THEY WORK!! Collagen Peptides. Does it matter which one you choose? All the science!!

People have different opinions on whether or not collagen works to support skin health. I’m not sure there’s any other topic out there in skincare that elicits more opinions about whether it works, how it works and which ones are best!!

I’ve reviewed the research and talked to several experts to understand the very latest science on collagen peptides, what evidence exists to support claims and discuss some of the mechanisms of action. BOY, HAVE I LEARNED A LOT, and I am sharing a consolidated version of my learning here! 

This blog is rather long, so feel free to skip through:

And if you want a real short cut, these are my favorite two collagen peptides.

While this blog is primarily about collagen for the skin (my first love!!) and bones, I want to share something I found very interesting: In an analysis of collagen clinical trials from 2010 until 2022 performed by the research company Phesi for The Guardian, it was found that only 5% of clinical trials on collagen were related to cosmetic applications. 

Fascinatingly, researchers around the world are more interested in collagen’s potential for some of the most serious consequences of aging, from treating bone diseases to improving wound-healing and regenerating arthritic joints. And applications related to increasing muscle mass and athletic endurance are among those studies too, as are applications for managing diabetes. I don’t know about you, but boy does that further validate supplemental collagen as a thing to look at for skin!! 

But back to collagen + skin + bones. That’s what this blog (and accompanying video) is all about!  I’ve said recently that I’ve been evaluating collagen peptides for over a year…. That might seem crazy – why would it take me so long to evaluate something?

Collagen peptides aren’t a ‘one and done’ transaction. To see and maintain the benefits of taking food supplements we normally need to commit. For good.  So I wanted to have time to really understand the science and try a variety of types. 

Let’s start with the $100,000 question: Do collagen peptides help skin? What does the science say? In the past few years I’ve read dozens of the 6,667 published papers on collagen peptides and skin. The amount of research is stunning.  So, while it’s all very encouraging, after taking the time to read SO MANY of these studies, I still wasn’t 100% sure about how I felt about collagen peptides and, importantly which ones I wanted to take (and recommend!).

LUCKILY, in the past few years there have been a handful of ‘meta-studies’. I looked at three meta studies and one systematic review. A meta-study effectively combines data from multiple studies to generate more robust conclusions than any single study can provide, enhancing the reliability and generalizability of research findings. I also found a ‘review’ which differs from a meta study as it isn’t as analytical.

Meta studies combine the data from multiple studies in a very controlled way so that we can have a ‘bird’s eye’ view of the data – in a way that’s been combed through in a systematic and rigorous way.  These meta studies are invaluable, as they allow us a snapshot not only into viewing whether there is overall agreement into the positive impacts of collagen peptides on skin health, but also where the consensus is on the benefits – and were the data just doesn’t stack up.

Here’s the summary data for each of the meta studies (plus an additional systematic review done in 2019):

If you want to learn more I encourage you to have a deep dive into the meta studies, linked above.

So we know that from the “studies of the studies”, collagen can and DOES help delay and improve signs of skin aging! Yes, there is an opportunity to conduct more studies to get a more fine-tuned understanding (there always is with science!) but I think it is more than safe to say that taking collagen is good for our skin.

Research indicates that by the time women are 80 we can lose upwards of 50% of bone mass. We normally think just about skin when we think about collagen, but in fact collagen is a structural protein that provides bones with their strength and flexibility, allowing them to withstand stretching and bending forces. It forms a matrix in which minerals like calcium and phosphate are deposited, giving bones their rigidity and hardness.  Without collagen, our bodies succumb to osteoperosis.

Curtis, E., Litwic, A., Cooper, C., & Dennison, E. (2015). Determinants of muscle and bone aging. Journal of Cellular Physiology, 230(11), 2618. https://doi.org/10.1002/jcp.25001

Of course having adequate collagen is only one element of keeping our bones solid as we age. I cannot underscore enough the importance of weight bearing exercises (strength training with heavy weights) and the impact of estrogen on our bones as we age. I’ve covered both of these topics in my interviews with Dr. Mary Claire Haver and especially with Dr. Vonda Wright, and I strongly encourage you to view these videos!!

Typically when we think about osteoporosis we think about hip fractures and frail spines. But, in fact, no bone is spared when osteoporosis hits.

‘Osteoperosis of the skull is significantly related to wrinkles, sagging and the shape of the face. Facial lines around the eyes gradually spread widely with aging and this causes wrinkles around the eyes, puffy eyes and slackness of the eyes which tends to make the person look older.

Research indicates that collagen peptides may help with osteoporosis by improving bone mineral density, promoting bone formation, and enhancing calcium absorption. Studies suggest that collagen supplementation can support osteoblast activity (cells that build bone) and inhibit osteoclast activity (cells that break down bone), potentially slowing bone loss and strengthening bones. Additionally, collagen peptides can improve joint health, which is crucial for maintaining mobility and reducing fracture risk in individuals with osteoporosis.

While the research on collagen’s impact on bone health isn’t any where near as vast as that for skin health, there are a handful of studies that got my attention:

As I mentioned in my video, the body of information on collagen peptides for skin and bone health is robust enough for me to commit to daily supplementation!!

First off, let’s establish that PEPTIDES play various roles in biological processes, acting as hormones, enzymes, or signalling molecules.  Peptides are short chains of amino acids linked by peptide bonds. They are smaller than proteins and typically consist of 2 to 50 amino acids. Peptides play crucial roles in various biological processes, and their functions depend on their amino acid sequence and structure.

No doubt you’ve heard of the peptides we put on our skin like Argireline – sometimes referred to ‘Botox in a bottle’ . Argireline works by inhibiting the release of neurotransmitters in the neuromuscular junction, producing a temporary (and FAR less pronounced!!) “Botox-like” effect. And then we have collagen peptides. All peptides are potentially powerful in impacting biological processes, clearly these are each VERY different. But they’re all peptides made from amino acid chains! I think it’s fascinating to consider peptides this way!!

DO COLLAGEN PEPTIDES REALLY MAKE IT THROUGH OUR GUTS INTACT?

So we know that collagen peptides are not inert white powder!! Or a ‘simple’ food supplement. They have the potential to impact important biological processes. But how do they actually help hydrate our skin, improve elasticity and strengthen our bones (among so many other things)? Here are the (grossly simplified!!) steps:

1. We consume collagen peptides

2. In the digestive system, collagen peptides are initially broken down by gastric juices into free amino acids – but some peptides remain intact.

3. The free amino acids are easily absorbed by the small intestine via the microvilli

4. The peptides that have remained intact are absorbed intact through the intestinal wall too (it seems via paracellular transport, but research is ongoing.)

5. Amino acids and peptides are distributed through the bloodstream to the extracellular matrix surrounding the fibroblasts, osteoclasts and any number of other cell types.

6. Amino acids in the extracellular matrix act as ‘raw materials’ to for the fibroblasts to create new collagen fibrils

7. Intact peptides act as ‘signalling agents’ to little receptors on the cells called integrins

8. Those peptides communicate with Integrins which in turn pass the message on to the cell to turn on certain processes favorable to collagen production and turn off other processes that are unfavorable to collagen survival!
   
   This video from one of the Rousselot is great at bringing steps 1-5 above to life!!

So do collagen peptides really make it through our guts intact? This is one of the biggest questions people seem to have.  There’s a common notion that all collagen peptides would get broken down to amino acids by the gut, so what’s the point? 

First of all, it’s those specific amino acids (mainly glycine, proline and hydroxy-proline) that are needed in the extracellular matrix as ‘raw material’ for our fibroblasts to make that new collagen in their collagen factory. So even if they’ve been broken down into amino acids, they’re very much key to the process of new collagen production!  Secondly, studies show that upwards of 10% of dipeptides and tripeptides (and perhaps even larger chains of amino acids) actually pass through the gut lining in-tact. That’s because hydroxyproline is a super strong amino acid – and it resists the gut environment. The other reason is that the way these little fragments of collagen peptides present is very ‘slim’. So they’re more like a bit head of a drill than your ‘average’ peptide – which is more a spring shape.

So there you have it! Depending on the collagen peptides consumed and the digestive environment, up to 10% of collagen peptides get through the gut wall to go on to their target cell and help to stimulate the creation that all important new collagen!!

Image courtesy Gelita: Spring vs drill. A peptide chain is often a linear chain of amino acids. However, each amino acid has a slightly different shape that influences the final structure of the peptide. The unique Proline- Hydroxyproline-Glycine repeats in collagen give Bioactive Collagen Peptides (BCPS) a functional form and resistance to hydrolysis so that BCPs do not encounter the same permeability resistance as standard collagen peptides.

BIOACTIVE COLLAGEN PEPTIDES

Each company that makes collagen peptides will have its own process of heating the intact collagen and using enzymes to break it down further. 

There are companies (Gelita and Rousselot, among a few others)  who have been making and studying collagen for decades (even centuries). And, of course, there are governmental groups, universities and independent research organizations that are investing in understanding collagen peptides and how they might be used in all sorts of health and wellness applications. There is significant work around developing ‘functional collagen peptides’ or what Gelita and Rousselot call ‘Bioactive Collagen Peptides’ which are targeted at specific cells and functions. 

Effectively scientists have discovered that small differences in the amino acid sequence and protein structure in collagen peptides can significantly impact the absorption of the peptides and how well they’re able to stimulate specific cells.

So how can one brand of collagen peptide do a better job than others at, say, building strong bones? Well it turns out that tiny variations in the molecular weight and structure of the collagen peptide can ultimately significantly affect how well it stimulates target cells.

BIOACTIVE COLLAGEN PEPTIDES VS ‘NORMAL’ COLLAGEN PEPTIDES

So what’s really the difference between a ‘Bioactive Collagen Peptide’ and a ‘normal’ collagen peptide?

This is an analogy that I heard used by Susan Leser who is in the nutritional supplement industry: So, we have 20 amino acids – a limited quantity – sort of like we have 26 letters in the alphabet. But by the way we combine these letters, we form different words which, in turn, we can use to form different sentences – with completely different meanings. This is a silly example, but consider that the same exact letters are used in making these two sentences:

Same exact letters, used in different sequences have completely different meanings!!  And so it is with amino acids turning into peptides!  And as we saw above, peptides can have VASTLY different functions and applications, depending on these combinations.

By using this combinations of 26 alphabet letters or 20 amino acids, we have an enormous number of possibilities for communicating with words, in the first example, and signalling to our cells, in the second example!

THE MAGIC IS IN THE ‘RECIPE’ – AND THE EXECUTION

So the difference between Bioactive Collagen Peptides and regular collagen peptides is that companies like Gelita and Rousselot have created the formula for hydrolysis of the collagen (the right heat, the right enzymes and the right pH) and they apply those controls so that they consistently achieve the peptide sequence that is good for say, skin health (Verisol), bone health (Fortibone), cartilage health (Fortigel).

This hydrolysis also impacts the peptide’s polarity and molecular weight – critical factors that influence the Bioactive Peptide’s ability to stimulate collagen production in in the target cells. Peptides that are moderately polar and have low to medium molecular weight are more likely to be bioavailable, penetrate tissues effectively, and interact with fibroblast receptors to enhance collagen synthesis.

When the bioactive collagen peptides reach the target cells  (fibroblasts for skin, osteoblasts for bones, chrondrocytes cartilage, etc) they are able to signal or ‘speak’ to receptors (called integrins) on those target cells to encourage up-regulation of good processes and down-regulation of bad processes.  And there is a ready ‘pool’ of those free amino acids waiting in the extracellular matrix – as raw material for new collagen fibrils!!

A key thing about Bioactive Collagen Peptides is that the ‘formula’ for getting the best collagen response from a fibroblast (skin), osteoblast (bone) and chondrocyte (cartilage) is different for each one. The osteoblast speaks a slightly different language from the fibroblast. Bioactive Collagen Peptides are optimized to communicate optimally to the cell types they’re intended to target.

While the science is still evolving, Gelita’s current understanding is that when Bioactive Collagen Peptides (BCPs) bind to a cell’s Integrin receptor, they shift it into their ‘active’ mode, producing a signal transmitted within the cell, activating its metabolism to produce new extracellular matrix proteins. This creates a positive feedback loop for healthier skin, joints, tendons and ligaments, bones, etc depending on the BCP used.

Gelita, the maker of Verisol, Fortibone and several other ‘functional’ collagen peptides has very recently done a set of experiments, testing their BCPs against ‘regular’ collagen peptides and, intriguingly, each other!!  The Gelita team wanted to see, for example, how Verisol, their skin collagen peptides did in supporting Chondrocyte (the cells that produce cartilage) – interestingly, not so well!!

Fascinatingly (to me – no surprise to them!!), Gelita found that the BCPs that were optimized for skin health really did a lackluster job supporting the cells that make new cartilage!!  And the BCPs made for bone health did an underwhelming job supporting skin health! 

You can see from the above graphic that Fortibone does much better than ‘regular’ collagen peptides in the bone experiment. You’ll note that Verisol didn’t do very well at stimulating osteoblasts (bone) – because it’s been optimized for stimulating fibroblasts (skin.)

While these images represent a single experiment and aren’t (yet) part of a more robust study, I think it’s fantastic that a brand is willing to share information on the merits AND limitations of its own products.

In my recent collagen video I used the analogy of regular collagen peptides being the ‘jack of all trades’ of collagen support and Bioactive Collagen Peptides (such as Verisol for skin health) acting like an expert electrician. The former can do lots of jobs but isn’t an expert on any of them whereas the latter is ideal to produce the best quality output on a specific job.

Pause Life Skin & Bone by Dr. Mary Claire Haver has both Verisol (the skin ‘expert’) and Fortibone (the bone ‘expert’). Until June 28th you can get 10% off by using the code ‘Penn’

All collagen peptides good for you!! (assuming from a reputable company, free of heavy metals, etc.).

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