A hurrah for type 2 collagen...and green lipped mussel extract?

Updated: Apr 17, 2019

The last two posts have commented largely on the effects of very well known osteoarthritis supplements: glucosamine/chondroitin and omega 3 fatty acids. Click on the links to read the full discourse. In my searches for objective, high-quality evidence on supplements, I came to the conclusion that it's pretty sparse. Many studies are either performed or funded by supplement companies or are just not that robust! Aside from a supplement called diacerein, most supplements are, however, fairly safe to consume at their recommended doses. I did briefly want to talk about two lesser known supplements that did actually have some efficacy in reducing osteoarthritis pain in the medium term.

First, type 2 collagen is the most abundant kind of collagen in cartilage and comprises about 85% of the protein weight of articular cartilage. Keep in mind that there is cartilage like in the nose and ear and articular cartilage which is the business end of what keeps our joints well lubricated and provides the gliding or sliding surface between bones. This cartilage is important structurally because it actually has the ability to trap proteoglycans.

Proteoglycans are basically just amino acid chains with lots and lots of sugar bound to them. Interestingly, sugar binds up lots and lots of water. So you can think of sugar as a sponge for water and the amino acid backbone as a backbone to which multiple water-laden sponges are attached. Now, type 2 collagen is able to sequester and retain these fluid-filled proteoglycan molecules, improving the ability of articular cartilage to absorb shock. Interestingly, the cells that make cartilage (chondrocytes; chonro-cartilage, cyte-cell) arrange the type 2 collagen in such a way as to help the cartilage both glide and shock absorb. Pretty cool stuff!

Image shown as published in Levangie PK, Norkin CC, eds. Joint structure and function: a comprehensive analysis. 3rd ed. Philadelphia: FA Davis; 2005: 80.)8

As you can tell, at the top of the image is the surface of the joint: basically the end of the bone which is covered in cartilage. The first layer of collagen is lain down in a linear pattern, parallel to the surface of the joint itself. This helps the cartilage glide against other cartilage.

The next layer, Zones 2 and 3, are arranged of seemingly haphazard collagen fibrils (the basic unit of one piece of collagen). This arrangement acts as a multi-directional shock absorber and is maintained by more chondrocytes than the first zone. Zone 4 is where the chondrocytes arrange themselves in a linear pattern radiating from the end of the bone itself. The collagen at this point is arranged similarly. Zone 4 is perpendicular to Zone 1. These chondrocytes will theoretically make their way upward and outward as cartilage is worn and remodeled. While the mechanism is not known, the prevailing theories are that type 2 collagen supplementation decreases the degree to which our bodies catabolize (break down) type 2 collagen in the knee by means of inhibiting inflammation. While inflammation is an easy molecular target for drug or supplement companies, there is evidence that the eating and digesting of various substances decreases our auto-immunity (the tendency of our immune system to attack things it perceives as foreign) to it. Notably, the type 2 collagen must be undenatured (not broken down) for the improvement to occur, lending the idea that there must be some need for the structure to be intact for the regulatory activity to occur.

Now, if you're like me, the idea of green lipped mussel extract is a bit outlandish. Who in the world would think that mussels would be the key to knee pain? While the particular chemistry is unclear, there has been empiric evidence that suggests the meat of the mussel does improve knee pain and range of motion scores in those with arthritis. It known that the pharmacology has to do with inhibiting lipoxygenase and with a degree of anti-inflammatory action.

Above is an example of the green "lipped" mussel.

Some work on the mussel has suggested it's osteoarthritis-fighting ability is also linked to a change in the gut's microbiome (the bacteria which live inside your intestines and provide beneficial actions to the host). While some evidence is less compelling, there is also a decent preliminary body of literature that supports the benefit of the shellfish. While an earlier systematic review (the highest form of evidence for medical literature to that date) in the journal of Clinical Rheumatology from 2006 was highly dubious as to the benefit of GLM, a more recent systematic review from 2008 suggests that not only is there likely benefit to patients suffering from osteoarthritis but that there was likely a clear biological mechanism for the benefit

What's my take? Well, the British Journal of Sports Medicine recently published a review of dietary supplements and their pros and cons as they pertain to osteoarthritis and showed through their meta-analysis and systematic review that the preponderance of evidence on GLM was positive. Given its high safety profile and potential, I think it's reasonable to try it out and make your own decision!

Keep moving!


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