Arthritis relief: can collagen supplements help?

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 ‘the collagen industry funds all the research’, the reality is very different.

In past blog posts, I’ve delved into hydrolysed collagen supplements and skin health. There are now dozens of blinded randomised controlled trials showing a consistent benefit in increasing skin moisture and elasticity and reducing wrinkles. However, for this article, I want to focus on another reason people may take collagen: to relieve joint pain and stiffness from arthritis. Read on as I outline what the clinical trial evidence has to say and what biological mechanisms could be at play to support a beneficial effect of collagen supplements for arthritis.

The topic of collagen supplements is one I’ve covered many times on this blog. That’s 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 this post. And then there is this article I wrote recently about the emerging role of collagen supplements in tendon injury repair and recovery.

Collagen 101

So a bit of background 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 disease of vitamin C deficiency, 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. While 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

It’s all about the peptides

When collagen is eaten, it is digested and absorbed into the bloodstream. Soon after, 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 the breakdown of our collagen 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 such a vital 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.

Collagen for skin health

So, can collagen supplements promote healthy skin? As I outlined in my earlier post on this topic, from 19 clinical trials, supplementation with hydrolysed collagen had a statistically significant effect on skin hydration, skin elasticity, skin density and wrinkles. 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 updated review could analyse 26 randomised controlled trials of oral collagen supplements that looked at skin hydration and skin elasticity.

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

Playing the ‘industry funding’ card

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 health areas where collagen supplements seem to offer a benefit.

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 way 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. That’s because of the unique peptides that are absorbed into the bloodstream after you eat collagen.

Arthritis relief: can collagen supplements help?

So that’s got you up to speed on collagen. Now for the main topic today and that is what research has to say about another health reason 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 of 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.

Rheumatoid arthritis on the other hand 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. That’s because collagen supplements could help with both forms, but act through different mechanisms.

Collagen for osteoarthritis

Osteoarthritis is common – afflicting more than 500 million people worldwide. This article though is not about the current medical management of this painful condition. Treatment centres around the use of pain-relieving anti-inflammatory medications along with positive lifestyle changes such as regular exercise and maintaining a healthy weight.

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

If we look at the extensive research already done on collagen supplements and skin health, we can clearly see specific effects of oral hydrolysed collagen. So it isn’t such 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) to collagen shows an increase in collagen production.

What do clinical trials have to say?

So let’s move on to the real stuff of interest and see what clinical trials have to say about collagen supplements for helping with osteoarthritis. And fortunately, there have been quite a few published. Not to the level seen for skin health, but certainly enough to assess a possible benefit.

The initial collection of research on collagen and osteoarthritis in humans came from a systematic review published in 2018. Five randomised controlled trials involving over 500 people could be analysed where people with osteoarthritis took oral collagen supplements 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 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 milligrams of undenatured type II collagen. I’ll write more about this special type of undenatured collagen shortly.

So what did the review uncover? The news was very positive. There was a clear significant reduction in arthritis symptoms which was reflected in the pooled data of all the studies, but also evident 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 well as the length of treatment.

With just 5 studies included, this review is by no means a ‘slam dunk’ for the benefit of collagen in osteoarthritis, but it is giving a very positive signal. But the review only included research published before 2018. What has happened since then?

The latest research

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.

Not surprisingly, there was a large degree of variability between the studies in terms of study designs, comparators, dosages, collagen source and treatment length. Yet despite this, all of the studies could show some degree of improvement in osteoarthritis symptoms. Self-reported improvements in physical function, quality of life and pain showed 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 from the review looked specifically at proteoglycan content in knee cartilage 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.

Hydrolysed collagen via its absorbed peptides is also proposed to have an anti-inflammatory action. So this could also be an explanation for an improvement in some of the arthritis symptoms seen in the research.

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 of hydrolysed collagen in osteoarthritis at this stage. 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.

What is this ‘undenatured collagen’ stuff?

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 the pure, fully functional protein without any structural deformation. To isolate this from an animal source needs some very careful treatment because 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 found 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. 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 milligrams. Yes, you read correctly, that’s ‘milligrams’ compared to grams of hydrolysed collagen used in other studies. That’s because we’re talking about a possible immune effect going on.

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. The studies showed a low degree of potential bias which is good. Yes, there was a lot of individual variability between 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 easily enough with a bit of Internet 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. While pilot clinical trials find that undenatured type II collagen may stimulate immune suppression and improve rheumatoid arthritis symptoms though results so far are mixed. I see the evidence as looking much stronger for collagen supplements and osteoarthritis at this stage, but I’m keeping a watch on this space closely.

What it all means

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 that there is a good base of science to support many of the claims made about collagen. 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.

There is now plenty of research to read. So I suggest you digest some of that to form your own views rather than get your advice from the latest newspaper article dismissing collagen supplements out of hand for completely wrong reasons.

In the end, it is your choice if you want to trial collagen for skin or joint health 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 so the final judge of if there is a benefit is going to be the person taking it.