References

Avila Rodríguez MI, Rodríguez Barroso LG, Sánchez ML. Collagen: a review on its sources and potential cosmetic applications. J Cosmet Dermatol. 2018; 17:(1)20-26 https://doi.org/10.1111/jocd.12450

Bailey RL, Gahche JJ, Lentino CV Dietary supplement use in the United States, 2003–2006. J Nutr. 2011; 141:(2)261-266 https://doi.org/10.3945/jn.110.133025

Barati M, Jabbari M, Navekar R Collagen supplementation for skin health: a mechanistic systematic review. J Cosmet Dermatol. 2020; 19:(11)2820-2829 https://doi.org/10.1111/jocd.13435

Bauer J, Biolo G, Cederholm T Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J Am Med Dir Assoc. 2013; 14:(8)542-559 https://doi.org/10.1016/j.jamda.2013.05.021

Bolke L, Schlippe G, Gerß J, Voss W. A collagen supplement improves skin hydration, elasticity, roughness, and density: results of a randomized, placebo-controlled, blind study. Nutrients. 2019; 11:(10) https://doi.org/10.3390%2Fnu11102494

Borumand M, Sibilla S. Daily consumption of the collagen supplement Pure Gold Collagen® reduces visible signs of ageing. Clin Interv Ageing. 2014; 9:1747-1758 https://doi.org/10.2147%2FCIA.S65939

Burns EK, Perez-Sanchez A, Katta R. Risks of skin, hair, and nail supplements. Dermatol Pract Concept. 2020; 10:(4) https://doi.org/10.5826%2Fdpc.1004a89

Calleja-Agius J, Brincat M. The effect of menopause on the skin and other connective tissues. Gynecol Endocrinol. 2012; 28:(4)273-277 https://doi.org/10.3109/09513590.2011.613970

Chernoff R. Protein and older adults. J Am Coll Nutr. 2004; 23:627-630S https://doi.org/10.1080/07315724.2004.10719434

Choi FD, Sung CT, Juhasz ML, Mesinkovsk NA. Oral collagen supplementation: a systematic review of dermatological applications. J Drugs Dermatol. 2019; 18:(1)9-16

Czajka A, Kania EM, Genovese L, Corbo A, Merone G, Luci C, Sibilla S. Daily oral supplementation with collagen peptides combined with vitamins and other bioactive compounds improves skin elasticity and has a beneficial effect on joint and general wellbeing. Nutr Res. 2018; 57:97-108 https://doi.org/10.1016/j.nutres.2018.06.001

Davison-Kotler E, Marshall WS, García-Gareta E. Sources of collagen for biomaterials in skin wound healing. Bioengineering (Basel). 2019; 6:(3) https://doi.org/10.3390/bioengineering6030056

de Miranda RB, Weimer P, Rossi RC. Effects of hydrolyzed collagen supplementation on skin ageing: a systematic review and meta-analysis. Int J Dermatol. 2021; https://doi.org/10.1111/ijd.15518

Harris ED, Rayton JK, Balthrop JE, DiSilvestro RA, Garcia-de-Quevedo M. Copper and the synthesis of elastin and collagen. Ciba Found Symp. 1980; 79:163-182 https://doi.org/10.1002/9780470720622.ch9

Hexsel D, Zague V, Schunck M, Siega C, Camozzato FO, Oesser S. Oral supplementation with specific bioactive collagen peptides improves nail growth and reduces symptoms of brittle nails. J Cosmet Dermatol. 2017; 16:(4)520-526 https://doi.org/10.1111/jocd.12393

Inoue N, Sugihara F, Wang X. Ingestion of bioactive collagen hydrolysates enhance facial skin moisture and elasticity and reduce facial ageing signs in a randomised double-blind placebo-controlled clinical study. J Sci Food Agric. 2016; 96:(12)4077-4081 https://doi.org/10.1002/jsfa.7606

Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol. 2001; 15:(5)484-485 https://doi.org/10.1046/j.1468-3083.2001.00308.x

Katta R, Huang S. Skin, hair and nail supplements: an evidence-based approach. Skin Therapy Lett. 2019; 24:(5)7-13

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) https://doi.org/10.3390/nu10070826

León-López A, Morales-Peñaloza A, Martínez-Juárez VM, Vargas-Torres A, Zeugolis DI, Aguirre-Álvarez G. Hydrolyzed collagen—sources and applications. Molecules. 2019; 24:(22) https://doi.org/10.3390%2Fmolecules24224031

Lephart ED, Naftolin F. Menopause and the skin: old favorites and new innovations in cosmeceuticals for estrogen-deficient skin. Dermatol Ther (Heidelb). 2021; 11:(1)53-69 https://doi.org/10.1007/s13555-020-00468-7

Perez-Sanchez AC, Burns EK, Perez VM, Tantry EK, Prabhu S, Katta R. Safety concerns of skin, hair and nail supplements in retail stores. Cureus. 2020; 12:(7) https://doi.org/10.7759%2Fcureus.9477

PR Newswire. Global collagen supplement market (2021 to 2027)—by source, form and concentration. 2021. http://www.prnewswire.com/news-releases/global-collagen-supplement-market-2021-to-2027---by-source-form-and-concentration-301310968.html (accessed 24 August 2021)

Proksch E, Schunck M, Zague V, Segger D, Degwert J, Oesser S. Oral intake of specific bioactive collagen peptides reduces skin wrinkles and increases dermal matrix synthesis. Skin Pharmacol Physiol. 2014; 27:(3)113-119 https://doi.org/10.1159/000355523

Rees DC, Kelsey H, Richards JD. Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency. BMJ. 1993; 841-842 https://doi.org/10.1136%2Fbmj.306.6881.841

Sato K. The presence of food-derived collagen peptides in human body-structure and biological activity. Food Funct. 2017; 8:(12)4325-4330 https://doi.org/10.1039/c7fo01275f

US Food and Drug Administration. Dietary supplement labeling guide: chapter IV. Nutrition Labeling. 2005. http://www.fda.gov/food/dietary-supplements-guidance-documents-regulatory-information/dietary-supplement-labeling-guide-chapter-iv-nutrition-labeling (accessed 27 August 2021)

Collagen supplements: trend or truth for the treatment of ageing skin in menopausal women?

02 November 2021
Volume 10 · Issue 9

Abstract

In recent years, collagen drinks have become a popular supplement, which has been stimulating the appetites of collagen-conscious patients, due to their perceived health and beauty benefits. These beauty supplements are frequently promoted on social media and endorsed by celebrities for their glowing skin and the wrinkle-reducing results.

With collagen shots, powders, capsules, gels, gummy sweets, chocolates and coffee creamers filling shop shelves and advertised on social media channels, it may be challenging to avoid being swayed by all the hype. This article aims to help us explore the science behind the hype and if collagen supplements are safe and effective to take and why.

Consumable collagen supplements for health and beauty are fast gaining global popularity. The global beauty supplement market was valued at $3.5 billion in 2016, and it is projected to grow to $6.8 billion by the end of 2024, according to a report by Goldstein Research (PR Newswire, 2021).

Collagen supplements claim to reduce wrinkles and improve the skin's firmness, bounce and hydration, as well as being a key supplement for menopausal women. This is particularly attractive to perimenopausal women, who begin to notice changes in their skin when it becomes dull, dry and less firm, with more wrinkles. Other than chronological ageing, sun exposure, sugar consumption and smoking, one of the most significant factors influencing collagen breakdown in the skin is the decline in the hormone oestrogen (Calleja-Agius, 2012). Collagen deficit in the skin is associated with decreased attractiveness and psychological health and increased perception of ageing (Lephart, 2021). With this knowledge, it is understandable why collagen supplements have become so popular.

The benefits of collagen

Collagen is the most abundant protein in the body, and it is an essential component of every tissue. Known for its glue-like capacity, which holds the body together as connective tissue, it is aptly derived from the Greek word ‘kólla’, meaning glue.

Collagen types I, II and III are found in the extracellular matrix of the dermal layer of the skin, providing its strength and structure (Davison-Kotler et al, 2019). Collagen is a fibrilla protein, produced by fibroblast cells throughout the body. It is responsible for most of the connective and conjunctive tissues, such as skin, bones, joints and muscles, and it forms the matrix of the skin, giving it tensile strength, elasticity, bounce, glow, firmness and hydration.

Normally, the body synthesises its own endogenous collagen from protein-rich foods, such as meat, eggs, legumes, beans, dairy, fish and seafood. In its raw format, collagen is a tough, fibrous and insoluble protein, so it is broken down into shorter amino acid chains (peptides) in the stomach to be absorbed by the bloodstream and transported around the body.

During the body's ageing process, collagen in the skin starts to deplete faster than it can be replaced. Collapsed fibroblasts produce lower levels of collagen and higher levels of collagen-degrading enzymes. At around 25 years of age, collagen levels in the skin drop at a rate of 1% per year, but this speeds up to a grand loss of 30-50% during the menopause. Hence, the body's protein requirement increases with age, and older adults require more protein than younger adults to compensate for this collagen loss (Chernoff, 2004). The recommended dietary allowance (RDA) for protein is 0.8 g per kilogram of body weight for adults and 1.2 g per kilogram for the older population (Bauer, 2013).

Manufactured collagen

The nutraceutical industry's solution to the body's collagen deficit appears to be quite simple: replace the lost collagen with more collagen. The raw collagen material used within the nutraceuticals industry is derived from sustainable sources, such as discarded bovine bones and hide or marine sources, including fish skin and scales.

Collagen supplements can come in the form of powders, shots, capsules, gels, gummy sweets, chocolates and coffee creamers

Manufacturers break down this tough raw collagen material by a controlled enzymatic hydrolysis process to produce hydrolysed collagen, collagen hydrolysate or collagen peptides, the more bioactive form with a low molecular weight (León-López, 2019). In theory, these shorter or bioactive collagen peptides are then easily absorbed into the bloodstream through the gut wall of the small intestines, where the majority of nutrient absorption takes place. It is then transported and distributed throughout the body to influence cellular activity. For example, stimulating fibroblasts to make more hyaluronic acid to hydrate the skin. This theory is supported by a study that identified bioactive peptides in human blood, following ingestion of protein hydrolysates for a long period of time. The study concluded that this finding may consequently promote its beneficial effects in the body and skin (Sato, 2017).

Vitamins and minerals are added to the hydrolysed collagen to assist its efficacy within the fibroblast cells. For example, ascorbic acid or vitamin C assists in collagen synthesis. Additionally, the synthesis of elastin and collagen require the availability of copper (Harris et al, 1980).

Can ageing skin benefit from ingesting collagen supplements?

There are a limited number of clinical studies supporting the claims that consuming oral collagen supplements daily may boost collagen levels in the skin, reduce wrinkles and improve skin elasticity and hydration. Below is a summary of a double-blind, randomised, placebo-controlled clinical trial available and three literature reviews.

A study by Czajka et al (2018) demonstrated that consuming oral collagen peptides (combined with vitamins and other bioactive compounds) was effective for improving skin elasticity. Some 120 subjects consumed the test collagen product daily for 90 days, producing the following results:

  • A significant increase in skin elasticity, compared to the placebo (+40%; P<.0001)
  • Positive changes in the skin architecture, reduction in solar elastosis and improvement in collagen fibre organisation were seen in the histological analysis of skin biopsies
  • Subjects in the trial reported that their skin was more hydrated (Czajka et al, 2018).

There are three literature reviews looking at the effectiveness of collagen supplements and skin ageing, with all of the same inclusion criteria: randomised, placebo-controlled trials using collagen supplements in human subjects.

» Taken with consistency and caution, collagen supplements could improve skin elasticity and hydration and reduce wrinkles, but it cannot be determined exactly where these collagen peptides will be used within the body «

Choi et al (2019) reviewed 11 clinical trials, with 805 participants in total, and concluded that the outcome was positive for the use of oral collagen supplements (in the long and short term) for skin ageing, including increasing dermal collagen density, skin elasticity and hydration. Oral collagen supplements were also determined to be generally safe, with no reported adverse events. However, it was noted that further studies are required to elucidate optimal dosages for medical dermatological applications (Choi et al, 2019).

A second systematic review, which focused on the mechanisms of action and the effects of collagen supplements on skin health in healthy subjects, discovered 9057 relevant items, of which, only 10 publications met the inclusion criteria. The outcome of this review indicated that oral administration of hydrolysed collagen had skin health benefits, with no inconsistencies between studies. However, the authors did conclude that it is not possible to influence the body's decision about where the collagen is made or which tissues it affects (Barati, 2020).

The third systematic literature review included a meta-analysis to summarise the evidence of 19 studies involving 1125 subjects, 95% of whom were women, aged 20-70 years. Reports had to include at least one of the following outcomes: skin wrinkles, elasticity, hydration and/or firmness. Again, based on the results, the clinical findings were very positive, reinforcing that ingestion of hydrolysed collagen for 90 days is considered to be effective for skin ageing and improvement of hydration, elasticity and wrinkles (de Mirander et al, 2021)

Collagen brand-funded research to improve marketability

For the collagen supplements market, business is booming. However, in such a saturated arena, how can manufacturers stand out to the more discerning collagen supplement seekers? Several brands have produced their own clinical trials using their own version of hydrolysed bioactive collagen, with promising results.

Brand-funded clinical trials

Below, the results of clinical trials funded by collagen brands are summarised:

  • In Proksch et al's (2020) study, 114 middle-aged women took 2.5 g of VERISOL hydrolysed collagen type I daily for 8 weeks, which reduced wrinkle volume by 20% (Proksch et al, 2020)
  • Hexsel et al's (2017) study looked at VERISOL hydrolysed collagen type I for brittle nail syndrome. Some 25 human subjects took 2.5 g of VERISOL once a day for 24 weeks, which demonstrated increased nail growth, improved brittle nails and a notable decrease in the frequency of broken nails (Hexsel et al, 2017)
  • In Bolke et al's (2020) study, ELASTEN, a brand of hydrolysed collagen types I and II, was taken in 2.5 g doses by 72 women aged 35 years and over for 12 weeks. It reduced wrinkle depth by 27% and increased skin hydration by 28% (Bolke et al, 2020)
  • Borumand and Sibilla (2014) carried out an open label study to examine the effects of Pure Gold Collagen, a supplement of hydrolysed collagen, hyaluronic acid, vitamins and minerals. The subjects took 50 ml Pure Gold Collagen on a daily basis for 60 days. This led to a noticeable reduction in skin dryness, wrinkles and nasolabial fold depth. Additionally, a significant increase in collagen density and skin firmness was observed after 12 weeks (Borumand and Sibilla, 2014).

The disadvantages and potential dangers

Collagen supplements are not approved or regulated by the US Food and Drug Administration (FDA), and are treated as food supplements, rather than drugs (FDA, 2005). In the UK, collagen supplements fall under the Food Standards Authority (FSA), meaning that any company can bring dietary supplements to market without having to provide any evidence of its safety or efficacy. Vitamins, minerals, herbs and other substances may be added that have not been tested for their compatibility or interactions (Burns, 2020).

All current clinical trials have been conducted on relatively small numbers of healthy individuals. However, other health issues, such as underlying medical conditions, allergies, concurrent medications, differences in metabolism and any other variables that might have affected the results, were not taken into account. For example, for people with kidney disease, such nephrotic syndrome, taking excessive protein would not be safe.

Some of the safety issues with taking collagen supplements concern the vitamins and minerals that are routinely added to increase the supplement's efficacy, rather than the hydrolysed collagen itself. High doses of vitamins, such as vitamin C, B vitamins and zinc and selenium minerals, could lead to health complications in certain individuals (Burns, 2020). For example, high doses of ascorbic acid have also been associated with acute haemolysis in those with enzyme G6PD deficiency (Rees, 1993) and high doses of vitamins B6 and B12 have been associated with the development of rosacea fulminans (Jansen, 2001). The right dose in the right population may be beneficial, but to avoid any adverse side effects, all supplements should be evaluated for purity, potency, interactions, efficacy and safety (PPIES) (Katta, 2019).

As with all medications, it is not known whether taking medicinal amounts of collagen is safe during pregnancy or breastfeeding, and the risk of its teratogenicity leading to birth defects is unknown (Burns, 2020). Otherwise, reported side effects are transient and include a feeling of fullness, heartburn and bad taste in the mouth. All studies concluded that there were no harmful effects.

Conclusion

As with many nutritional trends, it is likely that the broad benefit of collagen supplements has been overstated in the media. More research, with larger trials, would be beneficial for collagen supplements' safety profile and scientific integrity. It is still unclear if the benefits found in the studies were specifically from a collagen supplement or whether eating a healthy diet with adequate protein would have achieved similar results.

Taken with consistency and caution, collagen supplements could improve skin elasticity and hydration and reduce wrinkles, but it cannot be determined exactly where these collagen peptides will be used within the body. While collagen supplementation may not be harmful, the additional vitamins and minerals could pose a health risk, especially if taken in addition to a healthy diet with other supplements or medicines or if underlying health conditions exist. With more research and regulation and post-sales surveillance, consumable collagen could become another viable weapon in our artillery against ageing.

Key points

  • Collagen is the most abundant protein in the body, forming most the connective tissues, such as the skin, bones, joints and muscles
  • Collagen supplements claim to improve the skin's firmness, bounce (elasticity) and hydration
  • Oestrogen loss during menopause has a significant impact on collagen production within the body
  • Collagen is a fibrous insoluble protein that needs to be hydrolysed and broken down into shorter peptide chains to become bioactive in the body
  • Collagen supplements are treated as food supplements rather than drugs, and, therefore, have less rigorous testing against their safety and efficacy profile.

CPD reflective questions

  • Where in the body are collagen supplements absorbed into the blood?
  • Which conditions are collagen supplements contraindicated for?
  • In the UK, which organisation regulates the collagen supplements industry?