Evidence-Based Nutrient Recommendations

Collagen

by Taylor Wolfram, MS, RDN, LDN and Jack Norris, RD, LD

Contents

Introduction

Collagen is a protein that makes up the connective tissue in animals, including humans. It provides structure for cartilage, tendons, blood vessels, bones, and skin. There are many different kinds of collagen.

Collagen is made up of amino acids, with a high proportion of glycine, proline, and hydroxyproline. Adequate protein and vitamin C intake are important for collagen production.

Some claim that ingesting collagen can increase collagen synthesis, but there is evidence that dietary collagen doesn’t increase collagen synthesis in humans compared to other protein sources.

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 didn’t include studies that used supplements containing active ingredients in addition to collagen.

A major limitation of the following collagen studies is that most don’t 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 as meat contains collagen).

Research on Vegans

There’s no direct research on collagen production among vegans. One study led researchers to theorize that vegans don’t produce optimal levels of collagen.

Fusano et al. (2000, Italy) conducted a prospective study comparing scar tissue healing between 11 male and 10 female vegans and 11 male and 10 female omnivores after surgical excision of a nonmelanoma skin cancer. Vegans had a poorer average Scar Cosmesis Assessment and Rating (SCAR) than omnivores. The authors believed that the healing pattern shown by the vegan patients indicated an alteration in collagen production.

Vegans had significantly lower average serum iron levels (48.71 ± 8.71 µg/dL vs 82.76 ± 24.26 µg/dL; normal range: 70-175 µg/dL for men and 50-150 µg/dL for women. This is the first we’ve seen of vegans with such low serum iron levels. There aren’t many studies reporting the serum iron levels of vegans because iron status is usually measured by way of serum ferritin, hemoglobin, transferrin, hematocrit, and total iron binding capacity. Weikert et al. (2020, Germany) found serum iron among 18 male and 18 female vegans to be 89 ± 31 µg/dL compared to 106 ± 39 µg/dL among 18 male and 18 female omnivores.

Vegans had significantly lower average serum B12 levels (129 ± 14 pmol/l vs 245 ± 128 pmol/l). Healthy B12 levels are considered to be >148 pmol/l (200 pg/ml). Severe deficiency tends not to be seen among vegans until levels drop below 75 pmol/l (Wokes, 1955) but perhaps moderately low levels could prevent optimal scar healing.

The study didn’t control for serum iron or B12 levels. Nutrient intakes weren’t assessed so we don’t have any information on protein or zinc intakes, which could impact scar healing.

Collagen for 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 is an area of interest.

Studies investigating the treatment for osteoarthritis typically include the following measurements:

  • 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 collagen proteins that have been hydrolyzed into fragments. The majority of peptides are broken down into individual amino acids during digestion, but a small amount are absorbed. In vitro studies (Ohara, 2010; Postlethwaite, 1978) and animal studies (Oesser, 1999) have found that collagen peptides may stimulate collagen production, but these effects haven’t been demonstrated in humans (Axtel, 2018).

Three randomized, double-blinded, controlled trials have found significantly improved VAS scores among the collagen peptide groups compared to the placebo groups (Kumar, 2015; Benito-Ruiz, 2009) or glucosamine (Trč and Bohmová, 2011). In two of the studies, the manufacturer of the collagen was either a financial supporter of the study or an employer of one or more authors (Kumar, 2015; Benito-Ruiz, 2009), while the third study didn’t report its funding (Trč and Bohmová, 2011).

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 with collagen (p=0.01) while those with above-average meat consumption did not (Benito-Ruiz, 2009). This could be because those eating more meat already had a higher intake of the amino acids that collagen supplies, but it could also be because meat contains collagen in amounts that are possibly functional (Paul, 2019).

A randomized, double-blinded study of older people with joint pain taking collagen peptides found improved VAS scores after 6 months (p=0.036) compared to placebo although there was no difference between groups in an overall definition of “clinical responder” in the joint-specific health-related quality-of-life questionnaire (Bruyère, 2012).

Type II Collagen and Osteoarthritis

Undenatured type II collagen is the primary type of collagen found in cartilage; it’s a type of collagen that’s supposed to prevent the body’s immune system from attacking its own collagen (Axtel, 2018).

There are two trials that investigated the effect of undenatured type II collagen on osteoarthritis. Both studies compared 40 mg collagen to 1,500 mg glucosamine and 1,200 mg chondroitin, and both were funded by the manufacturer of the collagen, UC-II®.

Crowley, et al., (2009) 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. However, there were no significant between-group differences in VAS or WOMAC.

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

Amino Acids and Osteoarthritis

One study of 50 individuals without diagnosed osteoarthritis or rheumatoid arthritis found that 12 g of the non-essential amino acids found in collagen, taken for 12 weeks, led to statistically significant improvement in knee joint symptoms compared to a placebo (Takeuchi, 2022).

Curcumin and Osteoarthritis

Two meta-analyses of randomized controlled trials on the use of turmeric extract and curcumin for treating OA found that these supplements significantly decreased VAS and WOMAC in people with OA, similar to that of ibuprofen (Daily, 2016; Wu, 2019). A more recent randomized controlled trial found that bioavailable turmeric extract is as effective as the drug paracetamol (acetaminophen) at reducing WOMAC scores in people with knee OA (Singhal, 2021). These supplements are promising plant-based options for treating OA.

Collagen for Skin Appearance

The clinical trials described below tested collagen supplements on various skin-related outcomes. We didn’t include studies that only tested products containing other ingredients such as vitamin C and hyaluronic acid.

Inoue, et al. (2016) 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. They found that collagen significantly increased skin moisture (p<0.05) 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, collagen density of the skin, and eye wrinkle volume among older women after 4-12 weeks of collagen peptide supplementation (Asserin, 2015; Choi, 2014b; Proksch, Schunck, et al., 2014; Proksch, Segger, et al., 2014; Sangsuwan, 2020Evans, 2021).

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 everyone with osteoarthritis (Axtel, 2018).

In this article, we focus on collagen supplementation for which there has been a notable amount of research. In Appendix A: Miscellaneous Uses of Collagen we mention a number of other uses for collagen beyond osteoarthritis and skin appearance, but these uses seem either unlikely to be anything vegans would feel are important to pursue (such as post-exercise uses) or for which vegans would likely make an exception if in an emergency situation and it was hospital protocol to treat a condition with collagen supplements (such as for burn healing).

This may provide an ethical dilemma for people with knee OA who don’t want to contribute to animal suffering but want to benefit from collagen supplements. Many vegans compromise in order to take medicines that 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.

It’s possible that eating extra protein or amino acids can substitute for taking collagen supplements, as described in the above section, Amino Acids and Osteoarthritis. There are also vegan collagen booster, collagen builder, and hydroxyproline supplements on the market, but we are unaware of any clinical research to support these products. There’s also the option of taking curcumin or turmeric supplements, which show promise for reducing pain in people with OA described in the above section, Curcumin and Osteoarthritis.

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

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.

Appendix A: Miscellaneous Uses of Collagen

At the time of this original writing (September 2020), there were some studies on various uses of collagen beyond osteoarthritis and skin appearance; we’ve added a few since then. Here’s a quick rundown.

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

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

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

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

Ankle sprains. There’s 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).

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

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

Burn healing. A randomized, double-blinded pilot trial compared a supplement consisting of gelatin (which contained 36 grams of collagen peptides), sugar, and yogurt to a placebo of 35 grams of soy protein (from 84 g of soy flour), sugar, and yogurt in 31 male burn patients (20-30% total body surface area burned) for 4 weeks (Bagheri Miyab, 2020). Calorie and protein content of the products was similar, as was the overall calorie and protein intake between intervention and placebo groups. Mean protein intake increased in both groups from 1.6 ± 0.3 g/kg of body weight at baseline to 2.6 ± 0.4 g/kg at the end of the study. Increases in prealbumin (a marker of nutritional improvement in burn patients) were significantly higher after 4 weeks in the intervention group compared to the control group (19.2 ± 7.5 vs. 8.5 ± 10.1mg/dL, P=0.002). Wounds in 100% of the intervention group and 40% of the control group were healed by the end of the study (P<0.001).

Post-exercise joint pain. 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 without diagnosed osteoarthritis (Bongers, 2020).

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

Increased muscle mass with exercise.

A 1-day double-blinded, parallel-group, randomized controlled trial of 45 male and female recreational athletes found that 30 g of collagen peptides didn’t significantly increase muscle protein synthesis following a session of resistance training compared to placebo whereas 30 g of whey protein did. Neither collagen nor whey significantly increased intramuscular collagen synthesis compared to placebo (Aussieker, 2023).

A 6-day double-blinded, randomized controlled trial of 22 healthy older women found 60 g/day of supplemental collagen was inferior to 60 g/day of supplemental whey protein in stimulating muscle protein synthesis in both periods of rest and exercise (Oikawa, Kamal, et al., 2020).

A 10-day double-blinded, randomized crossover trial of 11 endurance-trained individuals found muscle protein synthesis was significantly greater during a whey supplemented phase than a collagen peptide supplemented phase in response to cycling interval training (Oikawa, Macinnis, et al., 2020).

A 5-week double-blinded, parallel-group randomized controlled trial of 31 older adults found that neither collagen peptides nor whey protein protected lean mass during a period of energy restriction and inactivity. Only whey protein significantly increased leg lean mass and muscle protein synthesis once normal calorie intake and activity levels were restored (Oikawa, 2018).

A 12-week double-blinded, randomized controlled trial of 120 sedentary men ages 30 to 60 with a body mass index between 27.5 and 35 kg/m2 found significantly increased fat-free mass and significantly reduced fat mass from 15 g of bioactive collagen peptides (BODYBALANCE®) per day combined with resistance training compared to placebo (Zdzieblik, 2021). In an exploratory analysis, there was no significant difference in changes in fat-free mass between participants taking collagen and those taking an equivalent amount of whey protein.

Previous studies found that taking a collagen supplement along with resistance exercise may improve muscle mass and strength, but these studies didn’t compare collagen to other sources of protein (Jendricke, 2019; Kirmse, 2019; Oertzen-Hagemann, 2019; Zdzieblik, 2015).

Hypertension. 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 gave chicken-derived collagen peptides to 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).

Last updated: July, 2023.

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