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Quenching the Fires of Inflammation

By Jack Challem, The Nutrition Reporter™

Physicians have long recognized inflammation as the culprit in asthma, arthritis, and many painful "-itis" diseases. But almost overnight, medicine has been redefining inflammation as the root of most chronic diseases.

Amazing as it may sound, the latest findings point to chronic low-grade inflammation as the underlying cause of coronary heart disease, Alzheimer's, and some types of cancer. Even obesity and diabetes have powerful undercurrents of inflammation.

This changing view of inflammation has grown largely out of a new respect for C-reactive protein (CRP), a blood protein that both promotes and reflects inflammation levels in the body. Using a new and particularly sensitive blood test, known as high-sensitivity CRP, Paul Ridker, M.D., of the Harvard Medical School, has found that elevated levels of inflammation increase the risk of a heart attack by four and one-half times. That strong association makes CRP a far more accurate predictor of heart-attack risk than either cholesterol or homocysteine.

The fact that high blood levels of CRP are found in a variety of serious and chronic conditions points to what might best be called an "inflammation syndrome." For example, the inflammation in obesity and diabetes may "metastasize" throughout the body, setting the stage for inflamed blood vessels and an increased risk of heart disease.

A Normal Process Gone Awry

Inflammation is a normal part of the body's immune response to infection or injury. Activated white blood cells secrete a variety of inflammation-promoting compounds, including interleukin-6 (IL-6), CRP, free radicals, and prostaglandins, to fight germs and to dispose of damaged cells. After the body recovers, the immune system and its white blood cells should settle down.

But that doesn't always happen. Instead, low-grade inflammation will often simmer for years, eventually turning serious or repeated injuries to knee cartilage into osteoarthritis. Similarly, inflammation may quietly damage the heart or brain cells.

CRP and IL-6 are highly specialized molecules called cytokines, which function as chemical messengers between cells. Somewhat like a cellular Paul Revere, they help activate armies of white blood cells that, in chronic inflammation, can turn against normal tissues. The big question is: what stimulates this pro-inflammatory activity in the first place? Part of the answer lies in the foods people eat.

A Diet that Sets the Stage for Inflammation

Your body makes two families of hormone-like compounds, called prostaglandins, which either promote or reduce inflammation. The "parent" molecules of these prostaglandins occur in dietary fats, also known as fatty acids.

The largely pro-inflammatory omega-6 fatty acids are found in most cooking oils, such as corn, safflower, peanut, and soybean oils. In contrast, the anti-inflammatory omega-3 fatty acids are found in fish (particularly coldwater species, such as salmon), flaxseed, and leafy green vegetables. The body converts the fatty acids in these foods into more potent pro- and anti inflammatory prostaglandins.

Saturated fats have little influence on inflammation, but trans fatty acids (identified on labels as partially hydrogenated oils) interfere with the enzymes needed to process fatty acids, particularly the omega-3 fatty acids. A particular type of omega-6 fatty acid, gamma-linolenic acid, behaves more like an anti-inflammatory omega-3 fat. And oleic acid, an omega-9 fatty acid in olive oil, also has anti-inflammatory properties.

Your body's levels of all of these fatty acids reflect dietary intake. Historically, diets contained relatively equal amounts of omega-6 and omega-3 fatty acids, providing a balance between the body's pro- and anti-inflammatory activities. But in highly processed foods - think fast foods and packaged convenience foods - the ratio of omega-6 to omega-3 fatty acids has increased to roughly 15:1 to 30:1. The result primes people for chronic inflammation, while greatly reducing the body's ability to turn off inflammation.

And surprisingly, carbohydrates can be just as problematic as some fats. According to research by Simin Liu, M.D., Ph.D., of the Harvard Medical School, a diet high in refined carbohydrates and high-glycemic foods (which rapidly raise blood sugar levels) also seems to increase inflammation. In a recent study, Liu found that women eating large amounts of potatoes, breakfast cereals, white bread, muffins, and white rice had elevated CRP levels, indicating high levels of inflammation and an increased risk of heart disease. Overweight women who ate these foods had the highest and most dangerous CRP levels.

An Anti-Inflammatory Diet

Changing some of the foods you regularly eat will boost your body's levels of anti-inflammatory compounds. That can reduce the pain of rheumatoid arthritis and other "-itis" diseases and lower your long-term risk of many other chronic diseases.

Eat more fish

Coldwater fish, such as salmon, mackerel, and herring, contain large amounts of two potent omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Research by Bruce Caterson, Ph.D., of Cardiff University, Wales, has found that omega-3 fish oils inhibited "aggrecanases," a family of enzymes that breaks down cartilage. The fish oils also block the activity of several inflammation-promoting compounds, including tumor necrosis factor alpha (TNFa), and cyclooxygenase-2 (COX-2).

Cook with healthier oils. Olive-oil, macadamia nut oil, and cold-pressed canola oil are rich in oleic acid, an omega-9 fatty acid. Studies have shown that olive oil reduces the activity of "adhesion molecules," which promote inflammation and may play a major role in reducing symptoms of rheumatoid arthritis. Avoid all other cooking oils and margarine, which can be high in omega-6 fatty acids and trans fatty acids. Use only salad dressings made with olive oil.

Eat more vegetables

Nonstarchy and low-starch vegetables, such as broccoli, cauliflower, green beans, and salad greens, contain several anti-inflammatory nutrients. First, their antioxidants help neutralize free radicals, which promote inflammation. Second, greens are rich in alpha-linolenic acid, the basic building block of omega-3 fatty acids. Thirds, greens also contain small amounts of GLA, which enhances the anti-inflammatory effect of omega-3 fatty acids.

Cut back on refined carbs

Sugars, refined grains (white bread, pasta), and starchy vegetables (potatoes) raise insulin levels, which may in turn boost CRP levels. At the very least, these high-calorie foods displace healthier nutrient-dense choices, such as fish and vegetables. And all of the empty calories in high-carb foods may contribute to excess weight, which also leads to higher levels of pro-inflammatory CRP and IL-6. Here's list of foods high in protein to help you plan your meals.

Anti-Inflammatory Nutrients

Many studies have shown that dietary supplements can bolster the body's own ability to control and reduce inflammation. Unlike aspirin, ibuprofen, or Cox-2 inhibiting drugs, these supplements are exceptionally safe.

Fish oils

Fish oil supplements, rich in EPA and DHA, leapfrog the body's need to convert alpha linolenic acid to EPA and DHA. That's important because trans fatty acids, found in many processed foods, interfere with the enzymes involved in making EPA and DHA.

Fish oil supplements can speed up the benefits of eating fish two or three times weekly. They reduce levels of many inflammation-promoting compounds, including prostaglandin E2 and CRP. In one study, Scottish researchers found that daily fish oil capsules led to less pain and less need for anti-inflammatory drugs.

Dosage: 3 grams of fish oils daily. Flaxseed oil capsules may be used by vegetarians.

GLA - Gamma-Linolenic Acid

Although gamma-linolenic acid, or GLA, is technically an omega-6 fatty acid, it is part of the body's normal system of checks and balances to control excessive inflammation. GLA boosts levels of prostglandin E1, which reduces inflammation caused by prostaglandin E2.

Robert Zurier, M.D., of the University of Massachusetts, Worcester, conducted two studies using GLA to treat patients with rheumatoid arthritis. Both 1.4 and 2.8 grams of GLA daily, lead to significant reductions in symptoms.

Dosage: 1.4 grams to several grams daily. GLA supplements are derived from evening primrose, borage, or black currant oils. The amount of GLA is more important than the source, so read the fine print on the label.

Vitamin E

Several clinical studies have found that natural vitamin E can lower CRP levels by an impressive 30 to 50 percent and IL-6 levels by 50 percent. This effect may account for the vitamin's well-known heart benefits. The anti-inflammatory benefits of vitamin E were also noted in two clinical trials that found the vitamin of benefit in patients with rheumatoid arthritis.

Dosage: 400 IU daily, but a clearer anti-inflammatory effect may be achieved at 800 or 1,200 IU daily.

Vitamin C, glucosamine, and chondroitin

These three supplement are commonly used to reduce the pain of osteoarthritis and to rebuild articular (joint) cartilage. But they - along with methylsulfonylmethane (MSM) - may have far broader tissue-rebuilding benefits. Vitamin C is required for the formation of collagen, one of the most basic proteins in the body. Meanwhile, glucosamine, chondroitin, and MSM provide rich sources of sulfur, a mineral that helps hold tissues together.

Dosage: 500-1,000 mg of vitamin C and 1,000 mg each of glucosamine, chondroitin, and MSM daily.

Flavonoids

Thousands of antioxidant flavonoids have been identified in plants, and probably all have some anti-inflammatory properties - and are likely a big part of the reason why vegetables are good for health. Several specific flavonoids may be helpful in reducing inflammation, specifically quercetin, Pycnogenol®, and grape-seed extract.

Dosage: 300-500 mg of quercetin daily or 150-300 mg of Pycnogenol or grape-seed extract daily.

Botanical Herbs

All herbs are rich in flavonoids, which likely accounts for their anti-inflammatory properties. Boswellia, cat's claw, devil's claw, green tea extracts are particularly potent anti inflammatory herbs. Because of its mild taste, green tea has the advantage of being consumed as a beverage.

Dosage: Herbal potencies can vary depending on their form, such as capsule/tablet or tincture. Follow either label directions of advice from a naturopathic physicians or herbalist.

References

Ridker PM, Hennekens CH, Buring JE, et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. New England Journal of Medicine, 2000;342:836-843.

Liu S, Manson JE, Buring HE, et al. Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women. American Journal of Clinical Nutrition, 2002;75:492-498.

Curtis CL, Hughes CE, Flannery CR, et al. n-3 fatty acids specifically modulate catabolic factors involved in articular cartilage degradation. Journal of Biological Chemistry, 2000;275:721 724.

Yaqoob P, Knapper JA, Webb DH, et al. Effect of olive oil on immune function in middle-aged men. American Journal of Clinical Nutrition, 1998;67:129-35.

Linos A, Kaklamani VG, Kaklamani E, et al. Dietary factors in relation to rheumatoid arthritis: a role for olive oil and cooked vegetables. American Journal of Clinical Nutrition, 1999;70:1077-1082.

Lau CS, Morley KD, Belch JJF. Effects of fish oil supplementation on non-steroidal anti inflammatory drug requirement in patients with mild rheumatoid arthritis - a double-blind placebo controlled study. British Journal of Rheumatology, 1993;32:982-989.

Leventhal LL, Boyce EG, Zurier RB. Treatment of rheumatoid arthritis with gammalinolenic acid. Annals of Internal Medicine, 1993;9:867-873.

Zurier RB, Rossetti RG, Jacobson EW, et al. Gamma-linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled study. Arthritis & Rheumatism, 1996;11:1808 1817.

Upritchard JE, Sutherland WHF, Mann JI. Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes. Diabetes Care, 2000, 23:733-738.

Devaraj S, Jialal I. Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients. Free Radical Biology & Medicine, 2000; 29:790-792.

Edmonds SE, Yinyard PG, Guo R, et al. Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo controlled double blind trial. Annals of the Rheumatic Diseases, 1997;56:649-655.

Helmy M, Shohayeb M, Helmy MH, et al. Antioxidants as adjuvant therapy in rheumatoid disease - a preliminary study. Arzneimittel-Forschung/Drug Research, 2001;51:293-298.

The Inflammation Syndrome

By Jack Challem, The Nutrition Reporter™

Your morning stiffness may not yet qualify as arthritis, but it's likely a sign of inflammation simmering throughout your body. Other red flags include elevated blood sugar levels, high cholesterol levels, or a few extra pounds around the middle - each of which may help set the stage for serious inflammatory diseases.

This startling news comes as medicine is quickly changing its view of inflammation. Just a few years ago, chronic inflammation was pretty much defined as arthritis and other "-itis" diseases. Today, it's also regarded as a likely cause of heart disease, Alzheimer's, and some cancers.

Normally, inflammation helps fight infections and initiate the healing process after an injury. But it doesn't always routinely fade away. Sometimes, inflammation festers in one part of the body, perhaps related to allergies or an injured knee, then spreads out and eventually leads to a cluster of related disorders: the inflammation syndrome.

C-Reactive Protein

Over the past 10 years, researchers have found runaway inflammation in most major health problems. For example, white blood cells, which release large amounts of inflammation-causing substances, play an early role in damaging artery walls and setting the stage for cholee.

The development a simple, accurate, and inexpensive blood test for measuring inflammation has helped researchers and physicians zero in on one of the key players: C-reactive protein (CRP). In a major study, published in the New England Journal of Medicine, people with elevated CRP levels were four and one-half times more likely to have a heart attack. Not only is elevated CRP more accurate than cholesterol in predicting heart attack risk, but high CRP levels have turned up in people with diabetes and prediabetes and in people who are overweight.

The body makes CRP from interleukin-6 (IL-6), a powerful inflammation-causing chemicals. IL-6 is a key cell communication molecule, and it tells the body's immune system to go into a full rage, releasing CRP and many other inflammation-causing substances.

Being fat increases inflammation because adipose cells, particularly those around the tummy, make large amounts of IL-6 and CRP. As blood sugar levels increase, so do IL-6 and CRP. Both overweight and high blood sugar levels increase the risk of heart disease, very likely because of the undercurrent of inflammation.

Good Fats and Antioxidants

Unlike cholesterol, CRP is not found in foods. However, its levels in the body are strongly influenced by diet. A recent study by Simin Liu, M.D., Ph.D., of the Harvard Medical School found that women who ate large amounts of high-glycemic (or diabetes promoting) carbohydrates, including potatoes, breakfast cereals, white bread, muffins, and white rice, had very high CRP levels. Women who ate a lot of these foods and were also overweight had the highest and most dangerous CRP levels.

Dietary fats also influence inflammation. Most omega-6 fats, found in margarine and corn and safflower oils, are the basic building blocks of arachidonic acid and prostaglandin E2, two of several key inflammation-causing substances in the body. In contrast, omega-3 fats, found in fish, fish oils, and vegetables, have an inflammation-suppressing effect.

Gamma-linolenic acid (GLA) is an omega-6 fat that enhances the anti-inflammatory effect of omega-3 fats. Both GLA and omega-3 fish oils have been found helpful in arthritis and other inflammatory disorders. GLA is found in leafy green vegetables and dietary supplements. Similarly, oleic acid, an omega-9 fat found in olive oil, avocados, and macadamia nuts, has anti inflammatory properties.

In addition, antioxidants lower CRP levels. They also curb inflammation by quenching hazardous molecules called free radicals, which stimulate inflammation. In one study, researchers found that people with high blood levels of carotenoids, including beta-carotene and lutein, had the lowest CRP levels.

Granted, those carotenoids may have simply been a marker for vegetable intake. But other studies have clearly shown that natural vitamin E supplements (800 IU daily) can lower CRP levels from 30-50 percent.

Inflammation tends to increase with age, making us more susceptible to disease. However, it is possible to significantly slow this process. The keys are cutting back on inflammation promoting foods, such as refined carbohydrates and omega-6 fats, and emphasizing anti inflammatory fats and antioxidants.

References

Ridker PM, Hennekens CH, Buring JE, et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. New England Journal of Medicine, 2000;342:836-843.

Pradhan AD, Manson JE, Rifai N, et al. C-reactive protein, interleukin-6, and risk of developing type 2 diabetes mellitus. JAMA, 2001;286:327-334.

Festa A, D'Agostino R, Howard G, et al. Chronic subclinical inflammation as part of the insulin resistance syndrome. The insulin resistance atherosclerosis study (IRAS). Circulation, 2000;102:42-47.

Visser M. Higher levels of inflammation in obese children. Nutrition, 2001;17:480-484.

Liu S, Manson JE, Buring HE, et al. Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women. American Journal of Clinical Nutrition, 2002;75:492-498.

Lau CS, Morley KD, Belch JJF. Effects of fish oil supplementation on non-steroidal anti inflammatory drug requirement in patients with mild rheumatoid arthritis - a double-blind placebo controlled study. British Journal of Rheumatology, 1993;32:982-989.

Curtis CL, Hughes CE, Flannery CR, et al. n-3 fatty acids specifically modulate catabolic factors involved in articular cartilage degradation. Journal of Biological Chemistry, 2000;275:721 724.

Zurier RB, Rossetti RG, Jacobson EW, et al. Gamma-linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled study. Arthritis & Rheumatism, 1996;11:1808 1817.

Linos A, Kaklamani VG, Kaklamani E, et al. Dietary factors in relation to rheumatoid arthritis: a role for olive oil and cooked vegetables. American Journal of Clinical Nutrition, 1999;70:1077-1082.

Kritchevsky SB, Bush AJ, Pahor M, et al. Serum carotenoids and markers of inflammation in nonsmokers. American Journal of Epidemiology, 2000;152:1065-1071.

Upritchard JE, Sutherland WHF, Mann JI. Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes. Diabetes Care, 2000, 23:733-738.

Devaraj S, Jialal I. Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients. Free Radical Biology & Medicine, 2000; 29:790-792.


Diet and Rheumatoid Arthritis: A review of the literature.

2005 Oct - Department of Medicine, Health Sciences, University of Otago, New Zealand.

Rheumatoid arthritis is a common inflammatory condition. A large number of patients seek alternative or complementary therapies of which diet is an important component. This article reviews the evidence for diet in rheumatoid arthritis along with the associated concept of oral tolerization. METHODS: References were taken from Medline from 1966 to September 2004. The keywords, rheumatoid arthritis, diet, n-3 fatty acids, vitamins, and oral tolerization, were used. RESULTS: Randomized controlled trials (RCTs) indicate that dietary supplementation with omega-3 fatty acids (n-3) provides modest symptomatic benefit in groups of patients with rheumatoid arthritis. Epidemiological studies and RCTs show cardiovascular benefits in the broader population and patients with ischemic heart disease. A number of mechanisms through which n-3 fats may reduce inflammation have been identified. In a small number of patients with rheumatoid arthritis, other dietary manipulation such as fasting, vegan, and elimination diets may have some benefit. However, many of these diets are impractical or difficult to sustain long term. CONCLUSIONS: Dietary manipulation provides a means by which patients can a regain a sense of control over their disease. Dietary omega-3 fatty acid supplementation is practical and can be easily achieved with encapsulated or, less expensively, bottled fish oil.

Semin Arthritis Rheum. 2005 Oct;35(2):77-94.



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The Inflammation Syndrome
by Jack Challem
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Coat the bottom of a baking dish with olive oil. Rinse and pat excess water off salmon fillets, and place them in the baking dish. Thinly coat the fillets with olive oil (to add flavor and to prevent burning). Sprinkle basil and oregano on the fillets. Drizzle the balsamic vinaigrette on the fillets. Bake for approximately 10 minutes at 350 degrees. The cooking time may vary by a couple of minutes depending on the thickness of the fillets, so examine them after 8 minutes to ensure that they are not burning or undercooked. Side dish: sauté fresh mushrooms, spinach, and almond slivers together in a fry pan. Second side dish: short-grain brown rice.
Serves 2.


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