Collagen supplements: the science behind the health benefits

It was back in March 2021 that I first tackled the topic of collagen supplements. It proved to be one of my most popular blog posts of the year. And for good reason. There is growing scientific evidence to support many of the health claims made about collagen. From improving skin health to even helping with sports injury recovery and osteoarthritis. In this post, I give an update on the growing scientific evidence for the use of collagen supplements. I’ll also describe the plausible biological mechanisms for how collagen can have a targeted benefit even after digestion.

If you haven’t caught my previous blog post on collagen supplements, let’s do a quick refresh. Collagen’s key role in the body is as a major structural protein. You’ll find it in many tissues including tendons, ligaments, cartilage, blood vessels and skin. It is so abundant, that it makes up almost 30 percent of our total protein mass.

The structure of collagen has a triple helix arrangement of long chains of amino acids. Think of collagen as like a rope with many fibres intertwined. This gives collagen a lot of strength. No wonder its leading role is as a scaffold, giving structure and strength to tissues such as skin and bones.

One of the things that makes collagen different to other proteins is its unique amino acid mix. For starters, every third residue is a glycine amino acid. And it mostly follows a common repeating sequence of just three amino acids: glycine, proline and hydroxyproline. It is that last guy, hydroxyproline, that is unique to collagen.

Hydroxyproline is made from proline and you need vitamin C to make it happen. The classic vitamin C deficiency disease of scurvy is a disease of very weak collagen. That explains the bruising and bleeding gums seen in this disease.

Collagen though is not one molecule. There are at least 28 distinct types. But it is types I, II and III collagens that are the most abundant. You’ll find type I collagen in the connective tissue of tendons, ligaments, corneas, bones and skin. Type III collagen usually is found along with type I collagen in the skin and blood vessels. Type II collagen is mostly found in cartilage.

Why hydrolysed?

When it comes to oral collagen supplements, it is hydrolysed collagen that dominates the market. Hydrolysed simply means the breaking down of a molecule with water. If you heat collagen, you denature the protein and are left with gelatin. Gelatin is a great gelling agent for use in food and beverages, but it is a large molecule and fairly insoluble.

Hydrolysed proteins are smaller in length, so they’re absorbed faster. Hydrolysed collagen is also much more soluble in water than gelatin. That makes hydrolysed collagen more convenient to put into drinks.

The collagen used in most supplements comes from many sources including cattle, pigs, chicken, and marine sources. It is a nice use of what would be a waste product in the processing of these animals and fish for human consumption.

Collagen metabolism 101

But why even bother with taking a collagen supplement? Surely all protein just becomes an amino acid soup in our body after digestion? It’s a common criticism I read about collagen supplements in the popular press. Article after article completely dismissing any benefit of it because of this digestion issue.

If collagen was completely digested to single amino acids, then such criticism would be valid. The thing is that is not the case.

Collagen peptides are absorbed into the bloodstream and are available as single amino acids and unique dipeptides and tripeptides. These small peptides have a unique fingerprint. They contain lots of hydroxyproline-proline and hydroxyproline-glycine containing sequences. Remember: hydroxyproline is unique to collagen so these tiny peptide fragments can only exist in the blood from collagen breakdown.

After consuming collagen, it is possible to measure levels of these unique collagen peptides in the blood. So, they certainly can pass through the digestion and absorption process. The collagen peptides and free amino acids then distribute around the body, especially to the skin. At least in rat studies, those collagen peptides can remain in place in the skin for up to 2 weeks.

It gets even more interesting. These collagen peptides can also function as signalling molecules. One theory is that collagen peptides in the blood are a marker for collagen breakdown. Think of these peptides as acting to signal the body that it needs to produce more collagen.

Collagen peptides can bind to receptors on the surface of fibroblasts. Fibroblasts are skin cells that are major factories for….collagen. And guess what the binding of collagen peptides to fibroblast receptors does? It stimulates them to produce collagen. But it is not just collagen these peptides stimulate the production of. You see more elastin (for skin elasticity) and hyaluronic acid (for water retention) made too.

Now let’s look at what clinical trials have to say happens when you take collagen as a supplement.

The evidence is growing

Back in my previous blog post when I first profiled collagen, I wrote how surprised I was when I went digging into the evidence for just how much there was. At the time, I could count 12 double-blinded randomised-controlled trials showing favourable benefits of hydrolysed collagen on skin elasticity, skin hydration, wrinkles and collagen density. And with every study reporting some degree of a positive finding.

Since that first post, an in-depth systematic review and meta-analysis has been published. In the paper, published in the International Journal of Dermatology, 19 clinical trials were included. All the clinical trials were randomised double-blinded placebo-controlled trials. That means both the participants in the study and the researchers assessing the effects were blinded to if a person got the collagen or a placebo. That removes a lot of bias.

And the results of this systematic review were impressive. A clear and consistent benefit of hydrolysed collagen on skin hydration, skin elasticity, skin density and wrinkles.

Marine/fish collagen was the most common source of collagen used in the trials. But bovine, porcine and chicken were all popular as well. Doses used ranged from 0.6 g to 12 g per day for 1 to 3 months.

No, not all research is funded by collagen companies

The recent meta-analysis also reported that they could not see any evidence of a publication bias. Publication bias is a sign that positive studies were more likely to be published – at the expense of less favourable research which is buried.

That point on publication bias is a critical one. That’s because a common criticism I see of collagen supplements in dismissing any benefit they can have is that the positive evidence is because the research is industry-sponsored. That’s a dog whistle that it can’t be trusted.

Firstly, that is an absolute lazy argument when it comes to critiquing scientific evidence. Research should be evaluated on the merits of the study, not who funded it.

And do you know what else? Among those 19 clinical trials covered in the review, seven of them were not funded by a manufacturer of collagen supplements. Nor did any of the research team in those studies have any conflicts of interest to declare. And those ‘untainted’ studies were just as likely to report a positive benefit as studies funded by industry.

Other benefits of collagen

I’ve focussed this update on the benefits of hydrolysed collagen on skin health, but the research evidence in other areas such as osteoarthritis and recovery joint from injuries is growing. And the research looks promising so far and why such supplements are gaining wider adoption.

But it is not all about skin and joints. There is some interesting preliminary research showing that hydrolysed collagen may be effective at improving insulin sensitivity, glucose and lipid levels, and reducing hypertension in people with type 2 diabetes. So, watch this space as the research develops.

How much to take

If you want to trial collagen yourself, look past all the glossy promotion of expensive powdered supplements touted by Insta influencers. Just evaluate a supplement based on price. For that, look at how much actual collagen is in it and work out the price per gram. That is the best way to shop around to make valid comparisons.

Some supplements may have an extensive list of other ingredients such as vitamins, minerals and herbals. But it is the collagen that is the star of the show here so just focus on that.

Collagen from any animal or fish source are your options and just a few grams a day will be enough. Doses as low as 1 gram per day have shown benefits in clinical trials. Taking more than 10 grams per day is overkill. And it may be better to take it between meals to avoid interference from other protein sources.

And ignore claims made about ‘vegan collagen’. It is a scam. Yes, you read that correctly. What is promoted as ‘vegan collagen’ does not have any of the unique hydroxyproline peptides. It is normally just an amino acid soup with a lot of other vitamins, minerals and botanicals thrown in. It is promoted as a ‘collagen booster’ but don’t go looking for any human clinical research to support these claims. There is zilch.

There is lab-made collagen being developed which is done by microbial fermentation, but this is a niche early-stage development product. It is expensive and GMO. I have no issue with GMOs, but I doubt few people who follow a vegan diet would be up for it.

What it all means

For hydrolysed collagen, it reads like a shopping list of health benefits that sound too good to be true. But for those who are regular readers of this blog, you would know that I have a high evidence threshold for making claims. And at least with collagen, there definitely appears to be something to the story – especially for skin health. All for something that is naturally part of foods and has little evidence of any adverse problems.