Sean Moloughney, Editor04.01.13
Consumers in the U.S. spend approximately $128 billion on arthritis-related healthcare costs every year, according to the Arthritis Foundation, Atlanta, GA, a non-profit group that has contributed more than $450 million to arthritis research since 1948.
However, most of these consumer expenses go toward the treatment of osteoarthritis (OA), a chronic condition characterized by the breakdown of cartilage, which cushions the ends of bones and allows easy movement of joints. Cartilage breakdown causes bones to rub against each other, leading to stiffness, pain and loss of joint movement. The Arthritis Foundation estimated that 27 million people in the U.S. are currently living with OA. Many different factors play a role in its development, including age, obesity, injury/overuse, underuse/sedentary lifestyle and genetics.
A Bevy of Buyers
“The U.S. Center for Disease Control (CDC) estimates that half of all U.S. adults will experience osteoarthritic symptoms sometime in their life, with the prevalence sharply rising at age 45. This presents a huge socioeconomic impact and public health burden,” said Adeena Zabrowsky, executive vice president, Life Science Laboratories, Lakewood, NJ.
Baby Boomers, especially those who continue to lead active lifestyles, have been the largest group of buyers for joint care products. “Everybody wants to continue living an active lifestyle even after retirement by maintaining healthy joints,” said Suhail Ishaq, president, BioCell Technology, LLC, Newport Beach, CA. “Statistics show that 10,000 people in the U.S. turn the age of 65 every day, making them vulnerable to chronic joint problems such as osteoarthritis, which does not have a long-term, safe and effective medical treatment, let alone a cure.”
However, increasingly, the joint health market is attracting a younger demographic. “Athletes and the younger active population are recognizing the need for preventative care,” said Tim Hammond, director of sales and strategic relations for Bergstrom Nutrition, Vancouver, WA. “We are also seeing an increased desire in consumers of all ages to remain active and mobile as they age.”
Paul Dijkstra, CEO of InterHealth Nutraceuticals, Benicia, CA, agreed, adding, “There has been a lot of interest in joint support ingredients for sports nutrition products. Joint health is an increasingly popular issue among active Baby Boomers and 30- to 40-year-olds alike. Joint health is important in many sports, including cycling, running, climbing, etc.”
Conversely, less active consumers are feeling the effects of a sedentary way of life. “Lifestyle patterns and dietary habits have impacted joint health in even the younger age group,” said Anurag Pande, PhD, vice president of scientific affairs, Sabinsa Corporation, East Windsor, NJ. “Obesity related joint problems such as arthritis are becoming more prevalent.”
Traditionally, joint health products have been among the most popular condition-specific supplements. Indeed, while most consumers are forced to treat their arthritis symptoms, a growing base of supplement users remains focused on prevention. “Consumers are much more in tune with their bodies these days and are determined to live a full life—at any age,” said Becky Wright, communications and marketing manager, Aker BioMarine Antarctic US, Issaquah, WA. “For this reason, they are pretty proactive when it comes to addressing health issues early, before they become too serious. Supplements are perfect for those consumers who want to address joint health before drugs and surgery are the only options.”
Mr. Ishaq noted that consumers are also more aware of the science behind products they purchase, looking for joint ingredients that are substantiated by convincing research and at the same time convenient to take on a regular basis. “Over the past decade, many human clinical trials demonstrated the safety and efficacy of several joint ingredients in reducing joint discomfort potentially via modifying underlying molecular events. Now many consumers use dietary, cost-effective joint products containing these science-backed ingredients not only to maintain or improve their active lifestyle, but to prevent degenerative joint ailments.”
Dr. Pande agreed, noting that savvy consumers are taking it upon themselves to diagnose and address their own ailments. “When they have a health condition, they are more likely to research options than in the past.”
According to Jamie Spell, managing director of Nutraceuticals International Group, Paramus, NJ, demand for specialty supplements has been “growing at a heady pace, driven by scientifically-validated claims that have been primarily marketed toward self-help oriented customers. This is due to the increasing consciousness of end-users for healthcare expenditures, stress on healthy diets and training.”
These days, taking supplements as part of “self healthcare,” has become the new normal, according Dean Mosca, president, Proprietary Nutritionals Inc., (PNI), Kearny, NJ. “Consumers may go to their medical practitioners to check the status of their joints, but they are also making trips to the stores to check out what’s in the joint care aisle so they can start taking care of it now.”
Glucosamine, Chondroitin & Collagen
However, sales of traditional glucosamine and chondroitin supplements have remained flat in recent years, perhaps suffering from a lack of convincing evidence regarding their ability to treat symptoms of OA.
“Glucosamine and chondroitin sulfate have been the most popular ingredients in the market,” said BioCell’s Mr. Ishaq. “From a scientific point of view, their leading status is a bit puzzling, because recent human clinical trials cast a doubt about their efficacy in reducing joint discomfort.”
In particular, he noted a 2010 review published in the British Medical Journal that analyzed datasets available until 2009 from 10 well-controlled, large-scale clinical trials (3,803 subjects in total) on glucosamine and/or chondroitin sulfate. This meta-analysis concluded: “Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged.”
Likewise, the two-year Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) concluded that these ingredients performed no better than placebo in treating pain associated with knee osteoarthritis or improving joint space width (JSW).
According to Mr. Ishaq, a shortcoming of glucosamine/chondroitin appears to be a “mere partial approach via their supplementation” of glycosaminoglycans (GAGs), unbranched polysaccharides composed of repeating units of alternating uronic acids and amino sugars. The complex process of joint degeneration involves collagen type II as well as GAGs, such as chondroitin sulfate and hyaluronic acid (HA), he added.
“A better approach would address not only the loss of both collagen and GAGs, but potentially help regenerate worn-down cartilage through re-stimulation of the chondrocytes to synthesize these molecules. It is also expected to provide an effective supplementation of HA in the synovial fluid for better joint lubrication.”
The company’s patented BioCell Collagen provides multiple mechanisms of action in reducing joint discomfort, he added. “First, this ingredient offers a patented composition of a bioactive, naturally-occurring matrix of three major constituents—hydrolyzed collagen type II, chondroitin sulfate and HA—all of which are essential for the structure and function of the cartilage.”
HA is also a major lubricating molecule in the synovial fluid. “This cartilage-mirroring composition enables BioCell Collagen to provide an ideal nutritional support for both the cartilage and the synovial fluid at the same time. Second, a patented bio-optimized process reduces these physiologically large molecules into very low molecular weight form to ensure fast and effective absorption into the bloodstream. More importantly, this patented process creates a novel set of biological properties, including stimulation not only of the chondrocytes, but also the synovial cells to synthesize collagen and HA. This activity has a profound implication for regeneration of worn-down cartilage.”
Mr. Ishaq said the safety and efficacy of BioCell Collagen is substantiated by four human clinical studies—three on joint health and one on skin beauty. A recent randomized, double-blind, placebo-controlled clinical trial involving 80 subjects with joint discomfort confirmed findings that 71% of subjects who ingested BioCell Collagen (2 grams/day for 10 weeks) experienced significant improvement of their mobility-restricting joint discomfort whereas only 30% in the placebo group experienced a similar benefit. The outcome of this study was published in the Journal of Agricultural and Food Chemistry in 2012.
Oliver Wolf, head of global marketing and communication, said collagen peptides such as his company’s FORTIGEL tackle the root cause of joint problems, not just the symptoms. “Applied orally, collagen peptides stimulate the joint cartilage to increase the synthesis of collagen and proteoglycans, the two major components of cartilage tissue. This induces a noticeable regeneration of the cartilage, reduces pain and increases mobility of those affected. At the end of the day this leads to a significantly improved quality of life.”
As the collagen peptides in FORTIGEL are already hydrolyzed to a certain extent they are easily digestible and highly bioavailable, according to Mr. Wolf. Once inside the body, FORTIGEL accumulates in the joint cartilage, where it stimulates chondrocytes, combatting progressive degeneration of cartilage tissue.
Manufacturers need to review the science when selecting ingredients for a specific application, Mr. Wolf added. “Product developers and marketing managers should very carefully have a look at all the ingredients they intend to use in their products. What are they promising and to what extent is this promise based on solid science?”
According to Certified Nutraceuticals, Aliso Viejo, CA, demand for collagen in the marketplace will continue to rise as consumers become more educated on it’s benefits, especially considering a decline in glucosamine/chondroitin combination products.
Often referred to as the “Father of Collagen,” Ahmad Alkayali created and patented the company’s kollaGen II-xs, a type II denatured chicken collagen processed using an exclusive water extraction technology process without a solvent (ethanol) to change the original molecules for assimilation. The ingredient is recognized as a nutrient and building block for damaged cartilage. This process maintains the integrity of its delicate molecules. The long chain of amino acids are left intact, ensuring the body’s own superior natural enzymes recognize the precise genetic code for maximum assimilation for ultimate joint health.
Joe Mize, application scientist, Nitta Gelatin NA, Inc., Morrisville, NC, noted that collagen peptides are proteins composed of 17-19 amino acids. “They contain an unusually high proportion of glycine, proline, hydroxyproline and hydroxylysine, which are essential elements for production of lean muscles, healthy bones and firm, youthful skin. Collagen peptides are now becoming a widely studied food ingredient with clinically proven benefits for skin, bone and joint health. This functional protein has long been used in Japan and other Asian countries for its health benefits and is now beginning to experience popularity in North America and Europe.”
Nitta Gelatin recently released Wellnex collagen peptides, a new line of functional proteins that have been clinically proven to support skin, bone and joint health, Mr. Mize said. “Wellnex collagen peptides are specifically designed for use in functional foods and beverages.”
When developing new products, Mr. Wolf suggested manufacturers work closely with ingredient suppliers, as “they know their ‘baby’ by heart. They can tell how it interacts with other ingredients and how it behaves under certain conditions. Thus they can provide meaningful support to achieve better results and to save time and money.”
Active Athletes
On the sports nutrition front, InterHealth’s Mr. Dijkstra said his company has seen growing interest from manufacturers regarding its patented, undenatured type II collagen ingredient, UC-II. A recent randomized, double-blind, placebo-controlled study conducted in healthy subjects showed that 40 mg of UC-II significantly improved knee extension compared to placebo, he noted. Significant results in joint comfort during and after exercise compared to baseline were also seen.
“Maintaining knee joint function supports mobility, increases flexibility and may support the ability to exercise longer and more regularly,” Mr. Dijkstra noted. “The knee provides stability, flexibility and strength needed for comfortable workouts and sports-related activities. Knee extension is important for all movements in sports—running, jumping, kicking, lifting, lunging, etc. Maintaining knee health is important for everyone from a seasoned athlete to a weekend warrior.”
Loss of full knee extension can interfere with normal daily activities, as well as sport-specific activities. “The current UC-II research on healthy exercising subjects merits the use of UC-II in joint health products, sports nutrition products, multivitamins and other combination products,” Mr. Dijkstra added.
Bergstrom’s Mr. Hammond also noted an increase in sports nutrition products marketed for joint support. “Athletes and the younger active population are recognizing the need for preventative care,” he said.
Overall, joint health products continue to demand space on retail shelves. “Blends including recognized ingredients such as glucosamine, MSM (methylsulfonylmethane), chondroiton and hyaluronic acid remain category leaders, while the multiple benefits of fish oil have been popular and turmeric/curcumin are adding a bit of spice to the mix.”
Meanwhile, demand for his company’s OptiMSM is at record levels, he added. “Spurred by EFSA (European Food Safety Authority) demands, studies focusing on exercise recovery have been initiated and performed on healthy adults, leading to a better understanding of OptiMSM’s effects on oxidative stress and overall wellness.”
In September 2012, the Journal of the International Society of Sports Nutrition (ISSN) published Bergstrom’s proof of concept (POC) study regarding exercise recovery. This small human study supported a trend for reduction in muscle soreness in a dose-dependent manner and a significant increase in Trolox Equivalent Antioxidant Capacity (TEAC), Mr. Hammond said.
“With the market continuing to be dominated by blends, the delivery system of choice by consumers remains capsules and tablets. The challenge for functional foods is to create a delectable taste and flavor profile and still deliver efficacious amounts.”
Ms. Spell of Nutraceuticals International agreed that, progressively, bone and joint health ingredients are being included in functional foods and beverages, appealing to consumers who favor getting their vitamins and minerals from everyday nutrition instead of supplements.
“This is a move toward ‘real food nutrition,’ which includes blending different foods for maximum health benefits, choosing foods for their inherent nutritional value (such as nuts or fruits) and integrating whole food supplements such as coconut milk into the diet, rather than supplementing with a vitamin. End-users prefer to get nutrients and their health benefits naturally, versus fortified foods or vitamin and mineral supplements.”
Ms. Spell’s company supplies ExceptionHYAL sodium hyaluronate for food grade applications. The product is obtained through biofermentation technology, which allows for standardization of different ranges of molecular size and ensures quality and safety. ExceptionHYAL has a slow and long lasting absorption at the intestinal level for different applications, according to the company. It acts like a shock absorber by lubricating and plumping tissues, helping a cushion effect and reducing inflammation. It improves regeneration of endogenous synovial fluid and promotes a healing and film-forming effect for local applications, according to the company.
SAMe
“While all categories of consumers are always looking for new and trendy products, at the end of the day, only the most effective products will survive,” said Life Science Laboratories’ Ms. Zabrowsky. “There have been many joint supplements to hit the shelves. Many of these products appeared and disappeared without a trace as consumers realized that they were ineffective. SAMe (S-adenosyl methionine) has been around for decades and is constantly proven effective.”
SAMe is an important physiologic agent formed in the body and is involved in more than 40 biochemical reactions, Ms. Zabrowsky noted. An evidence-based research report published in October 2012 and conducted by Arthritis Research UK, a large medical-research organization in England, used data from randomized, controlled trials to evaluate complementary and alternative medicines for treatment of osteoarthritis, rheumatoid arthritis and fibromyalgia.
In the report, researchers evaluated 31 complementary medicines taken orally or applied topically. Each was scored for effectiveness based on improvements in pain, movement or general well-being, with “1” indicating the available evidence suggests the compound is not effective and “5” indicating there’s consistent evidence the compound is effective.
“SAMe received a ‘4,’ the highest rating of all the supplements for arthritis relief,” Ms. Zabrowsky noted. “In fact, no other non-herbal supplement received higher than a ‘2’ in this report. This includes glucosamine, chondroitin, MSM, etc. The only products to receive a ‘5’ rating were direct topical relief products (capsaicin), which of course are limited to immediate short-term pain relief.”
One of the biggest obstacles to SAMe’s widespread adoption among consumers has been its high price point. “For many years after its initial introduction, the consumer awareness for SAMe and joint health was mostly limited to sufferers of severe arthritis. This was largely due to the fact that SAMe was relatively expensive compared to other joint supplements for many years, and mild arthritis patients couldn’t afford to purchase SAMe regularly. Advertisers chose to focus on the more commonly used supplements, so awareness for SAMe remained stagnant.”
Over the last couple of years, Life Science Labs has worked to bring down the cost of SAMe to the consumer. “As SAMe becomes more affordable, it will become used by a larger spectrum of patients and should broaden consumer awareness,” she predicted.
The ‘Next Generation’
Sabinsa’s Dr. Pande noted that the joint health market, once dominated by glucosamine, has been evolving to include “next generation” products. “With inflammation seen as a root cause of arthritis and other joint ailments, natural anti-inflammatory compounds have come to the forefront in joint care support. Some of the most studied ingredients in joint care in the nutraceutical segment are boswellia, ginger, curcumin and omega fatty acids.”
Boswellia, also known as Indian Frankincense, has been part of traditional Ayurvedic formulations for ages. “Boswellia consist of boswellic acids, which are known to be the active component in the gum resin of the boswellia tree, he said. Boswellic acids are known to have an inhibitory effect on the lipoxygenase enzyme, which catalyzes one of the major pathways of inflammation implicated in joint problems.
“Natural, broad-spectrum anti-inflammatory ingredient formulations, with synergy to reduce inflammation, will be products to look for in the future,” Dr. Pande predicted.
Bob Berman, international marketing manager with P.L. Thomas, Morristown, NJ, which offers 5-LOXIN and AprèsFLEX patented boswellia extracts, said boswellic acids are natural, selective 5-lipoxygenase inhibitors. There are six boswellic acids; however, 3-Oacetyl-11-keto-beta-boswellic acid (AKBA) is the most active component of boswellia extracts and has been demonstrated to be a potent inhibitor of 5-lipoxygenase (5-LOX), which is a key enzyme in the biosynthesis of leukotrienes from arachidonic acid in the cellular inflammatory cascade.
The targeted inhibition of the 5-LOX enzyme may help to promote joint function and mobility, he said. 5-LOX inhibitors follow a distinctly different pathway than COX-2 inhibitors, and while both are involved in the breakdown of arachidonic acid, 5-LOX inhibitors do not exhibit potentially negative effects that have been associated with COX-2 inhibitors.
5-LOXIN and AprèsFLEX also inhibit matrix metalloproteinase (MMP-3), enzymes that break down cartilage, collagen and connective tissues. 5-LOXIN has been shown to improve joint comfort and flexibility within 7 days while AprèsFLEX, can work in 5 days.
Curcumin, a broad-spectrum anti-inflammatory known to reduce joint inflammation effectively, has also been growing in popularity. “There is a robust body of science on curcumin,” Dr. Pande noted. “Yet another ingredient, ginger, which belongs to the same family as the turmeric plant, has shown promising effects in reducing the inflammatory markers involved in joint inflammation.”
Sabinsa recently conducted an open label trial on an all-natural, proprietary ingredient combination known as NiLitis. The product consists of Boswellia extract, Ginger SCF extract, Curcumin C3 Complex and BioPerine, and showed significant improvement in the various indices of osteoarthritis in subjects in a short time. “Subjects reported improvement in joint mobility, reduced stiffness and pain. Interestingly, the product is free from glucosamine or any other allergens and hence has found wider acceptance in consumer groups,” Dr. Pande said.
Christian Artaria, marketing director and head of functional food development for Italy-based Indena S.p.A., noted that consumer awareness for curcumin has been growing, “underlined by the big jump in sales of the ingredient.”
“Curcumin is nothing exotic to consumers, since turmeric, its plant source, is such a well known spice,” he added. “Furthermore, the scientific literature generated in the last 30 years—curcumin is one of the most studied natural molecules—is slowly reaching the consumers. Greater awareness is being generated also in natural health food stores where store employees are selling curcumin products to end consumers as well as from supplement manufacturers introducing and marketing curcumin supplements. Additionally, curcumin has received broader exposure through being mentioned on ‘The Dr. Oz show’ for its anti-inflammatory properties.”
Indena’s Meriva is a proprietary formulation of bioavailable curcumin with non-GMO soy phospholipids, Mr. Artaria noted. “The clinical development of curcumin, that has been shown to act on a pleiotropy of targets, has been hampered by its very low oral bioavailability and absorption. At Indena, we were able to increase its bioavailability without resorting to pharmacological adjuvants or synthetic ingredients, but by formulating curcumin with a dietary ingredient (non-GMO soy phosphatidylcholine). And thus we are able to evaluate the ingredients in different clinical studies without using mega-dosages.”
The joint health benefits of Meriva were published in two long-term studies, he noted. These studies comprised 150 participants and demonstrated the effectiveness of Meriva for maintaining healthy joints. Five other published studies with Meriva have also shown it to support the healthy inflammatory response caused by different challenges.
Despite some contradictory clinical results, glucosamine and chondroitin sulphate have been shown to modulate the cartilage associated with joint challenges and both remain important ingredients in the joint health market, according to Mr. Artaria. Still, several other dietary ingredients have come on the scene, including omega 3 polyunsaturated fatty acids, avocado/soybean unsaponifiables (ASU) and botanicals like willow bark and boswellia.
Considering flat growth of some traditional products, new emerging ingredients and an aging Baby Boomer population, now is an ideal time for manufacturers to develop new products featuring effective joint health solutions, he added.
Omegas & Inflammation
Indeed, the joint health market is alive and well, according to Aker BioMarine’s Ms. Wright. “Millions of consumers continue to be stricken with joint ailments and supplements provide a first line of defense in staving off major issues down the road.”
Consumers also continue to turn away from drugs due to serious side effects. “Phospholipid omega 3s such as those found in krill are instrumental in modulating inflammation and thereby reducing the pain and discomfort associated with joint ailments,” Ms. Wright said. “Omega 3s are thought to play a role in supporting the integrity of articular cartilage and, hence, joint comfort. Dietary omega 3s also have the ability to modulate certain chemical reactions in joints. Scientifically speaking, the presence of omega 3s in cell membrane phospholipids shifts the production of hormone-like substances called prostaglandins away from the undesirable series 2 prostaglandins and toward the beneficial series 1 prostaglandins.”
Ms. Wright went on to say that phospholipid omega 3s from krill are “more bio-efficient, delivering 60% more omega 3s to the cells and tissues that need them most.”
Ben S. Winters, director of Christchurch-based Aroma New Zealand, agreed there will continue to be strong demand for joint care products, as inflammation remains one of the world’s most widespread diseases.
“Our two most popular joint care products today are GlycOmega-PLUS green-lipped mussel extract and green-lipped mussel oil,” he added. “GlycOmega-PLUS has been clinically tested to increase joint mobility and reduce joint pain in patients with osteoarthritis while green-lipped mussel oil is rich in omega 3 fatty acids and contains high levels of anti-inflammatory activity. Consumer awareness of our green-lipped mussel extracts is up, as many leading nutritional and veterinary companies use our branded raw materials to launch new joint care products into the market.”
Reducing inflammation and promoting joint health, Proprietary Nutritionals Inc. offers Celadrin, which according to the company’s Mr. Mosca, is “medically and clinically proven to alleviate discomfort and support enhanced mobility.”
The ingredient was developed through a proprietary process of esterifying fatty acids to ensure stability and prevent reactions with oxygen. Studies have shown that humans and animals have experienced reduction in pain and swelling and increased range of motion with Celadrin, with no reported side effects.
“Research has shown that the special fatty acids in Celadrin inhibit inflammation in endothelial cells (the thin cells that line the inside of various body cavities) and decrease the pro-inflammatory effects of arachidonic and other fatty acids,” Mr. Mosca said. “Celadrin has also been shown to reduce the production of the negative immune factor IL-6 and to control the immune factors responsible for inflammation. In addition, Celadrin may help to lubricate an affected joint, resulting in pain relief and increased mobility. We also have an equally effective plant-source Celadrin for vegans and vegetarians, called Vege-Celadrin.
PNI also offers Perluxan, a proprietary extract of hops cones shown to reduce joint discomfort. 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, Mr. Mosca noted. Another pilot study demonstrated that Perluxan was comparable to ibuprofen in reducing pain-causing inflammatory enzymes. Additional studies are planned.
Pycnogenol French maritime pine bark extract from Horphag Research has also shown anti-inflammatory activity. For example, in a study with 55 osteoarthritis patients Pycnogenol significantly lowered the inflammatory marker C-reactive protein (CRP) by 71%. This study also found a significant reduction of reactive oxygen species in arthritis patients by 30%.
Additionally, a double-blind, placebo-controlled study involving 156 OA patients, published in Phytotherapy Research in 2008, found that 100 mg Pycnogenol over a 3-month period led to a significant reduction in WOMAC pain scores; medication with NSAIDs also dropped by 58%. Overall, treatment costs were reduced significantly compared with placebo.
Eggshells & A New Approach
Matt Stegenga, director of marketing, Biova LLC, Johnston, IA, said that increased demand for new, efficacious products has coincided with interest in his company’s BiovaFlex egg membrane ingredient. “We’re seeing a lot of inquiry from both domestic and international companies and, most interestingly, across all types of brands and delivery systems. The market is clearly looking for new ingredients and new delivery systems to meet consumer demand.”
Egg membrane as a category is relatively new, and still unknown to most consumers, he said. “We partner with our customers to help promote awareness and create demand. We believe now’s an optimal time for consumer packaged goods to look hard at their current joint health line-ups and consider how to capitalize on the opportunities to create new demand and capture new market share.”
As a water-soluble egg membrane that benefits from a uniform ingredient profile and 450 mg/day efficacy, BiovaFlex can be included in functional foods and beverages, including trendy hybrid beverages, as well as gummies and drops, according to Mr. Stegenga.
From a supplement standpoint, there seems to be continued emphasis on combining known efficacious ingredients with newer ingredients to create a “boosted” or a “synergistic” formula. “Leveraging consumer trust in your brand with new, efficacious complementary ingredients is a proven growth model,” he said.
Nena Dockery, technical manager, ESM Technologies, Carthage, MO, said her company’s patented, food-sourced eggshell membrane ingredient, NEM, naturally contains the components that are found in healthy joint tissue, including glycosaminoglycans such as chondroitin sulfate, hyaluronic acid, collagen, glucosamine and several proteins and peptides.
“NEM has been the subject of multiple human clinical trials demonstrating its efficacy,” she noted. “These studies established an effective daily dose of only 500 mg compared to 1,200 to 1,500 required for chondroitin and glucosamine, respectively, and revealed a time period for a statistical measurement of efficacy of 7-10 days instead of weeks or months required for glucosamine. The efficacy studies along with safety studies and an in vitro mechanism of action study are all published in peer-reviewed journals.”
In addition, some consumers have become more interested in NEM because it is produced from a domestic food source and is not subject to adulteration or genetic modification.
Glucosamine, chondroitin and MSM products usually contain few if any additional active ingredients because of the high dosage, Ms. Dockery said. However, ingredients such NEM, which requires a much smaller dose and does not interfere with the metabolism of drug, supplement or food ingredients, can be used to create proprietary formulas that include other beneficial ingredients. “Formulas containing ingredients that have slightly different functionalities can provide a novel, multi-layered approach to joint care,” she said.
A newly established company, Bio-Rep, Pomona, CA, specializes in patented and clinically tested supplements that replenish, rebuild and revitalize the body’s core systems, according to president Sreus Naidu.
The company’s novel health technologies integrate essential bioactive molecules the human body regularly synthesizes to support vital processes. For the past several years, Bio-Rep has been involved in research in the areas of bone and joint health. “We have focused our attention on bioactive molecules present in milk because milk is the one vital food source that all mammalian species consume to support healthy growth and development (including within the skeletal system).”
From its research, Bio-Rep identified and isolated two multi-functional proteins involved in bone and joint health: ribonuclease (also known as angiogenin) and lactoferrin. “When complexed as ribonuclease-enriched lactoferrin (R-ELF), these proteins demonstrate potent synergism to promote osteoblastic activity (bone formation), optimize the rate of bone resorption (bone loss) and improve joint and cartilage integrity,” Mr. Naidu said.
In 2009, two double-blind human clinical studies were conducted on the R-ELF complex. The first study examined R-ELF’s effects on osteoblast and osteoclast activity, while the second assessed its impact on joint inflammation. Metabolic bone markers extracted from serum samples were used to measure the physiological effects of the R-ELF complex on bone and joints in study participants over a 6-month period. Both safety and efficacy outcomes were positive; to-date, no adverse events have been reported by study participants, Mr. Naidu noted. Study results were published in two peer-reviewed medical journals—Osteoporosis International and Inflammation Research.
However, most of these consumer expenses go toward the treatment of osteoarthritis (OA), a chronic condition characterized by the breakdown of cartilage, which cushions the ends of bones and allows easy movement of joints. Cartilage breakdown causes bones to rub against each other, leading to stiffness, pain and loss of joint movement. The Arthritis Foundation estimated that 27 million people in the U.S. are currently living with OA. Many different factors play a role in its development, including age, obesity, injury/overuse, underuse/sedentary lifestyle and genetics.
A Bevy of Buyers
“The U.S. Center for Disease Control (CDC) estimates that half of all U.S. adults will experience osteoarthritic symptoms sometime in their life, with the prevalence sharply rising at age 45. This presents a huge socioeconomic impact and public health burden,” said Adeena Zabrowsky, executive vice president, Life Science Laboratories, Lakewood, NJ.
Baby Boomers, especially those who continue to lead active lifestyles, have been the largest group of buyers for joint care products. “Everybody wants to continue living an active lifestyle even after retirement by maintaining healthy joints,” said Suhail Ishaq, president, BioCell Technology, LLC, Newport Beach, CA. “Statistics show that 10,000 people in the U.S. turn the age of 65 every day, making them vulnerable to chronic joint problems such as osteoarthritis, which does not have a long-term, safe and effective medical treatment, let alone a cure.”
However, increasingly, the joint health market is attracting a younger demographic. “Athletes and the younger active population are recognizing the need for preventative care,” said Tim Hammond, director of sales and strategic relations for Bergstrom Nutrition, Vancouver, WA. “We are also seeing an increased desire in consumers of all ages to remain active and mobile as they age.”
Paul Dijkstra, CEO of InterHealth Nutraceuticals, Benicia, CA, agreed, adding, “There has been a lot of interest in joint support ingredients for sports nutrition products. Joint health is an increasingly popular issue among active Baby Boomers and 30- to 40-year-olds alike. Joint health is important in many sports, including cycling, running, climbing, etc.”
Conversely, less active consumers are feeling the effects of a sedentary way of life. “Lifestyle patterns and dietary habits have impacted joint health in even the younger age group,” said Anurag Pande, PhD, vice president of scientific affairs, Sabinsa Corporation, East Windsor, NJ. “Obesity related joint problems such as arthritis are becoming more prevalent.”
Traditionally, joint health products have been among the most popular condition-specific supplements. Indeed, while most consumers are forced to treat their arthritis symptoms, a growing base of supplement users remains focused on prevention. “Consumers are much more in tune with their bodies these days and are determined to live a full life—at any age,” said Becky Wright, communications and marketing manager, Aker BioMarine Antarctic US, Issaquah, WA. “For this reason, they are pretty proactive when it comes to addressing health issues early, before they become too serious. Supplements are perfect for those consumers who want to address joint health before drugs and surgery are the only options.”
Mr. Ishaq noted that consumers are also more aware of the science behind products they purchase, looking for joint ingredients that are substantiated by convincing research and at the same time convenient to take on a regular basis. “Over the past decade, many human clinical trials demonstrated the safety and efficacy of several joint ingredients in reducing joint discomfort potentially via modifying underlying molecular events. Now many consumers use dietary, cost-effective joint products containing these science-backed ingredients not only to maintain or improve their active lifestyle, but to prevent degenerative joint ailments.”
Dr. Pande agreed, noting that savvy consumers are taking it upon themselves to diagnose and address their own ailments. “When they have a health condition, they are more likely to research options than in the past.”
According to Jamie Spell, managing director of Nutraceuticals International Group, Paramus, NJ, demand for specialty supplements has been “growing at a heady pace, driven by scientifically-validated claims that have been primarily marketed toward self-help oriented customers. This is due to the increasing consciousness of end-users for healthcare expenditures, stress on healthy diets and training.”
These days, taking supplements as part of “self healthcare,” has become the new normal, according Dean Mosca, president, Proprietary Nutritionals Inc., (PNI), Kearny, NJ. “Consumers may go to their medical practitioners to check the status of their joints, but they are also making trips to the stores to check out what’s in the joint care aisle so they can start taking care of it now.”
Glucosamine, Chondroitin & Collagen
However, sales of traditional glucosamine and chondroitin supplements have remained flat in recent years, perhaps suffering from a lack of convincing evidence regarding their ability to treat symptoms of OA.
“Glucosamine and chondroitin sulfate have been the most popular ingredients in the market,” said BioCell’s Mr. Ishaq. “From a scientific point of view, their leading status is a bit puzzling, because recent human clinical trials cast a doubt about their efficacy in reducing joint discomfort.”
In particular, he noted a 2010 review published in the British Medical Journal that analyzed datasets available until 2009 from 10 well-controlled, large-scale clinical trials (3,803 subjects in total) on glucosamine and/or chondroitin sulfate. This meta-analysis concluded: “Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged.”
Likewise, the two-year Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) concluded that these ingredients performed no better than placebo in treating pain associated with knee osteoarthritis or improving joint space width (JSW).
According to Mr. Ishaq, a shortcoming of glucosamine/chondroitin appears to be a “mere partial approach via their supplementation” of glycosaminoglycans (GAGs), unbranched polysaccharides composed of repeating units of alternating uronic acids and amino sugars. The complex process of joint degeneration involves collagen type II as well as GAGs, such as chondroitin sulfate and hyaluronic acid (HA), he added.
“A better approach would address not only the loss of both collagen and GAGs, but potentially help regenerate worn-down cartilage through re-stimulation of the chondrocytes to synthesize these molecules. It is also expected to provide an effective supplementation of HA in the synovial fluid for better joint lubrication.”
The company’s patented BioCell Collagen provides multiple mechanisms of action in reducing joint discomfort, he added. “First, this ingredient offers a patented composition of a bioactive, naturally-occurring matrix of three major constituents—hydrolyzed collagen type II, chondroitin sulfate and HA—all of which are essential for the structure and function of the cartilage.”
HA is also a major lubricating molecule in the synovial fluid. “This cartilage-mirroring composition enables BioCell Collagen to provide an ideal nutritional support for both the cartilage and the synovial fluid at the same time. Second, a patented bio-optimized process reduces these physiologically large molecules into very low molecular weight form to ensure fast and effective absorption into the bloodstream. More importantly, this patented process creates a novel set of biological properties, including stimulation not only of the chondrocytes, but also the synovial cells to synthesize collagen and HA. This activity has a profound implication for regeneration of worn-down cartilage.”
Mr. Ishaq said the safety and efficacy of BioCell Collagen is substantiated by four human clinical studies—three on joint health and one on skin beauty. A recent randomized, double-blind, placebo-controlled clinical trial involving 80 subjects with joint discomfort confirmed findings that 71% of subjects who ingested BioCell Collagen (2 grams/day for 10 weeks) experienced significant improvement of their mobility-restricting joint discomfort whereas only 30% in the placebo group experienced a similar benefit. The outcome of this study was published in the Journal of Agricultural and Food Chemistry in 2012.
Oliver Wolf, head of global marketing and communication, said collagen peptides such as his company’s FORTIGEL tackle the root cause of joint problems, not just the symptoms. “Applied orally, collagen peptides stimulate the joint cartilage to increase the synthesis of collagen and proteoglycans, the two major components of cartilage tissue. This induces a noticeable regeneration of the cartilage, reduces pain and increases mobility of those affected. At the end of the day this leads to a significantly improved quality of life.”
As the collagen peptides in FORTIGEL are already hydrolyzed to a certain extent they are easily digestible and highly bioavailable, according to Mr. Wolf. Once inside the body, FORTIGEL accumulates in the joint cartilage, where it stimulates chondrocytes, combatting progressive degeneration of cartilage tissue.
Manufacturers need to review the science when selecting ingredients for a specific application, Mr. Wolf added. “Product developers and marketing managers should very carefully have a look at all the ingredients they intend to use in their products. What are they promising and to what extent is this promise based on solid science?”
According to Certified Nutraceuticals, Aliso Viejo, CA, demand for collagen in the marketplace will continue to rise as consumers become more educated on it’s benefits, especially considering a decline in glucosamine/chondroitin combination products.
Often referred to as the “Father of Collagen,” Ahmad Alkayali created and patented the company’s kollaGen II-xs, a type II denatured chicken collagen processed using an exclusive water extraction technology process without a solvent (ethanol) to change the original molecules for assimilation. The ingredient is recognized as a nutrient and building block for damaged cartilage. This process maintains the integrity of its delicate molecules. The long chain of amino acids are left intact, ensuring the body’s own superior natural enzymes recognize the precise genetic code for maximum assimilation for ultimate joint health.
Joe Mize, application scientist, Nitta Gelatin NA, Inc., Morrisville, NC, noted that collagen peptides are proteins composed of 17-19 amino acids. “They contain an unusually high proportion of glycine, proline, hydroxyproline and hydroxylysine, which are essential elements for production of lean muscles, healthy bones and firm, youthful skin. Collagen peptides are now becoming a widely studied food ingredient with clinically proven benefits for skin, bone and joint health. This functional protein has long been used in Japan and other Asian countries for its health benefits and is now beginning to experience popularity in North America and Europe.”
Nitta Gelatin recently released Wellnex collagen peptides, a new line of functional proteins that have been clinically proven to support skin, bone and joint health, Mr. Mize said. “Wellnex collagen peptides are specifically designed for use in functional foods and beverages.”
When developing new products, Mr. Wolf suggested manufacturers work closely with ingredient suppliers, as “they know their ‘baby’ by heart. They can tell how it interacts with other ingredients and how it behaves under certain conditions. Thus they can provide meaningful support to achieve better results and to save time and money.”
Active Athletes
On the sports nutrition front, InterHealth’s Mr. Dijkstra said his company has seen growing interest from manufacturers regarding its patented, undenatured type II collagen ingredient, UC-II. A recent randomized, double-blind, placebo-controlled study conducted in healthy subjects showed that 40 mg of UC-II significantly improved knee extension compared to placebo, he noted. Significant results in joint comfort during and after exercise compared to baseline were also seen.
“Maintaining knee joint function supports mobility, increases flexibility and may support the ability to exercise longer and more regularly,” Mr. Dijkstra noted. “The knee provides stability, flexibility and strength needed for comfortable workouts and sports-related activities. Knee extension is important for all movements in sports—running, jumping, kicking, lifting, lunging, etc. Maintaining knee health is important for everyone from a seasoned athlete to a weekend warrior.”
Loss of full knee extension can interfere with normal daily activities, as well as sport-specific activities. “The current UC-II research on healthy exercising subjects merits the use of UC-II in joint health products, sports nutrition products, multivitamins and other combination products,” Mr. Dijkstra added.
Bergstrom’s Mr. Hammond also noted an increase in sports nutrition products marketed for joint support. “Athletes and the younger active population are recognizing the need for preventative care,” he said.
Overall, joint health products continue to demand space on retail shelves. “Blends including recognized ingredients such as glucosamine, MSM (methylsulfonylmethane), chondroiton and hyaluronic acid remain category leaders, while the multiple benefits of fish oil have been popular and turmeric/curcumin are adding a bit of spice to the mix.”
Meanwhile, demand for his company’s OptiMSM is at record levels, he added. “Spurred by EFSA (European Food Safety Authority) demands, studies focusing on exercise recovery have been initiated and performed on healthy adults, leading to a better understanding of OptiMSM’s effects on oxidative stress and overall wellness.”
In September 2012, the Journal of the International Society of Sports Nutrition (ISSN) published Bergstrom’s proof of concept (POC) study regarding exercise recovery. This small human study supported a trend for reduction in muscle soreness in a dose-dependent manner and a significant increase in Trolox Equivalent Antioxidant Capacity (TEAC), Mr. Hammond said.
“With the market continuing to be dominated by blends, the delivery system of choice by consumers remains capsules and tablets. The challenge for functional foods is to create a delectable taste and flavor profile and still deliver efficacious amounts.”
Ms. Spell of Nutraceuticals International agreed that, progressively, bone and joint health ingredients are being included in functional foods and beverages, appealing to consumers who favor getting their vitamins and minerals from everyday nutrition instead of supplements.
“This is a move toward ‘real food nutrition,’ which includes blending different foods for maximum health benefits, choosing foods for their inherent nutritional value (such as nuts or fruits) and integrating whole food supplements such as coconut milk into the diet, rather than supplementing with a vitamin. End-users prefer to get nutrients and their health benefits naturally, versus fortified foods or vitamin and mineral supplements.”
Ms. Spell’s company supplies ExceptionHYAL sodium hyaluronate for food grade applications. The product is obtained through biofermentation technology, which allows for standardization of different ranges of molecular size and ensures quality and safety. ExceptionHYAL has a slow and long lasting absorption at the intestinal level for different applications, according to the company. It acts like a shock absorber by lubricating and plumping tissues, helping a cushion effect and reducing inflammation. It improves regeneration of endogenous synovial fluid and promotes a healing and film-forming effect for local applications, according to the company.
SAMe
“While all categories of consumers are always looking for new and trendy products, at the end of the day, only the most effective products will survive,” said Life Science Laboratories’ Ms. Zabrowsky. “There have been many joint supplements to hit the shelves. Many of these products appeared and disappeared without a trace as consumers realized that they were ineffective. SAMe (S-adenosyl methionine) has been around for decades and is constantly proven effective.”
SAMe is an important physiologic agent formed in the body and is involved in more than 40 biochemical reactions, Ms. Zabrowsky noted. An evidence-based research report published in October 2012 and conducted by Arthritis Research UK, a large medical-research organization in England, used data from randomized, controlled trials to evaluate complementary and alternative medicines for treatment of osteoarthritis, rheumatoid arthritis and fibromyalgia.
In the report, researchers evaluated 31 complementary medicines taken orally or applied topically. Each was scored for effectiveness based on improvements in pain, movement or general well-being, with “1” indicating the available evidence suggests the compound is not effective and “5” indicating there’s consistent evidence the compound is effective.
“SAMe received a ‘4,’ the highest rating of all the supplements for arthritis relief,” Ms. Zabrowsky noted. “In fact, no other non-herbal supplement received higher than a ‘2’ in this report. This includes glucosamine, chondroitin, MSM, etc. The only products to receive a ‘5’ rating were direct topical relief products (capsaicin), which of course are limited to immediate short-term pain relief.”
One of the biggest obstacles to SAMe’s widespread adoption among consumers has been its high price point. “For many years after its initial introduction, the consumer awareness for SAMe and joint health was mostly limited to sufferers of severe arthritis. This was largely due to the fact that SAMe was relatively expensive compared to other joint supplements for many years, and mild arthritis patients couldn’t afford to purchase SAMe regularly. Advertisers chose to focus on the more commonly used supplements, so awareness for SAMe remained stagnant.”
Over the last couple of years, Life Science Labs has worked to bring down the cost of SAMe to the consumer. “As SAMe becomes more affordable, it will become used by a larger spectrum of patients and should broaden consumer awareness,” she predicted.
The ‘Next Generation’
Sabinsa’s Dr. Pande noted that the joint health market, once dominated by glucosamine, has been evolving to include “next generation” products. “With inflammation seen as a root cause of arthritis and other joint ailments, natural anti-inflammatory compounds have come to the forefront in joint care support. Some of the most studied ingredients in joint care in the nutraceutical segment are boswellia, ginger, curcumin and omega fatty acids.”
Boswellia, also known as Indian Frankincense, has been part of traditional Ayurvedic formulations for ages. “Boswellia consist of boswellic acids, which are known to be the active component in the gum resin of the boswellia tree, he said. Boswellic acids are known to have an inhibitory effect on the lipoxygenase enzyme, which catalyzes one of the major pathways of inflammation implicated in joint problems.
“Natural, broad-spectrum anti-inflammatory ingredient formulations, with synergy to reduce inflammation, will be products to look for in the future,” Dr. Pande predicted.
Bob Berman, international marketing manager with P.L. Thomas, Morristown, NJ, which offers 5-LOXIN and AprèsFLEX patented boswellia extracts, said boswellic acids are natural, selective 5-lipoxygenase inhibitors. There are six boswellic acids; however, 3-Oacetyl-11-keto-beta-boswellic acid (AKBA) is the most active component of boswellia extracts and has been demonstrated to be a potent inhibitor of 5-lipoxygenase (5-LOX), which is a key enzyme in the biosynthesis of leukotrienes from arachidonic acid in the cellular inflammatory cascade.
The targeted inhibition of the 5-LOX enzyme may help to promote joint function and mobility, he said. 5-LOX inhibitors follow a distinctly different pathway than COX-2 inhibitors, and while both are involved in the breakdown of arachidonic acid, 5-LOX inhibitors do not exhibit potentially negative effects that have been associated with COX-2 inhibitors.
5-LOXIN and AprèsFLEX also inhibit matrix metalloproteinase (MMP-3), enzymes that break down cartilage, collagen and connective tissues. 5-LOXIN has been shown to improve joint comfort and flexibility within 7 days while AprèsFLEX, can work in 5 days.
Curcumin, a broad-spectrum anti-inflammatory known to reduce joint inflammation effectively, has also been growing in popularity. “There is a robust body of science on curcumin,” Dr. Pande noted. “Yet another ingredient, ginger, which belongs to the same family as the turmeric plant, has shown promising effects in reducing the inflammatory markers involved in joint inflammation.”
Sabinsa recently conducted an open label trial on an all-natural, proprietary ingredient combination known as NiLitis. The product consists of Boswellia extract, Ginger SCF extract, Curcumin C3 Complex and BioPerine, and showed significant improvement in the various indices of osteoarthritis in subjects in a short time. “Subjects reported improvement in joint mobility, reduced stiffness and pain. Interestingly, the product is free from glucosamine or any other allergens and hence has found wider acceptance in consumer groups,” Dr. Pande said.
Christian Artaria, marketing director and head of functional food development for Italy-based Indena S.p.A., noted that consumer awareness for curcumin has been growing, “underlined by the big jump in sales of the ingredient.”
“Curcumin is nothing exotic to consumers, since turmeric, its plant source, is such a well known spice,” he added. “Furthermore, the scientific literature generated in the last 30 years—curcumin is one of the most studied natural molecules—is slowly reaching the consumers. Greater awareness is being generated also in natural health food stores where store employees are selling curcumin products to end consumers as well as from supplement manufacturers introducing and marketing curcumin supplements. Additionally, curcumin has received broader exposure through being mentioned on ‘The Dr. Oz show’ for its anti-inflammatory properties.”
Indena’s Meriva is a proprietary formulation of bioavailable curcumin with non-GMO soy phospholipids, Mr. Artaria noted. “The clinical development of curcumin, that has been shown to act on a pleiotropy of targets, has been hampered by its very low oral bioavailability and absorption. At Indena, we were able to increase its bioavailability without resorting to pharmacological adjuvants or synthetic ingredients, but by formulating curcumin with a dietary ingredient (non-GMO soy phosphatidylcholine). And thus we are able to evaluate the ingredients in different clinical studies without using mega-dosages.”
The joint health benefits of Meriva were published in two long-term studies, he noted. These studies comprised 150 participants and demonstrated the effectiveness of Meriva for maintaining healthy joints. Five other published studies with Meriva have also shown it to support the healthy inflammatory response caused by different challenges.
Despite some contradictory clinical results, glucosamine and chondroitin sulphate have been shown to modulate the cartilage associated with joint challenges and both remain important ingredients in the joint health market, according to Mr. Artaria. Still, several other dietary ingredients have come on the scene, including omega 3 polyunsaturated fatty acids, avocado/soybean unsaponifiables (ASU) and botanicals like willow bark and boswellia.
Considering flat growth of some traditional products, new emerging ingredients and an aging Baby Boomer population, now is an ideal time for manufacturers to develop new products featuring effective joint health solutions, he added.
Omegas & Inflammation
Indeed, the joint health market is alive and well, according to Aker BioMarine’s Ms. Wright. “Millions of consumers continue to be stricken with joint ailments and supplements provide a first line of defense in staving off major issues down the road.”
Consumers also continue to turn away from drugs due to serious side effects. “Phospholipid omega 3s such as those found in krill are instrumental in modulating inflammation and thereby reducing the pain and discomfort associated with joint ailments,” Ms. Wright said. “Omega 3s are thought to play a role in supporting the integrity of articular cartilage and, hence, joint comfort. Dietary omega 3s also have the ability to modulate certain chemical reactions in joints. Scientifically speaking, the presence of omega 3s in cell membrane phospholipids shifts the production of hormone-like substances called prostaglandins away from the undesirable series 2 prostaglandins and toward the beneficial series 1 prostaglandins.”
Ms. Wright went on to say that phospholipid omega 3s from krill are “more bio-efficient, delivering 60% more omega 3s to the cells and tissues that need them most.”
Ben S. Winters, director of Christchurch-based Aroma New Zealand, agreed there will continue to be strong demand for joint care products, as inflammation remains one of the world’s most widespread diseases.
“Our two most popular joint care products today are GlycOmega-PLUS green-lipped mussel extract and green-lipped mussel oil,” he added. “GlycOmega-PLUS has been clinically tested to increase joint mobility and reduce joint pain in patients with osteoarthritis while green-lipped mussel oil is rich in omega 3 fatty acids and contains high levels of anti-inflammatory activity. Consumer awareness of our green-lipped mussel extracts is up, as many leading nutritional and veterinary companies use our branded raw materials to launch new joint care products into the market.”
Reducing inflammation and promoting joint health, Proprietary Nutritionals Inc. offers Celadrin, which according to the company’s Mr. Mosca, is “medically and clinically proven to alleviate discomfort and support enhanced mobility.”
The ingredient was developed through a proprietary process of esterifying fatty acids to ensure stability and prevent reactions with oxygen. Studies have shown that humans and animals have experienced reduction in pain and swelling and increased range of motion with Celadrin, with no reported side effects.
“Research has shown that the special fatty acids in Celadrin inhibit inflammation in endothelial cells (the thin cells that line the inside of various body cavities) and decrease the pro-inflammatory effects of arachidonic and other fatty acids,” Mr. Mosca said. “Celadrin has also been shown to reduce the production of the negative immune factor IL-6 and to control the immune factors responsible for inflammation. In addition, Celadrin may help to lubricate an affected joint, resulting in pain relief and increased mobility. We also have an equally effective plant-source Celadrin for vegans and vegetarians, called Vege-Celadrin.
PNI also offers Perluxan, a proprietary extract of hops cones shown to reduce joint discomfort. 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, Mr. Mosca noted. Another pilot study demonstrated that Perluxan was comparable to ibuprofen in reducing pain-causing inflammatory enzymes. Additional studies are planned.
Pycnogenol French maritime pine bark extract from Horphag Research has also shown anti-inflammatory activity. For example, in a study with 55 osteoarthritis patients Pycnogenol significantly lowered the inflammatory marker C-reactive protein (CRP) by 71%. This study also found a significant reduction of reactive oxygen species in arthritis patients by 30%.
Additionally, a double-blind, placebo-controlled study involving 156 OA patients, published in Phytotherapy Research in 2008, found that 100 mg Pycnogenol over a 3-month period led to a significant reduction in WOMAC pain scores; medication with NSAIDs also dropped by 58%. Overall, treatment costs were reduced significantly compared with placebo.
Eggshells & A New Approach
Matt Stegenga, director of marketing, Biova LLC, Johnston, IA, said that increased demand for new, efficacious products has coincided with interest in his company’s BiovaFlex egg membrane ingredient. “We’re seeing a lot of inquiry from both domestic and international companies and, most interestingly, across all types of brands and delivery systems. The market is clearly looking for new ingredients and new delivery systems to meet consumer demand.”
Egg membrane as a category is relatively new, and still unknown to most consumers, he said. “We partner with our customers to help promote awareness and create demand. We believe now’s an optimal time for consumer packaged goods to look hard at their current joint health line-ups and consider how to capitalize on the opportunities to create new demand and capture new market share.”
As a water-soluble egg membrane that benefits from a uniform ingredient profile and 450 mg/day efficacy, BiovaFlex can be included in functional foods and beverages, including trendy hybrid beverages, as well as gummies and drops, according to Mr. Stegenga.
From a supplement standpoint, there seems to be continued emphasis on combining known efficacious ingredients with newer ingredients to create a “boosted” or a “synergistic” formula. “Leveraging consumer trust in your brand with new, efficacious complementary ingredients is a proven growth model,” he said.
Nena Dockery, technical manager, ESM Technologies, Carthage, MO, said her company’s patented, food-sourced eggshell membrane ingredient, NEM, naturally contains the components that are found in healthy joint tissue, including glycosaminoglycans such as chondroitin sulfate, hyaluronic acid, collagen, glucosamine and several proteins and peptides.
“NEM has been the subject of multiple human clinical trials demonstrating its efficacy,” she noted. “These studies established an effective daily dose of only 500 mg compared to 1,200 to 1,500 required for chondroitin and glucosamine, respectively, and revealed a time period for a statistical measurement of efficacy of 7-10 days instead of weeks or months required for glucosamine. The efficacy studies along with safety studies and an in vitro mechanism of action study are all published in peer-reviewed journals.”
In addition, some consumers have become more interested in NEM because it is produced from a domestic food source and is not subject to adulteration or genetic modification.
Glucosamine, chondroitin and MSM products usually contain few if any additional active ingredients because of the high dosage, Ms. Dockery said. However, ingredients such NEM, which requires a much smaller dose and does not interfere with the metabolism of drug, supplement or food ingredients, can be used to create proprietary formulas that include other beneficial ingredients. “Formulas containing ingredients that have slightly different functionalities can provide a novel, multi-layered approach to joint care,” she said.
A newly established company, Bio-Rep, Pomona, CA, specializes in patented and clinically tested supplements that replenish, rebuild and revitalize the body’s core systems, according to president Sreus Naidu.
The company’s novel health technologies integrate essential bioactive molecules the human body regularly synthesizes to support vital processes. For the past several years, Bio-Rep has been involved in research in the areas of bone and joint health. “We have focused our attention on bioactive molecules present in milk because milk is the one vital food source that all mammalian species consume to support healthy growth and development (including within the skeletal system).”
From its research, Bio-Rep identified and isolated two multi-functional proteins involved in bone and joint health: ribonuclease (also known as angiogenin) and lactoferrin. “When complexed as ribonuclease-enriched lactoferrin (R-ELF), these proteins demonstrate potent synergism to promote osteoblastic activity (bone formation), optimize the rate of bone resorption (bone loss) and improve joint and cartilage integrity,” Mr. Naidu said.
In 2009, two double-blind human clinical studies were conducted on the R-ELF complex. The first study examined R-ELF’s effects on osteoblast and osteoclast activity, while the second assessed its impact on joint inflammation. Metabolic bone markers extracted from serum samples were used to measure the physiological effects of the R-ELF complex on bone and joints in study participants over a 6-month period. Both safety and efficacy outcomes were positive; to-date, no adverse events have been reported by study participants, Mr. Naidu noted. Study results were published in two peer-reviewed medical journals—Osteoporosis International and Inflammation Research.
