March 2019 Issue

Dietary Collagen — Should Consumers Believe the Hype?
By Jamie Santa Cruz
Today’s Dietitian
Vol. 21, No. 3, P. 26

The never-ending desire of consumers to lose weight and look and feel younger has caused the market for dietary collagen to explode in recent years. Sales of collagen supplements reached $46.6 million in 2018, an increase of nearly 34% over the previous year.1 In addition, collagen is now being added as a functional ingredient to a variety of foods and beverages, including protein bars, teas, coffee creamers, and even baked goods. Some collagen manufacturers even have begun collaborating with food bloggers to produce collagen cookbooks, which promote adding collagen powder to everything from smoothies to macaroons to tacos.

There’s some justification for the hype: Early research suggests that collagen consumption may do everything from improving joint pain and reducing wrinkles to promoting muscle growth and aiding weight regulation. Still, the hype may have gotten ahead of the evidence, according to Libby Mills, MS, RDN, LDN, FAND, a spokesperson for the Academy of Nutrition and Dietetics. “Some of [the studies] look a little bit more promising than others,” Mills says. “Everything’s in the beginning stages of the research. Right now, there’s not a lot to say that we should 100% embrace this [trend].”

What Is Collagen?
Collagen is a protein, and it’s the main component of the various connective tissues in the body—in other words, the substance that holds the body together. It’s present primarily in fibrous tissues such as tendons and skin, and it represents at least 30% of whole-body protein content.2

Twenty-nine different types of collagen have been identified,3 but the vast majority of collagen in the human body is type I, II, or III. All three types form long, thin fibrils and have the basic structure of a triple helix.4 Collagen type I is by far the most common and is distributed in bones, ligaments, and tendons. Type I also is present in skin, where it’s largely responsible for skin’s elasticity and strength. Collagen degradation in skin results in wrinkles and aged appearance. By contrast, collagen type II is primarily distributed in cartilage, and collagen type III, which is always found alongside type I, is most prevalent in skin, blood vessels, and internal organs.5

Nutritional Background
All collagen contains 19 different amino acids, with a particularly high content of hydroxyproline, glycine, and proline. The abundance of hydroxyproline is noteworthy because this amino acid isn’t found in other proteins.6 However, collagen has long been considered an inferior protein because it lacks tryptophan, one of the nine essential amino acids.

The body can’t absorb collagen in whole form; rather, the protein must be broken down during the digestive process before absorption into the bloodstream. To increase collagen’s bioavailability, collagen supplements typically are hydrolyzed, meaning that collagen’s long amino acid chains are broken down via a chemical or enzymatic process into peptides consisting of just two or three amino acids together. These peptides are then easily absorbed through the gastrointestinal tract.

Collagen peptides (also called collagen hydrolysates) have several functions, according to Patricia Farris, MD, a clinical associate professor of dermatology at Tulane University School of Medicine in New Orleans. At the most basic level, they serve as the building blocks for production of collagen or other proteins in the body. Beyond this, the peptides bind to the receptors on the fibroblasts that produce collagen and stimulate those fibroblasts to boost their collagen production. Finally, the peptides also function as antioxidants, helping to protect existing collagen in the body from oxidative stresses that would degrade it.

Importantly, it’s impossible to determine in advance where collagen peptides will be used in the body—or even if they will be used to produce collagen at all (collagen peptides can just as well be used for the synthesis of other proteins). Consumers often take collagen to achieve a specific benefit, such as improving skin elasticity or joint function. But according to Mills, “Our bodies have a way of prioritizing. So if we need protein for wound healing, that’s going to be the body’s number one priority in terms of where it’s going to allocate amino acids and build a protein. … We might be taking a collagen supplement for our skin, [but] once we digest and absorb it, they become part of the amino acid pool and get used where they’re needed.”

Food Sources
In addition to supplements, there are several food sources naturally rich in collagen. According to Ashley Barrient, MEd, LPC, RD, LDN, a bariatric dietitian at Northwestern Medicine’s Digestive Health Center in Chicago, the most common food source currently is bone broth, made popular through the influence of the Paleo diet. Unlike stock, which is typically simmered for only a few hours, bone broth is often simmered for 24 hours or more to break down the bones and release from them as many nutrients and minerals as possible.

In both humans and animals, collagen is concentrated in connective tissues such as muscle; thus, any meat that contains muscle or other connective tissue (as opposed to organ meats) will be a rich source of collagen, according to Mills. Fish, egg whites, and spirulina are other good animal and algal sources of collagen, Mills adds.

While it’s possible to consume collagen directly, either in the form of a supplement or in the form of foods containing collagen, doing so isn’t necessary to support production of collagen in the body, Farris says. Again, the body doesn’t absorb collagen molecules in whole form, but rather breaks them down into their component amino acids, which it then uses to synthesize its own collagen and other proteins. In theory, the amino acids necessary for collagen production can come from any protein source—whether it be bone broth, cheese, beans, or quinoa.

Getting the proper array of amino acids is easier for meat eaters, Mills says. But vegetarians and vegans also can consume all the necessary amino acids for collagen production, as long as they’re eating a well-balanced diet. “For most vegetarians, having complementary proteins throughout the day is enough to make sure that their bodies have all of the amino acids they need for building proteins, building collagen,” Mills says. “For example, pairing beans with brown rice—beautiful. Or nuts with whole grains—peanut butter with toast is a perfect example. Having these pairings throughout the day is one way they’re going to get all the amino acids they need.”

Besides amino acids, several other nutrients are important for the production of collagen in the body. The most significant of these is vitamin C, which is a necessary cofactor in collagen synthesis and that also functions as an antioxidant to combat oxidative stresses that would degrade existing collagen. Good food sources of vitamin C include citrus fruit, peppers, strawberries, and tomatoes, among others. According to Mills, other relevant vitamins and minerals include zinc and sulfur, which are additional cofactors in collagen production. Sulfur is commonly found in broccoli, onions, and garlic, and zinc is found in foods such as red meat, poultry, beans, nuts, certain types of seafood, whole grains, and dairy products.

Science Behind the Benefits
Almost all of the existing research on the benefits of collagen has focused on collagen supplements, not food sources or food products containing collagen as a functional additive.

Supplements vary in their source and type: Bovine collagen supplements are the most common and consist of collagen types I and III; these are popularly promoted for hair, skin, and nail health. Collagen sourced from fish, which is growing in popularity, contains primarily type I collagen. Supplements sourced from chicken, by contrast, consist of collagen type II, which is mainly promoted for cartilage and joint health. Little research exists showing that a given source or type of collagen supplement produces superior results over another. “Some are thought to be better for one thing or another,” says John Ivy, PhD, Teresa Lozano Long Endowed Chair Emeritus at the University of Texas at Austin. However, “the research on that isn’t as clear—whether one collagen is better than another as far as supplementation goes.”

Joint Health and Arthritis Symptoms
Much of the research on the benefits of collagen has focused on its potential for improving joint health. In small trials, oral collagen has been shown to reduce exercise-related joint pain among healthy volunteers.7,8 A few other studies likewise have found a reduction in activity-related joint pain among athletes.9,10 However, currently there’s no evidence on whether collagen supplements can decrease joint injuries or speed up athletes’ return to play after injury.11,12

As for arthritis, a 2018 systematic review in the British Journal of Sports Medicine found that hydrolyzed collagen supplements provided significant relief from osteoarthritis-associated pain, at least in the short term.13 Yet, the review also noted that the quality of evidence was low, with only a few small trials available, and that there was no evidence of benefit in the long term.

Most collagen supplements consist of hydrolyzed collagen (ie, collagen broken down into peptide fragments); however, some studies on joint health also have evaluated another type of supplement, namely undenatured type II collagen (UC-II). UC-II is collagen that hasn’t been broken down into peptides and isn’t intended to promote collagen synthesis; rather, its purpose is to stimulate oral tolerance and temper immune reactions that cause inflammation and joint pain. Multiple studies have tested the efficacy of UC-II for treatment of both osteoarthritis and rheumatoid arthritis, with promising results.14-18 However, most of these have been small studies. A 2017 review concluded that while collagen supplements (both hydrolyzed collagen and UC-II) show promise for treating osteoarthritis, the evidence is inconclusive without further large-scale, long-term trials. The same review also concluded that the efficacy of oral collagen to help improve rheumatoid arthritis is still questionable.19

Skin Health
Much of the research on collagen focuses on joint health, but the other major focus in the literature has been skin health. One double-blinded, randomized, placebo-controlled trial found that daily oral supplementation with fish collagen resulted in a significant improvement in skin elasticity (based on subjective participant reports as well as objective analysis of skin biopsies).20 Another small placebo-controlled trial found that supplementation with collagen peptides for eight weeks significantly improved skin hydration and increased collagen density in the skin, while also reducing collagen fragmentation in the skin.21 Moreover, in a randomized controlled trial of 105 women with moderate cellulite, collagen supplements derived from pig skin resulted in a “clear” improvement in skin appearance.22 Several other studies also have suggested that collagen supplements can reduce visible signs of skin aging, including wrinkles and skin dryness.23-25

Weight Regulation and Muscle Growth
Claims that collagen can aid in weight regulation are largely based on the premise that protein in general and collagen in particular promote fullness. The research relating to collagen specifically, however, is slim, and all of the existing studies involve small populations.

For instance, one study found that intake of gelatin prompted an increase in gut hormones associated with satiety, but it involved just 22 participants.26 In another study of 24 subjects, researchers gave participants breakfasts containing various kinds of protein, such as casein, soy, whey, alpha-lactalbumin, or gelatin. Those who ate a breakfast containing alpha-lactalbumin or gelatin had 40% greater satiety than those who ate breakfasts containing other proteins, and they also ate 20% fewer calories at lunch.27 Finally, a study of single-protein diets found that a gelatin diet produced greater appetite suppression than a casein diet, but this study likewise involved only 23 participants.28

Collagen often is touted as beneficial for maintaining muscle mass, but the supporting evidence comes from studies of older adults, who often have low intake of dietary protein in general.29 The study most commonly referenced to support collagen’s benefits for muscle growth is a small randomized trial of 53 older men with sarcopenia. It found that collagen peptide supplements in combination with resistance training resulted in improved muscle strength and muscle mass over resistance training combined with placebo, but such findings may not be generalizable to younger populations or athletes.30

Other Potential Benefits
Some studies have suggested that collagen intake may speed wound healing. Several randomized controlled trials of individuals with pressure ulcers have found that giving standard care in combination with a collagen hydrolysate supplement resulted in significantly faster recovery than giving only standard care.31-33

Collagen peptides also are thought to hold potential for maintaining bone health and guarding against osteoporosis. In lab studies, collagen peptides have been shown to stimulate the proliferation and differentiation of osteoblasts, the cells that synthesize bone.34,35 A handful of small human trials suggest that collagen supplementation may help improve bone mass and prevent bone loss.36,37 However, the evidence to date is minimal.

Among the least-supported claims relating to collagen are that it supports hair, nail, and gut health. One study did find that consumption of collagen peptides increased nail growth and decreased nail brittleness and breakage; however, this study had only 25 participants and lacked a control group.38 And while one study found that individuals with inflammatory bowel disease had lower levels of serum collagen compared with healthy controls,39 there’s no evidence to show that supplementing with collagen improves gut health.

Takeaways for RDs
• Be skeptical about health claims surrounding collagen. Even if studies show benefits to consuming collagen, it’s unclear whether consumption of collagen in particular is necessary to see those results, Mills says. “Maybe if people just consumed adequate protein [in general], they would get that same benefit,” she says.

One particular reason for skepticism is that many existing studies on collagen’s benefits have been funded by industry. “This is another factor we should consider,” says Xiaoquin Liu, a PhD student at the Institute of Bone and Joint Research at Sydney Medical School and the first author of a review article last year on the benefits of supplements for osteoarthritis. “[Industry funding] is a risk of bias in the scientific world.”

• Consider other aspects of lifestyle that affect collagen. Although consumers are increasingly focused on increasing collagen production in the body, it’s equally important to consider dietary and lifestyle factors that damage existing collagen. High sugar intake is of particular concern, Farris says. Sugar molecules bind to collagen fibers and result in the formation of advanced glycation end products. These bindings cause irreversible loss of strength and flexibility in collagen fibers, making skin more prone to sagging.40

According to Barrient, other significant lifestyle factors that affect collagen integrity are smoking and sun and pollution exposure. “Even if more data and research comes out that oral collagen ingestion is helpful, all of those lifestyle behaviors and habits need to be also healthful and in line to make a supplemental form actually effective,” Barrient says.

• Supplements might not hurt, but opt for natural sources of protein when possible. “Spending money on supplements doesn’t seem to be necessary, because there are many food sources and if you’re eating a well-balanced diet, you should have the nutrients you need,” Mills says.

There also may be some risk involved with supplements. “Heavy metals and toxins collect in the bones of animals,” Mills warns. “In the extracting of collagen from bones, some of these metals and toxins may become part of the broth. Supplements made from animal bones and connective tissue may too have these heavy metals and toxins in them. In both cases—the bones for making broth and the supplements made from animal parts—it may be worth looking for organic and grass fed.”

As for Barrient, she advocates skipping supplements, powders, and functional foods with collagen additives and opting for natural sources of protein whenever possible. “The less processed, the better,” she says. “If we can get nutrients from a natural source, it’s better than a powdered form. Real food is always better.”

— Jamie Santa Cruz is a freelance writer of health and medical topics based in Parker, Colorado.

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8. Czajka A, Kania EM, Genovese L, et al. 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.

9. Clark KL, Sebastianelli W, Flechsenhar KR, et al. 24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Curr Med Res Opin. 2008;24(5):1485-1496.

10. Zdzieblik D, Oesser S, Gollhofer A, König D. Improvement of activity-related knee joint discomfort following supplementation of specific collagen peptides. Appl Physiol Nutr Metab. 2017;42(6):588-595.

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13. Liu X, Machado GC, Eyles JP, Ravi V, Hunter DJ. Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Br J Sports Med. 2018;52(3):167-175.

14. Bagchi D, Misner B, Bagchi M, et al. Effects of orally administered undenatured type II collagen against arthritic inflammatory diseases: a mechanistic exploration. Int J Clin Pharmacol Res. 2002;22(3-4):101-110.

15. Crowley DC, Lau FC, Sharma P, et al. Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial. Int J Med Sci. 2009;6(6):312-321.

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17. Wei W, Zhang LL, Xu JH, et al. A multicenter, double-blind, randomized, controlled phase III clinical trial of chicken type II collagen in rheumatoid arthritis. Arthritis Res Ther. 2009;11(6):R180.

18. Bakilan F, Armagan O, Ozgen M, Tascioglu F, Bolluk O, Alatas O. Effects of native type II collagen treatment on knee osteoarthritis: a randomized controlled trial. Eurasian J Med. 2016;48(2):95-101.

19. Woo T, Lau L, Cheung N, Chan P, Tan K, Gardner A. Efficacy of oral collagen in joint pain — osteoarthritis and rheumatoid arthritis. J Arthritis. 2017;6:233.

20. Czajka A, Kania EM, Genovese L, et al. 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.

21. 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 randomized, placebo-controlled clinical trials. J Cosmet Dermatol. 2015;14(4):291-301.

22. Schunck M, Zague V, Oesser S, Proksch E. Dietary supplementation with specific collagen peptides has a body mass index-dependent beneficial effect on cellulite morphology. J Med Food. 2015;18(12):1340-1348.

23. 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.

24. Schwartz SR, Park J. Ingestion of BioCell Collagen(®), a novel hydrolyzed chicken sternal cartilage extract; enhanced blood microcirculation and reduced facial aging signs. Clin Interv Aging. 2012;7:267-273.

25. Borumand M, Sibilla S. Daily consumption of the collagen supplement Pure Gold Collagen® reduces visible signs of aging. Clin Interv Aging. 2014;9:1747-1758.

26. Rubio IG, Castro G, Zanini AC, Medeiros-Neto G. Oral ingestion of a hydrolyzed gelatin meal in subjects with normal weight and in obese patients: postprandial effect on circulating gut peptides, glucose and insulin. Eat Weight Disord. 2008;13(1):48-53.

27. Veldhorst MA, Nieuwenhuizen AG, Hochstenbach-Waelen A, et al. A breakfast with alpha-lactalbumin, gelatin, or gelatin + TRP lowers energy intake at lunch compared with a breakfast with casein, soy, whey, or whey-GMP. Clin Nutr. 2009;28(2):147-155.

28. Hochstenbach-Waelen A, Westerterp-Plantenga MS, Veldhorst MA, Westerterp KR. Single-protein casein and gelatin diets affect energy expenditure similarly but substrate balance and appetite differently in adults. J Nutr. 2009;139(12):2285-2292.

29. Hays NP, Kim H, Wells AM, Kajkenova O, Evans WJ. Effects of whey and fortified collagen hydrolysate protein supplements on nitrogen balance and body composition in older women. J Am Diet Assoc. 2009;109(6):1082-1087.

30. Zdzieblik D, Oesser S, Baumstark MW, Gollhofer A, König D. Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: a randomised controlled trial. Br J Nutr. 2015;114(8):1237-1245.

31. Yamanaka H, Okada S, Sanada H. A multicenter, randomized, controlled study of the use of nutritional supplements containing collagen peptides to facilitate the healing of pressure ulcers. J Nutr Intermed Metab. 2017;8:51-59.

32. Lee SK, Posthauer ME, Dorner B, Redovian V, Maloney MJ. Pressure ulcer healing with a concentrated, fortified, collagen protein hydrolysate supplement: a randomized controlled trial. Adv Skin Wound Care. 2006;19(2):92-96.

33. Sugihara F, Inoue N, Venkateswarathirukumara S. Ingestion of bioactive collagen hydrolysates enhanced pressure ulcer healing in a randomized double-blind placebo-controlled clinical study. Sci Rep. 2018;8(1):11403.

34. Fu Y, Zhao XH. In vitro responses of hFOB1.19 cells towards chum salmon (Oncorhynchus keta) skin gelatin hydrolysates in cell proliferation, cycle progression and apoptosis. J Funct Foods. 2013;5:279-288.

35. Guillerminet F, Fabien-Soulé V, Even PC, et al. Hydrolyzed collagen improves bone status and prevents bone loss in ovariectomized C3H/HeN mice. Osteoporos Int. 2012;23(7):1909-1919.

36. Elam ML, Johnson SA, Hooshmand S, et al. A calcium-collagen chelate dietary supplement attenuates bone loss in postmenopausal women with osteopenia: a randomized controlled trial. J Med Food. 2015;18:324-331.

37. König D, Oesser S, Scharla S, Zdzieblik D, Gollhofer A. Specific collagen peptides improve bone mineral density and bone markers in postmenopausal women: a randomized controlled study. Nutrients. 2018;10(1).

38. 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.

39. Koutroubakis IE, Petinaki E, Dimoulios P, et al. Serum laminin and collagen IV in inflammatory bowel disease. J Clin Pathol. 2003;56(11):817-820.

40. Danby FW. Nutrition and aging skin: sugar and glycation. Clin Dermatol. 2010;28(4):409-411.