Thinking Nutrition

Arthritis relief: can collagen supplements help?

• Dr Tim Crowe • Episode 124

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Interest in collagen supplements continues to grow – and for good reason. That’s because despite rubbish claims that are way off the mark that there is ‘no evidence they work’ and ‘all the research is funded by the collagen industry’, the reality is very different. In past podcasts I’ve delved into the topic of hydrolysed collagen supplements and skin health and where there are now dozens of blinded randomised controlled trials showing a benefit in increasing skin moisture and elasticity and reducing wrinkles – with many of the studies free from any conflict of interest and all supported by plausible mechanisms as to why collagen, and not other protein sources, can do this. But for this podcast, I want to focus on one of the other reasons that people may take collagen: and that’s to give relief from joint pain and stiffness. So for this episode, I’m going to focus on arthritis and outline what the clinical evidence says and what unique biological mechanisms could be at play to support a unique effect of collagen supplements.

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Interest in collagen supplements continues to grow – and for good reason. That’s because despite rubbish claims that are way off the mark that there is ‘no evidence they work’ and ‘all the research is funded by the collagen industry’, the reality is very different. In past podcasts I’ve delved into the topic of hydrolysed collagen supplements and skin health and where there are now dozens of blinded randomised controlled trials showing a benefit in increasing skin moisture and elasticity and reducing wrinkles – with many of the studies free from any conflict of interest and all supported by plausible mechanisms as to why collagen, and not other protein sources, can do this. But for this podcast, I want to focus on one of the other reasons that people may take collagen: and that’s to give relief from joint pain and stiffness. So for this episode, I’m going to focus on arthritis and outline what the clinical evidence says and what unique biological mechanisms could be at play to support a unique effect of collagen supplements.

 Today I’m going to dip back into the topic of collagen. Now, this is a topic that I’ve so far devoted three podcasts to – and for good reason. Because what the science has to say about some of the health claims, especially around skin health, is becoming more and more of a positive news story. This contrasts with newspaper article after article dismissing it out of hand for a variety of….well, completely wrong reasons – which I’ll outline shortly.

If you want to get up to speed on hydrolysed collagen in skin health, you can check out the most recent podcast I did on this topic which I’ve linked to in the show notes. And then there is a podcast I did recently about the emerging role of collagen supplements in tendon injury repair and recovery – also linked to in the show notes.

So a bit of a background summary on the collagen story to date. Collagen is the most abundant protein in our body, making up 30 percent of our total body protein. Its primary role in the body is to serve as a major structural protein. Collagen is present in many tissues including tendons, ligaments, cartilage, blood vessels and skin.

The collagen protein is constructed by three intertwined amino acid chains. These amino acid chains are largely composed of repeating units of glycine (which is every third amino acid), proline and hydroxyproline. That last one hydroxyproline is unique to collagen and is derived from proline which needs vitamin C for this to happen. Scurvy, a vitamin C deficiency disease, presents as extremely weak collagen.

Collagen is not a single molecule; there are 28 distinct types. The most abundant are types I, II and III. Type I collagen is found in tendons, ligaments, corneas, bones and skin. Type III collagen is typically found alongside type I collagen in the skin and blood vessels. Type II collagen is mostly found in cartilage.

Hydrolysed collagen is the most common form in the supplement market. When native collagen is heated, it denatures to form gelatin. However, gelatin has low solubility, so hydrolysing collagen creates shorter amino acid chains, increasing their solubility and absorption rate.

When collagen is eaten, it is digested and absorbed into the bloodstream where both single amino acids and unique dipeptides and tripeptides appear. These small peptides have a unique fingerprint because of the presence of the amino acid hydroxyproline. Remember, hydroxyproline is unique to collagen so these small peptide fragments only exist in the blood from collagen breakdown or from the collagen we eat.

Absorbed collagen peptides not only redistribute to the skin but can act as signalling molecules, binding to receptors on the surface of fibroblasts. Fibroblasts are skin cells that are major producers of collagen. This receptor binding stimulates fibroblasts to produce collagen, elastin (which is needed for skin elasticity) and hyaluronic acid (for water retention). This is a key point as it provides a plausible mechanism by which collagen consumption could directly affect our skin. And similar types of pathways exist in cells that produce collagen found in cartilage and tendons.

So, can collagen supplements promote healthy skin? As I outlined in my earlier podcast on this topic, at the time over 25 randomised-controlled trials have investigated this question, and the answer is remarkably consistent: yes. Supplementation with hydrolysed collagen had a statistically significant effect on skin hydration, skin elasticity, skin density and wrinkles. And many of these clinical trials were independently funded, with no commercial conflict of interest from the authors. Effective collagen doses used in the trials ranged from 0.6 g to 12 g per day for 1 to 3 months. And not a single study reported an adverse health problem from taking collagen.

But research never stands still and there has been yet more research since then. So much so, that late in 2023, a new systematic review was published. This new review could analyse 26 randomised controlled trials of oral collagen supplements that looked at skin hydration and skin elasticity. And I’ll link to the review in the show notes. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10180699

And just like in prior reviews, a significant benefit was seen with almost every study pointing in the right direction for a benefit.

But isn’t all the research funded by the collagen industry? No. Of those 26 studies on skin health I just mentioned, 11 had no funding from the collagen industry (trust me, I checked) nor did any of the research team report a conflict of interest. And these ‘untainted’ trials were just as likely to show a benefit as those with industry links. Playing the ‘industry funding’ card is a lazy form of critical analysis.

Sure, you can always find fault with any individual study. But for anyone to claim that there is ‘no evidence collagen supplements work’ is living in scientific denial. If anything, I am more sceptical of people who dismiss collagen out of hand. That was a valid position 10 years ago with a limited research base. But not today. And especially when faced with growing evidence across many different areas where collagen supplements seem to benefit many conditions.

And those dismissive claims that collagen is no different to any other protein you eat so it can’t have a unique biological effect are just so far off the mark. There is a plausible and well-understood mechanism where collagen can have direct effects on collagen production in the body different to any other protein source – and that’s because of the unique peptides that are absorbed into the bloodstream after you eat collagen.

Okay, that’s your lengthy introduction and summary of the main collagen story so far. Now into the topic of today, and that is what research is saying about the other main area that people may take collagen supplements: and that’s for joint health – especially for the condition of arthritis.

Arthritis is the swelling and tenderness of one or more joints. The main symptoms of arthritis are joint pain and stiffness, which typically worsen with age. The most common types of arthritis are osteoarthritis and rheumatoid arthritis.

Osteoarthritis is characterised by a breakdown in cartilage which covers the ends of bones where they form a joint. Osteoarthritis is more common in women and usually affects people from the age 45 onwards. The parts of the body most commonly affected are the knees, hands, hips and back. So think of this form of arthritis as more like a disease of wear-and-tear causing loss of the protective cartilage.

While rheumatoid arthritis is a disease in which the immune system attacks the joints, beginning with the lining of joints.

The differences between these two forms of arthritis are worth noting as there is now evidence for collagen supplements to help with both forms, but acting through potentially different mechanisms.

Let’s start with by far the most common form of arthritis and that’s osteoarthritis -  a condition affecting 1 in 5 Australians over the age of 45. This podcast though is not about the current medical management of this painful condition which centres mainly around pain-relieving anti-inflammatory medications along with positive lifestyle changes like regular exercise and maintaining a healthy weight.

Where the interest in collagen supplements comes from the fact that cartilage is mostly made up of collagen – in particular type II collagen. Contrast that with skin where type I and III are predominant. But just because cartilage is mostly collagen, does that mean taking collagen will help repair it?

If we look at the extensive research already done with collagen and skin health, you can clearly see direct and specific effects of oral hydrolysed collagen on the skin so it isn’t a crazy stretch to think there could be some benefit on the joints too. Interestingly, from in vitro cell culture studies, exposing chondrocyte cells, which are the cells responsible for cartilage production, shows an increase in collagen production so that is evidence of a direct mechanism.

Okay, so let’s move on to the real stuff of interest and see what clinical trials have to say. And fortunately, there have been quite a few done. Not to the level seen for skin health, but certainly enough to assess the likely benefit.

The first collection of this research came from a systematic review published back in 2018. Five randomised controlled trials involving over 500 people could be analysed where people with osteoarthritis took collagen or a placebo for 10 to 48 weeks. Arthritis symptoms of pain, stiffness and physical function were assessed by use of both a validated scoring index scale as well as self-reported measures. Four of the studies used hydrolysed collagen taken at between 2 to 10 grams per day while the fifth study used 40 mg of undenatured type II collagen – I’ll talk more about this special type of undenatured collagen shortly. And I’ll link to the study in the show notes. https://pubmed.ncbi.nlm.nih.gov/30368550

So what did they find? The news was very positive with a clear significant reduction in arthritis symptoms which was reflected in both the pooled data but also visible when you looked at individual studies which mostly all reported a significant benefit. There was though a lot of variability seen between studies, but this is not so surprising when you consider differences in doses of collagen used as too the length of treatment. With just 5 studies, this review is by no means a ‘slam dunk’ for the benefit of collagen in osteoarthritis, but it clearly is giving a very positive signal. But the review I just profiled only included research published before 2018. What has happened since then?

In March 2023 a new review was published looking at collagen supplementation in joint health. It made an effort to summarise the research to date, and for hydrolysed collagen and osteoarthritis, 6 randomised controlled trials and 3 observational studies were looked at. And I’ll link to the review in the show notes. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058045

Not surprisingly, there was a large degree of variability in terms of study designs, comparators, dosages, collagen source and treatment length. Yet despite this, all of the studies could show some degree of improvements in osteoarthritis symptoms with self-reported improvements in function, quality of life and pain showing the greatest level of improvement. And keep in mind, most of the studies were blinded so the participants weren’t aware if they were taking collagen or a placebo so this removes some level of bias from the expectation of a benefit.

Interestingly, one study looked specifically at proteoglycan content in knee cartilage and which saw an increase in its content. Proteoglycan is used as a proxy measure of cartilage production so this provides some evidence that collagen supplementation could be restoring some of the collagen lost in osteoarthritis. And remember, at least in cell culture studies, you can see greater collagen synthesis in cartilage-producing chondrocyte cells when exposed to hydrolysed collagen as well as greater growth and proliferation of these cells. Hydrolysed collagen via its absorbed peptides is also proposed to have some degree of anti-inflammatory action so this could also be an explanation for an improvement in some of the arthritis symptoms.

So I would firmly say that the research is looking positive so far and while ‘more research is always needed’, even an uber-sceptical person would be unwise to dismiss claims about a benefit for hydrolysed collagen in osteoarthritis – all from something that is a food and has no real adverse events linked to it outside of a person already having some degree of sensitivity to it, but this applies to all forms of collagen in food – not just supplements.

Okay, so let’s circle back to that random form of collagen I mentioned earlier which is undenatured type II collagen. Undenatured simply means the collagen protein hasn’t been unwound and degraded so it is essentially the pure, properly functioning protein without any structural deformation. To isolate this from an animal source needs some very careful treatment as acid, heat and enzymes are going to destroy the protein. Not a problem if you’re talking about hydrolysed collagen as you want the peptides, but undenatured collagen is a different beast.

So why the interest in this form of collagen? Firstly, it is type II collagen that is isolated (usually from chicken sternums) as that is the predominant form found in cartilage. When you consume undenatured protein, it can have a specific immune-mediated mechanism of action known as oral tolerance. Oral tolerance allows us to tolerate and not mount an immune response against ingested substances like food antigens or harmless microorganisms present in the gut

In theory, this can lead to a decrease in autoimmune reactions against collagen in cartilage. This contrasts with the effects of hydrolysed collagen which are thought to have positive effects on cartilage collagen synthesis.

There has been quite a bit of research looking at undenatured type II collagen in osteoarthritis and only last year, a systematic review was published. Eight randomised controlled trials involving 243 people were included where undenatured type II collagen or a placebo was given to adults with knee osteoarthritis. The dose used in most of the trials was 40 mg. Yes, you heard correctly, milligrams compared to grams of hydrolysed collagen used in other studies. That’s because we’re talking about a possible immune effect going on. Trials ran for 3 to 6 months and I’ll link to the study in the show notes https://pubmed.ncbi.nlm.nih.gov/37854210

So what did the review find? From the meta-analysis, it was again possible to see an indication for a benefit with collagen supplementation reducing pain and severity of arthritis. And the studies showed a low degree of potential bias which is good. Yes, there was a lot of individual variability in the studies, but they were all pointing in the right direction for a benefit.

Now don’t go looking for undenatured type II collagen from your local pharmacy or friendly collagen Insta influencer. It is a much more specialised supplement, but you’ll find it easy enough with a bit of Google searching.

Considering the effects of undenatured type II collagen could be via the immune system, it raises the question of how it may work for rheumatoid arthritis which has its origin in the immune system. In vitro and animal studies suggest undenatured type II collagen can have anti-inflammatory effects, and pilot clinical trials find that undenatured type II collagen may stimulate immune suppression and improve RA symptoms though results so far are mixed. I would say the evidence looks stronger for osteoarthritis at this stage, but I’m keeping a watch on this space closely.

So, let’s wrap all this up. For collagen supplements, it can read like a shopping list of health benefits that sound too good to be true. But this is a rare case, and this is coming from a career research scientist who has seen all manner of fads and trends come and go with most not supported by much science, that there is actually a good base of science to support many of the claims made about collagen.

There is now plenty of research to read so I suggest you digest some of that rather than get your advice from the latest utterly wrong newspaper article dismissing it out of hand for the same completely wrong reasons. In the end, it is your choice if you want to trial collagen or not and you can make your own personal assessment. As even with plenty of clinical trials to support a benefit, every person’s response in those trials was different.

What’s my overall assessment of the research evidence then? Hydrolysed collagen is one of the few supplements that I take on a daily basis and have been doing so for several years. And no, I don’t have my own brand of collagen to sell you nor do I promote anyone else’s and never will.

So that’s it for today’s show. You can find the show notes either in the app you’re listening to this podcast on, or else head over to my webpage www.thinkingnutrition.com.au and click on the podcast section to find this episode to read the show notes.

If you find this podcast of value, then please consider sharing it with your friends and colleagues. This all helps to increase the reach of the podcast, which means a big win for credible evidence-based nutrition messages and making the world a slightly less confusing place.

I’m Tim Crowe and you’ve been listening to Thinking Nutrition. 

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