Received: 22 October 2018 | Revised: 13 April 2019 | Accepted: 23 July 2019 DOI: 10.1111/jocd.13096 C O S M E T I C C O M M E N TA RY Oral collagen supplementation for skin aging: A fad or the future? Nikita Jhawar BS1 | Jordan V. Wang MD, MBE, MBA2 | Nazanin Saedi MD2 1 Drexel University College of Medicine, Philadelphia, Pennsylvania Abstract 2 Department of Dermatology and In recent years, oral collagen supplements have become a popular and trendy treat‐ Cutaneous Biology, Thomas Jefferson ment in the world of skin health. It has been widely marketed to consumers for pur‐ University, Philadelphia, Pennsylvania ported benefits in wrinkle reduction, skin‐rejuvenation, skin‐aging reversal, and skin Correspondence plumping. However, there are currently limited data available in the literature and Jordan V. Wang, Department of Dermatology and Cutaneous Biology, much regarding its possible effects on the skin has yet to be fully elucidated and Thomas Jefferson University, 833 Chestnut understood. Here, we summarize some of the prominent studies in the literature and Street, Suite 740, Philadelphia, PA 19107. Email: firstname.lastname@example.org offer an evaluation of oral collagen supplementation for skin health. KEYWORDS aesthetics, aging, collagen, collagen supplements, dermatology 1 | I NTRO D U C TI O N stronger collagen fibrils, and increase water content of the stratum corneum. 2 Aging of the skin is a degenerative process driven by a decline in In recent years, oral collagen supplementation has become ex‐ physiological function. While it is partially intrinsic, extrinsic factors, tremely popular as it has been increasingly marketed to consumers such as pollution, sun exposure, and lifestyle can increase oxidation as an anti‐aging remedy. Purported benefits include wrinkle re‐ levels and contribute to chronic inflammation, which can acceler‐ duction, skin‐rejuvenation, skin‐aging reversal, and skin plumping. ate aging processes.1 Lifestyle factors can include nutritional and However, the data behind these claims are not particularly robust, smoking statuses. The progression of skin aging is associated with which continues to perpetuate the controversial nature of this treat‐ decreased collagen density and dermal thickness in addition to a re‐ ment. Here, we summarize some of the prominent studies in the duction in the synthesis and replacement of vital structural proteins. literature in order to familiarize clinicians with oral collagen supple‐ This causes the dermis to lose its integrity and pliability, which man‐ mentation for skin health, so that they can more effectively discuss ifests itself clinically as lax and wrinkled skin. this therapy with patients. An effort to combat the visible signs of skin aging has been a driving force in the rise of the nutraceutical market. Supporters have claimed that oral collagen supplements can help to reduce the 2 | REVIEW aging appearance of skin. In many of these supplements, the bio‐ active ingredients are collagen peptides, which are peptides rich in Asserin et al administered collagen peptides to patients and observed the amino acids proline, glycine, and hydroxyproline. Upon diges‐ skin hydration and transepidermal water loss (TEWL). 2 In the first tion, these peptides are cleaved into di‐ and tri‐peptides, which are part of their study, they recruited 66 Japanese women, who were claimed to be used by the body as building blocks for proteins, such 40‐59 years old, and treated half with either 10 g of daily collagen as collagen. treatment for 56 consecutive days or placebo. Their results showed It has been theorized that the availability of these protein pep‐ a statistically significant increase in skin moisture for the treatment tides can help to maintain and increase the collagen in the skin. It group. However, this was without an effect on TEWL. In the sec‐ is also believed that the peptides may increase hyaluronic acid pro‐ ond part of their study, they recruited 106 French women, who duction in skin fibroblasts, induce migration of fibroblasts, promote were 40‐65 years old, and treated half with either 10 g of collagen J Cosmet Dermatol. 2019;00:1–3. wileyonlinelibrary.com/journal/jocd © 2019 Wiley Periodicals, Inc. | 1 2 | JHAWAR et al. treatment for 84 consecutive days or placebo. After 12 weeks of Wang et al found that administering collagen hydrolysates to 9‐ treatment, measurements of echogenicity using high frequency ul‐ month‐old mice for 6 months led to significantly increased collagen trasound demonstrated significantly greater collagen density in the content in addition to improvements in the density and distribution treatment group. of collagen fibers and the ratio of type I to type III collagen in a dose‐ Kim et al conducted a double‐blind, randomized, placebo‐con‐ dependent manner.7 Additionally, Le Vu et al administered collagen trolled trial to study the effects of low‐molecular‐weight collagen peptides to mice for 6 weeks. Treatment was associated with an in‐ peptide (LMWCP) on skin hydration, wrinkling, and elasticity.3 They creased expression and upregulation of genes in the skin associated enrolled 64 Korean women, who were 40‐60 years old, and treated with the development of the epidermis and the hair cycle.8 Another them with either 1000 mg of LMWCP or placebo daily for 12 weeks. study fed mice a collagen hydrolysate‐containing diet for 12 weeks, After 6 and 12 weeks, there were significant increases in skin hydra‐ which was associated with improvements in stratum corneum water tion in the LMWCP group compared to placebo. Three parameters content and skin elasticity compared to control mice.9 DNA micro of skin wrinkling (average roughness, skin roughness, smoothness array analysis suggested that gene changes preceded effects in depth) were significantly higher in the treatment group. However, skin barrier function and mechanical properties. Similarly, Shimizu only one out of three parameters for skin elasticity (overall elasticity, et al10 fed mice a diet rich in prolyl‐hydroxyproline and hydroxypro‐ net elasticity, ratio of elastic recovery to total deformation) was sig‐ lyl‐glycine for 5 weeks. The collagen hydrolysates were associated nificantly higher in the treatment group. with decreased TEWL and increased water content of the stratum In a study by Proksch et al, 69 women, who were 35‐55 years corneum. Animal studies can be helpful for further elucidating the old, were randomly placed into one of four groups: 2.5 g of collagen mechanisms behind collagen supplementation. hydrolysate (CH), 5.0 g of CH, 2.5 g of placebo, and 5.0 g of placebo.4 Supplements were taken daily for 8 weeks. At the end of the study, both CH groups had a statistically significant increase in skin elas‐ 3 | D I S CU S S I O N ticity compared to the placebo groups. After 4 weeks of follow‐up treatment, a statistically significant increase in skin elasticity was These few limited studies suggest that there may be some benefits seen in elderly women. This study also observed positive correla‐ for the skin associated with oral collagen supplementation. However, tions between CH treatment and both skin moisture and skin evapo‐ there are many factors that should first be considered. For one, the ration. However, these were not statistically significant. collagen supplements used in these studies are not comparable, Genovese et al performed a double‐blind, randomized, placebo‐ which can lead to inconsistencies when aggregating the data. Many controlled trial investigating the efficacy of an oral liquid supple‐ of the studies are also limited by only involving patients of particular ment containing collagen peptides and antioxidants as an anti‐aging geographic regions, sex, and age groups. This does not control for 5 product. In this study, 120 subjects were randomly assigned to con‐ the roles that they may play in skin appearance. While there were sume either 50 mL of the supplement or placebo daily for 90 days. many different types of objective measurements, it is unclear how They found no significant difference in skin elasticity between the each translates into clinical appearance or why each was affected treatment and placebo groups. However, subjects that had under‐ by collagen supplements. There is also no reliable evidence to sug‐ gone cosmetic procedures during the study period had significantly gest that orally digested collagen becomes preferentially localized increased skin elasticity if they were part of the treatment group. to the dermis as opposed to other parts of the body.11 It has been Post‐treatment self‐assessment questionnaires completed by sub‐ argued that the amino acids required for collagen synthesis can be jects showed higher ratings of various perceived skin parameters in consumed from a normal protein diet, which negates the need for the treatment group. additional collagen supplementation.11 There are additionally many Inoue et al conducted a randomized, double‐blind, placebo‐con‐ other vital proteins, other than collagen, that contribute to the ap‐ trolled trial to compare the clinical effects of CH composed of the pearance and properties of skin. While some proponents may rely bioactive dipeptides, prolyl‐hydroxyproline and hydroxyprolyl‐gly‐ on the body of evidence from animal studies,12-14 these findings can‐ cine.6 They enrolled 85 Chinese women, who were 35‐55 years old, not necessarily be extrapolated to humans due to differences in di‐ and placed them into one of three groups: higher content of the gestion, enzyme activity, and metabolism.11 collagen peptides, lower content of the collagen peptides, and pla‐ cebo. They underwent daily administration for 8 weeks. The results showed significantly greater skin moisture of the cheek and can‐ 4 | CO N C LU S I O N thus in both treatment groups compared to placebo. Additionally, the higher content group showed significant and more improvement On balance, additional clinical studies are needed in order to more than both the lower content group and placebo in measurements of completely understand the cutaneous effects of oral collagen sup‐ skin moisture, elasticity, and wrinkles and roughness. plementation. As this trend continues to gain in popularity, especially In addition to human studies, there are also those utilizing animal with its widespread availability for consumers, there is a need for models. Observations based upon clinical and histological appear‐ more rigorous research to validate its effects. Until then, clinicians ance as well as gene expression are key elements of these studies. should be aware of the current evidence in the literature in order to JHAWAR et al. | 3 inform patients accordingly. Although proponents for oral collagen 6. Inoue N, Sugihara F, Wang X. Ingestion of bioactive collagen hy‐ supplements have been able to market many purported benefits, drolysates enhance facial skin moisture and elasticity and reduce facial ageing signs in a randomised double‐blind placebo‐controlled physicians are not afforded the same opportunity to endorse such clinical study. J Sci Food Agric. 2016;96(12):4077‐4081. claims without strong and convincing evidence. 7. Wang Z, Wang Q, Wang L, et al. Improvement of skin condition by oral administration of collagen hydrolysates in chronologically aged mice. J Sci Food Agric. 2017;97(9):2721‐2726. C O N FL I C T O F I N T E R E S T 8. Le Vu P, Takatori R, Iwamoto T, et al. Effects of food‐derived col‐ lagen peptides on the expression of keratin and keratin‐asso‐ The authors have no conflict of interest to declare. ciated protein genes in the mouse skin. Skin Pharmacol Physiol. 2015;28(5):227‐235. 9. Oba C, Ito K, Ichikawa S, et al. Effect of orally administered collagen ORCID hydrolysate on gene expression profiles in mouse skin: a DNA mi‐ croarray analysis. Physiol Genomics. 2015;47(8):355‐363. Jordan V. Wang https://orcid.org/0000-0001-7437-2745 10. Shimizu J, Asami N, Kataoka A, et al. Oral collagen‐derived dipep‐ tides, prolyl‐hydroxyproline and hydroxyprolyl‐glycine, ameliorate skin barrier dysfunction and alter gene expression profiles in the REFERENCES skin. Biochem Biophys Res Commun. 2015;456(2):626‐630. 11. Spiro A, Lockyer S. Nutraceuticals and skin appearance: is there any 1. Addor F, Cotta Vieira J, Abreu Melo CS. Improvement of dermal evidence to support this growing trend? Nutr Bull. 2018;43(1):10‐45. parameters in aged skin after oral use of a nutrient supplement. Clin 12. Song H, Zhang S, Zhang L, Li B. Effect of orally administered col‐ Cosmet Investig Dermatol. 2018;11:195‐201. lagen peptides from bovine bone on skin aging in chronologically 2. Asserin J, Lati E, Shioya T, Prawitt J. The effect of oral collagen aged mice. Nutrients. 2017;9(11):1209. peptide supplementation on skin moisture and the dermal 13. Watanabe‐Kamiyama M, Shimizu M, Kamiyama S, et al. Absorption collagen network: Evidence from an ex vivo model and ran‐ and effectiveness of orally administered low molecular weight col‐ domized, placebo‐controlled clinical trials. J Cosmet Dermatol. lagen hydrolysate in rats. J Agric Food Chem. 2010;58(2):835‐841. 2015;14(4):291‐301. 14. Zhang Z, Wang J, Ding Y, Dai X, Li Y. Oral administration of ma‐ 3. Kim DU, Chung HC, Choi J, Sakai Y, Lee BY. Oral intake of low‐mo‐ rine collagen peptides from Chum Salmon skin enhances cuta‐ lecular‐weight collagen peptide improves hydration, elasticity, and neous wound healing and angiogenesis in rats. J Sci Food Agric. wrinkling in human skin: A randomized, double‐blind, placebo‐con‐ 2011;91(12):2173‐2179. trolled study. Nutrients. 2018;10(7):826. 4. Proksch E, Segger D, Degwert J, Schunck M, Zague V, Oesser S. Oral supplementation of specific collagen peptides has beneficial How to cite this article: Jhawar N, Wang JV, Saedi N. Oral effects on human skin physiology: A double‐blind, placebo‐con‐ trolled study. Skin Pharmacol Physiol. 2014;27(1):47‐55. collagen supplementation for skin aging: A fad or the future? 5. Genovese L, Corbo A, Sibilla S. An insight into the changes in skin J Cosmet Dermatol. 2019;00:1–3. https://doi.org/10.1111/ texture and properties following dietary intervention with a nutri‐ jocd.13096 cosmeceutical containing a blend of collagen bioactive peptides and antioxidants. Skin Pharmacol Physiol. 2017;30(3):146‐158.