Collagen supplementation for joint health – an in depth analysis

Collagen is currently one of the most popular supplements. The promise is better cartilage, tendon and joint health, which would be important for every athlete, because it may reduce the likelihood of injury and/or improve recovery after a connective tissue injury. Hence, it is worth looking at the mechanism and overall scientific evidence of its effectiveness on pain reduction and joint health.

 

Background

In 2019, it was estimated that 57 million people in Western Europe had osteoarthritis, a condition in which the articular cartilage wears away, exposing the underlying bone, often causing chronic pain and requiring surgical treatment (1). In athletes, connective tissue injuries are the most frequently reported injuries. Therefore, it is not surprising that there is significant interest in finding strategies that may lead to better soft tissue quality and/or support the healing properties of cartilage, tendons, and ligaments.

In this context, collagen is of major interest, as it provides structural support to the extracellular space of connective tissues. Collagen is the most abundant protein in connective tissue, particularly type I collagen. The strength and stiffness of our connective tissues and tendons are determined, in part by the amount of collagen they contain. It is reasonable to assume that improving collagen synthesis may indirectly lead to better joint and connective tissue quality and decrease the risk of injuries (2).

 

In this article, you” find a summary of the current evidence of collagen supplements on improving cartilage and tendon health

Collagen is a protein-based structure made of amino acids. In contrast to muscle tissue, it contains fewer essential amino acids and more proline and glycine.

 

 

This leads to the hypothesis that consuming certain nutrients high in proline and glycine could potentially stimulate collagen synthesis and improve joint health for athletes and individuals with arthritis. Two notable dietary protein sources in this context are gelatin and collagen hydrolysate, as they contain higher amounts of proline and glycine compared to other protein sources.

 

 

 

 

 

But aren’t gelatine and collagen of low protein quality?

Gelatine and collagen indeed have relatively low protein quality, especially when assessed by their biological value. The biological value compares the amino acid composition of protein-rich foods to that of human muscle (4). So yes, gelatine and collagen are not well-suited candidates to make you look jacked. While gelatine and collagen may not be effective for promoting muscle growth—as recent studies have shown no positive effect of collagen supplementation on muscle protein synthesis (5). However, this does not mean they cannot positively impact other tissues.

 

How well is gelatine digested and absorbed?

A mechanistic study conducted in 1999 found that gelatin hydrolysate is absorbed by mice, leading to an accumulation of gelatin hydrolysate in their cartilage tissue (6).

Nearly two decades later, researchers verified these findings in humans. (7).  In a crossover study, eight healthy subjects consumed either 0, 5, or 15 grams of gelatin enriched with 48 mg of Vitamin C one hour before completing 6 minutes of rope skipping.

 

The findings:

Consumption of 15 grams of Vitamin C-enriched gelatin resulted in a significant increase in the concentrations of glycine and proline in the blood. This indicates that these “lower quality” proteins are indeed absorbed and significantly increase the levels of these amino acids, which play a crucial role in collagen synthesis.

 

 

Furthermore, a significant positive effect on the collagen synthesis rate (an increase of 153%) was measured through the levels of amino-terminal propeptide (PINP), a precursor of collagen that contains a short signal sequence and terminal extension peptides. The researchers also noted an increased concentration of collagen in the engineered ligament.

 

 

What about collagen?

The same group of researcher did a follow-up study where they compared the effect of 15g of hydrolysed collagen vs. 15g gelatine (vitamin-c enriched) vs. gummi bears that contained both gelatine and collagen (8).

The results?

The results showed that both collagen supplementation and gelatine (vitamin-C enriched) led to approximately a 20% increase in collagen synthesis rate. However, this change was not statistically significant.

When looking closely at the individual responses of the participants, a significant variance becomes evident. Further analysis revealed that the overall positive effect may have been driven by one positive outlier in both the gelatine and collagen groups. Notably, in the gelatine group, three out of eight participants showed no positive change in collagen synthesis, while four out of eight exhibited no effect in the collagen group.

 

 

Therefore, it is questionable whether these positive findings can be reliably applied to the general public

 

is important to note that the researcher again utilized a manufactured ligament in both studies. Up to this point, we still lack human studies that confirm these findings. Given these circumstances, I believe that more studies with larger cohorts are necessary to verify these results before we can confidently state that gelatin or collagen supplementation positively impacts collagen synthesis.

However, there are additional studies we can examine to better understand the overall effects on joint and ligament health.

For instance, McLindon and colleagues (9) investigated the effects of daily supplementation with 10g of collagen hydrolysate on mild knee osteoarthritis over a duration of 48 weeks. The extended duration of the study is certainly a significant advantage. The researchers also evaluated cartilage function using dGEMRIC imaging, which serves as a more reliable indicator of changes in cartilage tissue than measuring its acute synthesis rate over shorter periods (10, 11).

And indeed, a positive effect can clearly be seen when looking at the images below:

 

 

Does that prove that collagen supplementation is indeed effective for improving cartilage damage?

 

Not so fast!

The dGEMRIC images showed improvements of cartilage in the posterior lateral femur region, with the collagen group demonstrating statistically better improvement than the control group.

However, further MRI images of cartilage tissue in other regions (such as the medial tibia, central medial femur, posterior medial femur, lateral tibia, and central lateral femur) did not reveal any differences between the collagen and placebo groups.

The author’s conclusion was:

In contrast to the dGEMRIC results, the T2 cartilage measures showed little variability or change with time, and no differences in any region between groups […] because of the pilot nature of this study, and its small sample size, we do not regard these results to be definitive, and the CH intervention merits further testing in a larger study.

Additionally, it remains unclear why the collagen group showed improvements in certain areas while exhibiting no changes in others. With only 15 participants per group, the sample size is insufficient for drawing definitive conclusions, and there are currently no other studies utilizing dGEMRIC images to evaluate changes in cartilage structure.

 

Effect of collagen on tendon and ligament stiffness & functionality

The same study from above (9) also assessed potential changes in physical functionality and stiffness but failed to find a positive effect of collagen supplementation. It should be noted that participants did not follow a systematic training regimen to strengthen muscles, tendons, or other soft tissue. This may explain why McAlindon et al. (2011) (9) did not observe a positive effect, as resistance exercise is a required stimulus for collagen synthesis (12).

In another study, Leet et al. (2003) found a small benefit of 30g of daily collagen hydrolysate supplementation (+ 500mg of vitamin C) on patellar tendon stiffness in female football players [COL, +18.0 ± 12.2% (d = 1.11) vs. PLA, +5.1 ± 10.4% (d = 0.23), p = 0.049]. However, tendon growth was similar between groups (13).

In another study 40 healthy young men trained their calve muscle and Achilles tendon for 14 weeks, 3 training sessions per week, and took 5g of collagen peptides (CP – Temdeforte®) (14). As far as I know, this is the only study where participants followed a structured resistance training protocol for more than a three-month period while progressively increasing training weight. This may explain why the authors detected a significantly (p = 0.002) greater increase in tendon growth (CSA +11.0%) compared to the PLA group (+4.7%). In contrast, there was no difference in tendon stiffness or muscle strength increase between groups.

Praes et al. (2019) conducted a double-blinded randomized controlled trial (RCT) with a cross-over design involving 10 participants who had Achilles Tendinopathy. The participants were administered 2.5g of collagen peptide (CP) daily over a period of 6 months, combined with a bi-daily calf-strengthening program (15). Their findings indicated that there was no significant benefit of CP on tendon micro-vascularity, which was assessed using contrast-enhanced ultrasonography (CEUS). CP supplementation had no impact on ankle functionality and tendon pain, as measured by the VISA-A questionnaire.

The author did find a positive trend towards faster return to sport was observed in athletes who took CP. However, the small sample size made it impossible to conduct a thorough statistical analysis. This raises the question of whether the observed differences were merely due to chance rather than actual effects of the supplementation.

Interestingly, this study is often referenced in discussions regarding the effectiveness of CP

 

 

 

 

Can it reduce pain?

Multiple studies suggest that there may be a small benefit of collagen supplements on arthritis-related pain (16,17,18). This improvement in pain sensation was measured both subjectively from the patients and confirmed by standardized tests by doctors.

 

 

However, it should be noted that other studies didn’t find a positive effect on pain reduction (19).

So what does that mean for using collagen as an anti-pain treatment?

 

From a practical standpoint, I would categorize collagen as “worth trying” if someone is really suffering from arthritis-related pain. If you don’t notice a difference after about 8 weeks, just stop taking it. The overall effect will likely be small to moderate, as most studies report a reduction in pain sensation in the range of 15-20% compared to placebo.

 

 

Effectiveness of Whey and Casein

It seems natural to assume that high-quality protein sources, such as Whey or Casein protein, are likely to have a positive effect on collagen synthesis, considering that lower quality protein sources have been reported to work.

Surprisingly, this does not seem to be the case. Multiple studies using Whey protein did not find any positive effect on intramuscular connective tissue or collagen synthesis rate (20, 21).

One hypothesis as to why these studies failed to find an effect on connective tissue synthesis is that Whey protein is metabolized “too fast,” meaning that the activation of connective tissue occurs too late and hence requires a slower absorbed protein to optimally stimulate the process.

 

 

This hypothesis was investigated by Trommelen et al., (2020) (22). They discovered that while exercise activates the rate of connective tissue synthesis, consuming 30g of casein protein post-resistance training did not yield any additional benefits

Connective tissue proteins contain high concentrations of proline (12%) and glycine (25%) relative to other proteins within skeletal muscle. Casein on the other hand contains only small amounts of proline (6.5%) and glycine (2%) and may, therefore, provide insufficient amounts of these important amino acids to support postexercise increase in muscle connective tissue protein synthesis rate (23). This hypothesis is supported by the fact that the administered Casein by Trommelen et al. (2020) failed to elevate glycine concentrations in the blood.

 

What if the amount of consumed protein would be increased?

This question was investigated by a follow-up study of the same researchers (24): they raised the protein intake to 40g of casein protein to assess its effects on connective tissue synthesis after resistance training in older men. The findings revealed that this increased consumption had a positive impact on the rate of connective tissue synthesis.

 

 

we demonstrate for the first time that dietary protein-derived amino acids are incorporated into de novo muscle connective tissue protein in older adults

 

The consumption of 40g of casein protein did indeed have a positive effect on connective tissue synthesis rate.

 

 

Summary:

 

• Mechanistic in-vitro studies indicate that collagen and gelatine may significantly enhance cartilage synthesis rates.
• In individuals suffering from chronic joint pain, ongoing collagen supplementation for 8 weeks or longer could lead to a reduction in subjective pain levels by 15-20%.
• Evidence supporting the idea that collagen supplementation improves cartilage health is quite weak.
• There is weak to moderate evidence suggesting that collagen might enhance tendon stiffness.
• It appears that both Whey and Casein proteins do not have a significant impact on cartilage tissue, even when taken in higher quantities.
• The availability of high-quality randomized controlled trials (RCTs) in humans is lacking, which hinders our ability to draw definitive conclusions regarding the potential benefits of collagen supplementation on joint and tendon health.

 

My assessement

Overall evidence for improving joint health

The overall evidence is mixed; with some studies showing promising results. However, if you look at the details of those studies, almost all of them contain methodological weaknesses. The results from mechanistic studies, as well as the positive results with regards to pain reduction, are somewhat promising, but we need more high-quality RCT’s with humans to be able to draw a more distinct conclusion.