This is a question I have been asked regularly over the last 7 or 8 years in our skin clinics. A lot of my patients take collagen supplements, and they say they definitely notice an improvement in their skin, hair and nails.

However, are collagen supplements really effective?

Until recently my answer had always been, “I don’t know, the evidence is weak, but it certainly won’t do any harm because collagen is made up of amino acids that our body can always put to use.”

Over the last 10 years a lot of different centres have researched collagen. Earlier this year a significant review of all of these studies was published.

The scientific evidence has arrived

In March 2021 a systematic review was published in the International Journal of Dermatology that collated the results from 19 high impact (double blind, randomised control trials) studies of over 1,125 people in which hydrolysed collagen was being compared with a placebo. The authors concluded that:

“Ingestion of hydrolysed collagen for 90 days is effective in reducing skin ageing, it reduces wrinkles and improves skin elasticity and hydration”. (1)(2)

What is a double blind randomised control trial? In medicine this is the highest level of clinical evidence. It is a trial where a substance is tested against a placebo. Importantly both the tester and the subject do not know which is which. Only after results have been measured is this revealed, so it removes any bias unconscious or otherwise.

Once a number of these have been completed by different centres, collating these together under a systematic review gives a high degree of certainty if the results show the same thing.

During the last six months we at humanpeople have been analysing the evidence and have also been working with a manufacturer to understand the practicalities and formulation for the perfect combination of collagen type and co-factors.

As promised in an earlier blog, we said we would share some of the research we have been analysing recently so that you know what to look for.

We give answers to eight important questions about collagen:

  1. What is the difference between natural collagen and hydrolysed collagen?
  2. How does collagen work? The “mechanism” of action is probably not what you think…
  3. Which type of hydrolysed collagen is best for skin?
  4. What co-factors are needed to make collagen?
  5. What strength should I take? And in what form: powder, liquid or capsules?
  6. What does the research say about the other benefits of collagen?
  7. Are collagen supplements safe?
  8. What exactly is collagen?

1. What is the difference between natural collagen and hydrolysed collagen?

For a lot of substances ingesting higher amounts of them leads to an increase in the blood stream. This is the case for vitamin D, magnesium and omega 3. These are all small molecules, however, that can easily cross the small intestine barrier and be absorbed.

Natural collagen is an enormous molecule and is built to be resistant to enzymes. So when it is eaten it just passes through the gut, unaffected and unabsorbed.

Collagen supplements therefore have to be chopped up into smaller fragments to be absorbed. These fragments are called collagen peptides (because they are chains of amino acids). (3)

This process is mixture of a chemical and an enzymatic process. The resulting peptides are what we call hydrolysed collagen. They trigger receptors in the body as well as being a rich source of the important amino acids.

2. How does it work? The “mechanism” of action is probably not what you think…

The presence of increased amino acids does not account for all of the benefits that are seen with collagen supplementation. There is a separate and more important mechanism. (4)

When collagen is broken down into fragments these fragments become bioactive. That means they are able to bind on to special collagen receptors and evoke a response:

    • They increase collagen synthesis (the body’s natural process of producing collagen).
    • They slow down MMP enzymes (5) and the rate at which collagen is broken down (discussed in more detail later).

How to choose the best collagen?

What is the best collagen source: marine, cow or pig?

What strength and formulation is best capsule, powder or liquid?

3. Which type of hydrolysed collagen is best for skin?

The most abundant and important collagen in skin is type I. Marine collagen is almost solely type I, so for skin, bones and joints marine collagen is best. It has the highest concentration of the required amino acids and has been shown to give the best response. (6)

For muscle strength and conditioning, which has more type III collagen, bovine collagen is better because is comprises types I and III. Type III is also more common in the gut. (7)

Marine collagen tends to be a bit more expensive than bovine (cow) or porcine (pig) collagen, but it is the best.

Hydrolysed collagen is formed using a process called hydrolysis to break it down into smaller particles that can be absorbed in the body into purified collagen peptides.

Type I collagen is the most important of the 28 types of collagen in skin.

4. What co-factors are needed to make collagen?

Collagen is made up of a sequence of amino acids: Glycine-proline-X or Glycine-hydroxyproline-X, where X can be any of the other 17 amino acids.

The fragments need to be assimilated to form new collagen, so the raw ingredients to do that must be present as well as other essential ingredients, called cofactors. (3)

Essential

Vitamin C: to make collagen vitamin C is an essential cofactor – the body cannot make collagen without it. If you are buying a supplement make sure that it has vitamin C mixed in with it, otherwise boosting your natural vitamin C with lots of fresh fruit will help.

Important

B vitamins are essential for production of healthy skin, hair and nails (8):

  1. B1 niacin, is essential for skin. Deficiency will cause hypersensitivity, increasing redness, dryness and leading to flaky skin. It has been shown to reduce fine lines, wrinkles and age spots.
  2. B2 riboflavin is essential in the production of glutathione, which is important in detoxification. A lack leads to eczema, dry skin and dermatitis.
  3. B3 niacin is an essential for healthy skin reducing inflammation, dermatitis, sun-damage and dry skin. It helps with the production of ceramides and NMF (natural moisturising factor) in the skin.
  4. B5 pantothenic acid helps to improve elasticity and hydration. It is particularly helpful in acne-prone skin.
  5. Biotin (B7) is an important vitamin for skin health, hair and nails. It helps to promote healthy growth and repair of cells and the synthesis of amino acids that are all-important in collagen production.
  6. B9 folic acid is essential for cell production and the fibroblasts that produce collagen. As skin cells have a high turnover rate they are sensitive to low levels of folic acid. It is essential in multiple body functions including detoxification and ridding the body of unwanted metabolic waste.
  7. B12 is essential for many functions including the regulation of pigment in the skin

Nice to have

Hyaluronic acid: studies have shown that hyaluronic acid ingested does end up in the skin dermis. It is an important factor in skin hydration. The evidence on hyaluronic acid is promising, but to date there are a low number of studies so we await further evidence.

5. What strength should I take? And in what form: powder, liquid, or capsules?

For skin improvement you should take a minimum of 5-7g daily. (9)(10)

For joint health 10g daily.

To get the maximum benefit we recommend taking 10g daily for at least 90 days.

10g of collagen would mean taking an enormous number of capsules – that’s why we recommend either powder or liquid collagen. We prefer powder as it can be mixed into smoothies or breakfasts, but both are absorbed equally well.

6. So what does the research say about the other benefits of collagen?

Reduction in joint pain – strong evidence (11)

Over 60 clinical papers have now been published.

A review has concluded that 10g of collagen hydrolysate consumed daily decreases joint pain, and bone mass increases after 4-24 weeks.

It stimulates collagen tissue repair and collagen synthesis.

Better exercise recovery – weak evidence (12)

A 2020 paper looked at the effect of taking collagen exercise after vigorous exercise and concluded that post exercise soreness was reduced, but this was only significant over the following 24 hours. The collagen biomarkers were not changed.

This was stronger evidence than that for branched chain amino acids which is often recommended for post exercise recovery. (13)

However the strongest evidence by far for recovery and post exercise soreness was for omega 3 fatty acids. (14)

Sleep and mood – weak evidence (16)

Marine collagen is made up of mostly type 1 collagen and triple helical collagen molecule consists of about 1000 glycine, 360 prolines and 300 hydroxy prolines. That means a lot of glycine. Glycine is well known to improve the quality of sleep and also improve mood.

It would make sense, therefore, that a high intake of collagen and therefore glycine amino acids will help to produce a calming effect on the brain and sleep. There is anecdotal evidence to suggest this, but no good studies have been published.

Gut healing properties – medium evidence (15)(17)

There are a number of studies that show collagen helps to improve gut healing and improves the tightness of the cells not only lining the gut, but also the blood brain barrier. In the gut this appears to be partially due to the effect on the microbiome as well as providing the raw material to help heal the gut. Type III collagen is found in the gut – this is not present in marine collagen, but is present in bovine collagen. So for gut healing properties bovine may be better whereas for skin and joints Type I, which is prominent in marine collagen, is better.

7. Are collagen supplements safe?

Hydrolysed collagen supplements are recognised as safe. The FDA (the US regulator for foods and medicine) has defined hydrolysed collagen as GRAS “generally recognised as safe”. Due to the fact it has been long consumed as a food product with no history of significant side effects it is given the GRAS status.

As collagen is a highly modified animal product there are strict regulations and licensing requirements. Most good quality collagen supplements will be from recognised manufacturers and will be a trademarked product, such as verisol, naticol or peptan.

What side effects do they cause? Side effects from collagen supplements are very rare. A high consumption can leave you feeling full,which is common when consuming a lot of protein.

A high consumption of collagen may cause diarrhoea however there is no clinical data to back this up.

In summary, collagen is a protein made up of amino acids that the body recognises and therefore does not cause any allergies or reactions.

Can collagen cause kidney problems / kidney stones? As discussed earlier, collagen strands are made up of repeating sequences of amino acids: Glycine-Proline-X or Glycine-Hydroxyproline-Y. X and Y can be one of 17 other amino acids.

Marine collagen is made up of mostly type 1 collagen. The triple helical collagen molecule consists of about 1000 glycine, 360 prolines and 300 hydroxy prolines.

There are a number of different types of kidney stones, a common type is calcium oxalate stones. A genetic disorder affects oxalate levels and increases the risk of kidney stones. Hydroxyproline is a precursor to oxalate and some animal studies have shown consuming high levels of hydroxyproline will therefore increase oxalate level in the urine and therefore cause stones and kidney health issues. (19).

In short, if you are prone to kidney stones collagen supplements are probably best avoided.

8. What exactly is collagen?

Collagen is the most abundant protein in the human body, accounting for about 30% of the total protein mass. It provides structure to many parts of the body including skin, bones, ligaments and tendons.

  • Collagen fibres consist of three polypeptide chains called “ɑ chains” and are numbered with roman numerals.
  • They can be very large molecules ranging from 600 to over 3000 amino acids chains. Absorbing an enormous molecule of this size whole does not happen in the gut.
  • Certain collagen types are cleaved to release bioactive fragments. These fragments display biological activity in the body, which is an important part of how collagen supplements work.
  • The 5 most important collagen types in the body are:
    • Type I collagen: occurs widely and is found in connective tissue such as skin, bone and tendons.
    • Type II is solely found in cartilage
    • Type III collagen is age-related: 50% of young skin which declines to 5-10% with age
    • Collagen V
    • Collagen XI
  • Collagen is an elastic protein with a high resilience, meaning that it can be deformed and it will restore to its original shape. This is due to its shape and high number of bonds with other collagen molecules.
  • Sugar. (18) Collagens are long-lived proteins, but they are altered by glycation, which is the process of cross-linking with glucose molecules (a sort of caramelisation). When this happens they lose their flexibility and become stiff. That’s what happens when you eat too much processed sugar.

Collagen degradation / ageing and the MMP family.

Matrix metalloproteinases (“MMPs”) are a set of enzymes that break down collagen. This is a normal process in development and in the repair of damaged tissue. This is important because these enzymes are sensitive to the release of bioactive collagen fragments. This is how collagen supplements work as regards slowing down skin-ageing – they trick the body into thinking collagen is being broken down so the body produces more collagen.

Function of collagens in the body

Fibrillar collagens are the most abundant type in humans and they play an important structural role:

  • Tensile strength of skin
  • Traction in ligaments
  • Collagen VII – although it only makes up about 0.001% of the collagen in skin it is essential for holding the dermis and the epidermis together.
  • Collagen X is particularly important in bone development from cartilage.
  • A deformity in collagen XVIII is linked to chronic skin inflammation like eczema.

Other collagen types are found in the brain neurons, hippocampus and the nervous system.

Collagen deposits binding to B amyloid in the brain are a feature of Alzheimer’s disease.

Bioactive properties of collagen peptides

Collagens also interact with cells through a set of collagen receptors to exert certain functions.

  • Anti-tumour behaviour
  • Tissue repair
  • The amino acids glycine, proline and hydroxyproline are present in high concentrations

References:

  1. Effects of hydrolyzed collagen supplementation on skin aging: a systematic review and meta-analysis In J Dermatol 2021 March Miranda et al
  2. Oral Collagen Supplementation: A Systematic Review of Dermatological Applications J Drugs Dermatol 2019
  3. The Collagen Family Cold Spring Harb Perspect Biol 2011
  4. Collagen supplementation for skin health: A mechanistic systematic review Epub 2020
  5. Physiology and pathophysiology of matrix metalloproteases.Klein T, Bischoff R Amino Acids. 2011 Jul; 41(2):271-90.
  6. An overview of the beneficial effects of hydrolysed collagen intake on joint and bone health and on skin ageing Nutr Hospital 2015
  7. Functional Characterization of Undenatured Type II Collagen Supplements: Are They Interchangeable? J Dietary Supplement 2021
  8. B-Vitamins and Bone Health–A Review of the Current Evidence Nutrients 2015
  9. A Dermonutrient Containing Special Collagen Peptides Improves Skin Structure and Function: A Randomized, Placebo-Controlled, Triple-Blind Trial Using Confocal Laser Scanning Microscopy on the Cosmetic Effects and Tolerance of a Drinkable Collagen Supplement JMed Food 2020
  10. Oral Intake of Low-Molecular-Weight Collagen Peptide Improves Hydration, Elasticity, and Wrinkling in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study Nutrients 2018
  11. An overview of the beneficial effects of hydrolysed collagen intake on joint and bone health and on skin ageing Nutr Hospital 2015
  12. Effects of Collagen Peptides on Recovery Following Eccentric Exercise in Resistance-Trained Males-A Pilot Study In J Sport Nutr Exerc Metab 2020
  13. Effect of Branched-Chain Amino Acid Supplementation on Recovery Following Acute Eccentric Exercise Nutrients. 2018 .
  14. Impact of Varying Dosages of Fish Oil on Recovery and Soreness Following Eccentric Exercise Nutrients. 2020.
  15. Diet Supplementation with Fish-Derived Extracts Suppresses Diabetes and Modulates Intestinal Microbiome in a Murine Model of Diet-Induced Obesity Mar Drug 2021
  16. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. J Pharm Sci 2012
  17. Diet Supplementation with Fish-Derived Extracts Suppresses Diabetes and Modulates Intestinal Microbiome in a Murine Model of Diet-Induced Obesity Mar Drug 2021
  18. The effects of the Maillard reaction on the physical properties and cell interactions of collagen. Avery NC, Bailey AJ Pathol Biol (Paris). 2006 Sep; 54(7):387-95.
  19. Dietary hydroxyproline induced calcium oxalate lithiasis and associated renal injury in the porcine model J Endourol 2013