- Collagen for Osteoarthritis and Skin Appearance
- Collagen and Osteoarthritis
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 two 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; 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) who took the collagen supplement showed a significant reduction in VAS (p=0.01) while those with above-average meat consumption who took the collagen supplement 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. Both studies compared 40 mg collagen to 1500 mg glucosamine and 1200 mg chondroitin, and both were funded by the manufacturer of the collagen, UC-II®.
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).
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).
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 (also known as acetaminophen) at reducing WOMAC scores in people with knee OA (Singhal, 2021). These supplements are promising plant-based options for treating OA.
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; Evans, 2021).
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 without diagnosed osteoarthritis (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; Kirmse, 2019; Oertzen-Hagemann, 2019; Zdzieblik, 2015).
A 6-day double-blind, randomized controlled trial of 22 healthy older women found 60 grams of supplemental collagen per day was inferior to 60 grams of supplemental whey protein per day in stimulating muscle protein synthesis in both periods of rest and exercise (Oikawa, 2020).
A 12-week double-blind, 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 grams 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.
We are unaware of any studies investigating the impact of collagen protein on muscle outcomes compared to plant protein.
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).
A randomized, double-blind pilot trial from Iran 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, 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 well as the overall calorie and protein intake between intervention and placebo groups. Mean protein intake increased in both groups from 1.6±0.3 gram per kilogram 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).
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). They point out that our bodies break down protein we eat into amino acids and it doesn’t matter where amino acids come from.
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.
There is also the option of taking turmeric supplements, which, as described above, show promise for reducing pain in people with OA (note they may be in capsules made from gelatin).
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.
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