Throughout its history, the never-ending quest to defy aging has taken some strange twists and turns. To my mind, the idea that simply eating more collagen could enhance the skin seems—at first blush—a bit like cargo cult science. Although collagen is clearly a critically important skin structural protein and is very much connected to the changes that are seen in aging, it seems a bit of a stretch that just supplementing it in the diet could result in improvement in skin elasticity and wrinkles. Indeed, the beautiful triple helix structure of collagen, rich in hydroxyproline, almost certainly breaks down quickly in the stomach and intestinal tract. The acids, proteases, peptidases, and of course the gut barrier, essentially ensure that only the amino acids and, at best, some small peptides are absorbed. And yet, a very compelling paper by Tan et al demonstrated that both in vitro and in a clinical setting, adding L-histidine to the diet enhanced the production of filaggrin (known to be rich in L-histidine), suggesting that, as unlikely as it may seem, increasing the dietary raw materials could potentially result in enriched production of a desired protein.¹

De Miranda et al do a very nice job of reviewing the literature on oral collagen supplementation for anti-aging benefits and come to a somewhat surprising conclusion: “…[I]ngestion of hydrolyzed collagen… is effective in reducing skin aging, as it reduces wrinkles and improves skin elasticity and hydration.” In fact, similar to the filaggrin paper, the supplements are generally broken-down collagen, hydrolyzed into di- and tripeptides. Importantly, in animal models at least, it has been shown that these peptides are absorbed and do make their way to the skin to end up as part of new collagen.^2,3 In over 1000 pooled patients across 19 articles, they nicely lay out the findings and discuss the outcome measurements such as ultrasonography, corneometry, and use of silicon skin replicas. They use forest plots to show that the hydrolyzed collagen intervention is favored over the placebo groups across the studies in terms of skin hydration and elasticity, and also help reassure against bias by use of a funnel chart. Finally, they point out that studies using supplements with higher concentrations of Pro-Hyp and Hyp-Gly dipeptides showed visible improvements of the evaluated parameters after 4 weeks, and that these may be the ones to seek.

Given the safety and relative accessibility of hydrolyzed collagen supplements, I am happy to admit that my mind has been changed after reading this meta-analysis. Although it is always difficult to know the degree of improvement and how clinically relevant it would be for a given patient, on the whole supplementation with hydrolyzed collagen seems reasonable and evidence-based when thinking about reducing the signs of aging.

References

1. Tan SP, Brown SB, Griffiths CE, et al. Feeding filaggrin: effects of l-histidine supplementation in atopic dermatitis. Clin Cosmet Investig Dermatol. 2017;10:403-411. https://www.dovepress.com/feeding-filaggrin-effects-of-l-histidine-supplementation-in-atopic-der-peer-reviewed-article-CCID
2. Liu C, Sugita K, Nihei KI, et al. Absorption of hydroxyproline-containing peptides in vascularly perfused rat small intestine in situ. Biosci Biotechnol Biochem. 2009;73(8):1741-1747. https://www.tandfonline.com/doi/abs/10.1271/bbb.90050
3. Kawaguchi T, Nanbu PN, Kurokawa M. Distribution of prolylhydroxyproline and its metabolites after oral administration in rats. Biol Pharm Bull. 2012;35(3):422-427. https://www.jstage.jst.go.jp/article/bpb/35/3/35_3_422/_article