Triggered by damage to the body, inflammation is normal and necessary when we have an injury, but at the root of almost all serious illnesses when chronic.

Inflammation is the body’s natural response to outside invaders it perceives as threats. Specifically, it’s a process in which white blood cells protect the body from foreign substances such as bacteria and viruses.

However, when the body is in a chronic state of inflammation, the inflammation can lodge in muscles, joints and tissues. In fact, chronic inflammation is a leading cause of many diseases, both physical and neurological, including heart disease.

“Inflammation is one of the most critical functions in the body and it can promote a balance or an imbalance in one’s health,” said Steve Holtby, president and CEO, Soft Gel Technologies, Inc. (Los Angeles, CA). “Its primary purpose is to protect the body from stress. When the body is exposed to stress, the white blood cells that are part of the immune system deliver defensive compounds, such as cytokines and interleukins, to the site of that stress. Inflammation is characterized by fluid buildup, heat and redness, joint pain, stiffness and loss of joint function.”

Holtby explained that nutrients supply the most basic building blocks of the body’s powerful inflammatory compounds.

“The ‘parent’ nutrient is linoleic acid, found in many foods but especially concentrated in vegetable oils (e.g., corn, soy and safflower oils),” he said, adding that the body converts linoleic acid to the omega-6 family of fatty acids, including arachidonic acid. COX-2 plays a critical role in converting arachidonic acid to the hormone-like prostaglandin E2 (PGE2) and to the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFa), all of which promote inflammation.

“The COX-2 enzyme is naturally created in us all and is considered by many to be stimulated by injury or some form of attack on the body,” Holtby added.
“Simply put, it controls the creation of a hormone-like substance that creates inflammation. And not just the common inflammation many experience in a knee or shoulder, but also inflammation throughout the body, even in the brain of an Alzheimer’s sufferer.”

Holtby stressed that it is important to understand how the enzyme works to create threatening disease conditions.

“The COX-2 enzyme, or cyclooxygenase- 2, has the job of oxidizing, or burning, a fat in the body called arachidonic acid. This fat is an omega-6 fatty acid, and it occurs naturally in all of our cell membranes or walls,” he explained.

“Picture the COX-2 enzyme as a sparkplug that ignites this fat and cooks up inflammatory substances. Simply put, the enzyme is the spark, the fat is the fuel and the flame of inflammation is the end result. That ‘fire’ is needed: it helps the body defeat enemies like bad bacteria, and helps it marshal its forces to respond to trauma and injury. But sometimes the fire burns too hot or gets out of control, and when that happens our bodies can be casualties of ‘friendly fire.’”

Inflammation Susceptibility

Researchers are just beginning to discover some of the problems that result from chronic systemic inflammation, noted Kevin Ruff, PhD, MBA and director of scientific and regulatory affairs with ESM Technologies (Carthage, MO).
“Localized chronic inflammation, in arthritis for example, leads to localized tissue damage which then exacerbates the condition.”

Ruff also noted that acute inflammation tends to be an equal opportunity issue, affecting all ages. However, chronic inflammation tends to affect older adults.

Holtby agreed, noting that as humans grow older, systemic inflammation can inflict devastating degenerative effects throughout the body.

But he pointed out that over the past 30 years or so, Americans have replaced much of their dietary saturated fat with omega-6 fatty acids. “It is estimated that people are now eating 20 times more omega-6s than omega-3s. From a biochemical standpoint, this lopsided imbalance in dietary intake of the omega-6 and omega-3 fatty acids sets the stage for powerful and chronic pro-inflammatory reactions,” Holtby said.

People who rely on a junk food diet, a stressful lifestyle, those carrying excess weight, smokers and even people with negative attitudes are those that may more readily fall into an excess inflammation situation, added Julie Dennis, national science educator with Threshold Enterprises, Ltd. (Scotts Valley, CA), distributor of Source Naturals and Planetary Herbals products.

“People who are prone to anger, hostility and mental health symptoms respond to stress by an increased production of the stress hormone norepinephrine, which triggers the immune system and the expression of genes that cause metabolic inflammation,” she said.

“Inflammation can start to build from an early age depending on the child’s lifestyle and environment. For example, sitting in front of a TV or computer screen instead of getting fresh air and healthy outdoor play, eating fatty junk foods and exposure to second hand smoke may trigger early development of excess metabolic inflammation.”

Ingredients for Inflammation

There are a number of wellness ingredients known to have anti-inflammatory properties. Two of the oldest ingredients are Boswellia serrata (frankincense) and turmeric root (containing curcumins), said Ruff. “Both ingredients are believed to act at the later stages of the inflammatory cascade by inhibiting eicosanoid biosynthesis of prostaglandins—mediators of pain and inflammation that are the end products of cyclooxygenases, specifically COX-2.” Preliminary experiments from a new ingredient derived from eggshell membranes, ESM’s NEM®, show that it may act earlier in the inflammatory cascade through the inhibition of pro-inflammatory cytokines, such as TNF-a and IFN-g, Ruff said.

Curcumin (from turmeric) is particularly potent at addressing inflammation—if one can absorb enough to make a difference, added Cheryl Myers, chief of scientific affairs and education with EuroPharma, Inc. (Green Bay, WI).

EuroPharma, Inc. (Green Bay, WI).

“Curcumin has a broad spectrum impact on reducing substances called cytokines that trigger an inflammatory response in the body,” she said.

However, plain 95 percent curcumin is poorly bioavailable, meaning that it doesn’t pass easily from the gastrointestinal tract into the bloodstream. The curcumin that does reach the bloodstream quickly converts into other compounds, so huge doses of curcumin powder are necessary to get significant health benefits.

“Our company uses a special, high bioavailability curcumin called BCM-95,” Myers said. “We use this exclusively in our curcumin-based products, the most well known of which is Curamin, the best natural pain relieving product in the market. Our other very popular product, CuraMed, is the single curcumin ingredient in a highly bioavailable form.”

Along with turmeric, other wellresearched ingredients include ginger, fish oils, quercetin, bromelain and other systemic enzymes, N-acetyl cysteine, glutathione, as well as many well-known building block nutrients such as vitamin E, selenium and vitamin C, said Nancy Angilini, national science educator at Source Naturals and Planetary Herbals.

“First, it must be understood that there are many enzyme pathways that result in many different types of inflammation.So, in truth, there are many different ingredients that can have a balancing effect in regards to many, if not all of these inflammatory pathways,” Angilini said.

From a dietary standpoint, ingesting the best “ingredients” means switching from vegetable oils to extra-virgin olive oil (high in anti-inflammatory omega-9 fatty acids), Holtby added. “It also means avoiding most processed (boxed, canned or frozen) foods, because their makers frequently add omega-6 fatty acids. By eating simple unprocessed foods, such as baked chicken, a salad and steamed vegetables, it becomes easier to consume a more balanced ratio of omega-6 and omega-3 fatty acids.

“Scientists discovered many herbs that can safely, powerfully and naturally inhibit the COX-2 enzyme,” Holtby continued.

That list includes, along with turmeric, green tea, ginger, holy basil, chamomile, Chinese goldthread, barberry, Baikal skullcap, Hu zhang (Japanese knotweed), rosemary, hops, feverfew and oregano. “A blend of the appropriate extracts of those herbs, if sufficiently concentrated, may offer substantial relief from the ‘fires’ of COX-2 inflammation, without the known and unknown side effects of synthetic drug inhibition,” he said. “And the even better news is that when these herbs inhibit the COX-2 enzyme, many of them also powerfully inhibit platelet aggregation (thus helping to prevent strokes and heart attacks) and heal ulcers. This is the genius of nature, and why cultures for thousands of years have obtained healing benefits from extracts of these botanicals.”

Holty also noted that antioxidant-rich foods and/or supplements provide powerful compounds that not only slow oxidation, but also serve as anti-inflammatory agents.

Bioflavonoids such as quercetin, resveratrol and polyphenols have natural anti-inflammatory properties. A diet that includes coldwater fish, such as salmon and tuna, plus abundant vegetables and fruits and limits the amount of saturated fats and trans fats, would be helpful in combating inflammation.
A Mediterranean diet, exercise, marine lipids (a source of essential fatty acids), CoQ10 and other dietary supplements can impact oxidative stress and inflammation.

While food is our medicine and medicine is our food, in many ways supplements can offer an ease in creating regularity with intake that food may not always offer, said Angilini. “Different dosage forms (supplements, foods, beverages) are all fine for addressing chronic inflammation—the key is to take the product long term so as to gradually normalize the immune system response,” added Ruff.

Trends and the Market

For ingredient suppliers, the latest trend in products for inflammation is that more emphasis is being placed on absorption and bioavailability. “It is clear from the existing body of science that many of these valuable anti-inflammatory ingredients like eriocitrin, quercetin, curcumin, hesperitin and PMF (polymethoxylated flavones) are highly insoluble limiting their efficacy,” said Mike Khalil, president and CEO with Apex Nutraceuticals, LLC (Irvine, CA).

“More emphasis is being placed on delivery systems that improve solubility, absorption and ultimately bioavailability.”

Several elements are at work making inflammation a growing problem.

“Perhaps the greatest factor affecting the use levels of these ingredients that address inflammation is the steady aging of the American population, and the increased incidence of rheumatoid arthritis and other medical conditions induced by inflammation, typically seen among the middle aged and elderly,” said Khalil.

An increasing incidence of obesity among Americans is also resulting in greater numbers of diseases and illness— and at younger ages—due to the potential for increased stress placed upon joints, heart and other organs, Khalil added. “This obesity epidemic is being seen not only in America and Canada, but also in many other economically advanced countries. The use of such ingredients/products is likely continue to increase in the US, Canada and Europe as well as developing countries as consumers have more disposable income to spend on discretionary items—and as they become ever more aware of popular consumer trends in America and other advanced economies.”

“When our caloric intake is increased and our activity level is decreased, this, of course, leads to weight gain,” said Holtby. “What we fail to understand is that where the fat gets deposited, particularly around our abdomen (central obesity) and our internal organs (visceral fat), it leads to an increased secretion of many important hormones and chemicals, including pro-inflammatory cytokines. These chemicals increase oxidative stress and inflammation in the Body, which then leads to a cascade of problems, such as increased insulin production.

Insulin resistance also causes stress and inflammation, so you can see the vicious cycle.”

Understandably, when joint pain hits, many consumers reach for NSAIDs such as aspirin, ibuprofen and naproxen— potent inhibitors of the COX enzymes, which cause pain and inflammation, Holtby pointed out. “Unfortunately, NSAIDs aren’t selective; they inhibit both the COX-1 and COX-2 enzymes with varying intensity. So, while pain may be reduced by blocking the COX-2 enzyme, non-selective inhibition of COX- 1, whose job is to protect the gastrointestinal (GI) tract lining, can lead to dangerous side effects.” As a result, GI-related adverse events are common, he said.

The pharmaceutical industry’s answer to the COX problem was to develop selective COX-2 inhibitors—drugs that would shut down COX-2 enzymes, but not COX-1, Holtby added. Prescription medications such as Vioxx, Bextra and Celebrex soon became available but these drugs had even worse side effects than traditional NSAIDs, dramatically increasing the risk of heart attack and stroke.

“The problem was that they were too selective. By completely shutting down COX-2, these drugs are theorized to suppress production of the blood-clotting hormone prostacyclin and other cardioprotective enzymes, thus increasing cardiovascular events,” Holtby explained.

“With the prevalence of chronic joint pain and the dangers presented by pharmaceutical drugs, it’s no surprise that sales of joint health supplements have recently soared,” he said. “In fact, the joint health category has surpassed calcium to become the largest market of condition-specific dietary supplements, according to a recent Packaged Facts report. The category was worth $174 million in 2007, up 11 percent from 2006 figures.”

With numerous studies pursuing the angle that inflammation is the root of all things negative to health, the market is expanding rapidly, noted Chris Haynes, director of sales with ESM Technologies.

“If this line of thinking is to be supported and followed, there is really no telling how large this category can become.” 

So are suppliers and manufacturers ready for the demand? “To some extent, our marketing hands are tied due to regulatory issues,” Haynes answered.
“While there are some very promising studies, creating marketing and health claims for anti-inflammatory materials can be very challenging. Over the course of the next decade, material suppliers will have to continue to pursue studies to support their claims.”