Newsletter #308

This week, I’d like to take a look at collagen peptides, and a new dose-response study that sheds some light on how much might be needed for enhancing the strength of our connective tissue — specifically the tendons.

First of all, let’s go over what happens to connective tissue as we get older, and why you want to build up your tendon strength in the first place.

Collagen is synthesized by a class of cells known as mesenchymal cells. As we age, the function of these cells (like many parts of the body) becomes compromised, causing collagen production to become more sluggish. This is perhaps most evident in the formation of wrinkles in the skin, which is due in part to deterioration of fibroblasts, a type of mesenchymal cell.

We also see this in the tendons. Tendons become less stiff with age, leading to both impaired strength and increased risk of injury. If you are a sports fan, you are probably all too aware of how devastating such injuries can be.

Indeed, if you want to perform at your very best, the robustness of your tendons is arguably as important as your muscles. Great sprinters, for instance, have immensely stiff tendons, which can store more energy and recoil more powerfully, driving them across the finish line.

So what can we do to enhance connective tissue strength, and maintain their function for years to come? Fortunately, some very smart researchers have been working on this.

Much like our muscles, our tendons can respond to resistance training. Mechanical loading (via exercise) ramps up collagen synthesis, while inactivity causes it to languish. In fact, just one resistance training session can double the rate of collagen synthesis. Over time, this results in stronger tendons, even in older individuals.

However, connective tissue doesn’t get a ton of blood flow. So while it can adapt through mechanical loading, it does not do so nearly as quickly or as readily as skeletal muscle. One way to help augment collagen synthesis induced by exercise is consumption of supplemental collagen, either in the form of gelatin or hydrolyzed collagen peptides. Keith Baar at UC Davis, whom we interviewed previously, has performed experiments with human subjects, in which he has them consume gelatin shortly before jumping rope. After consuming the gelatin, biomarkers related to collagen synthesis went up substantially.

Yet, the proper dose to drive these adaptations remains unclear. If you look at systematic reviews and meta-analyses of this area, you will see a fairly wide range of doses, and only one prior trial has actually compared different doses.

This raises two questions: is there a threshold dose needed to see a rise in collagen synthesis? And is there a dose-response relationship, wherein a low dose spurs some increase in collagen synthesis, and a higher dose provides a greater effect?

Researchers in the UK hypothesized that a bigger dose of hydrolyzed collagen, consumed in close proximity to exercise, would lead to a greater increase in biomarkers related to collagen synthesis compared to a smaller one.

To assess whether such a dose-response relationship exists, the team recruited 10 resistance-trained, healthy young men for a double-blind, randomized crossover trial.

First, every participant checked in at the lab to assess their 10-rep maximum at the barbell back squat.

Then, participants visited the lab on three different occasions, in random order, with each session separated by one week.

At the beginning of each session, they were given a drink, which contained 50 mg of vitamin C as well as:

After consuming the supplement, they performed 4 sets of barbell back squats at their 10-rep max.

Finally, subjects rested after their workout, and blood samples were collected at various intervals over the next six hours.

You can assess collagen synthesis directly by harvesting tendon biopsies. But that's not much fun for the participants, so the researchers went with blood-borne biomarkers instead. You can measure collagen synthesis indirectly by looking at serum concentrations of procollagen type Ⅰ N-terminal propeptide (PINP). During the maturation process of collagen, PINP is cleaved off and subsequently floats around in the blood, so higher concentrations of PINP in circulation reliably reflect the synthesis rate of collagen. More PINP means more collagen synthesis, generally speaking.

They also measured β-isomerized C-terminal telopeptide of type I collagen (β-CTX), which is released in the bloodstream during collagen degradation, and thus reflects collagen turnover.

After participants had gone through every experimental condition, the researchers analyzed and compared the effects of the three different conditions on these biomarkers within each subject.

So, first of all, plasma β-CTX concentration decreased by around 30% after the resistance exercise, and there was no difference between the groups. It is already known that resistance exercise inhibits collagen breakdown, ensuring that the brand new collagen is retained and incorporated, and it looks like these guys were enjoying this effect, without any added benefit from the collagen. Just another good reason to lift weights, if you needed one.

Next, let’s look at serum PINP, the biomarker of collagen synthesis. PINP rose in all three groups within an hour after squatting, indicating an increase in exercise-induced collagen synthesis as you’d expect. However, during that six-hour window, distinct differences emerged between the groups.

Notably, 30 grams of hydrolyzed collagen elicited a bigger increase in PINP than either 15 grams and 0 grams. Meanwhile, 15 grams produced about the same serum level of PINP as 0 grams — in other words, it was not effective, based on this biomarker, at boosting collagen synthesis beyond the effects of the resistance exercise.

The researchers concluded, based on this finding, that "at least 30 g hydrolyzed collagen is required to provide greater exogenous collagen amino acid availability."

So does this mean that any dose under 30 grams is a waste?

Well, bear in mind that the other dose-response study that I alluded to earlier showed significantly enhanced collagen synthesis in response to 15 grams of hydrolyzed collagen, in direct contrast to this study. And another trial found increases in Achilles tendon synthesis and cross-sectional area in response to just five grams of hydrolyzed collagen. So I would say that we still don’t really have consensus on the proper dose for this purpose.

Nevertheless, it does seem like a higher dose elicits a greater and more reliable effect for tendon stiffness specifically. That having been said, 30 grams of hydrolyzed collagen is a lot, and it could become rather expensive if that was your daily dose.

I think the logical way to approach this is to take the 30 gram dose strategically before your strength training, rather than as a regular daily supplement. Since most people only engage in resistance training 2-3 times per week, that should make the high dose a little more practical and economical, and ensure that it is being used when it’s most likely to be therapeutic.

And keep in mind, first and foremost, that physical activity  – especially plyometric and weight-bearing exercise – is the key for stimulating collagen synthesis and fighting collagen breakdown.

What we refer to as the 6-pack is actually the rectus abdominis. This muscle is made up of two connected muscle bands running parallel to one another, with bands of connective tissue (fascia) running horizontally across the muscle. These bands of fascia are what make the rectus abdominis look like packs stacked on top of one another.

And although a 6-pack is the most common appearance of toned abdominal muscles, you might have noticed that other configurations are possible, and this is dictated by the number of bands of fascia. Some people have 4-packs, some have 8-packs, and some rare individuals, who have four bands of fascia, can sport a 10-pack.

Although he had a “Six-Pack Routine,” Arnold Schwarzenegger himself appears to have a four-pack, due to his fascia.

Research suggests that any form of collagen probably works just fine. However, one big advantage for a product like this one is that it dissolves readily in any liquid, cold or hot, and it has a very neutral flavor, making it easy to take even in larger amounts. It also comes with vitamin C already added in, so it's a little bit more convenient. Finally, it's been independently lab-tested and found to be free of heavy metals or other nasty stuff, so it's a safe choice.

An ergogenic aid is simply a supplement that enhances physical performance. Dietary intake of these substances can, in theory, affect training adaptations in a couple of different ways. They can achieve this by simply increasing the exercise stimulus from a single training bout — basically just enabling an athlete to train longer or harder, or reducing perceived exertion — or by altering cellular responses to exercise-induced stress. But it’s important to note that these changes in cell signaling may not be universally beneficial from the standpoint of adaptation. For example, it is theoretically possible that a supplement could simultaneously make it easier for an athlete to exercise hard, but also have effects on cellular signaling that actually have a long-term negative impact on the adaptive response to training.

In this guide, we review some of the most rigorously researched supplements, discuss how best to use them, and talk about why some supplements that sound like a good idea may actually not be helpful at all. If you are looking for a quick reference sheet of the latest evidence-based guidance on supplements to maximize your performance and adaptations, check it out! 👀

Wishing you the best,

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