How Collagen Works and What the Science Tells Us (So Far)

by Admin Ancient and Brave January 22, 2024

As the collagen trend is growing and people are crediting their glowing skin and supple joints to this wonder ingredient, it’s not surprising that many are starting to ask questions about whether or not collagen is too good to be true. We think it’s fantastic, and an absolute must, that people are inquisitive about what they are putting into their bodies. Where is it sourced from? What is the science telling us? And crucially, how does it even work?

Along with these questions, are some inevitable misconceptions. Because the rise of collagen (as a supplement at least) has been so speedy, we are learning new things all the time. Whilst collagen has been part of our ancestors' diet and used by traditional medicine practices such as Traditional Chinese Medicine, where Ejiao (gelatine from donkey-hide) has been used since ancient times, modern nutrition research is now starting to catch up.

As with anything in nutritional science, there are many variables to consider and many much needed hurdles to overcome. However, with now more than a few decades of research since the method of hydrolysation allowed scientists to create hydrolysed collagen peptides, we are beginning to see bigger and more robust trials, studies and meta analysis of all the data we are gathering with exciting and promising results for our future health.

In this article, we want to help make sense of collagen, follow the journey of our collagen from sourcing to whole body benefit and cover some of the key questions we are often asked.

It hopefully goes without saying that we recommend collagen peptide supplementation alongside a balanced healthy diet and lifestyle choices, and it should be viewed as part of the tools used in the bigger picture of health.

We will be taking a real deep dive into the science of collagen and for those of you who would like a refresh into the jargon of amino acids and peptide bonds, we recommend reading this article to accompany it or this article if you are a collagen newbie.

Step 1: Sourcing

First and foremost collagen is an animal based product. Whilst this may cause the ‘ick’ for some people, it is worth noting that many of our ancestors will have eaten a lot more collagen than we typically do in the western world today. During this time, nose-to-tail eating was commonly practised, which meant they cooked and consumed the entire animal. This would of course include skin, tendons and other collagen rich cuts. With time, this practice has been lost, with many of our modern meals focusing on muscle meat, breast, fillet or lean cuts and those fattier cuts often undervalued or even discarded. This also means we are missing out on a whole subset of certain amino acids.

This is significant because on top of our natural decline in collagen production, which begins in our twenties, our standard diets don’t usually prioritise these organ meats or skin-on, bone-in meats, which means we may not get enough of the collagen specific amino acids (like proline, glycine and hydroxyproline) that we need to rebuild collagen naturally.

As we are using animal derived products, sourcing of these ingredients should be of high priority. It is important to avoid collagen from low quality animal or marine sources that have been grain-fed or produced with poor farming practices. Whilst ethically this is an important choice, nutritionally it also makes a difference to the quality of the collagen.

Looking for words such as ‘grass-fed’ or ‘wild-caught’ can give you some indication of where animal derived products are sourced. Grass-fed means the animal has been able to feed on its natural diet, much different to animals fed exclusively grains as well as also containing lower levels of antibiotics, pesticides, and other toxins. This is one of many reasons why, in True Collagen, Ancient + Brave choose grass fed cows sourced from the EU.

When using Bovine collagen, it’s also key to look at ensuring that it is sourced from the hide rather than derived from bone or cartilage. Collagen sourced from the hide is thought to be the cleanest, as this part of the animal is constantly being regenerated and regrown throughout its life.

Similarly, wild-caught fish are also more likely to have a better nutrient profile compared with farmed fish, thanks to their natural diets and active lifestyle. Farmed fish are often fed grains or pellets and are kept in small enclosures. This can mean they are at greater risk of lice and bacteria so are often treated with antibiotics and in some cases, hormones too. Not nice for the fish and this has an impact on your own health when you ingest these compounds. Ancient + Brave's Wild Collagen comes from fish that are wild caught, free from hormones and antibiotics and sourced sustainably from the North Atlantic.

Why does Ancient + Brave use powdered collagen peptides?

What form you choose to take your collagen is highly personal. Collagen products come in many forms of powders, drinks, tablets, liquids, shots, gummies and even coffee creamers, all formulated with the promise to help restore your natural levels by boosting your collagen production.

Ancient + Brave have opted for powdered collagen for several reasons. First, getting the dose right is key. Most studies indicate that we need to supplement 5-15g per day for optimal benefits, which is why powders and/or high strength liquid filled sachets are often recommended over capsules and tablets, as you simply cannot fit enough collagen into a single capsule and many people don’t like taking several at once. As sustainability is high on our list, we also see the huge impact of the waste from daily liquid sachets. Powdered collagen from a glass jar or one of recyclable pouches allows you to get a more meaningful dose of collagen, fewer additives, and save the environment from more plastic or packaging waste.

Whilst we see the potential benefits of some formulations out there which include extra ‘collagen boosting’ nutrients, a concerning issue in some collagen products is the use of artificial flavours, sugars and fillers which can greatly reduce the benefit of taking the powder in the first place. On top of this, some of these substances can be harmful for our gut health.

Our powdered collagen is 100% Hydrolysed Type 1 Collagen Peptides - nothing added; simple, pure and potent.

Finally, when it comes to purity, it is worth noting how your supplements are stored. Glass packaging, as well as being a better choice for the environment, also forms a natural barrier against contamination and safely preserves its contents for longer. Dark coloured glass particularly protects the ingredients from light. Glass is also one of the few containers that does not leach hormone disrupting chemicals into its contents like many plastic containers can.

Which collagen is best type 1, 2 or 3?

There are in fact 28 different types of collagen in the human body, and rather than focusing on the different types for different purposes, the more pertinent question should lie around how well it is absorbed and how bioavailable it is (we’ll get onto this). Type 1 collagen makes up 90 per cent of the collagen in the body, so it is certainly the one we should try and focus on the most. Type I collagen is arguably the most researched (at this point in time) and the most abundant type of collagen in the human body. It is found in nearly all connective tissues — such as tendons, ligaments and the skin— and is also prevalent in the gut, helping to provide structure and strength.

Step 2: Using your collagen

So, you’re happy with where you have sourced your collagen. Next up is how you use it - will the collagen become less effective if you add it to a hot drink?

The simple answer is no. Although this doesn't mean that collagen is completely indestructible in heat (it’s a natural ingredient remember), it is very stable. According to a study published in the Biophysical Journal (1), the amount of heat you are going to need to destroy collagen isn’t going to happen in your kitchen. The collagen samples used in the study did not begin to degrade until 300 degrees celsius - boiling water is only 100 degrees, so your hot drink shouldn’t make a difference to the peptides.

Does caffeine affect how well our body uses collagen?

Whilst there are some emerging studies and anecdotal accounts that suggest that caffeine may have negative effects on certain aspects of the body, such as wound healing and bone growth, it is unclear whether caffeine or coffee would interfere with collagen absorption when taken as a supplement. These studies do not specifically investigate this relationship.

It is important to also note that coffee and caffeine have a huge range of health benefits documented in studies and are safe in moderate amounts for most people. If you enjoy drinking coffee with your collagen supplement, you can continue to do so without worrying about negative effects on collagen absorption, based on the current scientific evidence available.

Step 3: Absorption and Action

Once you have had your collagen, how does it get to work in the body? Key to any supplement is whether or not you are actually able to absorb the nutrition you are taking in. Rather than ‘you are what you eat’, the more accurate statement is ‘you are what you absorb and assimilate’. For you to do that, you have to be able to break compounds down, then use them effectively. Hydrolysed collagen peptides are a great example of a highly absorbable nutrient, as they have already been broken down into a bioavailable form.

In its natural form, the collagen molecule is actually pretty huge and far too large to be absorbed by the body, which is why, when making (the good) supplements, it is broken down into smaller collagen peptides. This process is called hydrolysation. On top of this, these peptides must then be of a sufficiently low molecular weight to ensure almost immediate absorption; this is especially key for digestion in the small intestine. Hold on to your hats, we’re about to get super geeky.

The brilliant thing about hydrolysis is that, instead of breaking the collagen molecule down into the various separate amino acids, it essentially 'cuts up' the collagen strands into peptides (amino acids still chained together but in short sequences), so that they are smaller, but still essentially recognised as collagen by the body.

The size of these collagen peptides is important as it determines their absorbability and further action in the body and this is measured by their molecular weight in units called Daltons (DA). The small peptide chains between the range of 2000 DA to 5000 DA are known to be small enough for your protein digesting enzymes to complete the final steps of breaking the peptides down into even smaller units of three amino acids (tripeptides), two amino acids (dipeptides) and free amino acids. The molecule size of our True Collagen is 2000 DA to 5000 DA (2).

It was historically hypothesised that the collagen peptides were broken down into separate amino acids in the gastrointestinal tract (gut) before being absorbed into the blood circulation. However, increasing evidence suggests that these small peptides are also absorbed (3)

Further evidence shows that collagen peptides ingested, end up in the sites where collagen is found, as di-peptides and tripeptides, having travelled through the bloodstream to get there (4). Some of these di- or tri-peptides have then been shown to stimulate fibroblasts and osteoblasts (collagen producing cells).

The exact mechanism behind the uptake of hydrolysed collagen by the intestinal epithelial cells (which line the surface of the gut) is extremely complex, and as such still being researched, however there are 3 different mechanisms of action that have been identified and tested so far (5).

As detailed above, the first step in digestion at this point consists of splitting the hydrolyzed collagen to form dipeptides and tripeptides (often proline-hydroxyproline and glycine-proline-hydroxiproline) and free amino acids. Several proteases (enzymes which do this job) are involved in this degradation process.

These smaller peptides and amino acids are then ready for uptake into enterocytes (intestinal absorptive cells) and transport into the blood across the basolateral membrane. What we are seeing in studies is that collagen peptides specifically are thought to be absorbed through the PEPT1 transporter and into the bloodstream (6).

Through the network of blood vessels, these collagen peptides and free amino acids are then distributed around the body, such as to the dermis in the skin, where studies have shown they can remain for up to 14 days (7). Interestingly, (for us nutrition geeks at least) the dipeptide named proline-hydroxyproline (Pro-Hyp) appears to be one of the main peptides appearing in the body after collagen peptide ingestion. Keeping these molecules as peptides rather than breaking them down further into single amino acids seems to be the key to the way collagen supplements work.

From Absorption to Action

Remember, we synthesise our own collagen, via specialised cells such as fibroblasts, when they are given the building blocks of nutrients such as vitamin C and amino acids. Collagen supplements are believed to have a dual action by first providing these building block components for collagen production and then secondly, stimulating the synthesis of collagen, elastin and hyaluronic acid.

Peptides act as signalling molecules. Put simply, they communicate with cells (like fibroblasts), telling them what to do; whether that’s repairing tissues, producing certain hormones, or promoting anti-inflammatory healing - in this case it would be; ‘make more collagen!’ They act as ligands, binding to receptors present on the fibroblasts’ membrane and stimulate the cells into action, strengthening, repairing and reinforcing tissues in our skin, joints and across the body's tissues. On top of all of this action, it is believed that these peptides may also send a signal to ‘stop breaking existing collagen and bone down’ using pathways involving TReg cells and M2 like macrophages.

M2 like macrophages, cells which reside in our tissues and are in charge of integrity, play a key role in extracellular matrix turnover and remodelling. The T Regulatory Cells are key for maintaining homeostasis - the balance of the breakdown and rebuilding process.

Furthermore, some peptides appear to also increase synthesis of hyaluronic acid, the substance we often thank for hydrating our skin but also lubricating our joints and other tissues (8)

Key to understanding all of this is that the intelligent human body is always trying to get into a state of homeostasis; a healthy balance. Because our body makes its own collagen, it aims to maintain the balance of collagen being broken down and collagen being produced. As the theory goes, when the body detects ‘collagen peptides’, it essentially believes there is a collagen breakdown and therefore must produce more collagen to maintain the balance.

There are still other properties of collagen being investigated such as anti-inflammtory, antioxidant, antihypertensive, and lipid-lowering activities and therefore the science hasn’t stopped at only reducing lines and wrinkles.

Step 4: Whole Body Benefits

What does all this absorption and activation of fibroblasts result in? Whole body benefits.

When people think of collagen, they usually think of skin benefits first. But because collagen is so ubiquitous in our body, the benefits reach much further and are much wider ranging than we give it credit for.

Clinical data analytics company Phesi ran an analysis of collagen clinical trials for the Observer from 2010 onwards and only 5% were actually related to cosmetics (9). The other 95% are scientists from around the world looking at the potential for using collagen to aid in the prevention of some of the more damaging consequences of ageing such as bone diseases, joint pain, frailty and improving wound-healing. On top of this, research has accelerated over the past 5 years thanks largely to the Sports Industry.

Whilst there are now thousands of studies (some very promising, some of course not so robust) to sift through, in this article we have focused largely on systematic reviews of studies which aim to meticulously summarise all the available primary research but through which you can find and research the studies included further.

Joint, Bone and Body Composition Benefits

Active lifestyles and high intensity exercise can have many benefits and can in fact support natural collagen synthesis, but can also put strain on hard-working joints, especially as we age. When it comes to joint pain in particular, damage to cartilage - the shock absorbing cushion found in joints - is often the cause. Unsurprisingly, collagen makes up two-thirds of the weight of cartilage in many joints and whilst it isn’t yet certain that supplementing collagen won’t ‘grow back’ lost cartilage, studies have shown improvements in performance across the musculoskeletal system.

A 2021 systematic review of 12 studies conducted by the University of Huddersfield and University of Loughborough (10) looked at various measures including joint pain, recovery from joint injuries, body composition, muscle soreness, recovery from exercise, muscle protein synthesis (MPS) and collagen synthesis. The results from the studies indicated that out of these measures, collagen was most beneficial for reducing joint pain and improving functionality. Some of the studies also showed improvements in body composition, strength and muscle recovery, which is a growing area of research. Most of these results were further accelerated when paired with some rehabilitation or resistance based exercises. Read; collagen peptides + exercise = besties.

Another recent review published by the Institute of Sports Sciences and Medicine at Florida State University, found that when paired with resistance training, collagen peptide supplementation was shown to promote recovery, decrease pain, and improve strength and body composition (11).

A separate 24-week study in the USA found that joint discomfort in athletes was improved after hydrolysed collagen supplementation (12).

Another 2019 study found that combining calf strengthening exercises with collagen peptides reduced Achilles tendon pain, a challenging issue for those who experience it (13). Yet another encouraging starting point to establish future research in the area.

Bones

It’s easy to forget that bones aren’t dry and fossil like, but in fact living tissues that repair themselves. As the main ingredient in bones, Type I collagen is what gives them strength and suppleness. So it’s not surprising that researchers have started to look at collagen supplementation for this reason. In studies, collagen supplementation has been shown to impact osteoblast activity which helps with bone and joint health.(14)

Bones lose density and get weaker as we age, which makes us more susceptible to fractures. This is particularly the case for post-menopausal women as oestrogen plays an important role in maintaining bone strength. Alongside good levels of vitamin D, calcium and magnesium, recent research also shows that collagen supplementation may help you preserve bone mass and other markers of bone health (15).

As well as improving BMD, collagen also appears to improve the structure of bones, binding to bone minerals in a cross-link formation, creating a super strong structure. When looking to improve bone health, studies have found that results have been even better when collagen was taken in conjunction with vitamin C, magnesium, vitamin D, vitamin K and calcium.

Osteoarthritis

Whilst this has wholly been positive, it is worth noting there are more mixed outcomes when it comes to osteoarthritis, possibly due to its complex nature and many variable causes dependent on each individual suffering with OA.

Two meta-analyses which both included five studies on using collagen for osteoarthritis reported improvements to pain in short and long term; however in one, physical function did not see an improvement compared with placebo (16).

A 2018 systematic review in the British Journal of Sports Medicine also found that hydrolyzed collagen supplements provided significant relief from osteoarthritis-associated pain, although the review also noted that as trials haven’t yet been long enough or large enough, we do not know the benefits of this in the long term.

What this tells us is, even though collagen has demonstrated some evidence of efficacy, more studies are needed to really nail down which collagen products and nutritional interventions are needed specifically for diseases such as osteoarthritis. Type 2 Collagen is currently being investigated for this use.

Muscle and Body Composition

Collagen protein has a beautifully complex amino acid profile, however does not contain leucine - the amino known for activating muscle protein synthesis for muscle building. Collagen does however contain amino acids glycine and arginine, which are important blocks for creatine. As well as the 2021 review referred to above, there are many (many) studies that show how creatine can help improve muscle mass, build strength, and improve athletic performance (17).

Skin benefits:

As well as being what we see in the mirror, our skin, hair and nails are the body’s natural protective barriers. So they need strength - which is where collagen plays its role.

The beauty industry has really taken collagen under its wing, and we can see why. As the body’s largest organ, skin is composed of two layers; the dermis is the deepest and collagen is its main player. As well as naturally ageing, many of our modern life habits can contribute to collagen damage such as over exposure to UV, poor nutrition, pollution and cigarette smoke - creating wrinkles and decreased elasticity. The aim of oral collagen supplementation is to reach the dermis from within to restore collagen synthesis, positively influencing the skin ageing process.

There is an abundance of clinical reports that provide evidence for collagen supplementation to supports the health of our skin

A key systematic review looked at all measures of skin ageing including wrinkle number, dryness, moisture and elasticity. Across 10 publications it reported that all of the studies on collagen peptides, ranging from 8 weeks to 12 months duration, resulted in improved skin health using these parameters (18).

In 2019, the J Drugs Dermatol also published a review of oral collagen's effects on the skin, further showing that collagen peptides positively support skin elasticity and hydration levels (19).

In 2015, two placebo-controlled clinical trials were also used to assess the effect of daily supplementation of collagen peptides on skin hydration and collagen density. They found dermal collagen significantly increased after four weeks of supplementation, and by eight weeks, skin hydration significantly increased (20).

A new 2023 systematic review of 26 studies showed consistently improvements in skin hydration and elasticity when supplementing collagen peptides, supporting the claim that marine based collagen showed the best results for skin health.

When using systematic reviews and meta analysis of the data, it is worth noting that they are only as good as the sum of its parts; this particular review did pick up some bias in a few of the Randomised Control Trails they included, which points to the need for more large-scale randomized control trials to continue to examine and further cement those clinical benefits of oral collagen supplements in this field (21).

Other Signs of Ageing

One of the key drivers for research in collagen has been to look for solutions for the prevention of some of the downsides to ageing such as risks of falling. One reason older people are at a higher risk of falls is that collagen keeps the body supple, especially our muscles and tendons. When it is no longer being replenished, this can cause joints to stiffen and our tendons no longer work well as shock absorbers.

To support the research in this area, scientists at Liverpool John Moores University are currently leading a clinical trial where they plan to give older people collagen supplements over the course of four months to see if it can improve the function of their muscles and tendons, and therefore make them less vulnerable to tripping (22).

An area which doesn’t get much airtime, but could have extremely interesting benefits, is cardiovascular health. Some studies have advocated that collagen peptide supplementation may positively affect our circulation and heart health. Collagen helps to provide structure to your arteries, therefore it is being researched as to whether collagen supplements may reduce artery stiffness. More research is needed but this indicates the ubiquitous nature of collagen supplementation (23).

New research into collagen peptides is also looking towards the potential antiimflammatory effects which may be contributing to the benefits users are feeling. This is thought to be largely due to its content of proline and glycine. These amino acids help to reduce inflammation by inhibiting the production of inflammatory cytokines. This provides us with some great starting points to looking into how collagen may support some inflammatory conditions. Watch this space…

Hair and Nails

When it comes to the body’s job of allocating collagen, as part of our innate survival mechanisms, it will always prioritise its most important organs and components first such as connective tissues, joints, arteries and bones. This may be why we see a downturn in our skin, brittleness in our nails and thinning of our hair as we age as our collagen is focused elsewher.

Some preliminary and granted, small studies, have shown that collagen is deposited in the hair follicles and nail bed (24) improving brittle nails and potentially strengthening hair. The theory goes that by providing additional collagen peptides in the form of supplementation, it is thought that we can support hair and nail growth by essentially giving the body more collagen to allocate to parts of the body usually left at the bottom of the pile.

Gut Health

This is most likely the area in need of more research, perhaps due to the complexity of measuring the gut lining and microbiome. Because of the location in the body it is much harder to measure and so much of the current research is in vitro or using aminal models.

Collagen appears to play an integral role in rebuilding and strengthening the lining of our digestive tract as it contains the amino acids—particularly glycine and glutamine—that are essential for its repair (25).

The researchers in this study found that collagen peptides may improve the gut barrier and tight junctions in the gut, should it be in poor function. It also looked at how collagen may play a part in reducing inflammation, often associated with poor gut health (26).

Another animal study has looked at the potential effects of collagen peptides on the gut microbiota, showing a reduction in some pro-inflammatory cytokines which are a known contributor to gut dysbiosis.

How Long Will it Take to Work?

This is a common question we get and the honest answer is, it will look different for everyone. Depending on your age, your need for collagen (e.g. if you have an injury), your current diet and nutritional status, your lifestyle and many other variables, will affect how long it will take for collagen to show benefits. A 30yr old non-smoker with a good diet will have different collagen status than a 60yr old sun-drenched marathon runner with a sweet tooth for example. The body will also allocate the collagen to parts where it’s needed the most. If you have some gut healing or joint repair to do, that’s what the body is likely to proiritise. We can look at studies however to gauge some documented timing to help you along;

Skin support benefits: around 4 to 12 weeks (1 to 3 months)

Muscle mass and strength (often combined with resistance training): 3 months

Less soreness after physical training: within a few days

Joint health support: 4 to 6 months

Tendon support (combined with strengthening exercise): 3 to 6 months

Bone-density support: 12 months

Hair and Nails: still being researched but some studies show 6 months

Getting the Dose Right

The turn-over rate of collagen is estimated at 1.4% per day, but because we are all so different the optimal supplement amount for replacement of collagen is still unknown, however much of the research and data supports the use of 5-15 grams per day. In clinical practice, some practitioners are recommending up to 20 or 30g a day but this may not be needed for everyone. What we do know is taking it consistently is key, as the effects will become more sustainable with regular use.

We recommend taking 5-10g of True or Wild collagen daily for good maintenance.

If using collagen for performance, taking between 10-12 grams per day seems to be a good range for improving soft tissue health and reducing muscle soreness. Research also suggests that taking collagen around 30-60 minutes before your workout session is the ideal time to ensure that those key amino acids and peptide chains are present during the session and enhance the delivery to the target tissues.

Safety

A huge benefit of collagen peptide supplements is its great safety profile. We have used collagen for thousands of years in our diets and the supplement version has been regarded as safe by the European Food Safety Authority and has no known drug−nutrient interactions so far - however we will always aim to update our audience with current research should this change.

Due to the severity of the disease, we do urge caution around cancer and breast cancer diagnosis however. Research is lacking on the effects of collagen supplementation during cancer treatment and so it is advised to speak to your personal health professional during these instances.

Additional Extras

Collagen is an incredible compound and yet we’re under no illusion that it is a panacea for all. We highly recommend using collagen as part of a healthy diet and lifestyle to really benefit from the full effects. Studies also show that vitamin C can double collagen production in joints. Vitamin C plays an important role in switching on key enzymes allowing the formation of collagen. It is also highly likely that exercise and supportive movement would also further aid the benefits of collagen supplementation too. See it as (an extremely versatile and easy) part of the complex puzzle of what it is to feel healthy.