Cherries and arthritis

by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

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If you’ve got arthritis, you've probably investigated what the natural approaches are to treatment. Cherries may be one of them.

From the editors of Arthritis Today... and the Arthritis Foundation...

Researchers from Michigan State University found anthocyanins, the same chemicals that give tart cherries their color, may have powerful anti-inflammatory effects that are equal to and perhaps even stronger than aspirin.

Dr. Muralee Nair, associate professor with the Bioactive Natural Products Laboratory in the Department of Horticulture and National Food Safety and Toxicology Center at MSU, isolated various components of tart cherries. He was aided in this research by Dr. Gale Strasburg, MSU associate professor of Food Science and Human Nutrition. Dr. Strasburg developed a technique to rapidly assess the antioxidant activity of the purified components. Dr. Nair used frozen tart cherries blended with water to isolate the compounds. Then Dr. Strasburg tested the compounds to find out whether they showed promising antioxidant activity.

They discovered that a number of the tart cherry compounds analyzed by Dr. Strasburg's method had excellent antioxidant properties. "This was the first time that we knew these compounds had antioxidant properties," says Dr. Nair. "The antioxidant activity of the tart cherry compounds, under our evaluation systems, is superior when compared to vitamin E, vitamin C and some synthetic antioxidants." In particular, there are three anthocyanins associated with the bright red color of tart cherries that are excellent antioxidants. However, as many as 14 other compounds in tart cherries also have antioxidant activity. During the next year, the MSU researchers plan to investigate what levels of tart cherry consumption are needed to obtain beneficial antioxidant effects.

Antioxidants are believed to inhibit free radicals, which occur in normal human metabolism but may be causative in diseases, such as arthritis. There is interest in the identification and use of naturally occurring antioxidants to replace synthetic ones. "Based on the combined research at MSU, we hypothesize that tart cherries are a rich source of naturally occurring antioxidants, which could be effective replacements for synthetic antioxidants in foods," says Dr. Strasburg.

"Twenty cherries provide 25 milligrams of anthocyanins, which help to shut down the enzymes that cause tissue inflammation in the first place, so cherries can prevent and treat many kinds of pain," says Muraleedharan Nair, the lead researcher on the cherry project at Michigan State University. The anthocyanins also may protect artery walls from the damage that leads to plaque build up with subsequent heart disease. In fact, the latest research shows that anthocyanins perform better than vitamins C and E in protecting arteries.

The current research on the health benefits of cherries began with a study conducted by Dr. Alden Booren, professor of Food Science and Human Nutrition at MSU, in 1994. He investigated the use of cherries in very lean ground beef. "Our trained taste testers found the cherry-beef mixtures to be very desirable and had equal to or better flavor than those from lean ground beef," says Dr. Booren. "We also found that reheated ground beef with cherries was essentially devoid of oxidized or rancid flavors." Dr. Booren and other researchers suspected that it was the antioxidant properties of tart cherries that were responsible for these effects, which lead to the current research projects.

Dr. Won Song, a professor in the Department of Food Science and Human Nutrition at MSU and a registered dietitian, reviewed all of the previously published literature on the health benefits of cherries. She was amazed at the number of references in consumer publications. "There is even anecdotal information on the Internet," says Dr. Song. "While I found no scientific research to support the anecdotal information in these publications, we have learned enough that I believe there is a potential scientific connection that can be tested and proven." Dr. Song believes that tart cherries in some way modify enzyme and/or chemical activity in the body.

Research cited above by the Cherry Marketing Institute is from research conducted by the National Safety and Toxicology Center at Michigan State University;

Wang, H. et al. 1999 Anti-oxidant and Anti-inflammatory Activities of Anthocyanins and their Alglycon, Cyanid, from Tart Cherries. Journal of Natural Products 62(2): 294-296.

In this study (Journal of Natural Products, 1999), researchers used the equivalent of 20 tart cherries. They found anthocyanins in the tart cherries inhibited two enzymes, COX-1 and COX-2, that play a role in the body's production of prostaglandins, natural chemicals involved in inflammation. This process to block inflammation is similar to the effects of aspirin and traditional non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen. Tart cherries are also good sources of antioxidants, substances which destroy free radicals, the damaging molecules thought to contribute to many diseases, including arthritis.

Other fruits, berries, and vegetables may contain substantial amounts of similar substances as well. According to lead researcher Muralee Nair, Ph.D., both cherries and blueberries, for example, contain potent antioxidants. However, Nair found that the inflammation-blocking activity of tart cherries was considerably greater. It's still unknown how sweet cherries would stack up.

One caveat is research in humans has not yet been done to determine whether cherries will actually relieve arthritis symptoms outside the lab. "The Arthritis Foundation does not see any harm in eating cherries for antioxidant protection, but does not believe there is enough proven clinical evidence to suggest that eating cherries is beneficial for reducing the pain and inflammation associated with arthritis," says John Klippel, M.D., the foundation's medical director.

If you still want to give tart cherries a try, there is also the question of how to consume them. The raw cherries are tart and cooking destroys many of the beneficial compounds. So, eating a slice of cherry pie won't do. Other options are tart cherry juice and tart cherry concentrate, both of which are sold at supermarkets and health food stores. According to the Cherry Marketing Institute, an 8-ounce glass of cherry juice contains the equivalent of about 100 cherries. Once again, though, some beneficial compounds can be lost during processing. Says Nair, "If the juice has been heated too much, there will be less anthocyanins in it." The juice is also acidic, so people with a sensitive stomach may not be able to tolerate it.

According to even more recent research at Michigan State University, tart cherries are an excellent source of compounds with anti-oxidant and anti-inflammatory properties. Anti-oxidants are generally recognized as useful in preventing cancer and other diseases. The anti-oxidant activity of the tart cherry compounds, under the MSU evaluation system, is superior when compared to vitamin E, vitamin C and some synthetic anti-oxidants.

Tart cherries contain natural anti-inflammatory compounds. In laboratory tests, MSU research indicates that tart cherry compounds are at least 10 times more active than aspirin. The advantage of tart cherries is that they are more effective without any of the adverse side effects of aspirin.

In addition, other research has revealed that the production of a hormone (prostaglandin) is the cause of joint pain. The production of this hormone is directly related to two enzymes. The tart cherry anti-inflammatory compounds are suspected to have the ability to inhibit the enzymes that ultimately cause joint pain."

This research, which is still ongoing, substantiates what some consumers have believed for years -- that tart cherries have important health benefits. There are numerous references in consumer publications, such as newspapers, magazines, books and even Web sites, that link cherries to beneficial health effects. In addition, a recent survey of cherry growers (see below) shows that they have a lower incidence of cancer and heart conditions than the general public. The growers, on average, eat about six pounds of tart cherries per year, while other Americans eat about one pound of tart cherries annually.

Recently published research conducted at Michigan State University investigated a range of fruits and berries for the level and activity of anthocyanins found in each.

Researchers analyzed the ability of the fruits to inhibit cyclooxygenase and act as antioxidants to destroy free radicals. The researchers then quantified the anthocyanin levels of tart and sweet cherries, raspberries, strawberries, blackberries, blueberries, cranberries, elderberries and bilberries.

Cyclooxygenase is produced in the body in two or more forms, termed COX-1 and COX-2, for different purposes. COX-1 is built in many different cells to create prostaglandins, which are used for basic “housekeeping” messages throughout the body. The second enzyme, COX-2, is built only in special cells and is used for signaling pain and inflammation.

Some pain relief medication works by blocking the messages carried by COX-1, COX-2, or both, and thus the body does not feel pain or inflammation. The anthocyanins that are able to block COX-1 and COX-2 are called Anthocyanins 1 and 2, respectively.

Researchers discovered that the antioxidant activity of anthocyanins from cherries was superior to vitamin E at a test concentration of 125 µg/ml. The COX inhibitory activities of anthocyanins from cherries were comparable to those of ibuprofen and naproxen at 10 µM concentrations.

Anthocyanins 1 and 2 are present in both cherries and raspberries. The yields of pure Anthocyanins 1 and 2 in 100 g of cherries and raspberries were the highest of the fruits tested at 26.5 and 24 mg, respectively.

Fresh blackberries and strawberries contained only Anthocyanin 2 at a total level of 22.5 and 18.2 mg/100 g, respectively; whereas Anthocyanins 1 and 2 were not found in bilberries, blueberries, cranberries or elderberries.

Cyclooxygenase inhibitory and antioxidant cyanidin glycosides in cherries and berries.

2001 Sept; Seeram NP, Momin RA, Nair MG, Bourquin LD.Department of Horticulture and National Food Safety and Toxicology Center, Michigan State University, East Lansing 48824, USA.

Anthocyanins from tart cherries, Prunus cerasus L. (Rosaceae) cv. Balaton and Montmorency; sweet cherries, Prunus avium L. (Rosaceae); bilberries, Vaccinum myrtillus L. (Ericaceae); blackberries, Rubus sp. (Rosaceae); blueberries var. Jersey, Vaccinium corymbosum L. (Ericaceae); cranberries var. Early Black, Vaccinium macrocarpon Ait. (Ericaceae); elderberries, Sambucus canadensis (Caprifoliaceae); raspberries, Rubus idaeus (Rosaceae); and strawberries var. Honeoye, Fragaria x ananassa Duch. (Rosaceae), were investigated for cyclooxygenase inhibitory and antioxidant activities. The presence and levels of cyanidin-3-glucosylrutinoside 1 and cyanidin-3-rutinoside 2 were determined in the fruits using HPLC.

The antioxidant activity of anthocyanins from cherries was comparable to the commercial antioxidants, tert-butylhydroquinone, butylated hydroxytoluene and butylated hydroxyanisole, and superior to vitamin E, at a test concentration of 125 microg/ml.

Anthocyanins from raspberries and sweet cherries demonstrated 45% and 47% cyclooxygenase-I and cyclooxygenase-II inhibitory activities, respectively, when assayed at 125 microg/ml. The cyclooxygenase inhibitory activities of anthocyanins from these fruits were comparable to those of ibuprofen and naproxen at 10 microM concentrations.

Anthocyanins 1 and 2 are present in both cherries and raspberry. The yields of pure anthocyanins 1 and 2 in 100 g Balaton and Montmorency tart cherries, sweet cherries and raspberries were 21, 16.5; 11, 5; 4.95, 21; and 4.65, 13.5 mg, respectively.

Fresh blackberries and strawberries contained only anthocyanin 2 in yields of 24 and 22.5 mg/100 g, respectively. Anthocyanins 1 and 2 were not found in bilberries, blueberries, cranberries or elderberries.

Degradation products of cyanidin glycosides from tart cherries and their bioactivities.

2001 Oct.; Seeram NP, Bourquin LD, Nair MG.Bioactive Natural Products and Phytoceuticals, Department of Horticulture and National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824, USA.

The bioactive anthocyanins present in tart cherries, Prunus cerasus L. (Rosaceae) cv. Balaton, are cyanidin 3-glucosylrutinoside (1), cyanidin 3-rutinoside (2), and cyanidin 3-glucoside (3). Cyanidin (4) is the major anthocyanidin in tart cherries. In our continued evaluation of the in vivo and in vitro efficacy of these anthocyanins to prevent inflammation and colon cancer, we have added these compounds to McCoy's 5A medium in an effort to identify their degradation products during in vitro cell culture studies. This resulted in the isolation and characterization of protocatechuic acid (5), the predominant degradation product. In addition, 2,4-dihydroxybenzoic acid (6) and 2,4,6-trihydroxybenzoic acid (7) were identified as degradation products. However, these degradation products were not quantified.

Compounds 5-7 were also identified as degradation products when anthocyanins were subjected to varying pH and thermal conditions. In cyclooxygenase (COX)-I and -II enzyme inhibitory assays, compounds 5-7 did not show significant activities when compared to the NSAIDs Naproxen, Celebrex, and Vioxx, or Ibuprofen, at 50 microM concentrations. However, at a test concentration of 50 microM, the antioxidant activity of protocatechuic acid (5) was comparable to those of the commercial antioxidants tert-butylhydroquinone (TBHQ), butylated hydroxytoluene (BHT), and butylated hydroxyanisole (BHA), and superior to that of vitamin E at 10 microM concentrations

And even more evidence...

Researchers at the USDA Human Nutrition Research Center in Davis, California, recently found that women who ate 45 cherries every morning markedly reduced inflammatory indicators linked with gout, a very painful form of arthritis. (Agricultural Research, 2004; 52: 18). In the study of women aged 22 to 40, blood levels of uric acid, which deposit out in tissues and cause the pain and inflammation during a gout attack, decreased significantly after eating a breakfast of fresh Bing cherries. Additionally, urine levels of urate crystals increased significantly. While the study showed a decrease in nitric oxide and C reactive protein, two key markers of inflammation, the decrease wasn’t statistically significant but offered intriguing possibilities for the anti-inflammatory effects of cherries.

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