According to the CDC, osteoarthritis (OA) is the most prevalent musculoskeletal condition in the U.S., affecting more than 30 million Americans. OA is characterized by the progressive deterioration of the articular cartilage and inflammation of the synovium, manifesting as joint pain and stiffness.

In recent decades, nutrient and botanical ingredients have offered a safe and effective alternative to pharmaceutical drugs and surgery. Novel ingredients and innovative formulas are particularly attractive to consumers seeking natural solutions.

Haritaki (Terminalia chebula) fruit, used extensively in traditional ayurvedic, Unani and Iranian medicine, has demonstrated antioxidant and anti-inflammatory activities in clinical research. In one randomized, double-blind, placebo-controlled clinical trial, haritaki (as AyuFlex from Natreon) reduced knee discomfort and improved knee function during exercise in healthy overweight participants after 12-weeks. No significant differences occurred between the 250 and 500 mg twice daily doses, validating efficacy with the lower dose. AyuFlex also showed anti-osteoarthritic effects in a rat model by reducing levels of oxidative stress, pro-inflammatory mediators and pro-inflammatory cytokines. Additionally, haritaki inhibited the progression of OA by decreasing matrix metalloproteinase expression and suppressing synovial membrane and cartilage destruction.

Cucumber (Cucumus sativus), a familiar food and topical remedy for various skin problems, has gained traction recently as a dietary supplement ingredient. In a randomized, double-blind, parallel-group clinical trial, cucumber (as Q-actin from IminoTech) extract was significantly more effective at reducing pain and improving mobility than a glucosamine-chondroitin supplement in 122 participants with moderate knee OA. Oral supplementation included only 10 mg cucumber versus 1,350 mg glucosamine-chondroitin twice daily for six months. Preclinical evidence suggested the iminosugar amino acid, idoBR1, may be partially responsible for cucumber‘s anti-inflammatory effects by inhibiting sialidase or interacting with CD44-HA signaling.

While most studies are based on a single ingredient, researchers examined the effects of ginger (Zingiber officinale) combined with toothache plant (Acmella oleracea) in a 2020 experimental pilot study involving 50 participants with knee OA. Two tablets, each containing 37.5 mg ginger and 7.5 mg toothache plant (as Mitidol from Indena S.p.A.), administered daily for one month significantly reduced pain and inflammatory indices, C-reactive protein (CRP) and erythrocyte sedimentation rate. According to in vitro findings, the mechanisms may involve the endocannabinoid system.⁶ Both botanicals inhibited fatty acid amide hydrolase enzymes while only toothache plant targeted cannabinoid 2 receptors.