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