Evidence-Based Nutrient Recommendations

Collagen

Contents

Collagen is a protein that makes up the connective tissue in animals, including humans. It helps provide structure for cartilage, tendons, blood vessels, bones, and skin. Collagen is made up of amino acids, most abundantly glycine, proline, and hydroxyproline. There are many different kinds of collagen.

The amino acids found in collagen are nonessential, meaning the body can make them, and they can also be found in food.

Adequate protein and vitamin C intake are important for collagen production. There are claims that ingesting collagen (derived from non-human animals) can boost collagen synthesis. Many of these claims are unfounded, and there is little to no evidence to support the efficacy of collagen supplementation for any condition other than osteoarthritis.

Collagen for Osteoarthritis and Skin Appearance

Osteoarthritis and skin appearance are the only topics we encountered that have numerous controlled clinical trials showing a benefit of collagen supplementation in humans. We did not include studies that used supplements containing active ingredients in addition to collagen, such as vitamin C, because that makes it impossible to determine the impact of collagen versus other ingredients known to impact collagen production.

A major limitation of the following collagen studies is that most do not control for protein intake, a known factor in collagen production. To draw any conclusions about the efficacy of collagen, we’d want to see human trials testing collagen versus an equivalent amount of other protein (especially plant protein).

Collagen and Osteoarthritis

The most common form of arthritis, osteoarthritis, is defined by a breakdown of cartilage in the joints, especially the hands, knees, and hips (NIH, 2019). Osteoarthritis gets worse over time and treatment strategies focus on pain reduction and preservation of joint function.

Because collagen is a significant part of cartilage, strategies to rebuild joint cartilage by boosting collagen production and halting the body’s destruction of existing collagen are an area of interest. Enter collagen supplements.

Studies investigating the treatment for osteoarthritis typically use two main measurement tools:

  • Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) – a self-reported measure of joint pain, stiffness, and function for people with hip and knee osteoarthritis
  • The pain visual analogue scale (VAS) – a validated, subjective measurement of pain

Collagen Peptides and Osteoarthritis

There are a handful of clinical trials investigating the effect of collagen peptides on osteoarthritis. Peptides are the collagen proteins hydrolyzed into fragments so that the amino acids can be more readily absorbed and utilized. Whether this actually works is still controversial (Axtel, 2018).

We reviewed three randomized, double-blinded, controlled trials, all of which found significantly improved VAS scores among the collagen peptide groups compared to the placebo groups (Kumar, 2015; Trč and Bohmová, 2011; Benito-Ruiz, 2009).

In three of the studies, the manufacturer of the collagen was either a financial supporter of the study or employer of one or more authors (Kumar, 2015; Schauss, 2012; Benito-Ruiz, 2009).

The other study did not report funding (Trč and Bohmová, 2011). It compared collagen peptides to glucosamine sulfate, and found that those taking the collagen supplement had significantly improved VAS and WOMAC scores compared to glucosamine (p <0.05 for both).

While no studies reported protein intake, one reported meat intake and found that when meat consumption was taken into account, those with below-average meat consumption (<1,549 g/week, roughly 18 servings of meat) showed a significant reduction in VAS (p=0.01) while those with above-average meat consumption did not (Benito-Ruiz, 2009). This may be because those with higher meat consumption already had a higher intake of the amino acids that collagen supplies.

Type II Collagen and Osteoarthritis

Type II collagen is the primary type of collagen found in cartilage.

There are two trials that investigated the effect of undenatured type II collagen (collagen from chickens’ sternums) on osteoarthritis. Undenatured means the collagen has not been broken down. While ingesting collagen peptides are supposed to help the body produce new collagen, ingesting undenatured type II collagen is supposed to prevent the body’s immune system from attacking its own collagen (Axtel, 2018).

Both studies were funded by the manufacturer of the collagen, UC-II®. They compared 40 mg collagen to 1500 mg glucosamine and 1200 mg chondroitin.

The first study found that both treatments lowered VAS and that the collagen group experienced significantly improved WOMAC scores at day 90 (p>0.05) while the glucosamine and chondroitin group did not (Crowley, 2009). However, there were no significant between-group differences in VAS or WOMAC.

The second study found that collagen resulted in significantly improved VAS (p=0.025) and WOMAC (p=0.04) compared to glucosamine and chondroitin (Lugo, 2016).

Collagen Peptides and Skin Appearance

Because collagen helps provide structure in skin, and collagen production naturally decreases with age, it’s been a target of those interested in “anti-aging” skincare. We found a few clinical trials that tested collagen supplements on various skin-related outcomes. We did not include studies that only tested products containing collagen and other ingredients such as vitamin C and hyaluronic acid.

One study evaluated the efficacy of two types of collagen hydrolysates, one with a low ratio of dipeptide-to-product and one with a high ratio of dipeptide-to-product. It found that collagen significantly increases skin moisture (p<0.05) (Inoue, 2016). The low-ratio collagen group experienced no significant improvement in facial skin elasticity or number of wrinkles and no significant differences compared to placebo while the high-ratio group experienced significantly improved cheek and canthus skin elasticity and number of wrinkles (p<0.05). Two authors were employed by the manufacturer of the collagen.

There are a handful of other studies that found improvements in skin elasticity, skin hydration/moisture, collagen density of the skin, and/or eye wrinkle volume among older women after 4-12 weeks of collagen peptide supplementation (Asserin, 2015; Choi, 2014b; Proksch, 2014a; Proksch, 2014b; Sangsuwan, 2020).

Limited Research for Collagen for Most Uses

There is little research to support the use of collagen for brittle nails, diabetes, eczema, exercise-induced muscle soreness, hypertension, joint pain, muscle strength, osteopenia, pressure ulcers, sarcopenia, sprains, tendinopathy, and wound healing.

There is one small trial on collagen peptides and brittle nails, but it didn’t contain a placebo group (Hexsel, 2017).

A randomized, controlled trial found that fish-derived collagen may positively impact metabolic markers in people with type 2 diabetes and hypertension (Zhu, 2010). Two small trials used chicken-derived collagen peptides on people with hypertension; one study had no comparison group (Saiga-Egusa, 2009) and the other study showed collagen decreased systolic but not diastolic blood pressure compared with placebo (Kouguchi, 2013).

One small, non-controlled trial used collagen for atopic dermatitis (eczema) and found some benefit (Hakuta, 2017).

There are two studies suggesting collagen supplements may help reduce joint pain after exercise among college athletes (Clark, 2008; Zdzieblik, 2017). A more recent study found collagen peptide supplementation for 12 weeks did not improve knee pain in healthy, active older adults (Bongers, 2020).

As for post-exercise muscle soreness, there is one randomized, double-blinded controlled trial and it found no significant difference between people who took collagen peptides versus placebo, nor did it improve markers of inflammation or bone turnover (Clifford, 2019).

A randomized, double-blinded study of older people with joint pain found no difference in the proportion of clinical responders between groups receiving collagen peptides or placebo after 3 months, but did find a greater proportion of clinical responders according to VAS in the treatment group versus placebo after 6 months (p=0.036). However, using the definition of “clinical responder” in the joint-specific health-related quality of life questionnaire, there was no difference in proportion of clinical responders throughout the study (Bruyère, 2012).

There are a handful of studies showing that taking a collagen supplement along with resistance exercise may improve muscle mass and strength, including a sample with sarcopenia, but these studies did not compare collagen to another source of protein (Jendricke, 2019; Oertzen-Hagemann, 2019; Zdzieblik, 2015).

One randomized, controlled trial testing collagen peptides on osteopenia found no significant effect compared to placebo (Cúneo, 2010). A randomized controlled trial of post-menopausal women with reduced bone mineral density found collagen significantly increased bone mineral density in the spine and femoral neck compared to placebo group (König, 2018).

One randomized, double-blinded study found significant benefits with collagen compared to placebo for pressure ulcers (Sugihara, 2018).

There is one trial investigating the impact of collagen on ankle sprains and it found that collagen appears to improve subjective ankle stability but not objective stiffness (Dressler, 2018).

A small pilot study tested collagen plus calf-strengthening exercises on Achilles tendinopathy and found improvements but was too small to make meaningful conclusions (Praet, 2019).

A small pilot study found collagen may help wound healing after fractional photothermolysis (laser skin treatment) (Choi, 2014a).

Collagen Conclusions

Although our bodies make collagen out of nonessential amino acids that are both endogenous and provided by the diet, the research to date indicates that most people with knee OA could benefit from collagen supplements. Despite this research, the Arthritis Foundation says there isn’t enough evidence to claim that collagen supplements will benefit people with osteoarthritis (Axtel, 2018).

It’s possible that eating extra protein can substitute for taking collagen supplements, but this hasn’t been studied. There’s also vegan “collagen booster” and “collagen builder” supplements and vegan hydroxyproline supplements on the market, but we are unaware of any clinical research to support these products.

This may provide an ethical dilemma for people with knee OA who don’t want to contribute to animal suffering but are searching for a way to alleviate their pain or further deterioration. Many vegans compromise in order to take medicines which are usually tested on animals and sometimes have animal ingredients. It’s possible that the collagen supplements might be slaughterhouse byproducts and so they don’t contribute much to the killing of animals. There’s also an argument for compromising a strict vegan lifestyle in order to relieve pressure on others who might be considering going vegan but feel that it’s an all-or-nothing thing for which they must choose nothing or else must forego collagen supplements.

Eventually, there will probably be synthetic collagen supplements to prevent the need for relying on animal products. Until then, we leave it up to each individual as to whether they take collagen supplements for their OA.

For skin appearance, collagen also appears to have an impact. Limiting sun exposure, using sunscreen when in the sun, meeting all nutrient recommendations, and maintaining adequate hydration are other options.

Bibliography

Asserin, 2015. 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.

Axtel, 2018. Axtel, B. Arthritis Foundation. Are Collagen Supplements Helpful for Arthritis? Published April 4, 2018. Accessed June 24, 2020.

Benito-Ruiz, 2009. Benito-Ruiz P, Camacho-Zambrano MM, Carrillo-Arcentales JN, et al. A randomized controlled trial on the efficacy and safety of a food ingredient, collagen hydrolysate, for improving joint comfort. Int J Food Sci Nutr. 2009;60 Suppl 2:99‐113.

Bongers, 2020. Bongers CCWG, Ten Haaf DSM, Catoire M, et al. Effectiveness of collagen supplementation on pain scores in healthy individuals with self-reported knee pain: a randomized controlled trial. Appl Physiol Nutr Metab. 2020;45(7):793-800. Abstract.

Bruyère, 2012. Bruyère O, Zegels B, Leonori L, et al. Effect of collagen hydrolysate in articular pain: a 6-month randomized, double-blind, placebo controlled study. Complement Ther Med. 2012;20(3):124-130.

Choi, 2014a. Choi SY, Kim WG, Ko EJ, et al. Effect of high advanced-collagen tripeptide on wound healing and skin recovery after fractional photothermolysis treatment. Clin Exp Dermatol. 2014;39(8):874-880.

Choi, 2014b. Choi SY, Ko EJ, Lee YH, et al. Effects of collagen tripeptide supplement on skin properties: a prospective, randomized, controlled study. J Cosmet Laser Ther. 2014;16(3):132-137.

Clark, 2008. 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.

Clifford, 2019. Clifford T, Ventress M, Allerton DM, et al. The effects of collagen peptides on muscle damage, inflammation and bone turnover following exercise: a randomized, controlled trial. Amino Acids. 2019;51(4):691-704.

Crowley, 2009. 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.

Cúneo, 2010. Cúneo F, Costa-Paiva L, Pinto-Neto AM, Morais SS, Amaya-Farfan J. Effect of dietary supplementation with collagen hydrolysates on bone metabolism of postmenopausal women with low mineral density. Maturitas. 2010;65(3):253-257.

Dressler, 2018. Dressler P, Gehring D, Zdzieblik D, Oesser S, Gollhofer A, König D. Improvement of Functional Ankle Properties Following Supplementation with Specific Collagen Peptides in Athletes with Chronic Ankle Instability. J Sports Sci Med. 2018;17(2):298-304.

Hakuta, 2017. Hakuta A, Yamaguchi Y, Okawa T, Yamamoto S, Sakai Y, Aihara M. Anti-inflammatory effect of collagen tripeptide in atopic dermatitis. J Dermatol Sci. 2017;88(3):357-364.

Hexsel, 2017. 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. Abstract.

Inoue, 2016. 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.

Jendricke, 2019. Jendricke P, Centner C, Zdzieblik D, Gollhofer A, König D. Specific Collagen Peptides in Combination with Resistance Training Improve Body Composition and Regional Muscle Strength in Premenopausal Women: A Randomized Controlled Trial. Nutrients. 2019;11(4):892.

König, 2018. 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):97.

Kouguchi, 2013. Kouguchi T, Ohmori T, Shimizu M, et al. Effects of a chicken collagen hydrolysate on the circulation system in subjects with mild hypertension or high-normal blood pressure. Biosci Biotechnol Biochem. 2013;77(4):691-696.

Kumar, 2015. Kumar S, Sugihara F, Suzuki K, Inoue N, Venkateswarathirukumara S. A double-blind, placebo-controlled, randomised, clinical study on the effectiveness of collagen peptide on osteoarthritis. J Sci Food Agric. 2015;95(4):702‐707.

Lugo, 2016. Lugo JP, Saiyed ZM, Lane NE. Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study. Nutr J. 2016;15:14.

NIH, 2019. NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases. Osteoarthritis. Last reviewed October 2019. Accessed June 2020.

Oertzen-Hagemann, 2019. Oertzen-Hagemann V, Kirmse M, Eggers B, et al. Effects of 12 Weeks of Hypertrophy Resistance Exercise Training Combined with Collagen Peptide Supplementation on the Skeletal Muscle Proteome in Recreationally Active Men. Nutrients. 2019;11(5):1072.

Praet, 2019. Praet SFE, Purdam CR, Welvaert M, et al. Oral Supplementation of Specific Collagen Peptides Combined with Calf-Strengthening Exercises Enhances Function and Reduces Pain in Achilles Tendinopathy Patients. Nutrients. 2019;11(1):76.

Proksch, 2014a. 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. [Abstract]

Proksch, 2014b. 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-controlled study. Skin Pharmacol Physiol. 2014;27(1):47-55. [Abstract]

Saiga-Egusa, 2009. Saiga-Egusa A, Iwai K, Hayakawa T, Takahata Y, Morimatsu F. Antihypertensive effects and endothelial progenitor cell activation by intake of chicken collagen hydrolysate in pre- and mild-hypertension. Biosci Biotechnol Biochem. 2009;73(2):422-424.

Sangsuwan, 2020. Sangsuwan W, Asawanonda P. Four-weeks daily intake of oral collagen hydrolysate results in improved skin elasticity, especially in sun-exposed areas: a randomized, double-blind, placebo-controlled trial [published online ahead of print, 2020 Mar 9]. J Dermatolog Treat. 2020;1-6.

Sugihara, 2018. 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.

Trč and Bohmová, 2011. Trč T, Bohmová J. Efficacy and tolerance of enzymatic hydrolysed collagen (EHC) vs. glucosamine sulphate (GS) in the treatment of knee osteoarthritis (KOA). Int Orthop. 2011;35(3):341‐348.

Zdzieblik, 2015. 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.

Zdzieblik, 2017. Zdzieblik D, Oesser S, Gollhofer A, König D. Improvement of activity-related knee joint discomfort following supplementation of specific collagen peptides [published correction appears in Appl Physiol Nutr Metab. 2017 Nov;42(11):1237]. Appl Physiol Nutr Metab. 2017;42(6):588-595.

Zhu, 2010. Zhu CF, Li GZ, Peng HB, Zhang F, Chen Y, Li Y. Therapeutic effects of marine collagen peptides on Chinese patients with type 2 diabetes mellitus and primary hypertension. Am J Med Sci. 2010;340(5):360-366.