Chronic Inflammation – The Culprit Behind Many Serious Disease Conditions

For the past 16 years, Life Extension has been warning of the dangers of systemic chronic inflammation. We revealed that inflammation is a causative factor in the development of heart attacks, cancer, stroke, and Alzheimer’s disease, along with autoimmune disorders such as lupus, multiple sclerosis, and asthma.

The cover of the February 23, 2004, issue of TIME magazine is titled, “The Silent Killer… The surprising link between Inflammation and Heart Attacks, Cancer, Alzheimer’s and other diseases.”

According to the TIME article, the recognition of inflammation’s role in disease causation “could radically change doctors’ concept of what makes us sick.”

Why People Are Confused About Inflammation

Most doctors view inflammation through the lens of its textbook definition: a part of the body’s defense against bacteria and viruses. Inflammation is also involved in the normal healing process.

What scientists are learning, however, is that aged people often lose the ability to “turn off” inflammatory reactions. This problem also occurs in younger people as a result of genetic factors or bad health habits such as poor diet, cigarette smoking, and obesity. In these cases, inflammation becomes “chronic” rather than transitory. The result is that the body’s immune system constantly attacks the arteries, brain cells, and joint cartilage, along with every organ system.

While doctors now know that “autoimmune disorders” cause diseases like lupus and rheumatoid arthritis, the medical establishment has failed to correlate this with the fact that aged people often suffer from similar autoimmune imbalances. The result is that pro-inflammatory cytokines (such as interleukin-6) and inflammatory-inducing eicosanoids (such as prostaglandin E2) wreak constant havoc throughout the body. High blood insulin levels, along with oxidative stress caused by free radicals, also induce inflammatory reactions.

The Culprit Behind Heart Disease and Cancer

High blood levels of C-reactive protein indicate an increased risk for destabilized atherosclerotic plaque. 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.

The best way to ascertain inflammatory status is blood testing to determine the level of C-reactive protein. People with C-reactive protein levels lower than 0.5 mg/L rarely have heart attacks, whereas a blood reading of 3.0 and higher can triple the risk of heart attack.

Those with elevated C-reactive protein also have a two to three times greater risk of stroke. In people who have already suffered a major stroke, higher levels of C-reactive protein predict a much greater likelihood of suffering another stroke or heart attack, or dying within the following year.

What most doctors do not know is that people with high levels of C-reactive protein in their blood also have an increased the risk of certain cancers. Chronic inflammation not only appears to facilitate the transformation of normal cells into cancer, but also increases the proliferation of existing cancers.

A recent study in the Journal of the American Medical Association (JAMA) showed that people with the highest blood levels of C-reactive protein were about three times as likely to contract colon cancer as those in the lowest ranges. Another study showed that inflammatory factors may increase the risk of developing esophageal cancer and suggested that therapies that suppress inflammatory enzymes (i.e., COX-2 inhibitors) should be considered in the treatment of these malignancies.

The top three killers today are heart attack, cancer, and stroke. Chronic inflammation plays a significant role in the development of each of these lethal diseases.

Inflammation Destroys Brain Cells

Chronic inflammatory reactions literally chew up brain cells, resulting in markedly higher rates of dementia. Scientific studies have shown that people who regularly use anti-inflammatory drugs like aspirin or ibuprofen have lower rates of Alzheimer’s disease.

In a study of 1,050 men, blood samples measuring high-sensitivity C-reactive protein were taken and the risk of dementias was evaluated 25 years later. Compared to the lowest quartile, men in the upper three quartiles of C-reactive protein were three times more likely to contract Alzheimer’s disease or vascular dementia. The doctors who conducted the study noted that these inflammatory processes “are measurable long before clinical symptoms appear.”

A growing body of research indicates that age-related dementias may be prevented if chronic inflammation is kept in check.

Increased Macular Degeneration Risk

Macular degeneration is the leading cause of blindness in people over age 55, currently affecting more than 10 million Americans. The disease occurs when the central portion of the retina (the macula) deteriorates, resulting in impaired vision or blindness.

The American Medical Association has published a new study indicating that systemic inflammation increases the risk of macular degeneration. The study evaluated 930 participants and found that people with high C-reactive protein levels were significantly more likely to develop advanced macular degeneration compared to those with low blood levels of C-reactive protein. The study concluded:

“Elevated C-reactive protein level is an independent risk factor for age-related macular degeneration and may implicate the role of inflammation in the pathogenesis of age-related macular degeneration.”

This may be the first study to implicate C-reactive protein as a marker for the development of macular degeneration.

Inflammation Predicts Type II Diabetes

People with high levels of C-reactive protein and interleukin-6 (IL-6) are significantly more likely to develop diabetes.

A group from the famous Women’s Health Study was evaluated to ascertain which risk factors could predict future development of type II diabetes. When the highest and lowest quartile were compared, women with higher IL-6 levels were 7.5 times more likely to develop diabetes, while women with higher C-reactive protein levels 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, synthetic estrogen drug therapy, and smoking) all sharply increase inflammatory markers in the blood. The doctors who conducted this study concluded:

“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.”

Frailty in Elderly Linked to Inflammation

In a study of nearly 5,000 elderly people, scientists discovered that frail seniors were more likely to have signs of increased inflammation than their more active counterparts. These frail seniors with elevated blood inflammatory markers also tended to show more clotting activity, muscle weakness, fatigue, and disability than active elderly people.

Chronic inflammation is an underlying cause of many seemingly unrelated, age-related diseases. As humans grow older, systemic inflammation inflicts devastating degenerative effects throughout the body. The medical establishment has long overlooked this fact, despite persuasive scientific evidence that correcting a chronic inflammatory disorder will help prevent or reverse many of the infirmities of aging.

Inflammatory Markers Predict Death

Research has firmly established that high levels of C-reactive protein, IL-6, and other inflammatory cytokines indicate significantly greater risks of contracting specific diseases such as heart attack, stroke, and Alzheimer’s.

A group of doctors sought to ascertain whether C-reactive protein and IL-6 could also predict the risks of all-cause mortality. They took a sample of 1,293 healthy elderly people and followed them for a period of 4.6 years. 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 high IL-6 were 2.6 times more likely to die during follow up than those with low levels of both inflammatory markers. These results were independent of all other mortality risk factors. The doctors concluded:

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

The Dangerous Pro-Inflammatory Cytokines

The following acronyms represent the most dangerous pro-inflammatory cytokines:

TNF-a = tumor necrosis factor-alpha
IL-6 = interleukin-6
IL-1b = interleukin-1 beta
IL-8 = interleukin-8

Health-conscious people should familiarize themselves with these terms because excess levels of these cytokines cause or contribute to many disease states.

Causes of Chronic Inflammation

In response to normal aging, there is an increase of inflammatory cytokines (destructive cell-signaling chemicals) that contribute to the progression of many degenerative diseases. 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-1b), and interleukin-8 (IL-8) are known to cause or contribute to the inflammatory syndrome.

As noted earlier, chronic inflammation is involved in diseases as diverse as atherosclerosis, cancer, heart valve dysfunction, obesity, diabetes, congestive heart failure, digestive system diseases, and Alzheimer’s.

What one eats plays a major role in chronic inflammatory processes. It is important to avoid overconsumption of foods high in arachidonic acid such as beef, egg yolk, and dairy products. The enzymes cyclooxgenase-2 (COX-2) and 5-lipooxygenase (5-LOX) degrade arachidonic acid into inflammatory-inducing prostaglandin E2 and leukotriene B4.

Obesity has been definitively linked to elevated levels of inflammatory blood markers such as C-reactive protein. Consuming lower-glycemic foods reduces the insulin surge that contributes to chronic inflammatory processes.

Eating foods cooked at high temperatures is another contributor to the production of inflammatory cytokines. In fact, it has been shown that eating such foods leads to the formation of advanced glycation end 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, cataracts, 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 (such as IL-6 and TNF-a).

We now know that eating too much overcooked food causes an increase in inflammatory cytokines. Since most “junk” foods are cooked at extremely high temperatures, it makes sense to avoid french fries, hamburgers, potato chips, and other fried foods and snacks that are scorched with hydrogenated fats.

Lack of sleep markedly increases inflammatory cytokines. This finding helps explain why pain flare-up occurs in response to sleep deprivation in various disorders. Even modest sleep restriction adversely affects inflammatory cytokine levels. In a carefully controlled study, sleep deprivation caused a 40-60% average increase in the inflammatory marker IL-6 in men and women, while men alone showed a 20-30% increase in TNF-a. Both IL-6 and TNF-a are potent pro-inflammatory cytokines that induce systemic inflammation.

How to Protect Against Chronic Inflammation

One can use a variety of dietary supplements to reduce levels of pro-inflammatory cytokines. The DHA (docosahexaenoic acid) fraction of fish oil is the best documented supplement to suppress TNF-a, IL-6, IL-1b, and IL-8. A study of healthy humans and those with rheumatoid disease shows that fish oil suppresses these dangerous cytokines by up to 90%.

Other cytokine-lowering supplements are DHEA (dehydroepi-androsterone), vitamin K, GLA (gamma linolenic acid), and nettle leaf extract.

In addition to suppressing in-flammatory cytokines, the omega-3 fatty acids found in fish oil help to suppress the formation of undesirable prostaglandin E2 and to promote synthesis of beneficial prostaglandin E3. Gamma linolenic acid (GLA) induces production of the anti-inflammatory prostaglandin E1. What you eat can significantly affect whether you have more of the beneficial prostaglandins (E1 and E3) as opposed to the pro-inflammatory prostaglandin E2.

Because prostaglandin E2 is a culprit in inflammation, reducing the consumption of foods that are high in omega-6 fatty acids (saturated fats) and increasing the consumption of omega-3 rich foods (such as walnuts, salmon, and other cold-water fish) can be beneficial. Limiting foods (like beef) that convert to arachidonic acid can help reduce inflammation. Arachidonic acid is a precursor to both prostaglandin E2 and the pro-inflammatory leukotrienes.

Another dietary factor that can lead to high levels of arachidonic acid is the overconsumption of high-glycemic carbohydrates that cause excess production of insulin. Food heavy in polyunsaturated fats or saturated fats can also increase prostaglandin E2.

Consuming at least 1000 mg a day of carnosine can inhibit pathological glycation reactions in the body. Avoiding foods cooked at high temperatures also reduces pathological glycation processes, which lowers the production of inflammatory cytokines that mount an autoimmune attack against glycated proteins.

Antioxidants such as vitamins C and E, along with N-acetylcysteine and green tea extract, may also lower proinflammatory cytokines and protect against their toxic effects.

Excess IL-6 and other inflammatory cytokines attack bone and promote the formation of fibrinogen, which can induce a heart attack or stroke. To prevent and treat the multiple diseases of aging, it is critical to keep these destructive immune chemicals (cytokines) in safe ranges.

The Newest IL-6-Suppressing Nutrient

Like a forest fire raging out of control, systemic inflammation is sometimes impossible to control no matter how many drugs and nutrients are tried. This is especially true in the elderly and the obese.

The best way to guard against an outbreak of uncontrolled systemic inflammation is to prevent it by eating right and taking the proper inflammation-suppressing supplements.

One of the most dangerous inflammatory cytokines that increases in the aged is interleukin-6 (IL-6). One of the benefits of caloric restriction is a marked reduction in IL-6 levels. Caloric restriction is considered the best-documented method to significantly slow aging.

Doctors Still Overlook Inflammation’s Dangers

Chronic inflammation inflicts devastating effects, especially as humans grow older. Aging people often suffer from many seemingly unrelated disorders. Mainstream medicine attributes these multiple diseases to “getting old” and fails to treat the underlying inflammatory disorder. Many aging people are needlessly suffering and dying from inflammatory disorders that are usually correctable.

Inflammation-Supressing Prescription Drugs

Those with elevated C-reactive protein can lower it using a variety of diet modifications, supplements, or drugs.

Diets low in arachidonic acid, omega-6 fatty acids, saturated fats, high-glycemic foods, and overcooked food can suppress inflammatory factors in the body. High dietary or supplemental intake of omega-3 fatty acids can be of enormous benefit.

Supplements such as vitamin E, borage oil, fish oil, DHEA, vitamin K, and nettle leaf extract can lower systemic inflammatory factors.

Drugs like Enbrel® ($10,000 a year) directly bind to TNF-a and block its interaction with TNF cell surface receptors. Enbrel® has demonstrated significant clinical improvement in rheumatoid arthritis patients, as have high-dose fish oil supplements. High levels of TNF-a, however, may persist even in people receiving Enbrel® drug therapy.

Even if Enbrel® brings TNF-a down to a safe level, other inflammatory cytokines such as IL-6 and IL-1b may continue to wreak havoc throughout the body. High levels of tumor necrosis factor-alpha (TNF-a) are destructive to many vital tissues such as joint cartilage (e.g., rheumatoid arthritis) and heart muscle (e.g., congestive heart failure). Nettle leaf extract has been shown to suppress TNF-a and IL-1b, while DHEA, fish oil, and other nutrients help suppress IL-6.

Metformin is a drug used to treat type II diabetes. It functions via multiple mechanisms to restore youthful metabolic-glucose metabolism. Metformin’s ability to lower elevated blood insulin levels helps explain why it has been shown to significantly lower C-reactive protein levels in human studies. The suggested dose for most healthy people is 500 mg every 12 hours.

Aspirin or ibuprofen can lower C-reactive protein levels. Some doctors are concerned that the higher doses of these drugs that are sometimes needed to reduce C-reactive protein could cause side effects. Anyone taking high-dose aspirin or ibuprofen regularly should supplement with polyenylphosphatidylcholine (sold under the tradename HepatoPro™) to help protect the stomach lining.

Statin drugs lower C-reactive protein levels, but there are increasing reports of side effects associated with this class of drug. Consider taking the lowest dose to start with (such as 5 mg/day of Lipitor® instead of the normal 10 mg) to determine whether the lower dose adequately reduces C-reactive protein levels.

The drug pentoxifylline has been shown to suppress TNF-a, IL-6, IL-1b, and other inflammatory cytokines. The suggested dose of pentoxifylline (as long as the drug is not contraindicated) is 400 mg twice a day. Several studies show that pentoxifylline is a potent inhibitor of TNF-a, IL-1b, IL-6, and other pro-inflammatory cytokines. Similarly, studies show that DHA fish oil suppresses the same cytokines. In people who have a chronic disease involving elevated levels of the inflammatory cytokines, the daily administration of 800 mg of pentoxifylline and/or 1000-2000 mg of DHA fish oil could be of enormous benefit.

The objective of dietary changes, supplements, and drugs is to lower C-reactive protein to below 1.3 mg/L of blood. The ideal level for C-reactive protein is under 0.5 mg/L of blood.

The good news for healthy people is that we have identified a multitude of ways to significantly reduce the inflammatory cascade, moving one step closer to gaining complete control over age-related inflammatory disorders.