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Inflammation: Chronic

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.

What one eats plays a major role in chronic inflammatory processes. Consuming low glycemic foods prevents the insulin surge that contributes to chronic inflammatory processes. It is also important to avoid over consumption of foods high in arachidonic acid (beef, egg yolk, dairy, etc.).

We now know that eating too much over-cooked 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, fried food and other snacks. These foods not only contain lots of glycotoxins, they also create other metabolic disorders that can induce degenerative disease.

Consuming at least 1000 mg a day of carnosine, and/or 300 mg of the European drug aminoguanidine can inhibit pathological glycation reactions in the body. Eating high temperature cooked foods also induces the formation of glycotoxins. Avoiding foods cooked at high temperature not only reduces pathological glycation processes, but also prevents the formation of numerous gene-mutating toxins that are known carcinogens.

Food is cooked to destroy bacteria and other pathogens that could cause a serious illness. It is important not to eat undercooked food, but avoiding food unnecessarily cooked at higher temperatures is desirable. Certain foods (like fried foods) have to cook at high temperatures. Health conscious people are increasingly avoiding fried foods because they are associated with many health risks.

With the availability of cytokine blood profile tests, it is now possible to ascertain the underlying cause of chronic inflammatory disease. The appropriate drugs, nutrients, dietary change(s) and/or hormones can then be used to suppress the specific cytokines (such as IL-6 or TNF-a) that are promoting the inflammatory cascade.

The Detrimental Effects of Sleep Deprivation

On June 22, 2002, researchers at the annual meeting of the Endocrine Society held in San Francisco reported that sleep deprivation markedly increases inflammatory cytokines. This finding helps explain why pain flare-up occurs in response to lack of sleep in a variety of disorders. According to the researchers, even modest sleep restriction adversely affects hormone and cytokine levels. In this carefully controlled study, sleep deprivation caused a 40% to 60% average increase in the inflammatory marker IL-6 in men and women, while men alone showed a 20% to 30% increase in TNF-a. Both IL-6 and TNF are potent pro-inflammatory cytokines that induce systemic inflammation (Vgontzas et al. 1999; Vgontzas et al. 2001).

The study results were presented by Dr. Alexandros Vgontzas, professor of psychiatry at The Pennsylvania State University in Hershey. Dr. Vgontzas stated that the findings indicate that getting a full night's rest of eight hours is not just a nice bonus, but a necessity. He stated that people who are missing even two to three hours of sleep function poorly the next day.

Dr. Vgontzas added that the finding that lack of sleep may stimulate an increase in chronic inflammatory response is worrisome because inflammation has been linked to the most common lethal conditions affecting humans today. Vgontzas warned: "Restriction of sleep a few hours is a major risk for public safety."

This study has significant implications for the treatment of chronic pain and inflammatory disorders. For many, following the recommendations in Life Extension's Insomnia Protocol could provide considerable relief from pain and other disorders by preventing the increase of pro-inflammatory cytokines.

The Dangerous Pro-Inflammatory Cytokines

• Reducing Inflammation
• Lowering Elevated C-Reactive Protein
• Blood Testing
• The Importance of Cytokine Testing
• Pentoxifylline Studies
• When to Avoid PTX and Other Anti-Inflammatories
• Sources of Pentoxifylline
• Diet and Inflammation

The following acronyms represent the most dangerous pro-inflammatory cytokines. Health-conscious persons should become familiar with these terms because excess levels of these cytokines cause or contribute to many diseases states:

• TNF-a tumor necrosis factor-alpha
• IL-6 interleukin-6
• IL-1(b) interleukin-1 beta
• IL-8 interleukin-6

Reducing Inflammation
Scientists have identified dietary supplements and prescription drugs that can reduce levels of the pro-inflammatory cytokines. The docosahexaenoic acid (DHA) fraction of fish oil is the best documented supplement to suppress TNF-a, IL-6, IL-1(b), and IL-8 (Jeyarajah et al. 1999; James et al. 2000; Watanabe et al. 2000; Yano et al. 2000). A study on healthy humans and those with rheumatoid disease shows that fish oil suppresses these dangerous cytokines by up to 90% (James et al. 2000).

Other cytokine-lowering supplements are DHEA (Casson et al. 1993), vitamin K (Reddi et al. 1995; Weber 1997), GLA (gamma linolenic acid) (Purasiri et al. 1994), and nettle leaf extract (Teucher et al. 1996). Antioxidants, such as vitamin E (Devaraj et al. 2000) and N-acetyl-cysteine (Gosset et al. 1999), may also lower pro - inflammatory cytokines and protect against their toxic effects.

Prescription 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 (Kremer 2000). High levels of TNF-a may persist even in people receiving Enbrel drug therapy. Even if Enbrel brings TNF-a down to a safe range, other inflammatory cytokines such as IL-6 and IL-1(b) may continue to wreak havoc throughout the body. High levels of tumor necrosis factor (TNF-a) are destructive to many vital tissues such as joint cartilage (e.g., rheumatoid arthritis) and heart muscle (e.g., congestive heart failure).

Excess IL-6 and other inflammatory cytokines attack bone and promote the formation of fibrinogen that can induce a heart attack or stroke (di Minno et al. 1992). To prevent and treat the multiple diseases of aging, it is critical to keep these destructive immune chemicals (cytokines) in safe ranges.

Methods of Lowering Elevated C-Reactive Protein
Those who are in relative good health, but have elevated C-reactive protein, can try to lower it using a variety of diet modifications, supplements and/or drugs. Supplements such as vitamin E, borage oil, fish oil, DHEA, vitamin K and nettle leaf extract can lower C-reactive protein. Diets low in arachidonic acid, omega-6 fatty acids, saturated fats, high-glycemic food and overcooked food can suppress inflammatory factors in the body.

If diet and supplements fail, drugs such as ibuprofen, aspirin, pentoxifylline or one of the statins (such as Pravachol®) should be tried. If the modified diet, nutrients and/or drugs lower C-reactive protein to below 1.3 (mg/L) of blood, then this is an indication that the underlying inflammatory fire has been extinguished. (The high-sensitivity C-reactive protein blood test is recommended to measure this indicator.)

For those whose blood tests reveal persistently high inflammatory cytokine levels despite taking the supplements mentioned above, a low-cost prescription drug may be of enormous benefit.

The generic name of this low-cost prescription drug is pentoxifylline (PTX); the brand name is Trental. This drug was first used in Europe in 1972 and long ago was removed from patent status (meaning it is not cost-prohibitive). PTX is prescribed to improve blood flow properties by decreasing its viscosity. It works by improving red blood cell flexibility, decreasing platelet aggregation, and reducing fibrinogen levels (de la Cruz et al 1993; Gara 1993; Gaur et al. 1993). PTX has fallen from favor because no drug company has the economic incentive to market it to physicians. PTX is primarily prescribed to patients with peripheral artery disease, although it may have potential efficacy in treating a wide range of diseases relating to chronic inflammation.

Numerous studies show that pentoxifylline (PTX) is a potent inhibitor of TNF-a, IL-1(b), IL-6, and other pro-inflammatory cytokines (Neuner et al. 1994; Noel et al. 2000; Pollice et al. 2001; Ventura et al. 2001). Similarly, studies also show that DHA fish oil suppresses these same cytokines (Das 2000; Yano et al. 2000). In people who have a chronic disease involving elevated levels of the inflammatory cytokines, the daily administration of 400-800 mg of PTX and/or 1000-2000 mg of DHA fish oil could be of enormous benefit.

Individuals with chronic disease sometimes find it difficult to suppress C-reactive protein. In these cases, it is important to identify the specific inflammatory cytokines that are responsible for the destructive inflammatory processes that is causing or contributing to the underlying disease state. This enables a custom tailored program to be implemented, and its success measured by suppressing the pro-inflammatory cytokine culprits. For instance, if levels of TNF-a levels are elevated, and natural approaches fail to lower it, the prescription drug Enbrel should be considered.

Inflammatory Cytokine Blood Testing
People suffering from chronic disease often have elevated levels of C-reactive protein in their blood. C-reactive protein indicates an inflammatory process is going on in the body, but does not identify the specific pro-inflammatory cytokine that may be the underlying cause.

Testing for pro-inflammatory cytokines has been prohibitively expensive because there has been so little demand for it. The Life Extension Foundation offers an inflammatory cytokine profile at an affordable price. Below is the cytokine panel for this test along with the optimal anti-inflammatory ranges:

As stated earlier in this chapter, an inexpensive C-reactive protein (high-sensitivity) blood test (CRP-hs) can help reveal if you have systemic inflammation. If your C-reactive protein level is over 1.3 (mg/L), this is an indication that you have an inflammatory event occurring in your body. Those with elevated CRP-hs levels (and who have a disease associated with chronic inflammation) should consider using a supplement protocol and/or prescription drugs known to suppress elevated pro-inflammatory cytokines.

The Importance of Cytokine Testing for Those Suffering From Chronic Illness
There are many chronic disease states that can now be managed by the proper utilization of the Inflammatory Cytokine Blood Panel. If you are elderly, or suffer from any serious disorder, these cytokine tests can enable your doctor to prescribe therapies that specifically target the inflammatory cytokine responsible for your poor state of health.

From a practical standpoint, if you suffer from congestive heart failure, and your levels of TNF-a remain persistently high, you may ask your doctor to prescribe the drug Enbrel®, which specifically counteracts the destructive effects of TNF-a.

If you suffer from cancer and your levels of IL-6 remain persistently high, you may consider high dose DHEA or asking your doctor to prescribe a bisphosphonate drug (such as Zometa® that protects against bone destruction that releases excess IL-6 into the body. Those with prostate, certain types of breast cancer, and other hormonally driven cancer should consider other IL-6 lowering therapies (such as high dose DHA fish oil extract) in lieu of DHEA.

Some cancer and patients display elevated levels of IL-8, which induces cancer cells to express growth factors that fuel their propagation. In hepatitis C, elevated IL-8 signals interferon drug resistance. An IL-8 suppressing therapy will soon be available to Americans (it is already used in Japan).

Those with systemic inflammatory disease often manifest high levels of IL-1b. If diet, the anti-inflammatory supplements (fish oil, borage oil, DHEA, etc.) and cytokine-suppressing drugs (pentoxifylline, 400 mg twice a day) fail to suppress this destructive cytokine, then ask your doctor to prescribe the drug Arava (leflunomide), starting at the low dose of 10 mg a day.