Below is what the experts have to say: Polymer Design and Development Christopher K. Arakawa, Cole A. DeForest, in Biology and Engineering of Stem Cell Niches, 2017 2.1.5 Chondroitin Sulfate Chondroitin Sulfate (CS) is an unbranched glycosaminoglycan consisting of N-acetyl-d-galactosamine and d-glucuronic acid connected by β-1,3 and β-1,4 glycosidic linkages. During synthesis, the polysaccharide is sulfated in different locations along its more than 100 glycan chain and conjugated to serine residues on proteins. CS is a common constituent of cartilage and skin ECM and contributes to the viscoelastic nature of both tissues due to its high degree of hydration.19 Hybrid polymer conjugates and polymer–polymer mixtures utilizing CS as their main component have been employed in cartilage tissue engineering, cardiac tissue engineering, dermal engineering, drug release, and for intervertebral disk regeneration.5 On a cellular level, CS has been shown to upregulate the synthesis of hyaluronan, glucosamine, and type II collagen by both bovine and human chondrocytes while also shown to downregulate expression of enzymes responsible for cartilage ECM breakdown including MMP-1, MMP-3, MMP-13, and aggrecanase-2.20 Recent studies have also highlighted the ability of CS to reduce inflammation by inhibiting human leukocyte chemotaxis and phagocytosis. 21 These factors have made CS a particularly important tool in the design of tissue engineering solutions to osteoarthritis. Maxime Dougados, in Osteoarthritis, 2007 Chondroitin Sulfate Chondroitin sulfate is a macromolecule that contributes to (like hyaluronic acid) a framework for collagen formation. The rationale for use and the discussion concerning the available data for symptomatic efficacy are very similar to those discussed previously for glucosamine, except that the number of well-conducted placebo-controlled trials is much smaller with chondroitin sulfate.90 A recent double-blind placebo-controlled 2-year trial focused on the evaluation of both the symptomatic and structural effect of 800 mg chondroitin sulfate.101 This study failed to show a significant difference in terms of symptoms but did reveal a significant difference in terms of radiologic joint space progression (0.00 ± 0.53 versus 0.14 ± 0.61 mm in the chondroitin versus placebo group, respectively). As with glucosamine, chondroitin sulfate seems to be very safe. Herbal and Nutritional Supplements for Painful Conditions Andrea H. Zengion ND, MSAOM, Eric Yarnell ND, in Pain Procedures in Clinical Practice (Third Edition), 2011 Glucosamine Sulfate and Chondroitin Sulfate Although they are not anodynes in the same sense as other remedies listed here, glucosamine sulfate and chondroitin sulfate are useful in the treatment of osteoarthritis pain because of their effect on joint structure. Glucosamine is a substrate for the glycosaminoglycans that comprise hyaluronic acid, a chief component of joint tissue. Chondroitin plays a number of roles in connective tissue synthesis. It is itself a glycosaminoglycan and, when hydrated, it creates osmotic pressure that increases the compressive resistance of synovial cartilage. It also stimulates the production of collagen and proteoglycan and inhibits enzymatic destruction of the synovium.22,111 Osteoarthritis: Numerous studies have been performed to evaluate the efficacy of glucosamine and chondroitin administration for osteoarthritis treatment with mixed results, although this may be due to combining different forms of the agents, or to some studies’ use of less effective forms of glucosamine and/or chondroitin or products with poor standardization.53 Industry bias may also account for some of the discrepancy between studies, although it should also be noted that many of the studies not funded by industry sources examined glucosamine hydrochloride.112 According to a meta-analysis, glucosamine sulfate used alone relieved pain due to osteoarthritis and prevented disease progression.113 Glucosamine hydrochloride, although cheaper, is not effective for osteoarthritis.114 Conclusions derived from studies of one form cannot be extrapolated to apply to the other form, even though data for glucosamine sulfate are mixed.115 Chondroitin treatment reduced pain, swelling, and effusion, and maintained or improved joint space and serum osteocalcin levels. Glucosamine sulfate and chondroitin sulfate taken together decreased pain and joint effusion in moderate-to-severe arthritis pain, but results were inconsistent between studies.111,116 Dosage: 1500 mg glucosamine sulfate per day. 400 to 1200 mg chondroitin sulfate per day. Caution/contraindication: Contraindication for glucosamine: shellfish or iodine allergy. Glucosamine may increase PT-INR when given with warfarin.117 Chondroitin may also increase the effects of anticoagulant therapies. Because of its structural similarities to heparin, some sources recommend that it be contraindicated in pregnancy.