A Joint Solution

April 27, 2009
Shazia Haq

Newspaper headlines jolted arthritis sufferers in March when Actemra, a drug treating rheumatoid arthritis, was taken off the market after 15 deaths were directly linked to its use. The producer of the drug, Chugai Pharmaceutical (Tokyo), the Japanese unit of Swiss drug maker Roche Holding AG (Basel, Switzerland), said in a report on its Web site that among 4915 rheumatoid arthritis patients who had been injected with Actemra between April 2008 and February 2009, there had been 15 deaths for which Roche could not deny the possibility of a link to the use of Actemra. "We can't deny that there is a causal relationship," a Chugai spokesman said.

Consumers, who may be wary of using pharmaceutical drugs to treat their painful joints, may look to more-natural supplement alternatives to alleviate their pain. Two new studies on tart cherries and hot chili peppers may provide manufacturers with some new glucosamine and chondroitin alternatives.

A Cherry a Day May Keep Arthritis Away

For the estimated 27 million Americans who suffer from osteoarthritis, joint relief may come with a cherry on top. According to researchers with the Baylor Research Institute (Dallas), tart cherries, in pill form, may be a promising pain reliever for this most debilitating form of arthritis.

More than half of the patients enrolled in a 2007 pilot study experienced a significant improvement in pain and function after taking the cherry pills for eight weeks. Osteoarthritis, the most common type of arthritis, is considered degenerative and typically affects the hands, feet, spine, and large weight-bearing joints, such as the hips and knees. Patients with osteoarthritis specifically in the knees were enrolled in this pilot study to assess the potential efficacy of tart cherry pills.

"The current treatment of osteoarthritis is largely focused on controlling pain through use of over-the-counter acetaminophen or prescription pain medications, as well as nonsteroidal antiinflammatory drugs," explains John J. Cush, PhD, rheumatologist and chief investigator of the study. He continues, "In some cases, overuse of medications may contribute to significant gastrointestinal, cardiovascular, hematologic, renal, and liver toxicity."

The preparation used in the study was made from ground whole Montgomery cherries and given to study participants as a soft gelatin capsule marketed under the brand name CherryFlex.

"This specific type of tart cherry is one of the best studied natural products and anecdotally has been claimed to have a salutary effect on osteoarthritis and other types of arthritis as well," adds Cush.

Baylor Research Institute, together with the Arthritis Care & Research Institute (Clearwater, FL), is currently enrolling patients in a second study, which will test cherry pills versus placebo in an eight-week double-blind study.

A Spicy Sensation

Another ingredient, capsaicin, is the active element in spicy hot chili peppers such as the jalapeño. Capsaicin's active compounds may help alleviate joint pain. Creams made with the ingredient may be an effective treatment for a variety of pain syndromes, from minor muscle or joint aches to those pains that are very difficult to treat, such as arthritis and neuropathic pain.

Published in the March issue of PLoS Biology, the study illustrates how capsaicin responds to pain, including one of the human body's most agonizing forms, joint pain. According to researchers, capsaicin binds to specific receptors on nerves responsible for pain.

The research used capsaicin to uncover new insight into how pain-receptor systems, such as human joints, can adapt to painful stimuli. Sensory systems are well known to adapt to prevailing stimuli, the study explained. For example, adaptation happens when your eyes adjust from a dark movie theater during a matinee to the bright sunlight outside. However an open question has remained as to whether pain receptors truly adapt or rescale their responses.

Capsaicin acts by binding to a receptor in the cell wall of nerve endings and triggering an influx of calcium ions into the neuron. When the cells open, extra calcium enters. The nerves become overwhelmed and shut down, thus numbing the pain from several weeks to months. Eventually, the nervous system interprets this cascade of events as pain or heat, depending on which nerves are stimulated.

I-SABI SENSATION

BIO-CELL TECHNOLOGY (Newport Beach, CA) has jumped on the spicy bandwagon by introducing its latest joint health ingredient, i-Sabi, made from Japanese horseradish. The ingredient offers pain relief qualities similar to those of the chili pepper. "Wasabi is the green horseradish condiment that spices it up. What gives the wasabi its sharp flavor are the isothiocyanates," said Toni Dizon of Bio-Cell Technology. "But isothiocyanates do much more than make wasabi flavorful-they can actually have a serious impact on your health," she said.

Scientists had previously linked the pain-relieving effects of capsaicin to a lipid called PIP2, found in cell membranes. When capsaicin is applied to the skin, it induces a strong depletion of PIP2 in the cell membrane.

"The receptor acts like a gate to the neurons," says Feng Qin, PhD, the study's leading author. "When stimulated it opens, letting outside calcium enter the cells until the receptor shuts down, a process called desensitization. The analgesic action of capsaicin is believed to involve this desensitization process." However, he adds, how the entry of calcium leads to the loss of sensitivity of the neurons was not clear.

By combining electrical and optical measurements, the authors now have been able to link directly the depletion of PIP2 and the desensitization of the receptor. The authors also showed that the receptor is fully functional after desensitization. For example, if consumers stop feeling pain or are desensitized, the desensitization does not affect new pain responses.

VITAMIN C MAY HALT THE DEVELOPMENT OF GOUT

MEN WITH HIGHER VITAMIN C intake appear less likely to develop gout, a painful type of arthritis, according to a report in the Archives of Internal Medicine. Researchers examined the relationship between vitamin C intake and the risk of developing gout in 46,994 men, ages 40 to 75, between the years of 1986 and 2006.

Men with the highest daily vitamin C intake of 1500 mg or more reduced their risk of developing gout by 45% compared with men who had a lower vitamin C intake of less than 250 mg a day.

The men who took part in the study were asked to complete a dietary questionnaire every four years. At two-year intervals, they reported whether they had been diagnosed with or had developed symptoms of gout. Over the follow-up spanning 20 years, a total of 1317 men went on to develop gout.

After adjusting for other risk factors, such as BMI and hypertension, the incidence of gout was found to fall with increasing vitamin C consumption.

"Gout is the most common type of inflammatory arthritis in men," the authors wrote in the study's conclusion. "Epidemiologic studies suggest that the overall disease burden of gout is substantial and growing."

Approximately 5 million people in the United States suffer from gout. The number of gout sufferers is rising, researchers say. The study revealed a 17% rise between 2007 and 2008 in the number of prescriptions made by general practitioners to treat severe attacks of gout.

"What changed was the responsiveness threshold," says Qin. "In other words, the receptor had not desensitized per se, but its responsiveness range was shifted. This property, called adaptation, would allow the receptor to continuously respond to varying stimuli over a large capsaicin concentration range."

With an adaptive response, the receptors are essentially autoregulated without a fixed threshold, Qin says. Thus, the intensity of the pain consumers experience is dependent on their recent, individual history of pain.