Inflammatory Conditions on the Rise

April 6, 2008



Inflammation is now a top health concern of consumers, thanks to the growing number of people with cardiovascular disease and arthritis. Every 26 seconds, one American will have a coronary event, and more than 45 million people are battling joint-related conditions, according to the Centers for Disease Control and Prevention (CDC; Atlanta).

Diet may play a strong role. Studies suggest that some foods and supplements possess antiinflammatory properties that offer protection against heart disease and the breakdown of cartilage. However, many of these studies are preliminary, and only a few have reached the stage of clinical trials. Moreover, the effects of natural ingredients are nuanced and difficult to predict, causing some studies to yield mixed or negative results. While it's too early to tell what effects foods and supplements have on various inflammation-related conditions, re­searchers are learning more, and they are optimistic about the future.

CHOLINE AND BETAINE

One promising study that examined the relationship between diet, inflammation, and cardiovascular health was the ATTICA study, a cross-sectional trial involving thousands of Greek men and women. In the February 2008 issue of the American Journal of Clinical Nutrition, a research team from Harokopio University (Athens) and the University of Athens reported that high intakes of two food-based ingredients, choline and betaine, may be inversely associated with inflammation.

Choline plays an important role in the structure of phospholipids and is also a component of the neurotransmitter acetylcholine. Betaine is a metabolite of choline involved in the methylation of homocysteine, a suspected risk factor for heart disease.

Using a combination of food-frequency questionnaires and blood samples, the researchers tried to determine if there were any associations between choline and betaine intake and known markers for inflammation, such as C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and homocysteine. They found that individuals with the highest choline and betaine intake had the lowest concentrations of IL-6, TNF-α, and homocysteine. Moreover, people with high choline and low betaine had the lowest CRP levels.

Noting that the cross-sectional design of the trial could not prove a cause-and-effect relationship between the ingredients and inflammation, the researchers called for more research, including randomized clinical trials. They added that two large, recent studies did not show a relationship.

In an editorial accompanying the article, Steven Zeisel, MD, PhD, a researcher from the University of North Caro­lina's School of Medicine (Chapel Hill, NC), suggested multiple biological mechanisms may be at work. "If the association between choline and betaine and inflammation can be confirmed in studies of other populations, an interesting new dietary approach may be available for reducing chronic diseases associated with inflammation," he wrote.

YEAST

Yeast (Saccharomyces cerevisiae) already has a multitude of uses, ranging from brewing to baking to biological re­search. One of its newest applications may be as a dietary supplement with immune-enhancing and antiinflammatory properties.

When the body is injured, immune system cells known as leukocytes migrate to the affected areas, initiating inflammation and swelling. In a study published in the June 2007 issue of Nutrition Research, researchers evaluated the antiinflammatory effects of a yeast-related ingredient by exposing it to a range of human leukocytes in a panel of in vitro, cell-based assays.

Using EpiCor, a dietary supplement ingredient derived from S. cerevisiae and supplied by Embria Health Sciences (Ankeny, IA), the researchers identified several potential antiinflammatory mechanisms, including the reduction of reactive oxygen species (ROS) and the inhibition of the proinflammatory cytokine interferon gamma (IF-γ). In addition to supplying the ingredient, Embria also sponsored the study.

"As several ROS play roles in cell signaling, it is likely that EpiCor is capable of reducing the background noise of chronic inflammation, thereby increasing the capacity for maintaining balanced immune responses," wrote the researchers. The team added that while EpiCor did appear to activate types of lymphocytes known as NK cells, it did not lead to greater production of IF-γ.

MSM

The sulfur-based compound methylsulfonylmethane (MSM) was also the subject of a promising in vitro experiment. At the 2007 World Congress on Osteoarthritis, held December 6–9 in Fort Lauderdale, FL, a team of re­searchers from the University of California at San Diego (UCSD; La Jolla, CA) and the University of Arizona (Tucson, AZ) described the results of a study that examined MSM's effects on damaged joint cartilage.

In the study, which appeared in the December 2007 issue of Osteoarthritis and Cartilage, the researchers extracted 22 postmortem samples of osteoarthritic cartilage tissue, dividing them into four grades based on the level of damage. They then isolated chondrocyte cells from the tissues, grew the cells in culture, exposed the cells to various concentrations of MSM, and measured various markers for inflammation. Bergstrom Nutrition (Vancouver, WA), the manufacturer of OptiMSM, supplied the ingredient used in the study.

The researchers noted that cells grown from the samples with minimal fibrillation (i.e., grade II) that were exposed to 12 µg per ml of MSM showed less antiinflammatory activity. Specifically, they found a drop in TNF-α and interleukin-1 (IL-1) levels. However, the researchers did not find the same effect on cells collected from samples with more-advanced arthritis.

According to lead researcher David Amiel, PhD, a professor of orthopedic surgery at UCSD, the study suggests that MSM may "shield" cartilage in the early stages of osteoarthritis from further damage. The team plans further research this year to identify the optimal dose of MSM in people.

PINE BARK EXTRACT

Pine bark extract, like several of the ingredients mentioned earlier, is a rich source of antioxidants. While many clinical studies involving the extract have measured its effects on the cardiovascular system, some researchers believe it also may be useful for people with osteoarthritis. Last year, a team of researchers from Mashdad Medical University in Iran tested the extract in a small pilot trial with 37 volunteers.

Reporting in the No­vember 2007 issue of Nutrition Research, the team gave the volunteers either a placebo or 50 mg of Pycnogenol, a pine bark extract supplied by Horphag Research (Ge­neva) three times per day for three months. The re­searchers evaluated the extract by administering the WOMAC scale, which measures pain and physical function.

After 90 days, the participants in the placebo group felt no change, but the volunteers who received the extract experienced a 43% reduction in pain and a 35% drop in stiffness. The treatment group also relied less on pain relievers like nonsteroidal antiinflammatory drugs and COX-2 inhibitors.

According to the researchers, the extract may reduce pain by inhibiting COX-1 and COX-2 enzymes along with nuclear factor KB, a protein complex that helps regulate the immune system. Horphag, which provided funding for the research, expects more studies involving Pycnogenol and osteoarthritis to be published in 2008.

OLIVE VEGETATION WATER

Olives have been a staple of the Mediterranean diet for thousands of years. Although a number of the foods in the regimen may be responsible for its salutary effects, a new study suggests why olives could be a particularly important component of the diet.

Olives contain a high concentration of antioxidant poly­phenols, including hydroxytyrosol, a metabolite of oleuropein. Olive vegetation water (OVW), a by-product of olive oil production, is a particularly rich source of hydroxytyrosol.

In a study published in the August 2007 issue of Nutrition Research, Arizona State University (Tempe, AZ) scientists examined the effects of OVW on volunteers with osteo­arthritis and rheumatoid arthritis. For eight weeks, the volunteers received either a placebo or 400 mg of Hidrox, a freeze-dried OVW ingredient supplied by DSM Nutritional Products Inc. (Parsippany, NJ). Hidrox developer Cre­Agri Inc. (Hayward, CA) contributed funding for the study.

After administering joint pain questionnaires and taking blood samples to detect changes in homocysteine, the researchers found that the volunteers in the treatment group enjoyed significantly greater mobility and less discomfort. The team also noted lower levels of CRP and homocysteine in the volunteers with rheumatoid arthritis.

COLLAGEN HYDROLYSATE

Inflammation isn't just a concern of the elderly. Athletes also suffer from joint pain due to mechanical stress and injury. To shed some light on the problem, researchers from Penn State University studied the effects of collagen hydrosylate on 147 students.

In a randomized, double-blind trial, the students received either a placebo or a daily dose of 10 g of collagen hydro­lysate for 24 weeks. The researchers found that the students with knee pain in the treatment group experienced greater improvement than students in the placebo group. Moreover, the researchers also found that collagen hydrolysate also reduced the need for concomitant pain therapies. The research was presented at the 2007 World Congress on Osteoarthritis in Fort Lauderdale, FL.

"The clinical data collected show that collagen hydro­lysate significantly alleviates the joint symptoms in persons that pursue active sports," according to Klaus Flechsenhar, MD, head of medical research at Gelita AG (Eberbach, Germany), which supplied its CH-Alpha ingredient to the researchers. "This could well result in an increase in overall performance."

GLUCOSAMINE AND CHONDROITIN

Fermented Glucosamine a Solution for Vegetarians

Vegetarians get joint pains just like everyone else. Unfortunately for them, one of the most popular joint supplement ingredients, glucosamine, is usually derived from shellfish.

Several companies have begun to address vegetarian concerns by offering vegetable-source glucosamine manufactured via fermentation technology. Last March, the Coca-Cola Co. (Atlanta) launched a version of its Minute Maid orange juice with 750 mg of glucosamine per serving. Coke used Cargill's (Minneapolis) Regenasure gluco­samine, which attained generally recognized as safe status in 2007.

One of the newest sources of vegetarian glucosamine is GreenGrown, a kosher-certified ingredient supplied by Ethical Naturals Inc. (San Anselmo, CA). According to Ethical Naturals president Cal Bewicke, GreenGrown is 100% vegetable sourced and does not contain aquaculture byproducts, eliminating the need for shellfish allergen warning statements.

"With new uses for glucosamine in the beverage and food markets, combined with the expanded, ongoing demand for joint care supplements, the unique qualities of GreenGrown glucosamine are already attracting a substantial amount of interest in the supplement industry," says Bewicke.

Glucosamine and chondroitin are two of the most popular joint health supplements. While many studies and numerous anecdotal reports suggest that the supplements may be beneficial for some groups of people with arthritis, there is considerable disagreement among scientists about their benefits. Further complicating matters is the fact that many recent studies have used various methods, populations, formulas, and dosages, making it difficult to compare and contrast results.

In February of 2006, the organizers of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) reported that the combination of glucosamine and chondroitin produced only mixed results and helped only those with moderate-to-severe knee pain. More recently, Dutch researchers reported in the February 19, 2008, issue of the Annals of Internal Medicine that glucosamine failed to provide relief in patients with osteoarthritis of the hip in a two-year, placebo-controlled study.

On the other hand, different studies have produced positive outcomes. For instance, six clinical trials involving more than 1000 patients have explored glucosamine and chondroitin's ability to slow the progression of knee osteoarthritis, and two other studies have examined their ability to slow hand osteoarthritis, according to Bioiberica (Barcelona, Spain), which manufactures the chondroitin ingredient CSb Bio-Active.

Moreover, in the February 2008 issue of Osteoarthritis and Cartilage, the Osteoarthritis Research Society International (Mount Laurel, NJ) included glucosamine and chondroitin in a list of eight recommended treatments for the management of hip and knee osteoarthritis. The society based its recommendations on a review by 16 experts of research published between 1945 and 2006.

BOTANICAL FORMULAS

While specialty supplements like glucosamine, chondroitin, and MSM remain top choices for consumers, several botanicals may also be helpful for people concerned about inflammation. In fact, there is growing interest surrounding three tropical plants with antioxidant and antiinflammatory properties.

Prized by cold and flu suffers, the immunomodulating herb Andrographis paniculata naturally inhibits inflammatory cytokines and COX-2 enzymes, according to H.P. Ingredients (Bradenton, FL), which manufactures the andrographis ingredient ParActin. The herb is a bitter plant that grows in tropical regions in India and other parts of Asia.

Polypodium leucotomos is a South American fern that grows approximately 2000–8000 ft above sea level. According to Gourmetceuticals LLC (Big Horn, WY), which supplies an aqueous extract of the plant called PPL-240, the plant is a strong antioxidant that may help offer protection against damage induced by ultraviolet light.

The third tropical plant, Croton pa­lanostigma, also known as sangre de grado, is used traditionally in the Amazon region as an antiinflammatory and wound-healing agent. In the August 2007 issue of the Journal of Inflammation, Case Western Reserve University School of Medicine (Cleveland) researchers reported that an extract of the plant in­hibited the activity of cartilage-destroying enzymes known as matrix metalloproteases. Rainforest Nutritionals Inc. (Raleigh, NC) supplied its croton extract, Progrado, for the study.

CONCLUSION

Due to the aging of the baby boom­er population, healthcare providers are bracing for millions of new cardiovascular disease and arthritis patients. The growing incidence of heart disease is starting to take its toll, and a wave of new arthritis cases isn't far behind. Although nearly 20% of Americans already have arthritis, the number could expand by 40% by 2030, according to new CDC data released January 2. Making matters worse, nearly 300,000 people under the age of 18 also face arthritis or other rheumatological conditions.

"The prevalence of arthritis overall continues to grow in the United States, which is not surprising given that many of the specific conditions are age related and the general population is aging," according to CDC epidemiologist Charles Helmick, MD. "Increases in some of the more common types of arthritis suggest a growing impact on the healthcare and public health systems."

Diet and natural products may have a positive influence on these conditions in the near future. While much is still unknown, additional clinical research on supplements and functional foods should shed more light on their potential to alleviate inflammation as well as their limits.