominent markers of inflammation used in research and diagnosis. Some can be detected by blood tests (see “Diagnosis and Conventional Treatment of Chronic Inflammation”, below):

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Tumor necrosis factor alpha (TNF-α) is an intercellular signaling protein called a cytokine, which can be released by multiple types of immune cells in response to cellular damage, stress, or infection. Originally identified as an anti-tumor compound produced by macrophages (immune cells) (Green et al. 1976), TNF-α is required for proper immune surveillance and function. Acting alone or with other inflammatory mediators, TNF-α slows the growth of many pathogens. It activates the bactericidal effects of neutrophils, and is required for the replication of several other immune cell types (Sethi et al. 2008). Excessive TNF-α, however, can lead to a chronic inflammatory state, can increase thrombosis (blood clotting) and decrease cardiac contractility, and may be implicated in tumor initiation and promotion (Kundu et al. 2008).

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Nuclear factor kappa-B (NF-kB) is important in the initiation of the inflammatory response. When cells are exposed to damage signals (such as TNF-α or oxidative stress), they activate NF-kB, which turns on the expression of over 400 genes involved in the inflammatory response (Sethi et al. 2008). These include other inflammatory cytokines, and pro-inflammatory enzymes including cyclooxygenase-2 (COX-2) and lipoxygenase. COX-2 is the enzyme responsible for synthesizing pro-inflammatory prostaglandins, and is the target of non-steroidal anti-inflammatory drugs (ibuprofen, aspirin) and COX-2 inhibitors (Celebrex®).

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Interleukins are cytokines that have many functions in the promotion and resolution of inflammation. Pro-inflammatory interleukins that have been the subject of most research include IL-1β, IL-6, and IL-8. IL-1β helps immune cells to move out of blood vessels and into damaged or dysfunctional tissues. IL-6 has both pro-inflammatory and anti-inflammatory roles, and coordinates the production of compounds required during the progression and resolution of acute inflammation. IL-8 is expressed by both immune and non-immune cells, and helps to attract neutrophils (immune cells that can destroy pathogens) to sites of injury.

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C-reactive protein (CRP) is an acute-phase protein, one of several proteins rapidly produced by the liver during an inflammatory response. Its primary goal in acute inflammation is to coat damaged cells to make them easier to recognize by other immune cells (Meyer 2010). CRP elevation above basal levels is not diagnostic on its own, as it can raise in several cancers, rheumatologic, gastrointestinal, and cardiovascular conditions, and infections (Windgassen et al. 2011). Elevation of CRP (as determined by a high-sensitivity CRP assay or hs-CRP) has a strong association with elevated risk of cardiovascular disease and stroke (Emerging Risk Factors Collaboration et al. 2010).

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Eicosanoids. The cytokine factors mentioned above (interleukins, TNF-α) are “long-distance messages”. They are produced by cells at the site of inflammation and released into the blood, carrying information about the inflammatory response throughout the body. In contrast, eicosanoids are “local” messages; they are produced by cells that are proximal to the site of inflammation, and are meant to travel short distances (locally within the same organ, to neighboring cells, or sometimes only to different parts of the same cell) in order to elicit immune defenses (Luo et al. 2011). There are several families of eicosanoids (including prostaglandins, prostacyclins, leukotrienes, and thromboxanes) that are created by most cell types in all major organ systems. Aside from their roles in inflammation (and anti-inflammation), prostaglandins have a variety of functions in cell growth, kidney function, digestion, and the constriction and dilation of blood vessels. Thromboxanes are important mediators of the blood clotting process. Pro-inflammatory leukotrienes are important for recruiting and activating white blood cells during inflammation, and are best studied for their role in airway constriction and anaphylaxis.

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Cells produce eicosanoids using unsaturated fatty acids that are part of their cell membranes. The fatty acid starting materials for eicosanoid synthesis are the essential fatty acids linoleic acid (omega-6) and its derivative arachidonic acid (AA); and alpha-linolenic acid (an omega-3) and its derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). While generalizations about roles of these fatty acids in eicosanoid synthesis should be approached cautiously, the most potent inflammatory eicosanoids are produced from omega-6 fatty acids (linoleic and arachidonic acids). Diets high in omega-3 fatty acids are associated with lower biomarkers of inflammation and cardiovascular disease risk; proposed mechanisms include the production of less inflammatory or anti-inflammatory eicosanoids and through the cyclooxygenase and lipoxygenase enzymes (see below) (Serhan et al. 2001).

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Cyclooxygenases and Lipoxygenases. The eicosanoids (above) require several enzymatic steps to be synthesized from unsaturated fatty acids; the cyclooxygenase (COX) and lipoxygenase (LOX) enzymes catalyze the first steps in these reactions. Cyclooxygenases initiate the conversion of omega-3 and omega-6 derivatives into one of the many prostaglandins or thromboxanes. The interest in COX enzyme metabolism comes from the fact that its inhibition leads to decreased prostaglandin synthesis, and therefore a reduction in inflammation, fever, and pain. The analgesic and anti-inflammatory activity of aspirin and the non-steroidal anti- inflammatory drugs (NSAIDS, like ibuprofen and naproxen) is due to their inhibition of COX enzymes. There are two COX enzymes with well-defined roles in humans (COX-1 and COX-2). COX-2 has the most relevance to the inflammatory process: it is normally inactive, but is turned on during inflammation and stimulates this process of inflammation by creating pro-inflammatory prostaglandins and thromboxanes.

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Lipoxygenases convert fatty acids into proinflammatory leukotrienes, important local mediators of inflammation. Several potent inflammatory leukotrienes are produced by 5-LOX in mammals. Lipoxygenase enzymes, and the pro-inflammatory factors they produce, have a fundamental role in the inflammatory process by aiding in the recruitment of white blood cells to the site of inflammation. They also stimulate local cells to produce cytokines, which amplifies the inflammatory response (Luo et al. 2011). Thus, LOX enzymes may be involved in a wide variety of inflammatory conditions, and represent an additional target for anti-inflammatory therapy

While COX and LOX enzymes are most often associated with pro-inflammatory processes, it is important to remember that both enzymes also produce factors that inhibit or resolve inflammation and promote tissue repair (including the prostacyclins and lipoxins), The proper transition from the pro- to anti-inflammatory activities of the COX and LOX enzymes is an important for the progression of a healthy inflammatory response.

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Risk Factors for Chronic Inflammation

There are several risk factors which increase the likelihood of establishing and maintaining a low-level inflammatory response. These include:

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Age. In contrast to younger individuals (whose levels of inflammatory cytokines typically increase only in response to infection or injury), older adults can have consistently elevated levels of several inflammatory molecules, especially IL-6 and TNF-α (Singh et al. 2011). These elevations are observed even in healthy older individuals. While the reasoning for this age-associated increase in inflammatory markers is not thoroughly understood, it may reflect cumulative mitochondrial dysfunction and oxidative damage, or may be the result of other risk factors associated with age (such as increases in visceral body fat or reductions in sex hormones; see below).

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Obesity. Fat tissue is an endocrine organ, storing and secreting multiple hormones and cytokines into circulation and affecting metabolism throughout the body. For example, fat cells produce and secrete both TNF-α and IL-6, and visceral (abdominal) fat can produce these inflammatory molecules at levels sufficient to induce a strong inflammatory response (Trayhurn et al. 2005; Schrager et al. 2007). Visceral fat cells can produce three times the amount of IL-6 as fats cells elsewhere (Fried et al. 1998), and in overweight individuals, may be producing up to 35% of the total IL-6 in the body (Mohamed-Ali et al. 1997). Fat tissue can also be infiltrated by macrophages, which secrete pro-inflammatory cytokines. This accumulation of macrophages appears to be proportional to BMI, and appear to be a major cause of low-grade, systemic inflammation and insulin resistance in obese individuals (Ortega Martinez de Victoria et al. 2009, Weisberg et al. 2003).

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Diet. A diet high in saturated fat is associated with higher pro-inflammatory markers, particularly in diabetic or overweight individuals (Nappo et al. 2002) (Peairs et al. 2011). This effect was absent in healthy individuals (Myhrstad et al. 2011, Poppitt et al. 2008, Payette et al. 2009). Diets high in synthetic trans- fats (such as those produced by hydrogenation) have been associated with increases in inflammatory markers (IL-6, TNF-α, IL-8, CRP) in some studies (Mozaffarian et al. 2004) (Lopez-Garcia et al. 2005), but had no effect in others (Nielsen et al. 2011, Bendsen et al. 2011). The increases in markers of inflammation due to synthetic trans- fats may be more pronounced in individuals that are also overweight (Nielsen et al. 2011).

General dietary over-consumption is a major contributor to inflammation and other detrimental age-related processes in the modern world. Therefore, eating a calorie-restricted diet is an effective means of relieving physiologic stressors. Indeed, several studies show that calorie restriction provides powerful protection against inflammation (Ahmadi 2011; Gonzalez 2012). For more information about the metabolic benefits of eating fewer calories, readers should refer to the caloric restriction protocol.

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Low sex hormones. Amongst their many roles in biology, sex hormones also modulate the immune/inflammatory response. The cells that mediate inflammation (such as neutrophils and macrophages) have receptors for estrogens and androgens that enable them to selectively respond to sex hormone levels in many tissues (Gilliver 2010). A notable example is that of osteoclasts, the macrophages that reside in skeletal tissue and are responsible for breaking down and recycling old bone. Estrogens turn down osteoclast activity. Following menopause, lowered estrogen levels cause these bone depleting cells to maintain their activity, breaking down bone faster than it is rebuilt. This is one of the factors in the progression of osteoporosis.

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Experiments in cell culture have demonstrated that testosterone and estrogen can repress the production and secretion of several pro-inflammatory markers, including IL-1β, IL-6, TNF-α, and the activity of NF-kb (Keller et al. 1996; Ray et al. 1997; Deshpande et al. 1997). These observations have been corroborated by observational studies that have linked lower testosterone levels in elderly men to increases in inflammatory markers (IL-6 and IL-6 receptor) (Maggio et al. 2006, Khosla et al. 2002). Several studies have shown an increase in inflammatory IL-1β, IL-6, and TNF-α following surgical or natural menopause (reviewed in Gameiro et al. 2010) (Singh et al. 2011). Conversely, the preservation of sex hormone levels is associated with reductions in the risk of several inflammatory diseases, including atherosclerosis, asthma in women, and rheumatoid arthritis in men (reviewed in (Gilliver 2010). Hormone replacement therapy (HRT) may partially exert its protective effects through an attenuation of the inflammatory response. Reductions in the risks of coronary heart disease and inflammatory bowel disease in some individuals, as well as levels of some circulating inflammatory cytokines (including IL-1B, IL-8, and TNF-α) has been observed in some studies of women on hormone replacement therapy (Kane et al. 2008, Vural et al. 2006, Anderson et al. 2004).

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Smoking. Cigarette smoke contains several inducers of inflammation, particularly reactive oxygen species. Chronic smoking increases production of several pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8), while simultaneously reducing production of anti-inflammatory molecules (Arnson et al. 2010). Smoking also increases the risk of periodontal disease, an independent risk factor for increasing systemic inflammation (Lee et al. 2011).

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Sleep Disorders. Production of inflammatory cytokines (TNF-α and IL-1β) appears to follow a circadian rhythm and may be involved in the regulation of sleep in animals and humans (Vgontzas et al. 1997). Disruption of normal sleep can lead to daytime elevations of these pro-inflammatory molecules. Plasma levels of TNF-α and/or IL-6 were elevated in patients with excessive daytime sleepiness, including those with sleep apnea and narcolepsy (Vgontzas et al. 1997). These elevations in cytokines were independent of body mass index or age (Vgontzas et al. 2000, Vgontzas et al. 2003), although persons with higher visceral body fat were more likely to have sleep disorders. (Trakada et al. 2007)

Other Inciting Factors

Periodontal disease can produce a systemic inflammatory response that may affect several other systems, such as the heart and kidneys (Slade et al. 2003, Pradeep et al. 2011). It is by this mechanism that periodontal disease is thought to be a risk factor for cardiovascular diseases (Vaishnava et al. 2011).

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Stress (both physical and emotional) can lead to inflammatory cytokine release (IL-6); stress is also associated with decreased sleep and increased body mass (stimulated by release of the stress hormone cortisol), both of which are independent causes of inflammation (Pervanidou et al. 2011).

The maintenance of a proper inflammatory response may also involve the central nervous system. The recently identified vagal immune reflex senses inflammatory molecules through a network of nerves (branches of the vagus nerve), and sends this information to the brain. If the brain determines that the inflammatory response is too great, it sends signals to the site(s) of inflammation to attenuate the response (van Westerloo 2010). Preliminary data suggests that depressed nerve activity may be associated with exaggerated inflammatory responses seen in sepsis (Pontet et al. 2003). Smoking, itself a risk factor for inflammation, also decreases activity of the vagus nerve (Taylor et al. 2011).

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Excess Blood Glucose Fuels Inflammatory Fires

When glucose is properly utilized, our cells produce energy efficiently. As cellular sensitivity to insulin diminishes, excess glucose accumulates in our bloodstream. Like spilled gasoline, excess blood glucose creates a highly combustible environment from which oxidative and inflammatory fires chronically erupt.

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Excess glucose not used for energy production converts to triglycerides that are either stored as unwanted body fat or accumulate in the blood where they contribute to the formation of atherosclerotic plaque.

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As an aging human, you face a daily onslaught of excess glucose that poses a grave risk to your health and longevity. Surplus glucose relentlessly reacts with your body’s proteins, causing damaging glycation reactions while fueling the fires of chronic inflammation and inciting the production of destructive free radicals (Basta 2004; Uribarri 2005; Toma 2009).

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Avert Glycation and Inflammation by Controlling Glucose Levels with Green Coffee Extract

Unroasted coffee beans, once purified and standardized, produce high levels of chlorogenic acid and other beneficial polyphenols that can suppress excess blood glucose levels. Human clinical trials support the role of chlorogenic acid-rich green coffee bean extract in promoting healthy blood sugar control and reducing disease risk.

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Scientists have discovered that chlorogenic acid found abundantly in green coffee bean extract inhibits the enzyme glucose-6-phosphatase that triggers new glucose formation and glucose release by the liver (Henry-Vitrac 2010; Andrade-Cetto 2010). Glucose-6-phosphatase is involved in dangerous postprandial (after-meal) spikes in blood sugar.

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In another significant mechanism, chlorogenic acid increases the signal protein for insulin receptors in liver cells (Rodriguez de Sotillo 2006). That has the effect of increasing insulin sensitivity, which in turn drives down blood sugar levels.

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In a clinical trial, 56 healthy volunteers were challenged with an oral glucose tolerance test before and after a supplemental dose of green coffee extract. The oral glucose tolerance test is a standardized way of measuring a person's after-meal blood sugar response. In subjects not taking green coffee bean extract, the oral glucose tolerance test showed the expected rise of blood sugar to an average of 144 mg/dL after a 30 minute period. But in subjects who had taken 200 mg of the green coffee bean extract, that sugar spike was significantly reduced, to just 124 mg/dL—a 14% decrease (Nagendran 2011). When a higher dose (400 mg) of green coffee bean extract was supplemented, there was an even greater average reduction in blood sugar—up to nearly 28% at one hour.

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Ensuring that fasting glucose levels stay between 70 and 85 mg/dL, and that two hour post-meal glucose levels remain under 125 mg/dL can help combat chronic inflammation.

Diseases Associated with Chronic Inflammation

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Cardiovascular diseases (CVD). Inflammation is an integral part of atherosclerosis (recall that oxidized low-density lipoprotein cholesterol stimulates the inflammatory response). Circulating inflammatory cytokines are predictive of peripheral arterial disease, heart failure, atrial fibrillation, stroke, and coronary heart disease (Singh et al. 2011, Emerging Risk Factors Collaboration et al. 2010).

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Cancer. Several studies have established links between chronic low-level inflammation and many types of cancer, including lymphoma, prostate, ovarian, pancreatic, colorectal and lung (Aggarwal et al. 2006).(Kundu et al. 2008) There are several mechanisms by which inflammation may contribute to carcinogenesis, including alterations in gene expression, DNA mutation, epigenetic alterations, promotion of tumor vascularization, and the expression of pro-inflammatory cytokines that have roles in cancer cell proliferation (Kundu et al. 2008, Balkwill 2009).

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Diabetes. The infiltration of macrophages into fat tissue and their subsequent release of pro-inflammatory cytokines into circulation occur at a greater rate in type II diabetics than in non-diabetics (Pickup et al. 2000, Nappo et al. 2002, Ortega Martinez de Victoria et al. 2009). Pro-inflammatory cytokines clearly decrease insulin sensitivity (Bastard et al. 2006).

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Age-related macular degeneration (AMD). An evaluation of 11 population-based studies encompassing over 41,000 patients demonstrated a clear association between elevated serum CRP levels (> 3 mg/L) and the incidence of late onset AMD (Hong et al. 2011). The risk of AMD in these high-CRP patients was increased over 2-fold compared with patients with CRP levels < 1 mg /L.

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Chronic kidney disease (CKD). The chronic, low-grade inflammation in CKD can lead to the retention of several pro-inflammatory molecules in the blood (including cytokines, AGEs, and homocysteine) (Glorieux et al. 2009). The reduced excretion of pro-inflammatory factors by the diseased kidney can accelerate the progression of chronic inflammatory disturbances elsewhere in the body, such as the cardiovascular system.

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Osteoporosis. Inflammatory cytokines (TNF-α, IL-1β, IL-6) are involved in normal bone metabolism. Osteoclasts, the cells that break down (resorb) bone tissue, are a type of macrophage and can be stimulated by pro-inflammatory factors. Systemic elevations in pro-inflammatory cytokines push bone metabolism towards resorption, and have been observed to induce bone loss in persons with periodontal disease, pancreatitis, inflammatory bowel disease, and rheumatoid arthritis (Cao 2011). An increase in the levels of inflammatory cytokines is also a mechanism by which menopause stimulates bone loss.

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Depression. There is a small, but significant association between elevated IL-6 and CRP in depressed patients, which has been observed in many population studies (Dantzer 2012). It is unclear whether inflammation leads to stress or vice versa, and there is data supporting both hypotheses (Gimeno et al. 2009) (Copeland et al. 2012).

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Cognitive decline. Several observational studies have linked chronic low-level inflammation in older adults to cognitive decline and dementia, including vascular dementia and Alzheimer’s disease (Singh et al. 2011). One study found that people with the highest CRP and IL-6 levels (> 2.4 pg/mL) had a ~30-40% increased risk of cognitive decline compared to those with the lowest levels (< 1.4 pg/mL). (Yaffe et al. 2003). Inflammatory markers can be elevated before the onset of cognitive dysfunction, indicating their potential relevance as a prognostic tool in high-risk individuals (Singh et al. 2011).

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Others. Elevations in circulating inflammatory cytokines are associated with several other conditions, both inflammatory (rheumatoid arthritis, IBD/Crohn’s disease, pancreatitis) and non-inflammatory (anemia, fibromyalgia, frailty, sacropenia/cachexia/muscle wasting) (Kaser et al. 2011) (Jha et al. 2009) (Ferrucci et al. 2010, Kadetoff et al. 2011, Rolland et al. 2011). Again, whether inflammation incites these conditions or results from them is unclear, and requires further investigation.

Conventional Medicine Typically Overlooks Chronic Inflammation

Chronic inflammation or para-inflammation is generally not treated on its own by mainstream physicians. Interventions in conventional medicine are usually only undertaken when the inflammation occurs in association with another medical condition (such as arthritis). Currently, conventional preventive medical approaches to inflammation are limited to the use of CRP to predict cardiovascular disease in high-risk subjects, and the prophylactic use of drugs like aspirin to inhibit the inflammatory cascade linked to thrombosis (uncontrolled blood clotting). Indeed, the potentially asymptomatic nature of low grade inflammation is such that elevations of pro-inflammatory cytokines may progress undetected for some time, only being discovered after they have had time to cause enough cellular damage to produce disease symptoms. As future studies solidify the association between inflammatory mediators and different diseases, early detection of cytokine aberrations and anti-inflammatory therapy to reduce disease risk may gain more mainstream acceptance.