Infalmmation: Chronic Protocol


Chronic systemic inflammation is an underlying cause of many seemingly unrelated, age-related diseases. As humans grow older, systemic inflammation can inflict devastating degenerative effects throughout the body (Ward 1995; McCarty 1999; Brod 2000). This fact is often overlooked by the medical establishment, yet persuasive scientific evidence exists that correcting a chronic inflammatory disorder will enable many of the infirmities of aging to be prevented or reversed.

The pathological consequences of inflammation are well documented in the medical literature (Willard et al. 1999; Hogan et al. 2001). Regrettably, the dangers of systemic inflammation continue to be ignored, even though proven ways exist to reverse this process. By following specific prevention protocols suggested by the Life Extension Foundation, the inflammatory cascade can be significantly reduced.

The Causes of Age-Related Inflammation
Aging results in an increase of inflammatory cytokines (destructive cell-signaling chemicals) that contribute to the progression of many degenerative diseases (Van der Meide et al. 1996; Licinio et al. 1999). Rheumatoid arthritis is a classic autoimmune disorder in which excess levels of cytokines such as tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), interleukin 1b [IL-1(b)], and/or interleukin-8 (IL-8) are known to cause or contribute to the inflammatory syndrome (Deon et al. 2001).

Chronic inflammation is also involved in diseases as diverse as atherosclerosis, cancer, heart valve dysfunction, obesity, diabetes, congestive heart failure, digestive system diseases, and Alzheimer's disease (Brouqui et al. 1994; Devaux et al. 1997; De Keyser et al. 1998). In aged people with multiple degenerative diseases, the inflammatory marker, C-reactive protein, is often sharply elevated, indicating the presence of an underlying inflammatory disorder (Invitti 2002; Lee et al. 2002; Santoro et al. 2002; Sitzer et al. 2002). When a cytokine blood profile is conducted on people in a weakened condition, an excess level of one or more of the inflammatory cytokines, e.g., TNF-a, IL-6, IL-1(b), or IL-8, is usually found (Santoro et al. 2002). (See the Suggested Reading reference list for additional citations.)

Protecting Against Inflammatory-Related Disease

The New England Journal of Medicine published several studies in the year 2000 showing that the blood indicators of inflammation are strong predictive factors for determining who will suffer a heart attack (Lindahl et al. 2000; Packard et al. 2000; Rader 2000). The January 2001 issue of Life Extension Magazine described these studies and explained how individuals could protect themselves against these inflammatory markers (such as C-reactive protein, homocysteine, and fibrinogen).

A growing consensus among scientists is that common disorders such as atherosclerosis, colon cancer, and Alzheimer's disease are all caused in part by a chronic inflammatory syndrome.

Seemingly unrelated diseases have a common link. People who have multiple degenerative disorders often exhibit excess levels of pro-inflammatory markers in their blood. Here is a partial list of common medical conditions that are associated with chronic inflammation:

Diseases Related To Chronic Inflammation .....Disease Mechanism
Allergy ..........................Inflammatory cytokines induce autoimmune reactions
Alzheimer's ....................................Chronic inflammation destroys brain cells
Anemia .....................Inflammatory cytokines attack erythropoietin production
Aortic valve stenosis .....................Chronic inflammation damages heart valves
Arthritis .............Inflammatory cytokines destroy joint cartilage and synovial fluid
Cancer ..................................Chronic inflammation causes many cancers
Congestive heart failure .Chronic inflammation contributes to heart muscle wasting
Fibromyalgia .................................Inflammatory cytokines are elevated
Fibrosis .............................Inflammatory cytokines attack traumatized tissue
Heart attack ............Chronic inflammation contributes to coronary atherosclerosis
Kidney failure .....Inflammatory cytokines restrict circulation and damage nephrons
Lupus ...........................Inflammatory cytokines induce an autoimmune attack
Pancreatitis ..................Inflammatory cytokines induce pancreatic cell injury
Psoriasis ..........................................Inflammatory cytokines induce dermatitis
Stroke .....................Chronic inflammation promoted thromboembolic events
Surgical complications....................... Inflammatory cytokines prevent healing

A critical inflammatory marker is C-reactive protein. This marker indicates an increased risk for destabilized atherosclerotic plaque and abnormal arterial clotting. When arterial plaque becomes destabilized, it can burst open and block the flow of blood through a coronary artery, resulting in an acute heart attack. One of the New England Journal of Medicine studies showed that people with high levels of C-reactive protein were almost three times as likely to die from a heart attack (Ridker et al. 1997).

The Life Extension Foundation long ago advised members to have an annual C-reactive protein blood test to detect systemic inflammation that could increase the risk of heart attack, stroke, cancer and a host of age-related diseases. In fact, on January 28, 2003, the American Heart Association and Centers for Disease Control & Prevention (CDC) jointly endorsed the C-reactive protein test to screen for coronary-artery inflammation to identify those at risk for heart attack.

What Causes Elevated C-reactive Protein?

While some doctors are finally catching on to the fact that elevated C-reactive protein increases heart attack and stroke risk, they still know little about its other dangers. Even fewer practicing physicians understand that pro-inflammatory cytokines are an underlying cause of systemic inflammation that is indicated by excess C-reactive protein in the blood.

In an abstract published in the March 6, 2002 issue of the Journal of the American College of Cardiology (JACC), tumor necrosis factor-alpha (TNF-a) levels were measured in a group of people with high blood pressure and a group with normal blood pressure (Verdeccnia et al. 2002). The objective of this study was to ascertain if arterial flow mediated dilation was affected by hypertension and chronic inflammation as evidenced by high levels of the pro-inflammatory cytokine TNF-a.

The hypertensive subjects taking anti-hypertensive medications had about the same blood pressure as the healthy test subjects. Arterial flow medicated dilation, however, was significantly impaired in the hypertensives and this group also showed higher levels of TNF-a, indicating persistent inflammation despite blood pressure control. This study showed that even when blood pressure is under control, hypertensives still suffer from continuous damage to the inner lining of the arterial wall (endothelial dysfunction) caused by a chronic inflammatory insult. The doctors who conducted this study concluded by stating:

"Antihypertensive therapy alone may be insufficient to improve endothelial dysfunction in hypertensives with high plasma levels of inflammatory markers. Additional therapy to target inflammation may be necessary to improve endothelial function and to prevent progression of coronary atherosclerosis in high-risk hypertensives with subclinical inflammations."
A sensitive index to evaluate how much endothelial damage is occurring is the measurement of TPA (tissue-type plasminogen activator), a clot-dissolving enzyme found in the blood. This same study showed elevated TPA levels in hypertensives, indicating continued endothelial damage despite blood pressure reduction. These findings indicate that hypertensives should have their blood tested for both TNF-a and TPA to assess how much inner wall (endothelial) arterial damage is occurring (Vardecchia et al. 2002). If TNF-a and/or TPA levels are high, aggressive therapies to suppress the inflammatory cascade should be considered.

Elevated C-Reactive Protein and Interleukin-6 Predict Type II Diabetes
In a study published in the July 18, 2001 issue of the Journal of the American Medical Association, a group from the famous Women's Health Study were evaluated to ascertain what risk factors could predict future development of Type II diabetes (Prudhan et al. 2001). The findings showed that baseline levels of C-reactive protein and interleukin-6 (IL-6) were significantly higher among those who subsequently developed diabetes compared to those who did not.

When comparing the highest versus lowest quartile, women with the higher IL-6 levels were 7.5 times more likely to develop diabetes while those in the higher C-reactive protein ranges were 15.7 times more likely to become diabetic. After adjusting for all other known risk factors, women with the highest IL-6 levels were 2.3 times at greater risk, while those with the highest C-reactive protein levels were 4.2 times more likely to become diabetic. It should be noted that these other diabetic risk factors (such as obesity, estrogen replacement therapy and smoking) all sharply increase inflammatory markers in the blood. The doctors who conducted this study concluded by stating:

"Elevated C-reactive protein and IL-6 predict the development of Type II diabetes mellitus. These data support a possible role for inflammation in diabetogenesis."

C-Reactive Protein and IL-6 Predict Death

It is well established the elevated C-reactive protein, IL-6 and other inflammatory cytokines indicate significantly greater risks of contracting or dying from specific diseases (heart attack, stroke, Alzheimer's disease, etc.).

A group of doctors wanted to ascertain if C-reactive protein and IL-6 could also predict the risks of all-cause mortality. In a study published in the American Journal of Medicine, a sample of 1,293 healthy elderly people were followed for a period of 4.6 years (Harris et al. 1999). Higher IL-6 levels were associated with a twofold greater risk of death. Higher C-reactive protein was also associated with a greater risk of death, but to a lesser extent than elevated IL-6. Subjects with both high C-reactive protein and IL-6 were 2.6 times more likely to die during follow up than those with low levels of both of these measurements of inflammation. These results were independent of all other mortality risk factors. The doctors concluded by stating:

"These measurements (C-reactive protein and IL-6) may be useful for identification of high-risk subgroups for anti-inflammatory interventions."

Frailty in Elderly Linked to Inflammation
In a study of almost 5,000 elderly people, scientists discovered that frail seniors were more likely to have signs of increased inflammation than their more active counterparts. This study was published in the Archives of Internal Medicine (Walston et al. 2002) and showed that these frail seniors with elevated blood inflammatory markers also tended to show more clotting activity, muscle weakness, fatigue and disability than active elderly people.

Findings from these studies should motivate every health conscious individual to have their blood tested for C-reactive protein. If it is elevated, then the Inflammatory Cytokine Test Panel is highly recommended. Those who suffer from any type of chronic disease may also consider the Inflammatory Cytokine Test Panel in order to identify the specific inflammatory mediator that is causing or contributing to their problem.

Glycation's Role in Inflammation
Eating high temperature cooked food is another contributor in the production of inflammatory cytokines. In fact, it has been shown that eating high temperature cooked food leads to the formation of advanced glycation end (AGE) products. Glycation can be described as the binding of a protein molecule to a glucose molecule resulting in the formation of damaged protein structures. Many age-related diseases such as arterial stiffening, cataract and neurological impairment are at least partially attributable to glycation. These destructive glycation reactions render proteins in the body cross-linked and barely functional. As these degraded proteins accumulate, they cause cells to emit signals that induce the production of inflammatory cytokines.

The glycation process is presently irreversible, though an important study indicates a drug in clinical trials may be partially effective. According to a Proceedings of the National Academy of Sciences study, consuming foods cooked at high temperature accelerates the glycation process, and the subsequent formation of advanced glycation end products.

A more succinct descriptive term for "advanced glycation end products" is "glycotoxin," since "advanced glycation end products" are toxic to the body. We will use the word "glycotoxin" from here on to describe the term "advanced glycation end products."

Cooking and Aging Have Similar Biological Properties
Cooking foods at high temperatures results in a "browning" effect, where sugars and certain oxidized fats react with proteins to form glycotoxins in the food. Normal aging can also be regarded as a slow cooking process, since these same glycotoxins form in the skin, arteries, eye lenses, joints, cartilage, etc. of our body.

The Proceedings of the National Academy of Sciences study shows that consuming foods high in glycotoxins might be responsible for the induction of a low-grade, but chronic state of inflammation. In addition, the glycotoxins in food cooked at high temperatures also promote the formation of glycotoxins in our living tissues. The implication of these findings is profound.

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