Do collagen supplements really work?

The evidence suggests, yes.


Nutritionist Kay Ali explores the research behind collagen supplements for skin

There’s no denying how important collagen is for skin health. It’s the most abundant protein in our bodies, providing stability, structure and strength in various tissues like teeth, tendons and ligaments. It is especially the case in the dermal layers of our skin.[1],[2] Unfortunately, as we age the deposition of collagen decreases, starting as early as our 20s. Photo-ageing from excessive sun exposure speeds up the degradation process too.[3] The result is dermal damage and premature wrinkles on the skin.[4] While the cosmetic industry offers plentiful lotions that aim to enhance collagen and our youthful appearance; the pharmaceutical and supplement industry promote collagen potions that aim to do the same from within. Yet, despite an insatiable appetite for collagen supplements from consumers driving a global growth worth 3.7 billion USD (estimated to double by 2025), skepticism remains.[5] At least here in the UK. Do collagen supplements really work? And if so, where’s the evidence? Since formulating Beauty Pie’s Collagen Super Powder, these are the two most frequently asked questions I get every week. I’m finally answering them.


The big problem with sharing researched Collagen health claims


But first, there’s a huge elephant in the room that needs addressing. Regulatory compliant health claims A.K.A the laws that govern what brands can and can’t say about a supplement they sell. In the UK we’re regulated by the European Food Safety Authority. It reviews the scientific data and tells us what we can and can’t say about a given ingredient and its effects on our health. The Advertising Standards Agency and Trading Standards then police brand compliance. Sounds pretty sensible, right? The only problem is EFSA are overwhelmed and there’s a huge lag between new research and approved claims. Let me explain.


Since EFSA’s attempt to clean up the framework of health claims on supplements in the early 2000s, it’s only got around to updating the data on vitamins, minerals and a few other actives such as Omega 3. Most food compounds and herbs are yet to be updated, which means that there aren’t yet any legally compliant health claims that can be made in the UK for most active ingredients. They’re officially “on hold”. This goes for making gut, brain or immune health claims on probiotics; anti-inflammatory claims on turmeric as well as anti-ageing claims on collagen too.


So what does this mean for you? In short, brands that are behaving cannot talk about any research that proves efficacy of an ingredient in their supplement if it’s not yet been updated by EFSA. This makes shopping for high performance supplements for the average consumer challenging; not to mention transparency from brands. If they can’t talk about it, how do we know what to take and which works best? For example, whilst I sourced marine peptides for Collagen Super Powder from a Randomised Double Blind Placebo Controlled human study to help inform possible results for consumers, Beauty Pie can’t discuss the results in the UK. Pretty bonkers, I know. Of course, I appreciate the intention and need for a robust legal framework for brands to operate within that places consumer safety at the forefront. However, the reality of the current circumstance is that the deafening educational silence from trustworthy brands that are patiently waiting for EFSA to update their permitted health claims, leaves room for speculation and false information to dominate the market. This is as equally concerning.


Limitations with Supplement Science


Thankfully as a practitioner, I can dive into the available research and discuss studies that demonstrate collagen supplements work. Of course, there are some necessary acknowledgements that come with critically appraising the research. As far as design methods go and their reliability, there’s definitely a hierarchy. At the bottom are anecdotal reports. This is what your best friend, neighbour and great, great aunt swear they’ve noticed since taking collagen; testimonials of skin, hair and nail benefits are available in droves. Next up are cell culture studies A.K.A in vitro, followed by animal studies. Of course, the best and most reliable design methods are human trials of which Randomised Double Blind Placebo Controlled on a large scale are considered the gold standard. There is evidence that suggest collagen supplements work across the entire hierarchy, which I’m going to guide you through. However, there’s also the not so small issue of limitations from funding and bias that dominate biomedical research. The harsh truth is, supplement studies differ to skincare or drug therapy in that there isn’t much money to be made investing into a well-designed large scale study into a natural ingredient that cannot be patented. As a result, funding typically comes from brands or suppliers who are invested in understanding how their ingredient works. The pay-off is bias and most likely a small scale design due to limited funds. No, it’s not great, but it is what it is.


Collagen Sources and Biomedical claims


Kay Ali formulates Beauty Pie's Collagen Super Powder

Most collagen supplements are derived from bovine, porcine, human and marine organisms such as fish scales and fish skin.[6] There are also synthetic sources of collagen that are commercially known as ‘KOD’.[7]They are typically produced from mammalian, insect, yeast and plant cell cultures.[8] Whilst, I’m not going to focus on the ins and outs of each type of collagen explored in each of the studies we’re looking at, I do want to emphasise that marine sources are preferential to other sources of collagen due to their lower molecular weight and thereby better absorption, negligible biological contaminants such as toxins, and low inflammatory effects.[9],[10]


You might be surprised to learn that there are actually multiple beneficial biological properties of hydrolysed collagen that have been documented that go beyond skin health. These include antioxidant, antihypertensive and lipid-lowering activities.[11],[12],[13],[14] As far as its reparative actions on the skin goes they’re twofold; firstly, it provides the building block for collagen (and elastin) and, secondly, it binds receptors in fibroblasts located in the dermal layers to stimulate synthesis of collagen, elastin and hyaluronic acid. [15],[16],[17],[18]


A closer look at the evidence


In vitro studies: collagen enhances fibroblast and extracellular matrix proteins and decrease collagen cleaving metalloproteinases (MMPs).


In Vitro collagen studies

Several in vitro studies report collagen enhances fibroblast activities, increases collagen levels to improve collagen’s structural properties, and inhibits collagen destructing MMPs. [19],[20],[21],[22]


In 2018, Zague et al. reported that collagen peptides manage the metabolism of extracellular matrix proteins by human dermal fibroblasts that were derived from sun-protected and sun-exposed body sites.[23] The in vitro collagen hydrolysate treatment increased the dermal matrix precursors along with procollagen type I and collagen type I proteins. The increased levels of collagen were attributed to enhanced biosynthesis of collagens by fibroblasts but also decreased collagen type I metabolism through the inhibition of metalloproteinases (MMP 1 and MMP 2) activities. [24] Remember, the latter are proteins that breakdown collagen. The researchers concluded that supplement-derived collagen hydrolysates improved skin cells and dermal health by enhancing collagen production and inhibiting the enzymes that break it down.

As promising as these test-tube results might seem, it presumes two potentially prohibiting factors.

  1. Collagen is absorbed and

  2. It is distributed to the skin where it can carry out the aforementioned actions.

Thankfully, there is evidence that demonstrates feasibility of both.


Animal studies: Absorption, Distribution into the Bloodstream, and Deposition into the Skin and improvement in skin parameters



Nutritionist Kay Ali with Beauty Pie Collagen Super Powder



Generally speaking, it’s understood that collagens are hydrolyzed into amino acids in the gastrointestinal tract (GI) prior to being absorbed into the blood circulation. However, increasing evidence suggests that collagen peptides (i.e. pre-hydrolysed) might also be absorbed directly. [25],[26]


  • In 1999, Oesser et al., showed that when mice were fed a 14C-labeled gelatin hydrolysate, more than 90% of the radioactive tracer was absorbed by the GI tract after 6 h and, at 12 h, the radioactivity reached maximal values in the skin while more than 85% of the radioactivity disappeared from the blood plasma after 24 h.[27] This report showed that peptides with molecular weights ranging from 1 to 10 kDa were absorbed in the GI tract, transferred to the blood, and deposited into cartilage. [28]


  • In 2006, nine healthy piglets were orally administered porcine skin-derived collagen hydrolysate (0.2g/kg body weight) with a molecular weight range of 3 to 5 kDa for 62 days.[29] Compared to the control group, oral ingestion of collagen hydrolysate resulted in significant increases in both the diameter and density of the collagen fibrils, which suggests that the mechanical properties improved. [30]


  • In 2009, Tanka et al. examined the daily administration of collagen peptides (0.2 g/kg body weight) prepared from fish scales on skin damaged by repeated exposure to UV radiation (VU-B, 03. mW/cm2) for six weeks in six-week-old hairless mice.[31] The oral collagen treatment suppressed the UV-B-induced decreases in skin hydration, hyperplasia of the epidermis, and the decreased levels of collagen type I in the skin of the mice. [32]


  • In 2010, Watanabe-Kamiyama et al. tested the administration of 288 mg of chicken feet collagen hydrolysate at 800 Da, containing Gly-[14C]Pro-Hyp and [14C]Pro as radioactive tracers in mice.[33] The radioactivity in the plasma reached a maximal value at 3 h after oral administration along with peak values in the skin at the same time interval. After 14 days of administering this treatment, 70% of the radioactivity was found in the skin while, for the most part, other tissues such as the liver, kidney, spleen, brain, and muscle show decreased radioactivity. [34]


  • In 2011, Zague et al. examined how oral collagen hydrolysate administration increased skin collagen expression while, at the same time, it suppressed the activity of the matrix metalloproteinase enzyme (MMP 2) in Wistar rats.[35] The authors suggested that oral collagen hydrolysate administration may reduce skin aging in other mammals.


  • In 2012, Okawa et al. showed that the oral administration of collagen tripeptide improves dryness and pruritus in the acetone-induced dry skin model in mice.[36] The oral administration of collagen peptides (80 or 500 mg/kg body weight/day) for three days in mice significantly decreased trans-epidermal water loss, suppressed scratching behavior, and normalized axon-guidance factors in the epidermis in addition to reducing pruritus.[37]


  • In 2017, Song et al. examined the effects of collagen hydrolysates from sliver carp skin on UV-induced photo-aging in mice and found that lower molecular weight peptides exerted beneficial effects when compared to high molecular weight collagen hydrolysates on hyaluronic acid levels and moisture content of the skin.[38]


  • In 2017, Chen et al. tested the effect of early enteral nutrition supplemented with Alaska pollock skin-derived collagen peptides on post-burn inflammatory responses in mice.[39] The supplemental treatment decreased NF-κB and TNF-α and IL-6 levels (these are inflammatory markers), which suggests that the immune-nutrient supplement may improve post-burn outcomes in burn patients. [40]


Of course, the body of evidence I’ve listed presupposes that we digest, metabolise and distribute collagen peptides the same as rats and piglets. Thankfully, much of these results have been replicated in human trials, bridging the gap of any remaining doubt of relevance from these studies for humans. What we know for sure, is the lower the molecular weight of collagen, the better it’s absorbed.


Collagen supplementation Improves Skin Parameters in Human Studies


Human clinical trials: Benefits of Collagen supplements for skin

  • In 2005, Iwai et al. found that healthy human volunteers who ingested 9–23 g of hydrolysates from porcine skin, chicken feet, and cartilage after 12 h of fasting displayed a maximal concentration of 20–60 nmol/mL in plasma 1 to 2 h after ingestion, which was reduced to half the maximal values at 4 h after ingestion.[41] The porcine skin and chicken feet consisted of collagen type I while the chicken cartilage was collagen type II. [42]


  • In 2006, Matsumoto et al. investigated the effects of daily intake of 7 g of commercially available collagen hydrolysate containing 5 g of fish type I collagen hydrolysates on skin parameters of 25 Japanese female subjects (35 ± 5 years of age) who had dry and rough skin in the winter.[43] After six weeks of treatment, the moisture content of the stratum corneum (face-cheek, forearm, and the back of the neck) increased along with improvement in the pliability and elasticity of the skin, which resulted in greater smoothness, fewer wrinkles, and less skin roughness. [44]


  • In 2007, Ohara et al., in a single-blind crossover study examined five healthy volunteers (33 + 6 years old) who ingested type I collagen hydrolysates (0.385 g/kg body weight) with an average molecular weight of 5 kDa from fish scales, fish skins, and porcine skins after fasting for 12 h.[45] Within 24 h after ingestion, the different hydroxyproline containing peptides in human blood were quantified where fish scales > porcine skins ≥ fish skins, which suggests that the source of collagen provide clues about how these molecules are absorbed and transported into blood.[46]


  • In 2014, Proksch et al. conducted a double-blind, placebo-controlled trial examining 69 women aged 35 to 55 years of age that were randomized and received 2.5 or 5.0 g of collagen peptides or placebo once daily for eight weeks (n = 23 subjects per group).[47] At the end of the study, skin elasticity in both collagen groups significantly improved over the placebo group while skin moisture also improved in the collagen groups but did not reach significance over placebo levels. This suggests that oral supplementation of collagen peptides has beneficial effects on skin physiology. [48]


  • Additionally, in 2014, Proksch et al. examined the influence of a specific bioactive collagen peptide in 114 women aged 45 to 65 years of age that were randomized to receive 2.5 g collagen or placebo (n = 57 subjects per group) once daily for eight weeks.[49] By suction blister biopsies, a variety of skin parameters were analyzed. With the ingestion of collagen, at four and eight weeks, a significant reduction in eye wrinkle volume occurred and, at eight weeks, significantly higher procollagen type I and elastin levels were quantified, which suggests that oral administration of collagen peptides reduced skin wrinkles and skin aging. [50]


  • In 2015, Asserin et al. (psst… this is where the peptides in Collagen Super Powder are sourced from) used two placebo-controlled clinical trials to assess the effect of daily oral supplementation with collagen peptides on skin hydration and collagen density in volunteers.[51] After four weeks of supplementation, dermal collagen deposition significantly increased and, by eight weeks, skin hydration significantly increased. Both enhanced skin parameters persisted after 12 weeks and the ex vivo results showed that collagen peptides induced collagen as well as glycosaminoglycan production. [52]


  • In 2017, Yazaki et al. examined the oral ingestion of collagen hydrolysates in humans (and mice) where the tripeptide collagen was transported into blood with particularly enriched Gly-Pro-Hyp levels that were then deposited into the skin with enriched Pro-Hyp concentrations presumably after hydrolysis.[53]


  • In 2017, Hakuta et al. conducted a clinical study of seventeen patients with atopic dermatitis who were randomly assigned to receive a daily (for 12 weeks) 3.9 g of either collagen tripeptide or normal collagen peptides and each subject served as their own control.[54] When their keratinocytes were analyzed, several inflammatory biomarkers were reduced and, in the 13 subjects that completed the study, trans-epidermal water loss was significantly reduced, but the blood parameters were not improved in either treatment group.[55]


  • In 2017, Hexsel et al. performed a clinical study in which they examined an open label, single-center trial of 25 participants who took 2.5 g of collagen once daily for 24 weeks followed by a four-week off-therapy period to determine if nail growth and nail health was influenced by the oral collagen treatment.[56] The collagen treatment increased nail growth by 12% and decreased the frequency of broken nails by 42%. A majority of the participants (80%) agreed that the collagen supplement improved their nails’ appearance. [57]


Suffice to say, there is an abundance of pre-clinical and clinical reports that provide evidence for collagen hydrolysate supplementation and its supporting benefits for dermal health. For sure, there is opportunity to replicate results in human studies on a much bigger scale. However, even with the small scale human trials that are available, when reviewed in context of the overwhelming volume of positive testimonials consumers report, it is no longer a question of whether collagen supplements work. They clearly do. Rather, it's our understanding of how they work that needs further research and development.


Disclaimer: The statements made in this blog post are for educational and entertainment purposes only. They are not intended to diagnose or treat any individual or condition. If you are concerned about your health please consult your licensed medical doctor before changing your diet or taking supplements. This website uses affiliate links, which means the author may earn from products and services recommended although it should be noted that this is not at an additional cost to the consumer.


References

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Avila Rodríguez MI, Rodríguez Barroso LG, Sánchez ML.J Cosmet Dermatol. 2018 Feb; 17(1):20-26. [7] Collagen and gelatin. Liu D, Nikoo M, Boran G, Zhou P, Regenstein JM. Annu Rev Food Sci Technol. 2015; 6():527-57. [8] Collagen: A review on its sources and potential cosmetic applications. Avila Rodríguez MI, Rodríguez Barroso LG, Sánchez ML.J Cosmet Dermatol. 2018 Feb; 17(1):20-26. [9] Collagen: A review on its sources and potential cosmetic applications. Avila Rodríguez MI, Rodríguez Barroso LG, Sánchez ML.J Cosmet Dermatol. 2018 Feb; 17(1):20-26. [10] Collagen and gelatin. Liu D, Nikoo M, Boran G, Zhou P, Regenstein JM. Annu Rev Food Sci Technol. 2015; 6():527-57. [11] Farage M.A., Miller K.W., Elsner P., Maibach H.I. Degenerative Changes in Aging Skin. In: Farage M.A., Miller K.W., Maibach H.I., editors. Textbook of Skin Aging. Springer; Berlin/Heidelberg, Germany: 2017. pp. 15–30 [12] Skin ageing. Kohl E, Steinbauer J, Landthaler M, Szeimies RM. 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Asserin J, Lati E, Shioya T, Prawitt J. J Cosmet Dermatol. 2015 Dec; 14(4):291-301. [52] The effect of oral collagen peptide supplementation on skin moisture and the dermal collagen network: evidence from an ex vivo model and randomized, placebo-controlled clinical trials. Asserin J, Lati E, Shioya T, Prawitt J. J Cosmet Dermatol. 2015 Dec; 14(4):291-301. [53] Oral Ingestion of Collagen Hydrolysate Leads to the Transportation of Highly Concentrated Gly-Pro-Hyp and Its Hydrolyzed Form of Pro-Hyp into the Bloodstream and Skin. Yazaki M, Ito Y, Yamada M, Goulas S, Teramoto S, Nakaya MA, Ohno S, Yamaguchi K. J Agric Food Chem. 2017 Mar 22; 65(11):2315-2322. [54] Anti-inflammatory effect of collagen tripeptide in atopic dermatitis. Hakuta A, Yamaguchi Y, Okawa T, Yamamoto S, Sakai Y, Aihara M. J Dermatol Sci. 2017 Dec; 88(3):357-364. [55] Anti-inflammatory effect of collagen tripeptide in atopic dermatitis. Hakuta A, Yamaguchi Y, Okawa T, Yamamoto S, Sakai Y, Aihara M. J Dermatol Sci. 2017 Dec; 88(3):357-364. [56] Oral supplementation with specific bioactive collagen peptides improves nail growth and reduces symptoms of brittle nails. Hexsel D, Zague V, Schunck M, Siega C, Camozzato FO, Oesser S. J Cosmet Dermatol. 2017 Dec; 16(4):520-526. [57] Oral supplementation with specific bioactive collagen peptides improves nail growth and reduces symptoms of brittle nails. Hexsel D, Zague V, Schunck M, Siega C, Camozzato FO, Oesser S. J Cosmet Dermatol. 2017 Dec; 16(4):520-526.