Joint health issues are highly prevalent and commonly seen in clinical practice. 

Arthritis and musculoskeletal disorders affect almost 6.9 million or 1 in 3 Australians, where they continue to be major contributors to illness, pain and disability.¹  Here we briefly discuss Collagen, Glucosamine, Lysine, Proline and the research that points to their beneficial effects of improving joint health.

Collagen (Collagen Hydrolysate)

The name collagen comes from the Greek “kolla”, meaning “gum”, and suffix “gen”, denoting “producing”.² It is the most profuse protein found in the human body, principally due to its connective role in biological structures. This fibrous structural protein is comprised of a glycine-X-Y repeating helical structure, where Gly is glycine, X is typically proline and Y is hydroxyproline or hydroxylysine.^3,4,5,6 The nutritional value of collagen hydrolysate (CH) stems from this unique amino acid profile with high levels of glycine and proline. Taken orally, CH stimulates collagen synthesis in articular cartilage as well as the extracellular matrix of other tissues.^3,6 This induces a noticeable regeneration of cartilage, reduces pain and increases mobility of those affected.³

As CH is already hydrolysed, it is easily digestible and highly bioavailable.⁷ Studies have shown that after the ingestion of CH it is readily absorbed and distributed to joint structures where it stimulates chondrocytes, combatting progressive degeneration of cartilage tissue, as well as exerting analgesic and anti-inflammatory effects.^8,9 Type II collagen, the principle constituent that accounts for more than half the dry weight of cartilage, is stimulated by CH in joint tissue.^8,10

Although the mechanism by which CH exerts its effect remains unclear, it is theorised that it may have a regulatory effect on chondrocyte differentiation, thereby stimulating synthesis of proteoglycans, which leads to the initiation of repair processes in cartilage tissue.⁹

So what’s the science linking CH to improved joint health?

• A 2010 multi-centre, randomised, double-blind, parallel study comprised of 100 participants assessed the effects of 10g of supplemental CH daily versus 1.5g of glucosamine sulfate for 13 weeks. They were evaluating joint pain, mobility, and quality of life. At the end of this study it was determined that 10g of CH daily greatly reduced joint pain, improved mobility and enhanced the quality of life. It was also deemed more effective than glucosamine sulfate alone.¹¹
• Next we have a 2012 randomised, double-blind, placebo-controlled trial involving 200 participants. Researchers evaluated the effects of 1.2g of CH per day for 6 months versus placebo. Overall, results were considered to be not entirely conclusive: at 3 months, 44% of collagen patients reported less joint pain compared to 40% in the control group; later at 6 months, 52% for collagen group and 37% for the control group. This split isn’t large enough to statistically state that collagen reduced joint pain, however, it needs to be considered that the low end of CH supplementation was used in this study, which would probably account for this result.¹²
• In 2015, a randomised, double-blind, placebo-controlled trial evaluated the effects of 10g daily of CH on the control of knee osteoarthritis in 30 patients. The endpoints were measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), used to assess pain, stiffness, and physical function in patients with hip and/or knee osteoarthritis; a visual analogue scale (VAS) and quality-of-life (QoL) parameters. Patients in the CH group presented a statistically significant improvement in all endpoints (p<0.01) compared with those in the placebo arm.⁹
• Fast forward to 2016 where we have a randomised observational multicentre study to assess CH in the treatment of osteoarthritis. The study was comprised of 126 participants who took 10g daily of CH over the course of 3 months. Data collected at the end of the 3 month trial established that CH was able to exert an important reduction in pain, improved functionality in knee osteoarthritis, as well as being safe and well tolerated.¹³ 

Glucosamine

Glucosamine is found naturally in the body. It is a major building block of the water-loving proteoglycans found in joint cartilage and synovial fluid. As a natural precursor of the cartilage extracellular matrix component glycosaminoglycans, which form proteoglycans, it is thought to provide a substrate for matrix synthesis and repair. Essentially, glucosamine is a key factor in determining how many proteoglycans are produced by cells. It normalises cartilage metabolism, which helps keep cartilage from breaking down.^14,15

Research on glucosamine has focused on the potential for supplemental glucosamine to beneficially influence cartilage structure and alleviate conditions such as arthritis.¹⁶ However, the efficacy of glucosamine is still controversial and under debate, despite the large quantity of published evidence.¹⁷ This can be due ot the varying forms of glucosamine, dosage and lengthy of trial of poor supplemental quality from around the world.^18,19

• The Pharmaco-Epidemiology of GonArthroSis (PEGASus) study was a cohort experiment of patients with knee osteoarthritis pain, comparing Symptomatic Slow Acting Drug in Osteoarthritis (SYSADOA: included crystalline GS, glucosamine hydrochloride, chondroitin sulfate, avocado soybean unsaponifiables and diacerein), aimed to assess the impact of such medications on NSAIDS. Overall the study involved over 6000 participants, where 315 participants received 1500mg/day of crystalline GS for 2 years. Results revealed that crystalline GS was the only SYSADOA able to decrease NSAID use (36% compared to controls).²⁰ Remarkably, glucosamine hydrochloride did not decrease NSAID consumption, confirming the different efficacy profile than GS as previously emerged from clinical trials.^20,21
• In 2014, experts from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO), gathered to determine new guidelines in the management of osteoarthritis. Based on their findings, they concluded that the first step for patients with osteoarthritis is to recommend slow-acting drugs such as GS as opposed to NSAIDS, which are recommended to be used only as an advanced step and if response is not adequate.²²
• A systematic review and network meta-analysis conducted in 2015 comparing glucosamine, NSAIDS, diacerein and placebo. The results showed that glucosamine improved the symptoms, in terms of joint pain and joint function, and decreased the structural progression in knee osteoarthritis.²³

The efficacy of glucosamine has been demonstrated via its symptomatic and potential disease modifying effects. Clinical trials have shown that the use of oral GS 1.5g daily in patients with osteoarthritis of the knee results in a significant reduction in joint pain and an improvement in joint function.^18,23 In addition, GS appears to reduce the loss of cartilage in the knee joint over at least a 3 year period, based on measurement of Joint Space Narrowing in various studies.^24,25,26 When we filter the muddy waters from the abundant research on GS, the effects on pain and function are indeed clinically relevant, especially in long-term therapy and when adequate doses are utilised.^18,23

Lysine and Proline

Both lysine and proline promote collagen and muscle protein synthesis, thereby playing pivotol roles in aiding muscle and joint strength and flexibility.^27,28,29,30 Aside from glycine, lysine and proline are important constituents of collagen fibrils, where optimal tissue levels are required.^27,37 They act as precursors as they are hyroxylated into hydroxylysine and hydroxyproline respectively. Ascorbic acid is required as an essential co-factor in this conversion.^27,29,30,31 Lysine and proline also aid in skin repair and wound healing, especially post-surgery and for minor sport injuries.^28,32

There is growing scientific awareness for the use of hydrolysed collagen and glucosamine as an adjunct in the treatment of conditions such as osteoarthritis. A sufficient intake of the essential amino acids lysine and proline should also be maintained. If we take into account that arthritic and musculoskeletal disorders are commonplace, it is important that we as practitioners acquire as much knowledge as possible in the clinical management of these patients. 

References

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