Joint health supplements are soaring in popularity, with consumer demand for these products driving a wave of innovation. While legacy ingredients are falling out of favor, a flurry of research activity on newer ingredients has captured consumers’ attention. In fact, the joint health market is a dominating force among nutraceuticals, having reached an impressive $10.8 billion worldwide valuation in 2021, says Lindsey Toth, director of global marketing for capsules and health ingredients at Lonza (Basel, Switzerland).
Consumers adopted sedentary lifestyles in droves during the COVID-19 pandemic, Toth explains, which contributed to an increased prevalence of weight gain and joint stiffness. With consumers eager to move on from the pandemic and get moving again, demand for joint health products is now at an all-time high, she says. Here are some of the ongoing innovations in joint health ingredients that aim to meet the unprecedented demand for proven products.
Joint Health Demographic Gets Younger
While joint health ingredients have traditionally catered to an older demographic plagued by osteoarthritis and other joint health problems, Shalini Srivastava, MD, director of clinical development for contract research organization Vedic Lifesciences (India), says that today’s joint health consumers skew younger. Modern joint health consumers are also healthier than past demographics. Rather than ameliorating certain joint health conditions, these consumers are prioritizing preventative maintenance.
Collagen Recovers Function, Relieves Pain
Recent research shows that collagen—both by itself as a single-ingredient product and when incorporated in blends—has potent effects on joint function.
One 2022 study1 Lonza conducted examined the effects of Lonza’s branded UC-II, an undenatured type II collagen ingredient, on range of motion in knee flexion and extension angles in healthy subjects aged 20 to 55 with activity-related joint discomfort. Subjects received either 40 mg of UC-II per day or a placebo for 24 weeks. At the end of the study, subjects who received UC-II exhibited a 3.23-degree increase in flexion range of motion and a 2.21-degree increase in extension range of motion. These increases were statistically significant. And subgroup analysis found that subjects over the age of 35 exhibited even greater increases.
Toth says the 3-degree increase in knee range of motion represents a recovery of more than a decade’s worth of joint function. Furthermore, she explains that in this study, UC-II worked 15 times better than placebo.
Collagen also shows efficacy when incorporated in blends. One post-marketing surveillance study2—a single-arm, open-label, observational pilot study—assessed the efficacy of a product called AflaB2 on 40 male and female outpatients with knee osteoarthritis. AflaB2 is a blend of Laila Nutraceuticals’ (India) branded Boswellia serrata extract Aflapin and Bioiberica’s (Spain) branded Collavant n2 type II collagen.
All patients in the study were administered a once-daily dose of an oral solution containing 40 mg of type II collagen and 100 mg of Boswellia serrata extract. Subjects stayed on the protocol for three months and were assessed for Visual Analog Scale (VAS) pain scores and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores on days 0, 5, 15, 30, 60, and 90. After 90 days, subjects exhibited a 73% reduction in VAS scores and a 76% reduction in WOMAC total scores.
This study demonstrated that collagen may be more effective when incorporated in blends with herbal ingredients, says Jaume Reguant, healthcare director at Bioiberica. Reguant notes that in the AflaB2 trial, the researchers observed a significant reduction in VAS pain starting on day five of the study.
“Alone, the benefits of native type II collagen are typically observed in one or two months,” Reguant says. “This study suggests, however, that when used in combination with Boswellia serrata, results may come faster.”
“One of the most exciting developments in joint health right now is the exploration of how we can take ingredient efficacy to the next level with unique and powerful combinations,” he declares.
Trial Endpoints Shift and Diversify
Emerging clinical trials for joint health are moving away from the classic hallmark of chronic pain caused by osteoarthritis as a study endpoint, says Shalini Srivastava at Vedic Lifesciences. Instead, she says, studies are now measuring structural deterioration, disease-modifying activity, and acute pain induced by physical activity.
Curcumin Relieves Inflammation, Dispersion Boosts Absorption
Curcumin (Curcuma longa) is an effective multimodal ingredient for use in joint health formulations, but the ingredient’s poor absorption profile has historically limited its potential. The problem is worth addressing, as curcumin has been shown to be a valuable joint health ingredient.
Curcumin exerts anti-inflammatory, antioxidant, and pro-apoptotic effects on several biological systems, says Maggie McNamara, marketing director for Gencor (Irvine, CA). The ingredient may also reduce inflammatory cytokine and prostaglandin production by modifying COX-2 pathway signaling.
While curcumin has been a challenging ingredient to formulate with, suppliers have focused for years on innovating new forms of more-bioavailable ingredients. “The main factor restricting the use of curcumin as a therapeutic agent is its poor oral absorption,” McNamara says. She notes that Gencor’s branded HydroCurc ingredient combines curcumin and LipiSperse technology designed “to increase the bioavailability and functionality of lipophilic actives.”
One recent randomized, double-blind, placebo-controlled clinical trial assessed the efficacy of 500 mg/day of Gencor’s HydroCurc on morning joint pain over the course of two weeks. This study, which was accepted by an academic journal and is pending publication, found that HydroCurc was effective in reducing joint pain. HydroCurc demonstrated statistically significant efficacy relative to baseline starting on day 5. The ingredient also showed a significant difference relative to placebo starting on day 11.
Curcuma longa’s joint health benefits may be due to calebin A, a curcuminoid compound and curcumin analog with anti-inflammatory properties, one company has discovered.
Muhammed Majeed, PhD, founder and chairman of the Sami-Sabinsa Group (East Windsor, NJ), says calebin A works to inhibit inflammatory cytokines such as interleukin-6, TNF-alpha, and interferon-gamma. Majeed notes that calebin A has also been found in studies to inhibit the production of osteoclasts, indicating an osteoprotective effect. One in vitro study3 conducted by Sabinsa and the University of Texas (Houston) found that calebin A suppressed the production of osteoclasts in cancerous cells isolated from mice.
“Osteoclasts are responsible for bone destruction,” says Majeed, who coauthored the study. “[This study demonstrated that] calebin A kills the cells that destroy bone.”
In March 2022, Sabinsa launched its branded CurCousin ingredient, a nature-identical synthetic calebin A ingredient standardized to a 98% concentration. Sabinsa holds 13 patents on calebin A for protection of articular cartilage, with two more patents pending, and three patents as a therapeutic for osteoporosis.
Can Science Frankenstein a New Knee Together?
In Mary Shelley’s 1818 novel Frankenstein or the Modern Prometheus, Dr. Victor Frankenstein brings his namesake monster to life through galvanism—the application of electricity to reanimate dead body parts. Now, research is demonstrating there may be some science fact to this work of science fiction.
In January 2022, bioengineers at the University of Connecticut regrew cartilage in a rabbit’s knee using poly-L-lactic acid nanofibers that generate short bursts of electricity in response to pressure. Normal movement, such as walking, is sufficient to create a constant stream of electrical stimulation that prompts cartilage regrowth around the nanofiber mesh. The study’s lead author notes that piezoelectricity, the phenomenon on which the nanofiber device is based, already occurs naturally within the human body.4
Fast-Acting Ingredients on the Rise
Botanical ingredients continue to capture more of the joint health market. As consumers become more sedentary, and demand for joint health ingredient grows, traditional joint health supplements like glucosamine and chondroitin are unable to match consumer expectations, says Shalini Srivastava, MD, director of clinical development for contract research organization Vedic Lifesciences (India). Meanwhile, diversification within the consumer base is also splitting demand between vegan and non-vegan options.
The result? “Fast-acting ingredients are being appreciated,” Srivastava says. “Demand for botanicals has increased with the rise of the vegan trend, while eggshell membrane is meeting the needs of omnivores.”
Joint Health Market Offers Flexibility
Joint health ingredients are experiencing renewed interest as consumers seek validated products that can help maintain an active lifestyle. While more traditional ingredients like glucosamine and chondroitin are falling out of favor, newer ingredients like curcumin and collagen continue to see robust research investment and a welcoming consumer audience. Formulators have ample room to experiment with novel ingredient combinations, enabling brands to capitalize on consumer demand for unique and effective products.
References
- Schön C et al. “UC-II undenatured type II collagen for knee joint flexibility: A multicenter, randomized, double-blind, placebo-controlled clinical study.” Journal of Integrative and Complementary Medicine, vol. 28, no. 6 (June 2022): 540-548
- Jain AV et al. “AflaB2 and osteoarthritis: A multicentric, observational, post-marketing surveillance study in Indian patients suffering from knee osteoarthritis.” International Journal of Research in Orthopaedics, vol. 7, no. 1 (January 2021): 110-115
- Tyagi AK et al. “Calebin A downregulates osteoclastogenesis through suppression of RANKL signalling.” Archives of Biochemistry and Biophysics, vol. 593 (March 2016): 80-89
- Krieger K. “Regrowing cartilage in a damaged knee gets closer to fixing arthritis.” UConn Today. Published online January 12, 2022.
