As research consistently confirms chronic inflammation’s effect on overall health, manufacturers innovate to solidify supplements as an important part of the solution.

Inflammation is the body’s attempt at self-protection; the aim being to remove harmful stimuli, including damaged cells, irritants or pathogens, and begin the healing process. The natural biological response to a harmful or irritating factor is to try to remove it; inflammation is a part of the immune response to the invader.

“When a person sustains a bump or bruise, inflammation is a good sign as it shows that the body is responding to heal the localized physical assault that is the injury. However, sometimes inflammation can cause further inflammation— and this condition is chronic,” said Dean Mosca, president of Proprietary Nutritionals, Inc. (PNI) in New Jersey, noting that according to Medicalnewstoday.com, chronic inflammation often results from a low-intensity persistent irritant, an autoimmune response to a self-antigen and/or failure to eliminate the cause of acute inflammation.“When chronic inflammation exists, this state may cause and accelerate other destructive conditions such as periodontitis, atherosclerosis, rheumatoid arthritis and even some types of cancer.

“There is much work to do to increase awareness and understanding of the role of chronic inflammation, as it has multiple ways of presenting itself (conditions and diseases),” Mosca added. “In and of itself, the idea of eating and supplementing to control or manage chronic inflammation is not so easy to grasp, so there needs to be a continual managed effort by industry, notably companies with proven ingredients, to help in this area.”

Yet there are no available statistics for overall or chronic inflammation, said Jay Levy, director of sales with Californiabased Wakunaga of America Co., Ltd. “One reason is that, since much of the inflammation people experience is low level and systemic, they may not be aware of its existence. However, studies increasingly suggest that inflammation is a primary factor in a number of diseases … stress, a diet filled with inflammatory foods, hormonal changes during menopause and exposure to environmental toxins can all play a role in creating chronic inflammation.”

Becoming Conscious

Awareness in this area has significantly increased by researchers, medical professionals and consumers, as many of America’s deadliest diseases are now considered linked to a condition called “chronic inflammation.” “Heart disease, diabetes, stroke, Alzheimer’s and cancer are now all linked to the condition,” said Levy, noting that Wakunaga has been focusing more scientific research on inflammation not only related to immune and cardiovascular areas, but also inflammatory diseases of the gastrointestinal (GI) tract. “While the focus on treating chronic inflammation has been with drugs, researchers are now learning that healthier foods and natural products can play an important role in protecting against it.”

The company sees the market for anti-inflammatory supplements as strong with no expectation of slowing.

“The key market driver is Baby Boomer and elderly Americans seeking joint health products to enhance mobility and maintain an active lifestyle.”

This is true for retailer Elliott Sofhauser, general manager with Blue Water Natural Foods in Alpine, TX, who said that customers coming into the store seeking products that address inflammation usually have arthritis. “They are generally in their 40s to 70s.”

However, as people become increasingly aware of inflammation’s role in disease, more demand among those over age 65 is anticipated, Levy added. To that end, the category remains one of the top in the specialty supplement market, with three notable market drivers for this sector:

1) Further scientific and clinical confirmation that chronic inflammation is associated with numerous disorders such as cancer, atherosclerosis, inflammatory bowel diseases (IBD) and rheumatoid arthritis (RA).

2) As the Boomer population confronts diseases, the demand increases for dietary supplements targeted toward inflammation.

3) Dietary supplement ingredient and product companies take advantage of trends and develop new, more advanced products for the marketplace.

“When these products are supported by clinical trials, they will be more accepted by the medical community and the consumer,” said Levy.

A look at the numerous products on the shelves at a local food, drug or mass market store is a clear indication that the market is strong, Mosca agreed. “The bigger challenge is helping consumers distinguish between the variety of ingredients in terms of which are backed by research, what results can be expected and how to properly use them,” he said.

Products & Ingredients

Justin Zehrung, vice president of Arizonabased Essential Source Inc., offered that the market for products is growing at a rapid pace due to the plethora of conditions and ailments that stem from or are affected negatively by inflammation. “That growth is also due to the effectiveness and success stories of the standout natural products being used.”

The company has focused on nopal cactus fruit extract, which is used along with aloe vera, in its product NopaVera.“This comes from our research and development department spending the time and money it takes to identify attributes and effects that are greater than that of competing products,” Zehrung said.

Retailer Jim Adkisson, a sales associate with the family-owned Vita-Man Nutrition Center in Las Cruces, NM, said they were one of the first stores to carry NopaVera, which was launched in December 2012. “We’ve carried it for a few months and we have had a very positive response,” Adkisson said. “An older woman, who was one of the first to purchase the product, came back after one month to buy six more bottles.She said she was able to stop taking some of her pharmaceuticals.She was very impressed with it and has referred others to the store.”

Adkisson said the product is a “fastacting liquid form. I’ve been told it has the highest concentrate of nopal on the market. And it’s not bad tasting.”

Levy offered that aged garlic extract, the cornerstone of Wakunaga’s products, bears inflammation consideration due to the growing number of scientific studies showing its benefits. “Rich in antioxidant compounds, aged garlic extract has been shown to boost cellular antioxidants, including glutathione which protects cells from damage caused by oxidation and inflammation.”

Another key anti-inflammatory ingredient is curcumin, which is derived from the curry spice turmeric. Curcumin has been shown in numerous studies to downregulate COX-2 and iNOS enzymes, likely by suppressing NF-kB activations. It also inhibits arachidonic acid metabolism, scavenges free radicals, promotes apoptosis and inhibits the production of inflammatory cytokines, said Levy.

Since it is estimated that more than 70 percent of the immune system is tied to the gut, probiotics are also being studied for their role in boosting immune response to inflammation as well decreasing inflammation in the intestinal tract.Inflammatory diseases, such as IBD, are associated with alterations in microflora, and dietaryinduced changes in the gut’s microbial composition have been shown to be of therapeutic value in IBD and other inflammatory diseases.

Recent research out of UC Irvine Medical Center showed that Wakunaga’s Kyo-Dophilus probiotics may have both anti-inflammatory effects, and thus may be useful for GI inflammation, Levy noted.

Plant sterols have also been shown to help control chronic inflammation.Manufactured by Wakunaga, Kyolic’s Moducare plant sterols contain a proprietary mix of plant sterols and sterolins, in a clinically proven ratio of 100:1. “This mixture is derived from a natural pine source and has been show to have anti-inflammatory properties by switching off the release of proinflammatory factors such as interleukin 6 (IL6) and tumor necrosis factor-alpha (TNF-a) from activated monocytes,” Levy said, adding that Moducare’s antiinflammatory properties may help reduce the effects of stress on the immune system by managing the release of cortisol, a stress hormone.

Also addressing widespread inflammation, Michael Kramarczyk, enzyme specialist with Arizona’s HCP Formulas, said enzyme usage continues to increase as more sufferers are searching out natural alternatives for pain and inflammation. “Systemic enzyme blends have evolved such over the past decade that users no longer have to take handfuls of pills to get relief, resulting in better compliance and better economics,” he explained. “Powerful ingredients such as Seaprose-S and superoxide dismutase (SOD) have been introduced into formulations, making them even more effective for inflammatory conditions.

“Systemic enzymes are also recommended for their quadruple duty; in addition to their anti-inflammatory properties, they also help to dissolve excess fibrin, cleanse the circulatory system and detoxify the body,” he added.

In regard to inflammation from activity, Tim Hammond, vice president of sales and marketing for Washingtonbased Bergstrom Nutrition, supplier of the MSM ingredient OptiMSM, said several studies have found that MSM down-regulates the expression of inflammatory markers (from different stimuli) through interaction with nuclear factor kappa B. “Additional studies suggest its efficacy in a number of areas, with causality tied to inflammation. Our most recent studies on healthy populations suggest that MSM reduces the oxidative stress due to strenuous exercise.”

Another alternative is PNI’s Celadrin, a proprietary blend of esterified fatty acids, that when used topically or orally is an effective natural anti-inflammatory ingredient. Studies have shown benefits of reduced pain and swelling, increased movement and reduction of inflammatory factors from the ingredient, noted Mosca.

Results of a double-blind, multi-center, placebo-controlled trial published in the Journal of Rheumatology found that Celadrin, when taken orally, improved joint and mobility problems. Sixty-four participants between the ages of 37 to 77 were given Celadrin capsules for 68 days. Compared to those in the placebo group, participants who consumed Celadrin showed more flexibility, less aches and pain, and were able to walk longer distances.

Also published in the Journal of Rheumatology were results from research performed at the University of Connecticut involving 42 patients with osteoarthritis of the knee, who received either Celadrin applied topically or a placebo. The group receiving Celadrin had outstanding results with reduced pain and stiffness, improved balance and strength and better mobility. Within 30 minutes of applying Celadrin, patients experienced a dramatic improvement in all aspects tested.

Product Innovation

Most sufferers seeking natural remedies for pain and inflammation have chronic, rather than acute, symptoms, HCP Formulas’ Kramarczyk pointed out.“Users are looking for products that are not only effective, but also extremely safe as a long-term solution. The consumer is smarter than ever and is asking the right questions about fillers, excipients and artificial ingredients,” he said, noting that retailers are having tremendous success with the company’s new systemic enzyme, Fibrenza. “They are excited to talk about a formula that doesn’t contain phthalates or residual solvents from enteric coatings. And recent advancements in capsule technology have allowed for ‘clean’ delivery systems that offer the protection of traditional enteric coatings, resulting in effective products that users can still feel confident about taking for the long term.”

Key innovations for inflammation products revolve largely around absorption and bioavailability, particularly for curcumin, which is not well absorbed by the body, said Levy, adding that strides have indeed been made to improve its absorption. Wakunaga of America manufactures the Kyolic Curcumin product, which uses a proprietary combination of aged garlic extract and curcumin-phosphatidylcholine phytosome complex that increases both absorption and bioavailability of beneficial curcuminoids, he said. A recent pharmacokinetic study documented an average 29- fold increase in curcuminoid absorption compared to a conventional curcumin mixture. “With such a marked increase in absorption and bioavailability, this new form of curcumin can produce benefits at much lower doses than those currently used,” Levy noted.

Other news in the industry points to antioxidant-containing botanicals and fruits that have positive inclinations toward addressing healthy inflammatory response, added Mosca. “For example: caffeine may help block inflammation in the brain, good to support cognitive health; tomato juice rich in lycopene may cut down inflammation levels; and bilberries may help reduce inflammation in the bowels,” he said. “Again, all this illustrates advancements in understanding the link between foods/supplements and inflammatory response, which can create opportunities for developing novel products in the self-care market.”

A challenge is that inflammation is such a broad subject and only general statements can be made, added Bergstrom’s Hammond. “Consumers are normally interested in a condition-specific application—our OptiMSM sales continue to be strong because the consumer can easily relate to the joint health category.”

Fish Oil Science

Levy acknowledged that one of the best-known ingredients in the inflammation category is fish oil. “The fish oil compound DHA (docosahexaenoic acid) has long been known to have antiinflammatory effects, and now researchers have gained a better understanding of why this occurs,” he said.

“A new study in The FASEB Journal suggests that DHA is a vital player in the production of molecules called maresins, which are able to turn off inflammation,” Levy explained. “Other research has found that EPA and DHA specifically reduce inflammation implicated in cardiac dysfunction.”

Among the number of recently published studies involving fish oil and inflammation, suggest that supplemental fish oil reduces postsurgical inflammation as well as systemic inflammation in overweight subjects. And scientists at Ohio State University have also shown that fish oil supplementation reduces inflammation and modulates adipose tissue in women at high risk of breast cancer.

With that in mind, how does the recent study published in the Journal of the National Cancer Institute on the effect of fish oil and prostate cancer affect manufacturers in regard to inflammation?

“Because the validity of this particular study has been called into question, we do not anticipate that it will affect the popularity of fish oil supplements,” Levy stated. “This was not a prospectively designed trial in which the men were randomized to receive different doses to determine whether the omega-3 fatty acids actually did result in an increased risk for disease. More importantly, there are some issues about the design of the study that raise serious questions about the soundness of the data. For instance, the men in the control group were not diagnosed with prostate cancer. What’s more, the frequency of PSA testing was not mandated. Neither was how that PSA test was managed, whether they had a prostate biopsy or how the prostate biopsy was done.”

Another design flaw is that they assigned Gleason 3+4 tumors into the low-risk category and Gleason 4+3 tumors into the high-risk category, when the standard approach is to have Gleason 7 assigned to an intermediaterisk group of patients, Levy pointed out.

“There was also no uniform method for how men achieved their level of omega-3 fatty acids. Was it diet or was it supplements? Which supplements were used and what dosages were used?” he added. “All of these problems contribute to an uncertainty and potential bias in the results.”

Working With Customers

With all the news about research on inflammation, Essential Sources’ Zehrung shared that many of the company’s retailers find most consumers suffering from inflammation don’t know that it’s happening. “They usually come in unaware that the pains in the muscles or joints, difficulty breathing from respiratory inflammation, or bodily fatigue, could be from inflammation. So sharing inflammatory symptoms is always important, and also having firsthand experience using the products helps tremendously.”

And virtually everyone has some systemic low-level inflammation, added Levy. “However, the impact of this inflammation can vary based on the individual. Unless the customer is looking for a supplement to address a specific inflammatory condition like osteoarthritis, it may be best to provide them with information about more generalized anti-inflammatory supplements such as high-quality fish oil like Kyolic Omega-3,” he said. “Recommending a highly standardized, heavily researched product that works on many different facets of inflammation should give [retailers] confidence in knowing customers are getting a proven product that works, that will keep them healthy and coming back for more.”