Proven & Supported

Incidence of bone and joint health issues are on the rise as manufacturers seek scientifically backed ingredients to help consumers maintain their mobility and shore up skeletal foundations.

About one in two women and one in four men over age 50 will break a bone due to osteoporosis and, according to the National Osteoperosis Foundation, by 2020, half of all Americans over 50 are expected to have low bone density or osteoporosis. Meanwhile, The Burden of Musculoskeletal Conditions in the United States, a publication put out by the American Academy of Orthopaedic Surgeons, reported that nearly half the American population over the age of 18 (about 48 percent) are affected by musculoskeletal (bone and joint) conditions.

But while the data on the incidence of bone and joint Issues continues to rise, there is a disconnect between the statistics and consumers’ actual awareness. For instance, only about one half of individuals with osteoporosis are cognizant of their condition. In the National Health and Nutrition Examination Survey (NHANES), only one percent of men and 11 percent of women over 65 reported that they had osteoporosis. However, bone mineral density (BMD) testing revealed that four percent of male and 26 percent of female survey takers actually had the disease. The mismatch between perception and reality with regard to bone health gains importance from the fact that the number of individuals involved is huge.

“Recent statistics indicate that osteoporosis and osteoarthritis (OA) affect nearly 44 million and 34 million people, respectively, in the U.S.,” said Suhail Ishaq, president of Californiabased BioCell Technology. “About one third of adults over the age of 30 possess a clinical evidence for OA, which underlies 25 percent of visits to primary care physicians and the degenerative joint disease is one of the top 10 disease burdens in the world today.” 

A Growing Market 

Americans suffer joint issues earlier than in the previous generation, and this is likely because of increased rates of obesity. And, of course, rates of conditions such as arthritis increase with age.

“Putting aside genetic factors, aging and unhealthy lifestyle are considered key contributors to chronic joint diseases such as OA. In particular, obesity, which is closely associated with a combination of high-calorie diet and sedentary lifestyle, is one of its biggest risk factors,” said Ishaq, explaining that the natural aging process adds a significant burden to our joints because it entails the loss of macromolecular components, such as collagen type II, and glycosaminoglycans (GAGs), such as hyaluronic acid (HA), essential for the structure and function of the connective tissue such as the cartilage.

“Thus, poor choice of diet that fails to replenish both collagen type II and HA does not provide proper nutrition for gradually vulnerable joint tissues. In addition, various instant foods charged with oxidative and inflammatory insults worsen the problem.” 

Despite the unhealthy lifestyle choices that are leading to increased incidence of joint conditions, the market is also being driven by a population seeking to maintain its mobility. Aging Baby Boomers are an integral part of this demographic, as they want to continue living an active lifestyle even after retirement, and statistics show that approximately 10,000 people in the U.S. turn age 65 every day.

“Joint health is an increasingly popular issue among active Baby Boomers and 30- to 40-year-olds alike. Active consumers are looking for a way to maintain their exercise routines, and there has been a lot of interest in joint support ingredients for sports nutrition products,” said Paul Dijkstra, CEO of California-based InterHealth Nutraceuticals.“Joint health is important in many sports. Maintaining knee joint function supports mobility, increases flexibility and may support the ability to exercise longer and more regularly.Maintaining knee health is important for everyone from a seasoned athlete to a weekend warrior.” 

Dijkstra noted that his company has seen increased interest from manufacturers regarding its patented, clinically studied joint health ingredient, UC-II, which is sourced and manufactured in the United States.

“The prospect of the joint ingredient market is bright as health-conscious consumers and health care professionals eagerly look for joint ingredients that are substantiated by strong science and are also convenient to take regularly,” said Ishaq, adding that over the last 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.” 

Ingredient Uproar 

Traditional go-to joint health ingredients glucosamine and chondroitin sulfate have come under recent fire regarding their clinical relevance. Ishaq offered that a comprehensive scientific review published in 2010 concluded: Compared with placebo, glucosamine, chondroitin and their combination do not reduce joint pain or have an impact on narrowing of joint space, he noted. “A critical shortcoming of these two ingredients appears to lie in mere partial approach via their supplementation of GAGs only to complex joint degeneration process which involves collagen type II as well as GAGs such as chondroitin sulfate and HA.” 

Ishaq said his company’s patented BioCell Collagen provides a more comPrehensive approach to joint degeneration.“Its mechanism of action includes supplementing collagen type II, chondroitin sulfate and HA, and potentially helping regenerate worn-down cartilage through restimulation of the chondrocytes,” he said. “It can also provide an effective supplementation of HA in the synovial fluid for enhanced joint lubrication.” 

On the bone health front, Vladimir Badmaev, MD, PhD, head of research and development with Norwegianbased NattoPharma ASA, pointed out the paradox of calcium as both hero and villain has been highlighted by the results of a 2013 Journal of the American Medical Association (JAMA) published study by Xiao et al. The report discussed the outcome of the National Institutes of Health (NIH)–AARP Diet and Health Study, which evaluated the role of supplemental calcium on cardiovascular health. The prospective study involved a large cohort of 219,059 men and 169,170 women followed up for 12 years to ascertain their health status.The outcome revealed that intake of 1,000 mg per day of supplemental calcium from multivitamins or individual calcium supplements were associated with significant increase in heart disease death in men but not in women (7,904 and 3,874 reported deaths in men, and women, respectively).

“Although the JAMA study indicates that supplemental calcium may affect adversely cardiovascular health in men only, other studies indicate that supplemental calcium intake puts women at cardiovascular risk as well,” said Badmaev, offering an example of the WHI CaD Study reporting an increased risk of cardiovascular disease in women allocated to a calcium supplementation group. “In addition, use of calcium supplements with or without vitamin D was associated with a significant 24 percent increase in risk of coronary heart disease in a cohort of 10,555 Finnish women.

“These epidemiological findings suggest that guidelines for calcium supplements may have to be revised, and calcium and vitamin D supplements may need to be complemented with vitamin K2 intake for efficient delivery of calcium to ensure effective performance of the body’s physiological functions,” he added.

However, Badmaev noted that increasing clinical evidence is now available showing that vitamin K is critical for efficient metabolism of calcium in the body. “Calcium supplements, with or without vitamin D, have been widely used for the prevention and treatment of osteoporosis and general health support of an aging population.However, when nutritional vitamin K intake is low, the K-dependent protein is unavailable in its active carboxylated form and uncontrolled mineralization of calcium in arterial walls has been shown to contribute to cardiovascular disease,” he said.

Badmaev offered that his company’s proprietary MenaQ7 brand of Natural Vitamin K2 standardized to MK-7 content is supported by a patent granted and published on use of vitamin K in cardiovascular health, which is closely intertwined with bone health. In addition, a patent is pending based on the outcome of a recently published threeyear clinical study intervention.

Research-Backed Response 

One thing that is clear: marketers of finished products as well as consumers look for ingredients where the safety and efficacy is backed by human clinical trials.

The safety and efficacy of BioCell Collagen has been substantiated by four human clinical studies (three on joint health and one on skin beauty from inside). The studies demonstrated that BioCell Collagen is an effective option in the management of joint discomfort as its daily ingestion led to the significant reduction of discomfort, thereby improving activities of daily life in the study subjects, according to Ishaq.

A recent randomized, double-blind, placebo-controlled, clinical trial in 80 subjects with joint discomfort confirmed the study outcome from its earlier clinical trial, demonstrating that 71 percent of the subjects who ingested BioCell Collagen (2g/daily for 10 weeks) experienced a significant improvement of their mobility-restricting joint discomfort whereas only 30 percent in the placebo group experienced a similar benefit. No serious adverse events were reported. The outcome of this study was published in the Journal of Agricultural and Food Chemistry (2012).

Ishaq expressed that his company’s BioCell Collagen is a highly differentiated healthy-aging ingredient. “First, BioCell Collagen offers a patented composition of 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,” he said. “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 of the synovial cells to synthesize collagen and HA. This activity has a profound implication for regeneration of worn-down cartilage,” he added. “This regenerative activity appears specific to hydrolyzed collagen because undenatured collagen fails to stimulate these cells. Thus, BioCell Collagen is considered the most comprehensive joint health ingredient in the market.” 

InterHealth’s Dijkstra agreed that human clinical trials are the pinnacle of proof, but noted that a challenge facing the category is the lack of research conducted on healthy subjects. It’s a point InterHealth was sure to address with its UC-II ingredient for joint health products, sports nutrition products, multivitamins and other combination products.

UC-II is supported by two clinical research studies. The latest was on healthy subjects and was presented at the Scripps Natural Supplements Conference in San Diego, CA, January 31-February 2, 2013 (the research abstract will be published in the Journal of Alternative and Complementary Medicine). The randomized, double blind, placebo-controlled study was conducted on 55 healthy subjects for 17 weeks. As part of the protocol design, all subjects were evaluated to confirm that they did not meet the American College of Rheumatology criteria for osteoarthritis. Joint stress was induced via a standardized stepmill protocol.

The study showed that UC-II significantly improved joint flexibility as assessed by knee extension compared to placebo in healthy subjects. Additionally, UC-II significantly delayed the onset of joint discomfort compared to baseline when exercising and accelerated the offset of joint discomfort compared to baseline after exercising.

“The study showed that 40 mg of UCII significantly improved knee extension compared to placebo,” said Dijkstra.“UC-II subjects exercised longer before experiencing joint discomfort and recovered faster from joint discomfort after exercising compared to baseline.” 

Formulation Innovation 

NattoPharma’s Badmaev explained that his company’s MenaQ7Crystals (a singular ingredient) was developed because, up until that point, all fermentation technology menaquinone-7 ingredients also contained extraneous other menaquinones (e.g., MK-4, MK- 5, MK-8, etc.) and also other impurities from the fermentation process.

“Knowing that it is MK-7 in and of itself that is one of the most active menaquinone components, we adapted crystallization technology specific to this compound to arrive at the purest MK-7 on the market—no other menaquinones with the sole exception of a minute trace of MK-6, which is a marker of natural menaquinone-7 technology (note: MK2-6 is not present in a synthetic MK-7 product),” he said.“The resulting pure crystals allow brand manufacturers to save in final product weight and size. Traditional forms of oil, powder, and water-soluble powder also available, which affords opportunities to create more novel combination products.” 

MenaQ7Crystals are unique in the marketplace due to the process that creates it and its resulting purity. The menaquinone-7 is extracted in vegetable oil and subject to process of purification, concentration and crystallization to obtain the MenaQ7Crystals.The purification process leads to crystals that are the pure physical form of vitamin K2. The final commercial product is used either in the pure form of crystals or in the form of crystals diluted either in MCT oil or in a powder mixture containing non-animal, vegetable ingredients.

Badmaev offered that the resulting products of advanced MenaQ7Crystals are characterized by:

• No less than 95 percent content (up to 98 percent) of only trans-MK-7 with less than 0.5 percent MK-6

• No other detectable menaquinones

• Solvent under the detectable levels

• Soy-free process (preventing soy allergens)

• Improved stability profile in storage and in finished supplement and food preparations 

“Based on these characteristics it is implicit that MenaQ7Crystals will have an improved gastrointestinal absorption rate, higher rate of activating target proteins, e.g. osteocalcin and MGP, and an increased bioavailability of K2-dependent proteins activating target receptors in the body,” said Badmaev.

Manufacturer Tips 

While there’s no doubt that the demand for clinically proven safe and efficacious ingredients is there from both manufacturers of finished products and consumers, InterHealth’s Dijkstra noted that the responsibility lies with manufacturers to insist upon those ingredients as well as the proof.

BioCell Technology’s Suhail agreed: “Manufacturers should demand human clinical trial data when they consider ingredients for their products,” he said.“Joint discomfort interferes with a person’s quality of life and when alleviated offers immediate gratification.Therefore, if the product fails to deliver results, the consumer will not likely reorder the product and the business will be short lived.” 

In addition, Ishaq cautioned manufacturers to be wary of companies that do not have studies to back up their ingredients or companies that borrow science from other proprietors of the studies. “When this happens, it should immediately raise a red flag to the manufacturer or formulator of the finished product,” he said. “Using another company’s research data to promote a product that does not contain the ingredient that the research was done on is considered false advertising and is punishable under the law.”