Suppliers and manufacturers consider multi-faceted natural approaches for supporting the inflammatory response.

Normal healthy inflammation is an integral part of the body’s immune response to injury and the attack of irritants or pathogens. Just like a wellprepared and alert army sends out warriors to capture and isolate foreign invaders and wall off damaged areas so they can be repaired; so does our immune system, through the inflammatory process, constantly functioning to prevent infection and heal damaged tissue.

Most of the time we are not even aware of it. The immune system does its job, the inflammation subsides and the body returns to homeostasis, said Nena Dockery, technical services manager with Missouri-based ESM Technologies.

However, the inflammatory process can have a darker side, she added. Factors such as obesity, smoking and other environmental irritants and pollutants, stress, dietary habits, prolonged infections and even certain medications can trigger a subtle inflammatory response that doesn’t turn off. When this occurs, the pro-inflammatory substances that are so helpful in healing tissue damage can themselves begin to be a source of damage, increasing the risk for chronic diseases.

“One area that is particularly prone to inflammation is the area in and around our joints,” Dockery pointed out. “The causes of this type of inflammation are diverse. Sports mishaps, continual joint stress, obesity, the consequences of the aging process and an overzealous immune system can all contribute to discomfort and inflammation in and around our joints; and it can become an ongoing condition in which the inflammation is not effectively resolved.” 

As a result, the Centers for Disease Control and Prevention (CDC) reported that doctors have told an estimated 50 million adults in the U.S. that they have some form of arthritis, rheumatoid arthritis, gout, lupus or fibromyalgia. In addition, published studies indicate that almost half of us will have symptomatic knee osteoarthritis by the time we are 85, and the statistic is even higher if we are obese or have suffered any type of knee injury.

“Therefore, this is an area in which we should all be attentive in doing what we can to adopt a lifestyle that includes not only healthy eating and exercise habits, but also nutrient supplements that support the body’s ability to maintain and protect our joints and surrounding tissue,” Dockery added.

Currently, the state of the market for natural products that deal with inflammation is growing, slowly but surely, said Dean Mosca, president of New Jerseybased Proprietary Nutritionals, Inc. “Those consumers who have been diagnosed with an inflammatory condition are well aware of the need to control and/or maintain healthy levels. However, many people who do not yet have symptoms of a condition exacerbated or caused by inflammation are becoming more aware that inflammation does have a negative impact and can contribute to the onset of conditions.” 

Dockery agreed. “The market for natural anti-inflammatory products is definitely growing,” she said, adding that it is predominantly due to the increased awareness of the issue. “There have always been products that address the normal incidence of acute inflammation resulting from muscle stress and strain associated with exercise and aging, and the market for these types of products continues to be mostly among sports enthusiasts and those experiencing the normal aches and pains of aging. However, products that focus on chronic inflammation present a growing trend.” 

Core Ingredients 

As for supplements, herbal anti-inflammatories continue to be strong performers. “Trademarked forms of such botanicals as Boswellia serrata, ginger or turmeric (curcumin) are popular, and the research supporting their use is growing,” Dockery noted. “These trademarked ingredients may be of higher quality and purity than their generic counterparts and have often undergone specialized processing to make them more bio-assessable, since intestinal absorbability can often be an issue that diminishes their potential efficacy. In addition, herbal and plant-sourced ingredients containing the active components anthocyanins and proanthocyanidins, such as pine bark extract, grape seed extract or açai, have been around for many years, but remain strong in both the anti-inflammatory and antioxidant segments.” 

Proprietary Nutritionals’ Perluxan™ is a proprietary, standardized supercritical extract of hops cones (Humulus lupulus L. ) with multiple mechanisms of action based on alpha acids. These fractions were found to be potent and specific inhibitors of pro-inflammatory chemicals and derivatives, giving Perluxan the ability to reduce pain-causing compounds in a short time with a low dose.

A clinical study of patients with knee pain showed Perluxan had a fast-acting effect on relieving discomfort and significant improvement over placebo after only two hours following the first dose. Another pilot study demonstrated that Perluxan was comparable to ibuprofen in reducing pain causing inflammatory enzymes.

Other anti-inflammatory ingredients include certain enzymes, such as bromelain, papain or serratiopeptidase, that are sold alone or in combination with other proteolytic enzymes, and function predominantly to resolve existing inflammation by helping to break down some of the substances contributing to the inflammatory process, Dockery added. Omega-3 fatty acids, quercetin, alpha lipoic acid and astaxanthin are ingredients that appear in multiple product types including antiinflammatory products.

“It is important to keep in mind that many of the ingredients commonly used in natural anti-inflammatory products may simply work in one aspect of the inflammatory process,” said Dockery. “It is also vital that we recognize that not all inflammation is bad, and our bodies use this powerful mechanism to protect us and guard our health. Therefore, though in general natural products are much safer than pharmaceutical anti-inflammatories including NSAIDs and steroids, some natural anti-inflammatories are really more appropriate for use in acute conditions on an occasional basis.” 

For continual use, it is important to look for products that function more to support the inflammatory response rather than eliminate it, Dockery said, pointing out that an ingredient such as natural eggshell membrane (NEM®) is marketed principally for joint health. Published clinical studies support NEM’s effectiveness and safety for use in conditions that result in pain and inflammation in and around joint tissue. And unlike many ingredients marketed for joint health, the results can be experienced in as little as seven to 10 days.

However, this food-sourced ingredient appears to function as a general anti-inflammatory as well, by moderating the immune system response to inflammation rather than by eliminating it. A recently published human cell culture study demonstrated that NEM exhibits diffuse immunomodulatory properties. These findings indicate that NEM may work effectively with the body’s own immune system processes to help control inflammation in the joint and surrounding tissue. As a result, long-term safe use is more assured.

“In addition, many of the popular ingredients used in anti-inflammatories are subject to varying degrees of quality or require certain conditions for administration to facilitate absorption and improve efficacy or to ease the risk for gastric upset,” Dockery said. “For example, proteolytic enzymes should only be taken on an empty stomach to ensure that the intact enzymes are absorbed through the intestinal wall so they can function systemically. NEM exhibits advantages in this respect as well, since its efficacy and absence of side effects are not dependent upon the presence or absence of food in the gastrointestinal tract. And, since NEM’s effectiveness is neutral in respect to dosing conditions, it can be easily combined with other ingredients.” 

The Omega Balance 

Consumer awareness of inflammation and its causes are not very well known, agreed Becky Wright, communications and marketing manager with Washington-based Aker BioMarine Antarctic US Inc. “The exception would be the familiarity with products containing NSAIDs, which address acute inflammation and pain. However, these products should never be recommended for long-term use due to their side effects,” she said.

“We think a more holistic approach to inflammation is the way to go. Whereas things like NSAIDs approach the symptoms of inflammation, nutrients like omega-3s go right to the cause and bring the body back into balance with regard to the omega- 6/omega-3 ratio,” Wright added, noting that the American diet is typically very heavy in omega-6 fatty acids due to the over-consumption of processed foods. Omega-3 consumption, on the other hand, is very low by comparison. As a result, the ratio of omega-6 to omega-3 is about 30:1, when an ideal ratio should really be 4:1.

“Recent evidence has shown that omega-3 fatty acids have anti-inflammatory properties. In this vein, krill oil may be effective for the management of arthritic symptoms,” said Wright. “In fact, krill oil supplementation, in a mouse model of arthritis, has shown beneficial effects on inflammation processes in joint tissue by suppressing the development of collagen- induced arthritis (CIA). More specifically, krill oil was shown to reduce the arthritis scores and hind paw swelling when compared to a control diet containing no EPA and DHA. Mice supplemented with krill oil presented lower infiltration of inflammatory cells into the joint compared to control animals. In conclusion, krill oil provided inhibition of arthritis scores and joint pathology in the CIA model.” 

Innovative Ideas 

One area of innovation currently widespread within the industry is the use of select secondary ingredients or processing mechanisms that enhance the intestinal bioassessibility of nutrients, Dockery said. “This is particularly true for several botanical ingredients and isolated active compounds that have shown promise in in vitro studies but failed to have clinical significance because of their poor intestinal absorbability or their functioning is weakened or destroyed by the digestive process after oral administration.” 

In the most recent NEM study, one aspect was to demonstrate the comparative activity of NEM after exposure to digestive conditions. Not only did the digestive process not inhibit the functioning of NEM, but in one important study facet evaluating the effects on pro-inflammatory cytokine activity, it actually enhanced the positive results by decreasing the production of the pro-inflammatory cytokine, TNF-alpha.

Another area of ongoing innovation involves the unique delivery of nutritional supplements, and these developments have become a burgeoning part of the dietary supplement industry, Dockery pointed out. “Advances in nutrient dispensing forms including beverage stick packs (sachets) are convenient and an ideal way to consume efficacious doses of nutrients in tasty fluids. Gummies are another delivery form that is gaining in popularity. They are chewable and often taste more ‘candy-like’ even though they can be nutrient packed.” 

Most natural products sold for inflammation have been on the market for many years, added Larry Robinson, PhD and vice president of scientific affairs with Embria Health Sciences in Iowa. “Various herbs and spices have been around for decades and even centuries.” The company’s EpiCor® ingredient is actually one of the more innovative products recently introduced into the market place, he said. It is a natural whole fermentation product that has been clinically proven to support immune health by both strengthening the immune response when needed (defense against pathogens) while at the same time reducing undesirable immune responses (as to pollen and inflammation).

“Because of the large number of diverse anti-inflammatory products and the differences noted, it is not possible to discuss how each supplement may be beneficial or how they work,” Robinson explained. “However, it is important that the anti-inflammatory ingredient chosen be backed by sound clinical research as well as animal and in vitro studies. That is why EpiCor has developed such a strong science base, showing it can both strengthen and balance the immune system so that it is neither over-stimulated nor suppressed, but responds appropriately.

“Care needs to be taken, because many immune products claiming to balance the immune system, have only been shown through research to stimulate the immune system; which is not what you’re looking for when you want a product that helps with chronic inflammation,” Robinson continued. “While EpiCor science shows that it can effectively deal with inflammation, the science also shows that it doesn’t suppress the immune response, so that at the same time the consumer is better protected against pathogens.” 

While fish oil continues to be the best source of the most important omega-3s EPA and DHA, Keri Marshall, MS, ND, chief medical officer with Californiabased Nordic Naturals, said the company is seeing growth in algal oils as an alternative for vegetarians. The company has recently introduced Algae Omega™ and Baby’s DHA Vegetarian™, “both of which contain a unique algae oil that has significant amounts of EPA, as well as high levels of DHA,” she said.

Nordic Naturals also offers a popular effervescent product, Omega-3 Effervescent™, which is convenient for every day as well as for travel. And its latest innovation, Nordic Omega-3 Jellies™, is designed to capitalize on a delivery method’s growing popularity. “Chewables continue to be very popular, particularly (but not exclusively) with children’s products,” said Marshall. “Our Omega-3 Jellies has the fruit flavor and fun, chewy texture kids love, but parents appreciate the product’s potency (250 mg EPA and DHA) and the convenience of individual packs.” 

Research 

The medical reports on inflammation and its connection to overall health continue to mount. “In a society in which the majority of us are both overweight and inactive, the stress on our joints is overwhelming,” said Dockery. “But it is very difficult to overcome those conditions if pain and inflammation have already begun to take their toll. As a result, even a cursory internet search reveals countless articles on joint pain and inflammation. It is no surprise that, according to both the CDC and WebMD, musculoskeletal problems and arthritis are the leading causes of disability in the U.S.” 

A study of interest, Mosca pointed to new research by University of Pennsylvania (published in Immunology) that unveiled the mechanism of action of IL-27 (interleukin) by positively affecting Tregs (regulatory T-cells) in a way that helps suppress inflammation. Previously, researchers understood that various Tregs act as “brakes” on forms of inflammation, but how these Tregs became specialized was unclear. In tandem, researchers believed that IL-27 was responsible for helping cause inflammation, but in 2005, University of Pennsylvania researchers found IL-27 was actually suppressing inflammation. This newly published study exposed Tregs to IL-27 and found such a relationship promoted the Tregs’ ability to suppress a certain kind of inflammation. The research team believes that IL-27 is necessary to produce Tregs that normally restrain an inflammatory response, notably when infection occurs.

Natural Message 

While research is promising, there is no magic pill to rid the body of inflammation linked with disease—a dose of healthy discipline is still needed. “We are staunch believers in the power of a healthy diet and lifestyle to positively impact health and well-being,” concluded Mosca. “For those marketing partners, we would suggest as part of their literature, website or social media, to list the foods that nutrition science has shown helps control inflammation along with the foods that make it worse.”

Extra! Extra!

Visit niemagazine.com to read about Carnegie Mellon research linking stress and inflammation.

FORMOREINFORMATION:

Aker BioMarine Antarctic U.S.,(206) 855-6736

Embria Health Sciences, (877) 362-7241

ESM Technologies, (417) 358-4822

Nordic Naturals, (800) 662-2544

Proprietary Nutritionals, Inc.,(800) 526-0609