Collagen Supplements: Powders, Liquids, Potions, & Scams

Fork U with Dr. Terry Simpson

Common Collagen Claims (taken from actual websites selling collagen supplements):

• “improves skin elasticity,”
• “support bone and joint health,”
• “strengthen hair, skin, and nails,”
• “may benefit the bodies cellular structure,”
• “support healthy skin, bone, and joints.”
• “will feed your skin health”
• “will improve nail appearance and strength”
• “lead to a noticeable hair thickness”

Collagen as a supplement is not regulated by the Drug division of The Food and Drug Administration

If you look at the bottom of the websites, or on the bottles, you will see a disclaimer that the claims “have not been evaluated by the U.S. Food and Drug Administration. ” More telling is “these products are not intended to treat, diagnose, cure, or prevent any disease.” Such a disclaimer is provided by the lawyers because if one claims to cure, treat, or diagnose an actual medical condition then it must have passed a rigorous FDA approval. To be clear, there have been no FDA studies that show collagen as a supplement treats any disease.

Supplements commonly will use “support xyz health” – where you can fill in the blank with hair, nails, joints, skin – in the case of collagen.

One of the main issues with supplements is “If the composition and quality of ingredients cannot be reliably ensured, the validity of research on dietary supplements is questionable. Moreover, the health of the US public is put at risk.”

Starr RR. Too little, too late: ineffective regulation of dietary supplements in the United States. Am J Public Health. 2015;105(3):478-485. doi:10.2105/AJPH.2014.302348

As such, even when you look at the studies which promote collagen, or collagen byproducts, they do not meet the most basic of studies which are done to evaluate pharmaceuticals. In order to have an evaluation of a pharmaceutical you must have three phases in the trial:

• phase one is determining the dose for safety. While the supplement industry is happy if you think all supplements are good and all pharmaceuticals are evil – everything, every drug, every chemical from water to salt to formaldehyde has a toxic dose
• phase two is to test the drug for efficacy and side effects. Some people will react poorly to a supplement just as they will a drug. WE need to know what those side effects are. With a supplement people who don’t feel well often just stop it – or, like my cousin, die (yes, I had a cousin who died from a supplement).
• phase three testing is to determine if there is truly efficacy, what is the effectiveness and what is the safety.
• phase four is post-marketing surveillance in the public because even though you have gone through trials with a number of phases and under strict supervision when a drug is released to the public you have the chance to see millions of reactions.

Thalidomide, for example, was released in Europe and even had two drug trials in the United States but was NEVER approved in the United States by the FDA because of insufficient data.

Vioxx was a drug used worldwide and was taken off the market in 2004 because of the risk of a fatal heart attack, but was taken off after it had passed multiple drug tests previously.

FDA testing is rigorous and specific, with the highest standards in the world. Collagen has NEVER had such rigorous testing performed. These tests have not risen to the level and in 2022 one report noted “More research is needed to establish knowledge of the effects and physiologic mechanism of collagen supplementation. Dermatologists should be aware of the unsubstantiated proclamations of collagen made by companies and in social media, as well as what evidence is established thus far, to be equipped to discuss collagen supplementation with patients.”

Rustad AM, Nickles MA, McKenney JE, Bilimoria SN, Lio PA. Myths and media in oral collagen supplementation for the skin, nails, and hair: A review. J Cosmet Dermatol. 2022 Feb;21(2):438-443. doi: 10.1111/jocd.14567. Epub 2021 Oct 25. PMID: 34694676.

One of the most quoted meta-analysis looked at 19 studies with 1125 participants – which is barely enough in any given study to make bold statements about safety, efficacy, toxicity, and side effects of hydrolyzed collagen supplementation.

de Miranda RB, Weimer P, Rossi RC. Effects of hydrolyzed collagen supplementation on skin aging: a systematic review and meta-analysis. Int J Dermatol. 2021 Dec;60(12):1449-1461. doi: 10.1111/ijd.15518. Epub 2021 Mar 20. PMID: 33742704.

So when someone states that study as the basis for use of the product, one has to have caution that there is not enough data, not enough rigorous data, and when studies do not include toxicity, this should be a major red flag.

Collagen is regulated by the Center for Food Safety and Applied Nutrition

Meaning, collagen, like most supplements, is regulated as a food, not as a drug. This is not the celebrated division that worked hard to get a COVID vaccine or anti-viral medications, this is the division that is responsible for food safety. This is the division of the FDA that is slow-moving, filled with bureaucracy, and has not even responded in a timely manner to any of the recent bacterial contaminations of our food. Take the spinach contamination, where people across ten states became ill, by the time the FDA came out with a recall the shelf life for that spinach was long overdue.

The same division tasked with reducing salt in our diets, but fears industry so much that no regulations have been put into place.

This is the same division that does not have leadership, budget, or inspectors to police our food supply.

The only time the FDA has become involved in any supplements is when a proven threat to the public has been discovered, or if someone complains that a claim made by the company alleges to “treat a disease.” Which is why collagen manufacturers make the claims above.

The undisputed science of collagen

Collagen is the main protein that forms the connective tissue of our body: skin, muscles, tendons, bones, blood vessels, even our heart valves. There have been 28 different types of collagen identified in humans, but over 90% of the collagen is called “Type 1.” Type 1 collagen is a huge molecule with thousands of amino acids, and coded for by over 40 genes. Two chains are formed from the translation and these polypeptide chains are assembled, cut, arranged, glycosylated, and packaged in different parts of a cell called a fibroblast and then transported out of the cell where it is further trimmed, combined with other molecules of collagen and begins to form and reform and cross-link with other collagen molecules.

Gauza-Włodarczyk M, Kubisz L, Włodarczyk D. Amino acid composition in determination of collagen origin and assessment of physical factors effects. Int J Biol Macromol. 2017 Nov;104(Pt A):987-991. doi: 10.1016/j.ijbiomac.2017.07.013. Epub 2017 Jul 4. PMID: 28687386.

Brodsky B, Persikov AV. Molecular structure of the collagen triple helix. Adv Protein Chem. 2005;70:301-39. doi: 10.1016/S0065-3233(05)70009-7. PMID: 15837519.

Hulmes DJ. Building collagen molecules, fibrils, and suprafibrillar structures. J Struct Biol. 2002 Jan-Feb;137(1-2):2-10. doi: 10.1006/jsbi.2002.4450. PMID: 12064927.

In order to form in an orderly manner and to be strong, it must link with other collagen molecules in an organized manner and needing the help of Vitamin C to do this. Without vitamin C, the collagen doesn’t have strength and everywhere you have collagen you will suffer. Scurvy, the old name for Vitamin C deficiency, leads to loss of teach, wounds that come open again, blood vessels that break under the skin.

Peterkofsky B. Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. Am J Clin Nutr. 1991 Dec;54(6 Suppl):1135S-1140S. doi: 10.1093/ajcn/54.6.1135s. PMID: 1720597.

Orgel JP, Irving TC, Miller A, Wess TJ. Microfibrillar structure of type I collagen in situ. Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9001-5. doi: 10.1073/pnas.0502718103. Epub 2006 Jun 2. PMID: 16751282; PMCID: PMC1473175.

While collagen contains 19 amino acids, 17% of the amino acids are proline, and glycine is found usually in every third amino acid. Some of the amino acids are modified to others after the collagen has been formed, for example, hydroxyproline is derived from proline and hydroxylysine from lysine – and both of these require Vitamin C to assist in that modification.

What happens when you eat, drink, or otherwise consume collagen

Let’s say you eat some chicken skin that is rich in collagen, or you buy liquid collagen, or collagen peptides (short chains of amino acids bonded together).

The large molecule of collagen is broken down starting with the teeth, the enzymes in the mouth, the acid in the stomach as well as the enzymes in the stomach. Once these byproducts reach the small bowel they are further broken down by the pancreatic and bile from the liver into small chains of 2-3 amino acids. The small bowel can transport simple amino acids, as well as dipeptides (two amino acids bonded together) or tri-peptides (three amino acids bonded together) into the portal circulation. Through the portal system, even some five peptide units have been found. These amino acids are not passively absorbed, but rather actively transported by membrane proteins found on the brush borders of the small intestine designed just to transport amino acids.

Kleinnijenhuis AJ, van Holthoon FL, Maathuis AJH, Vanhoecke B, Prawitt J, Wauquier F, Wittrant Y. Non-targeted and targeted analysis of collagen hydrolysates during the course of digestion and absorption. Anal Bioanal Chem. 2020 Feb;412(4):973-982. doi: 10.1007/s00216-019-02323-x. Epub 2019 Dec 24. PMID: 31872275; PMCID: PMC7005076.

The first part of the small intestine is responsible for about 96 percent of the absorption of amino acids.

A number of non-digested collagen has been recovered in stool, or has been found to be metabolized by bacteria in the large intestine where they have been used by the gut microbiome as prebiotics, and may exert an influence on the body in that manner.

Larder CE, Iskandar MM, Kubow S. Gastrointestinal Digestion Model Assessment of Peptide Diversity and Microbial Fermentation Products of Collagen Hydrolysates. Nutrients. 2021;13(8):2720. Published 2021 Aug 7. doi:10.3390/nu13082720

That 57% of amino acids in collagen are hydroxyproline, glycine and proline. Hydroxy-proline is not actively transported across into the portal system, rather it is passively absorbed depending upon the concentration. While hydroxyproline is used in the synthesis of collagen, if there is an excess of this in the bloodstream it is filtered out through the kidneys. The synthesis of collagen typically takes proline to and once the molecule is formed will alter into the hydroxyproline. Meaning hydroxy-proline offers no benefit to the building of collagen in the human body.

Hueckel HJ, Rogers QR. Prolylhydroxyproline absorption in hamsters. Can J Biochem. 1972 Jul;50(7):782-90. doi: 10.1139/o72-109. PMID: 5050935.

Li P, Wu G. Roles of dietary glycine, proline, and hydroxyproline in collagen synthesis and animal growth. Amino Acids. 2018 Jan;50(1):29-38. doi: 10.1007/s00726-017-2490-6. Epub 2017 Sep 20. PMID: 28929384.

In summary: most of the collagen is broken down into amino acids or multiples of amino acids which are either transported or passively absorbed into the body. While food intake will briefly increase blood levels of amino acids, excess amino acids are oxidized and excreted into the urine.

Bröer S, Bröer A. Amino acid homeostasis and signaling in mammalian cells and organisms. Biochem J. 2017 May 25;474(12):1935-1963. doi: 10.1042/BCJ20160822. PMID: 28546457; PMCID: PMC5444488.

The ability of people to absorb and use dietary protein-derived amino acids for muscle protein synthesis is not impaired in healthy older men. Further studies showed that supplementation with whey protein brought greater increases in muscle protein synthesis and supported skeletal muscle retention more than collagen proteins.

Oikawa SY, Kamal MJ, Webb EK, McGlory C, Baker SK, Phillips SM. Whey protein but not collagen peptides stimulate acute and longer-term muscle protein synthesis with and without resistance exercise in healthy older women: a randomized controlled trial.

Am J Clin Nutr. 2020 Mar 1;111(3):708-718. doi: 10.1093/ajcn/nqz332. Erratum in: Am J Clin Nutr. 2020 Dec 10;112(6):1656. PMID: 31919527; PMCID: PMC7049534.

Does taking collagen supplements increase collagen synthesis, change hydration, or improve elasticity

Since collagen makes up 80 percent of our skin and with another protein, elastin, provides the elasticity of our skin. Does the absorption of collagen peptides increase collagen synthesis in some people?

In one non-blinded study of older adults in convalescent rehabilitation wards in Japan, the study did not study trans epidermal water loss, nor did they have a control group of the oral supplementation without collagen. The skin tears during the study were less, but this did not continue after the study. The oral supplementation not only included collagen peptides but other ingredients, such as vitamin C, Vitamin A, biotin, as well as other amino acids. Yet this study is often cited as proof that collagen supplementation works.

Nomoto T, Iizaka S. Effect of an Oral Nutrition Supplement Containing Collagen Peptides on Stratum Corneum Hydration and Skin Elasticity in Hospitalized Older Adults: A Multicenter Open-label Randomized Controlled Study. Adv Skin Wound Care. 2020;33(4):186-191. doi:10.1097/01.ASW.0000655492.40898.55

While aging does decrease collagen, it appears to be less a function of collagen synthesis and more a function of collagen breakdown by specific enzymes. There are clinically proven treatments to prevent this such as topical retinoic acid, laser resurfacing, and intradermal injection of cross-linked hyaluronic acid, that increase production of new collagen. However, ingestion of oral collagen supplements does not appear to make a difference.

Fisher GJ, Varani J, Voorhees JJ. Looking older: fibroblast collapse and therapeutic implications. Arch Dermatol. 2008 May;144(5):666-72. doi: 10.1001/archderm.144.5.666. PMID: 18490597; PMCID: PMC2887041.

Szoka L, Karna E, Hlebowicz-Sarat K, Karaszewski J, Palka JA. Exogenous proline stimulates type I collagen and HIF-1α expression and the process is attenuated by glutamine in human skin fibroblasts. Mol Cell Biochem. 2017 Nov;435(1-2):197-206. doi: 10.1007/s11010-017-3069-y. Epub 2017 May 19. PMID: 28526934; PMCID: PMC5632346.

In tissue culture (meaning, cells grown in a laboratory) the fibroblast cell is the cell responsible for collagen synthesis. It has been noted that higher levels of proline-hydroxyproline increased the synthesis of collagen. This does NOT indicate that if you take collagen, of which this dipeptide will be absorbed, that you will increase collagen synthesis. It probably is reasonable to assume that as collagen is broken down (something that happens in wounds, scar tissue, injury to tissue, or normal aging), that the breakdown products of that collagen would turn on both synthesis of collagen by fibroblasts, as well as stimulate more fibroblasts to come into the area. The level of hydroxyproline in the blood is stable, and excess hydroxyproline is excreted by the kidney.

That this dipeptide is carefully excreted when in excess makes sense from a feedback loop perspective. It is not helpful to a body to increase the production of collagen constantly. Thus the body would tightly regulate stimulation by the dipeptide. In other words, the excess collagen, or peptide you take, will be excreted into the skin, or not absorbed at all and sent to feed the colonic bacteria.

Ohara H, Ichikawa S, Matsumoto H, Akiyama M, Fujimoto N, Kobayashi T, Tajima S. Collagen-derived dipeptide, proline-hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblasts. J Dermatol. 2010 Apr;37(4):330-8. doi: 10.1111/j.1346-8138.2010.00827.x. PMID: 20507402.

Scientists from a Korean cosmetic company published a paper where skin moisture increased by 7.3% when given peptides from fish collagen. While this may not appear to be much of a change, it is worth noting that the change comes not from the collagen in the stratum corneum of the skin (which is the final layer of dead skin cells that serve to protect underlying tissue) by increasing something called natural moisturizing factor (this have hydrophilic amino acids) and provide a water gradient for the stratum corneum. In addition, the skin lipids, ceramides, form a permeability barrier which, when there is a loss of these two, leads to dry skin and increased transepidermal water loss.

Jung K, Kim SH, Joo KM, et al. Oral Intake of Enzymatically Decomposed AP Collagen Peptides Improves Skin Moisture and Ceramide and Natural Moisturizing Factor Contents in the Stratum Corneum. Nutrients. 2021;13(12):4372. Published 2021 Dec 6. doi:10.3390/nu13124372

This is similar to other industry studies showing that peptides derived from a Korean catfish provide increased moisture to the skin in a small sample of only 53 participants between the two groups. This is, in fact, the Achilles heel of all randomized studies involving collagen and its efficacy, a low number of individuals in all the studies performed to date.

Kim DU, Chung HC, Choi J, Sakai Y, Lee BY. 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;10(7):826. Published 2018 Jun 26. doi:10.3390/nu10070826

There have been a number of industry-sponsored studies showing beneficial effects of the hydrolysates with the addition of vitamin A, C, and other ingredients against a placebo. Amino acid supplements appear to improve skin, regardless of their origin.

We don’t know, but many will claim we do

The low quality of studies, most funded by industry, and the basic science, make it skeptical at best to look at collagen supplements for their role in skin, hair, nails, and other growth. Probably best summed up by the article from

Rustad AM, Nickles MA, McKenney JE, Bilimoria SN, Lio PA. Myths and media in oral collagen supplementation for the skin, nails, and hair: A review. J Cosmet Dermatol. 2022 Feb;21(2):438-443. doi: 10.1111/jocd.14567. Epub 2021 Oct 25. PMID: 34694676.

In their conclusion: “Although some studies have demonstrated that collagen supplementation can enhance skin qualities such as elasticity and hydration, dermatologic claims in the media surpass any evidence currently supported by the literature.” They went on to say, “More research is needed to establish knowledge of the effects and physiologic mechanism of collagen supplementation. Dermatologists should be aware of the unsubstantiated proclamations of collagen made by companies and in social media, as well as what evidence is established thus far, to be equipped to discuss collagen supplementation with patients.”

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