Whey + Collagen for the Best of Both Worlds?
This Week’s Research Highlight
Background
When you think about muscle growth and recovery, you probably picture the actual muscle fibers getting bigger and stronger. That is myofibrillar protein – it makes up the actual contractile machinery of muscle.
But there's another crucial component that often gets overlooked: the connective tissue framework that holds everything together. This network of proteins doesn't only provide structural support — it's essential for transferring force in basic activities of daily living, as well as athletic performance. Elite sprinters, for instance, don’t just have strong leg muscles, they also have powerful tendons, which help propel them across the finish line. Without this scaffolding, muscle fibers cannot work effectively.
It is well-established that resistance exercise stimulates the growth of muscle fibers. We also know that consuming protein after exercise can further boost muscle growth. This is particularly true for proteins that are high in leucine, which activates anabolic pathways, as well as other essential amino acids which form the raw materials for muscle tissue. The most leucine-rich protein source we have is whey, which is why it is considered a go-to for this purpose.
But here's where things get interesting: while whey protein effectively stimulates muscle fiber growth, it hasn't been shown to enhance connective tissue protein synthesis, even after exercise.
Why might this be?
One ongoing theory involves glycine. Oddly enough, when people consume dairy proteins like whey, blood glycine levels actually decrease. This could be a problem, because while muscle protein is highly responsive to leucine and other essential amino acids, connective tissue has different needs. Connective tissue relies heavily upon the amino acids glycine, proline, and hydroxyproline. Collagen, as a component within connective tissues, is an excellent source of these amino acids – indeed, glycine makes up about 30% of the amino acids in collagen.
This led researchers to wonder: What if we gave people a dose of whey protein, and supplemented it with just enough collagen to make up for the apparent shortfall in glycine?
A new study from Maastricht University, led by brilliant Dutch researcher Luc van Loon, set out to test this idea. He and his colleagues came up with a blend of whey and collagen proteins designed to optimize amino acid availability and promote remodeling of both types of tissue.
Study
To examine the potential advantages of combining collagen and whey, the researchers designed a double-blind, randomized controlled trial.
They recruited 28 healthy young men, and had them visit the lab fasted in the morning. Baseline blood samples and muscle biopsies were taken.
Then, participants were evenly split into two groups:
- One group received 30 grams of a protein blend (25gs of whey protein + 5g of collagen)
- The other group received a placebo.
After consuming the supplement, all participants went through an exercise protocol using leg press and leg extension machines.
But here’s the clever part: every participant performed the exercises using just one leg.
Think about it. That means, in effect, that each participant is serving as their own control. It enables the researchers to compare protein effects in the same person at the same time under the same conditions. Literally the only difference is exercise.
Then, over a five hour period, blood samples continued to be taken, and final muscle biopsies were taken from both the exercised leg and the rested leg of each man.
Throughout, the researchers were able to trace how the amino acids that participants had consumed were being incorporated into proteins via a technique called stable isotope tracer methodology, which works sort of like following a marked dollar bill through the banking system. The participants were given a continuous infusion of a labeled amino acid, and the researchers kept taking blood samples to see where the amino acids were going. After five hours, researchers took final muscle biopsies from both legs (exercised and rested) to see how many marked amino acids ended up in different muscle proteins.
In this way, the researchers could calculate exactly how much new protein the body was building, and they could distinguish between different types of protein (muscle vs connective tissue).
Findings
Let’s start by looking at muscle protein synthesis. For the most part, these results aren’t super surprising.
Myofibrillar Protein Synthesis (% / hour):
Baseline (before protein/exercise):
- BLEND: 0.028 ± 0.013
- PLACEBO: 0.023 ± 0.010
At rest:
- BLEND: 0.038 ± 0.008
- PLACEBO: 0.031 ± 0.006
The protein blend showed a significant benefit here (p<0.05), enhancing muscle protein synthesis above baseline.
Post-exercise:
- BLEND: 0.052 ± 0.011
- PLACEBO: 0.039 ± 0.009
In the exercised leg, the protein blend showed a significant additional benefit (p<0.01) — even beyond that of the resistance exercise.
Again, this is exactly what we would expect, based on what we already know about muscle protein synthesis. Myofibrillar protein is highly responsive to essential amino acids (especially leucine), and whey protein contains loads of them.
Now, let's take a look at the connective tissue protein synthesis rates, and compare the effect of the protein blend vs placebo in both conditions.
This shows a distinctly different pattern.
Connective Tissue Protein Synthesis (% / hour):
Baseline (before protein/exercise):
- BLEND: 0.050 ± 0.018
- PLACEBO: 0.042 ± 0.013
At rest:
- BLEND: 0.062 ± 0.013
- PLACEBO: 0.051 ± 0.010
So first of all, one thing that jumps out here is that baseline connective tissue protein synthesis rates are much higher than that of myofibrillar protein. We’ll come back to that.
And consuming the protein blend does significantly increase connective tissue protein synthesis above baseline in the resting condition (p<0.05). Now let’s take a look at what happens after exercise.
Post-exercise:
- BLEND: 0.090 ± 0.021
- PLACEBO: 0.079 ± 0.016
The difference here between the blend and placebo is not statistically significant (p=0.11). Meaning, while the protein blend increased connective tissue protein synthesis in the rested leg, it didn't provide any additional benefit beyond the exercise stimulus in the exercised leg.
This is a key finding, and maybe a little counter-intuitive at first. Let me try to break it down.
Exercise alone strongly stimulates connective tissue protein synthesis. In fact, exercise had a proportionally greater effect on connective tissue protein synthesis than on muscle protein synthesis! But adding the protein blend doesn’t further augment this exercise-induced increase.
Why not? That brings us back to glycine.
Remember, the original hypothesis was that low glycine availability might limit connective tissue protein synthesis, and that supplying glycine (via collagen) could help fill in the gap, compensating for the negative impact of dairy protein on plasma glycine.
But that doesn’t appear to be exactly right. Or at least, it may depend on timing.
During exercise recovery, the body seems to do a good job mobilizing glycine internally to meet demands for connective tissue protein synthesis.
As the researchers state,
"...these data imply that endogenous release of glycine and proline is sufficient to provide ample amino acid precursors to support the post-exercise increase in muscle connective protein synthesis rates."
But that doesn’t mean that collagen is useless for connective tissue. Remember that the protein blend did enhance connective tissue protein synthesis in the rested state. What explains this?
Take a look at the baseline protein synthesis rates for the two tissue types:
- Connective protein synthesis rates: 0.050-0.062%/hour
- Myofibrillar protein synthesis rates: 0.028-0.038%/hour
As I alluded to earlier, connective tissue has much higher rates of synthesis at rest — in fact, it’s roughly double the baseline synthesis rate of myofibrillar protein. This could imply a higher turnover rate — meaning greater repair demands. Which makes some sense. Connective tissue is constantly under mechanical stress, even when you’re not working out. Due to its critical structural role in the body, it has to renew itself continuously to avoid catastrophic failure. As a result, it requires a regular supply of building blocks — such as glycine and the other constituents found in collagen.
At the same time, connective tissue is far more responsive to the anabolic stimulus of exercise. In the post-exercise cellular milieu, these amino acids seem to be maximally mobilized. But at rest, when this internal mobilization, for whatever reason, is not triggered, some extra nutritional support for your hard-working connective tissue actually does pay off.
Key Takeaways
Muscle protein synthesis is boosted by high-quality protein.
High-quality protein (like whey) provides essential amino acids that form the building blocks for myofibrillar protein, as well as leucine which has a special role in triggering muscle protein synthesis.
Recent research suggests that muscle protein synthesis is maximized in most individuals at around 1.6 g per kg of body mass per day, which is double the current RDA. Over time, protein supplementation combined with training leads to gains in muscle mass, as well as improvements in strength and other performance metrics.
Exercise remains the most important stimulus.
That having been said, it’s not enough to just feed your muscles the building blocks. You have to apply stress to give the body a reason to adapt in the first place.
An analysis of 74 randomized trials that compared protein supplementation to placebo in individuals performing strength training programs does a nice job of illustrating this. They found that training by itself (placebo) led to 2.8-3 pounds of muscle mass. Meanwhile, protein supplementation resulted in 1.1-1.5 pounds of additional muscle mass.
We also see this in the data from today’s study. The impact of exercise on both muscle and connective tissue protein synthesis was significantly greater than the effect of protein. Even in the placebo group, with no supplemental protein at all, exercise spurred an increase in muscle remodeling.
This reinforces that while nutrition is important, it can't replace the fundamental stimulus of exercise.
Connective tissue responds even more strongly to the stress of exercise.
Connective tissue showed a more dramatic response to exercise than muscle tissue. Prior research has shown that connective tissue actively adapts to loading, but this further reinforces that exercise is crucial for connective tissue health.
This becomes particularly relevant when considering periods of inactivity or rehabilitation. Since connective tissue appears highly responsive to exercise, extended periods without appropriate loading might have substantial impacts on connective tissue health. This could influence everything from return-to-play protocols after injury to strategies for preventing age-related decline in connective tissue function.
The dramatic response to exercise also highlights why maintaining regular physical activity throughout life is crucial — it's not just about muscle strength, but about maintaining the integral connective tissue framework that supports all movement.
Connective tissue is constantly rebuilding, and benefits from supplementation of its amino acids (from collagen).
Connective tissue showed notably higher baseline protein synthesis rates compared to muscle protein (0.050 vs 0.028 percent per hour). This higher baseline activity suggests that connective tissue is constantly being remodeled, even when we're not exercising. This ongoing process likely requires a steady supply of specific amino acids, particularly glycine, which is abundant in collagen protein but pretty scarce in most other protein sources.
Furthermore, the study found that the protein blend (containing collagen) increased connective tissue protein synthesis during rest, but didn't provide additional benefits beyond exercise's effects. This suggests that the body might benefit more from having consistent access to collagen's building blocks throughout the day, rather than just around exercise sessions.
This makes intuitive sense when we consider that connective tissue maintenance is an ongoing process, not just something that happens in response to exercise.
Therefore, rather than focusing solely on pre- or post-workout collagen supplementation, maintaining consistent daily intake might be more beneficial. This could be even more important on non-training days, when we're not getting the strong stimulus of exercise but connective tissue synthesis and remodeling continues at its naturally higher baseline rate.
Random Trivia & Weird News
🎻 The term “collagen” comes from the Greek word for glue — and with good reason.
The English word "collagen" comes from the Greek word "kolla" meaning "glue" (plus "gen" meaning "producing"). This name came from the ancient practice of boiling animal sinews and skin to make glue. In fact, for thousands of years, before people even knew what collagen was, they were boiling animal parts to make "collagen glue" (also called hide glue).
This traditional hide glue was so effective that it was used in making the famous Stradivarius violins in the 17th and 18th centuries. Some violin makers still use it today because of its unique properties, as well as its reversibility — when you need to repair an antique violin, you can soften the old collagen glue with heat and moisture without damaging the wood.
So when we talk about collagen "holding things together" in our muscles and connective tissue, it's doing essentially the same job it did in ancient hide glue pots and priceless violins!
Podcasts We Loved This Week
- Shawn Arent: Nutrients for cognitive performance in sports. Via Sigma Nutrition Radio.
- Mike Murphy, Florencia Camus, & Nick Lane: Mitochondria. Via In Our Time.
Products We Like
Horbaach Multi Collagen Protein Powder
If you're looking to implement these findings, Horbaach Multi Collagen Powder offers a practical option. The product includes multiple collagen types (I, II, III, V, and X) and is hydrolyzed for better absorption.
It's also a very cost-effective way to add collagen to your supplement routine. On Amazon, it costs less than half as much as Vital Proteins, just $0.27 per 10-gram serving. And if you’re trying to replicate the study described above (five grams), that comes to just $0.14 per serving.
For study-aligned usage: Mix 5 g with 25 g of your regular whey protein. While the specific collagen used in the study discussed above was GELITA's Bodybalance, this product provides similar amounts of the key collagen peptides discussed in the study. It's unflavored, so it should be pretty easy to combine with your preferred whey protein.
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