Marine Collagen Supplement

Collagen accounts for 30% of the proteins in our body. So what is it used for?

Collagen is the body's main structural protein, including in the skin (type I collagen). In the skin, it provides support and firmness by contributing to the formation of connective tissues such as the dermis, the thickest layer of the skin. It is easy to understand why the benefits of collagen supplementation (providing building blocks and stimulating production) mainly impact the beauty and texture of the skin.

Collagen (with vitamin C) is also used to support joint health, since cartilage, the junction tissue between the bones in joints, is itself rich in collagen (type II). Vitamin C, for its part, contributes to normal collagen formation for the normal function of skin, cartilage and bones.

Collagen is the most abundant protein in the animal kingdom and makes up around 30% of all the proteins in the human body. It is found in all connective tissues (skin, tendons, cartilage, bones, muscle sheaths, blood vessels, etc.), to which it gives mechanical strength and elasticity. It is therefore essential to the proper functioning of our body and certain vital functions, such as maintaining skin integrity, normal heart function and bone strength.

To date, 28 different types of collagen have been identified, but types I and II are the main and best known:

Type I: it makes up 90% of the body's collagen and is therefore found in every corner of it: skin, tendons, ligaments, fibrous cartilage, brain, organic components of bone, skeletal muscle...

Type II: it is found in fibrous and elastic cartilage, in the cartilaginous areas of tendons...

Every protein in the body is made up of a specific assembly of amino acids. As a protein, collagen is therefore made up of amino acids whose organization forms alpha chains. These are mostly built from the repetition of a tripeptide motif (3 amino acids) starting with a particular amino acid, glycine (Gly): glycine - X - Y.

Within collagen proteins, certain amino acid sequences are more represented in the alpha chains:

The Gly-Pro-Hyp sequence (where "Pro" is proline and "Hyp" is hydroxyproline), the most common sequence (about 12%),

The Gly-Pro-Y and Gly-X-Hyp sequences (X and Y being amino acids other than Gly-Pro-Hyp), representing about 44%,

The Gly-X-Y sequence makes up the remaining 44%.

Type II collagen has a specific sequence present in abundance that sets it apart: the Gly-Pro-Hyl sequence, where Hyl is hydroxylysine.

Types I and II are collagens organized into fibrils, which is why they are called "fibrillar" collagens. This is the most abundant collagen in the body. In skin, bone and cartilage, only fibrillar collagen is found. In other tissues, fibrillar collagen is associated with non-fibrillar elements.

The alpha chains of fibrillar collagens have similar amino acid sequences and are distinguished by specific sequences. Once assembled, the alpha chains coil together to form triple-helix molecules that make up the fibrils, which in turn form the collagen fibers.

Whatever the tissue in which it is found, the collagen in our body has similar peptide sequences. The major difference between the 28 types of collagen present throughout our body lies in the specific composition and organization of the alpha chains, which differ depending on the collagen type and the tissue.

As mentioned, collagen is present throughout our body.

The skin is the largest organ of the human body, with an average surface area of 2 m². It is our first line of defense against the external environment, so guaranteeing its integrity is essential for our health.

The skin is made up of three layers:

• The epidermis: in direct contact with the outside, it is very thin and provides the skin's barrier function.
• The dermis: the skin's connective tissue, it is considerably thicker than the epidermis and extremely resistant thanks to its richness in type I collagen and elastin, which give the skin its firmness and elasticity. Fibroblasts, specific cells of the dermis, produce these major components of the dermis, including, precisely, type I collagen.
• The hypodermis: the deepest layer, it is rich in lipids (with its characteristic cells, the adipocytes), playing a nourishing and protective role (notably against cold), and contains collagen to a lesser extent.

The figure below diagrams the structure of the skin and the arrangement of collagen fibers within the dermis. You can easily visualize its structural and supporting function for the skin.

Cartilage is a flexible, elastic connective tissue that covers the two ends of bones to form the joint. It plays an essential role in ensuring smooth gliding between bones, limiting the intensity of friction, providing cushioning and controlling joint pressure. Cartilage has specific cells, the chondrocytes, which synthesize its components such as collagen, the main component of the matrix. Three types of cartilage exist: hyaline cartilage, elastic cartilage and fibrous cartilage. Hyaline cartilage is the most abundant, located at the joints and essentially made up of type II collagen.

Skeletal muscles (the main muscles, well ahead of cardiac muscle and smooth muscles) are made up of bundles of fibers themselves formed of myofibrils (i.e. fibrils with contractile power). Muscles consist of an alternation of these bundles of fibers with connective tissue mainly made up of type I and III collagen (another fibrillar collagen), which gives the muscle its elasticity and flexibility during contraction. This extracellular matrix containing collagen therefore plays a protective role around the muscle.

The dermis and cartilage are two connective tissues whose extracellular matrices are made up not only of collagen but also of carbohydrate molecules, glycosaminoglycans, such as hyaluronic acid (or hyaluronan) for the skin and chondroitin sulfate for cartilage. Some glycosaminoglycans are made up of glucosamine sulfate, which is present in large quantities in the joints in particular. Less abundant than collagen, glycosaminoglycans are nevertheless essential to maintaining the dermis and cartilage by helping to retain water, thereby ensuring hydration of the skin and joints. They are found in different proportions in the body: hyaluronic acid is more present in the dermis, while chondroitin sulfate is more abundant in cartilage.

The decline in collagen production linked to aging weakens the structure of the dermis and, consequently, the skin. It is estimated that an adult loses on average 1% of dermal collagen per year. This natural process also affects motor function in bone and cartilage. It is estimated that by age 80, we may have lost 75% of our collagen reserves.

In addition, these collagen-rich tissues are particularly exposed to external aggressions such as UV rays and pollution for the skin, or more or less intense physical activity for the joints (bone and cartilage). On this topic, see our article on sun damage to the skin.

To offset this drop in our endogenous production, a first approach can be to turn to our diet. As in our own body, collagen is mainly found in the connective tissues of animals (skin, cartilage, etc.), parts that we no longer really eat in our modern diet. Another method is to make a traditional bone broth (beef, chicken or fish), whose slow cooking extracts collagen from bones and cartilage. Unfortunately, this native collagen, whether from broth or directly from proteins, has a very high molecular weight (around 300 kiloDaltons), which makes its intestinal absorption difficult.

Another strategy can be to stock up on collagen precursors. Glycine is also found in collagen-rich foods, and in smaller quantities in meat (muscles), eggs and certain plants such as soy, sesame and legumes. Hydroxyproline and proline are more easily found in a large number of protein sources. Other nutrients, such as vitamin C, also take part in collagen synthesis, so any deficiency should be avoided to support production by our body.

But in the end, dietary intakes of collagen or even of precursors remain limited and cannot, on their own, offset the losses linked to aging. This is where nutraceuticals come in.

The interest that science has in collagen goes hand in hand with advances in our knowledge of bioactive peptides. For a long time, the scientific community considered that ingested proteins were cut into di- and tripeptides in the lumen of the intestine, before being absorbed by enterocytes and reduced to free amino acids inside these very cells. The free amino acids were then released into the blood serum. But since 2015 [15], we have known that some peptides pass intact into enterocytes and are found in the blood. Thus, 10 to 30% of ingested proteins are found in the blood as di- and tripeptides.

The collagen protein likely to be provided by food is very large, on the order of 300,000 Daltons, which makes it unabsorbable as is by enterocytes. By comparison, β-lactoglobulin, the main protein of whey, is on the order of 18,000 Daltons. The work of cutting (or hydrolyzing) the collagen protein by digestive enzymes is therefore considerable in order to obtain tri- and dipeptides capable of being absorbed. Since peptide transporters are present throughout the intestine (duodenum, jejunum and ileum), it is understandable that providing an intact protein will inevitably cause part of the possible absorption surface area to be lost, because di- and tripeptides will only be available late in the intestine.

To benefit from the whole absorption surface area of the intestine, it is therefore advisable to present small, absorbable peptides very early. This is the whole point of a dietary supplement formula.

Our knowledge of bioactive peptides is developing because, in addition to being building blocks for new proteins, these peptides also act as messengers. They can stimulate cellular activity. This specific role is not found (or to a much lesser extent) with free amino acids.

Looking more closely at type I collagen, 3 key peptides specific to the collagen protein have been identified for their ability to stimulate fibroblast activity. They bind to certain receptors present on their membrane. This is how the production of new endogenous collagen is increased, as well as that of other components of the extracellular matrix such as elastin or hyaluronic acid. The number of fibroblasts also increases through cell division. The best-documented peptides to date are:

• Proline-hydroxyproline, whose ability to pass intact into the blood plasma while stimulating fibroblasts was discovered in 2010 [16],
• Glycine-hydroxyproline, whose activity was discovered in 2011 [17] and which would be more potent at activating fibroblasts, but whose blood level varies greatly from one individual to another, implying that genetic material may play a role in the absorption of intact bio-peptides.
• Glycine-proline-hydroxyproline, the best known.

The tripeptide glycine-proline-hydroxylysine, specific to type II collagen and identified as a bioactive peptide in 2014, can also be added.

The value of the collagen peptides provided by nutraceuticals can therefore be summed up in two points:

• Unlike the intact collagen protein provided by food, peptides make it possible to benefit from a larger absorption surface area within the intestine and therefore increase the peptide level in the blood.
• In addition to being precursors, like free amino acids such as glycine, they are also messengers capable of activating the cells of the body responsible for making collagen.

Collagen can be of porcine, bovine, avian or marine origin. The latter is increasingly popular for health, cultural or supply chain traceability reasons. As we have seen, the value of collagen peptides in supplementation lies in their ability to benefit from a larger absorption surface area than the intact protein. Ingredient suppliers therefore extract collagen from their raw material, then start an enzymatic hydrolysis process similar to human digestion. Enzymatic hydrolysis of native collagen produces a set of small peptides, whose weights can vary from 300 to 10,000 Daltons, i.e. 30 to 1,000 times smaller than native collagen (or intact protein).

The Dalton has become a marketing issue, with each brand trying to present the lowest number. It is nevertheless important to know that, from a regulatory standpoint, there is no label control. An unscrupulous brand could therefore display 300 Daltons on its label without it being true and without being troubled by the control authorities. Before even asking the question of the right Dalton size, it is therefore essential to make sure the brand provides a guarantee regarding the labeling of the Dalton figure. Since analyzing the average Dalton figure is extremely expensive, you will not find this type of document on brands' websites. What serves as a guarantee is the brand making public the ingredient supplier it works with, ideally by displaying the ingredient's trademark on the label. Here is a non-exhaustive list of trademarks and their average molecular weight to help you :

Once the guarantee on peptide size is dealt with, the next question can be asked: what is the right size?

In reality, two factors truly influence the effectiveness of peptides:

• The content of the bioactive di- and tripeptides mentioned above, but to date no ingredient supplier seems to offer an effective method to assess this content,
• In the absence of a reliable method for analyzing bio-peptide content, we fall back on peptide size, whose unit is the Dalton. Since the figure generally communicated is only an average, it is also important to evaluate the distribution around this average. Several points need to be checked:

First, that there is a fraction of di- and tripeptides (200 to 500 Daltons) in order to benefit from the start of the absorption surface area of the intestine,

Next, it is important to make sure the mix does not contain too many amino acids (molecular weight below 150 Daltons), which do not have the bio-activating power of di- and tripeptides.

Finally, it is crucial to have an even distribution around the average in order to benefit from continuous absorption. Peptides that are too large (more than 30,000 Daltons) might then not have time to be reduced to absorbable di- and tripeptides.

As stated previously, analyzing the average molecular weight is an expensive analysis. There are several standard approaches, of which the most common are:

• Mn (number-average molecular weight) gives an idea of the average peptide size without taking into account the influence of larger peptides. This method does not reflect the distribution. For average molecular weights below 2,000 Daltons, this approach lacks precision. It is nevertheless one of the most widely used to date.
• Mw (weight-average molecular weight) is generally a complementary analysis to Mn. A large difference between Mn and Mw indicates a broad distribution, with a significant presence of large peptides.
• SEC (Size Exclusion Chromatography), also called gel chromatography, separates peptides according to their size or molecular weight. Smaller peptides enter the pores of the gel matrix and take longer to pass through the column, while larger peptides are excluded from the pores and pass through the column faster. It is one of the most reliable and most widely used methods. It is notably used in the GB 31645-2018 standard, which is a reference for quality standards. This method is often used to determine the size distribution of peptides in a hydrolyzed collagen sample. It makes it possible to generate a chromatogram showing the different molecular weights present. Depending on its resolution, this method can go below 2,000 Daltons.
• MS (Mass Spectrometry) identifies peptides by measuring their mass-to-charge ratio (m/z). Peptides are ionized, then separated according to their mass and charge in a mass spectrometer. It is a very precise method for characterizing the composition of peptides in a sample. This method can go below 2,000 Daltons.

To conclude on analysis methods, ingredient suppliers are currently working to evaluate the content of bioactive di- and tripeptides. While no method is recognized as a standard to date, progress is being made, so that in the years to come the challenge could be to display the highest content of the 3 bioactive peptides mentioned above for type I, and to steer production methods by enzymatic hydrolysis in this direction.

Scientific work comparing different sizes of collagen hydrolysate all reaches the same conclusion: the higher the content of di- and tripeptides (bioactive or not, since at this stage we cannot evaluate their respective content), the faster effectiveness is reached and for a smaller ingested quantity [18,19]. The best collagen hydrolysates are therefore currently around 2,000/1,500 Daltons and have a fraction of 10 to 25% of di- and tripeptides, without isolating the share of bioactive peptides.

Ingredient suppliers are currently working on 500-Dalton collagens, but certification methods are not yet recognized as a standard.

Now that the bioavailability of hydrolyzed collagen has been established, what about its clinical efficacy and concrete results? For about ten years, research on this protein has multiplied and evidence of its efficacy has accumulated, in particular in two areas: skin and joint health.

Note that the daily doses showing efficacy are generally in the range of 5 to 15 grams per day for skin benefits and in the range of 0.5 to 10 grams per day for joints. This is why the capsule format is generally poorly suited to taking collagen as a nutraceutical.

Skin appearance is a major beauty concern. Over time, the collagen stock declines and the signs of aging appear: wrinkles, sagging, loss of elasticity...

A 2019 review [20] listed various comparable clinical studies on hydrolyzed collagen supplementation and its impact on the skin. In this published work, 11 studies were included, totaling 805 subjects. Collagen dosages varied between 2.5 g and 10 g per day over durations of 56 days (8 weeks) to 180 days (24 weeks). On average, the collagen hydrolysates used were 2 kDa. All the studies showed significantly positive effects on various parameters related to skin aging: dermal thickness, wrinkles, elasticity...

Brazilian researchers had summarized the work on this subject in 2021 in a meta-analysis, and concluded that collagen peptide supplementation had positive results compared with placebo on skin hydration and elasticity, and on the appearance of wrinkles. These results appear on average between 60 and 90 days after the start of supplementation [21].

Finally, the most recent meta-analysis (2023), including 26 studies with 1,721 participants (98% women), also concluded to better hydration and greater skin elasticity, particularly beyond 8 weeks of supplementation [22].

Through these studies, hydrolyzed collagen has therefore proven effective (and safe) for improving the appearance of the skin. Supplementation with collagen hydrolysates therefore appears to be an asset in preventing skin aging and the appearance of signs of aging [23].

Joint pain affects many people, some populations being at higher risk, such as athletes and older people. In these people, cartilage erosion caused by impacts or the effect of time leads to osteoarthritis. It is moreover in the context of these issues that clinical studies are widely conducted. Compilations of the results of clinical work highlight the significantly positive effects of taking hydrolyzed collagen to relieve joint pain (sensation and structure) [24,25].

As always, these data must be considered within the clinical conditions in which they were observed. Most of these clinical studies were carried out at doses of 10 g per day of collagen peptides and of type I, and more recently at doses of 5 g at a molecular weight of 3 kDa [26,27].

Other studies used doses of 1.2 g of collagen peptides at a low molecular weight (<1 kDa) [28–30]. The important parameter of these studies is the duration of collagen supplementation. Indeed, this work revealed that significant positive effects appear with a duration of 24 weeks.

Associated with the joint issue is the question of the bone-collagen relationship. The improvement of bone mineralization through collagen supplementation is not yet sufficiently documented [31]. However, one clinical study demonstrated promising effects in postmenopausal women (131 subjects). In this work, collagen peptide supplementation (5 g per day) demonstrated better bone mineral density and improved plasma bone markers [32].

The most recent studies confirm these results. A meta-analysis of 35 studies published in 2024 showed positive effects on reducing the symptoms of knee osteoarthritis [42]. A randomized double-blind study from 2025 tested the intake of 10 g of low molecular weight collagen peptides in combination with vitamin C in 120 adults (30-81 years old, 50% women) with knee osteoarthritis, for 6 months. The results were tangible and positive, with a measurable clinical effect on pain and mobility [43].

As mentioned previously, muscle fibers are supported by connective tissue largely made up of collagen, such as ligaments, tendons, fascias and the extracellular matrix. Following physical effort, there is an adaptation phenomenon of the muscle fibers that results in their growth and hypertrophy, but also that of this connective tissue.

Collagen is a protein too low in essential amino acids to truly stimulate muscle protein synthesis, but as a structural protein of this connective tissue, it has nevertheless been the subject of studies alongside resistance training. In a first study, a group of young athletes took either 15 g of hydrolyzed collagen per day or a placebo for 12 weeks, alongside strength training. The group supplemented with collagen saw a significant increase in lean mass at the end of the study, with no difference in muscle fiber size. This therefore most likely comes from growth of the connective tissues [33].

Seniors may also have a particular interest in supplementing with collagen, in addition to athletes. Sarcopenia, this loss of muscle mass that accelerates with age, is a major public health issue. A 2015 study had a group of 53 men, 72 years old on average, take 15 g of collagen per day or a placebo, alongside resistance training. Both groups saw an increase in their lean mass and muscle strength, but to a greater extent in the collagen group [34].

The range of collagen-based products has grown strongly in recent years, but few meet all the criteria of an excellent collagen supplement. Rather than choosing a standard collagen, we chose two very high-quality ingredients for our Collagen:

• Naticol® Collagen: a type I, II and III collagen dosed at 5 g/day, with a very low molecular weight, which has clinical studies demonstrating its efficacy in improving the appearance of the skin (firmness and wrinkles) and joint comfort [35-39].
• Cartidyss® Collagen: a type II collagen dosed at 500 mg/day and benefiting from its own clinical studies. A first study carried out on 23 women aged 45 to 59, taking 500 mg per day for 90 days, demonstrated visible effects on wrinkle reduction, increased dermal density and improved skin smoothness [40]. Another study validated the efficacy of 500 mg of Cartidyss® taken twice a day for 3 months on pain reduction and better joint mobility [41].

• A combination of type I, II and III collagen hydrolysates, the most abundant fibrillar collagens in the body.
• A collagen amino acid profile rich in glycine (the majority), hydroxyproline and proline, the three main amino acids making up collagen.
• A broad spectrum of molecular weights, with a majority of low weights (see table below), for good assimilation and an interesting variety of proteins. Indeed, while type I and II collagens provide relatively similar peptides, type II collagen provides specific constituents of the extracellular matrix of cartilage such as chondroitin sulfate (about 50 mg per day for one dose of our Collagen) and glucosamine (about 30 mg per day for one dose of our Collagen).

• Impeccable traceability: our raw materials come from controlled and committed fish by-product supply chains.
• Ease of use: the high quality of our collagens makes it possible to obtain a powder with good solubility, while natural peach, chocolate, lemon, vanilla, matcha and red berry flavors, or an unflavored option, provide fine and delicate tastes. These organoleptic characteristics allow easy daily use of our Marine Collagen in different types of hot or cold preparations and drinks.