Research > Technology Reviews > Hydrolyzed Collagen > “Q&A”
Note: If you’re an expert and want to provide additional evidence, please contact me. In general, I will use the term “sinew” to refer to both tendons and ligaments, since the research used is on both. They’re similar in some ways, such as the fact that they both use collagen fibers to transmit force. However, they are also different in some ways, such as their structure (e.g. elasticity), function, and metabolism.[1]
Instructions: Skim the below section for the bolded questions you care about and read the answers. You don’t need to read it all. In general, I’ve ordered the questions *roughly* in terms of importance. If you came here directly, see this general overview here.
Why are you writing about ‘hydrolyzed collagen’, also sometimes known as ‘collagen peptides’? Two reasons: First, Eric Hörst’s new company PhysiVāntage recently began promoting a product specific to climbers called Supercharged Collagen. He also sent me some of his product and his white paper. Second, I received a few comments of interest in the background research behind hydrolyzed collagen as a supplement. You can see my overview of Supercharged Collagen here.
Update (6/27/2019): Will you include updates by nutritionists in the climbing world as you find them? Definitely! Brian Rigby at climbingnutrition.com recently offered an update (June 26th) and clarification to his position on collagen supplementation. You can view it here.
What is the supplement intended to help heal/strengthen? The evidence suggests that hydrolyzed collagen may be promising as a recovery tool for muscle and “sinew” (a “catch-all” phrase for tendons – which connect muscle-to-bone, and ligaments – which connect bone-to-bone), assuming the right stimulation (exercise) and a few additional assumptions (discussed later).
Climbers care about tendons, though, right?! Yes, but there is a lot of similarity between tendons (like the long flexor tendons which help you flex your fingers) and ligaments (like the “a-bands” or “pulleys” you always hear people are injuring). This is why I mostly refer to “sinew” even though there are differences in how flexible they are, and what they do.
Going a little deeper, sinew has an inner “core” and an outer series of sheaths.[2] The outer sheath is composed of something called an “extracellular matrix” (ECM) composed mainly of collagen that is “crosslinked” to one another in a kind of wrapping.[3] The ECM “signals” information, “guides” interactions between the tendon and muscle, “ferries” nutrients through connection points with bone, “stores” information about growing, and “regulates” the force issued through the tendon as a result of your crimping. The outer sheath is the area of the tendon that Supercharged Collagen is intended to affect. Collagen at the core doesn’t appear to change much after the age of 17 and may or may not heal.[4]
In addition to sinew, the evidence also discusses a role for this supplement in muscle and joint support.
How is sinew fed? Sinew rely on “synovial fluid diffusion” for feeding – in fact, synovial fluid accounts for about 90% of tendon nutrition.[5] The “diffusion” (or movement) of fluid occurs from actively exercising. We’ll discuss the specifics of how this nutritional intervention is believed to reach the synovial fluid, but in addition to exercise, timing is believed to be critical: the supplement needs time to reach synovial fluid.
Why do scientists believe that the ECM, and collagen specifically, play such an important role in recovery? After damage, scientists have observed direct indicators of ECM damage under a microscope as well as indirect indicators of collagen production.
What exactly are “collagen peptides”? Amino acids (glycine, proline, lysine, hydroxylysine, and hydroxyproline[6]) which link in a chain in order to facilitate the production of collagen. Peptides are intended to be easily digestible in order to facilitate uptake into the body. Collagen is the building block of tendons and ligaments, or sinew – which is why a supplement is hypothesized to be helpful, and why studies are underway to determine effect.
What’s an example of why an amino acid is so important? Take the smallest, glycine. It helps tighten the amino acids together, helping the overall chain to withstand stress.[7]
Is the use of Hydrolyzed Collagen Peptides safe? A study by Praet et al. notes that (1) Collagen Peptides are “generally recognized as safe” by the Food and Drug Administration (FDA), and (2) an adverse monitoring program found no adverse effects other than mild soreness in the calf they attribute to the strengthening program.[8] However, the individual manufacturing process and final formula will impact whether there are human side effects, and need to be studied independently.
What’s the difference between generic collagen and PhysiVāntage Supercharged Collagen? In keeping with the direction of the research studies the product is based on, Supercharged Collagen is vitamin C-enriched. It’s also enriched with leucine in order to signal protein synthesis, and tryptophan. Generic collagen has very little leucine and no tryptophan. The addition of both make it a “complete protein” – a label suggesting it has the chemical building blocks (the nine “essential” amino acids) necessary to build proteins in your body.
Do we know anything about PhysiVāntage’s manufacturing process? The PhysiVāntage website states their product is obtained from a reputable source (“the worldwide leading producer of gelatin and collagen products”) and blended/packaged at a GMP-certified, FDA-registered facility (which are regulated for quality and consistency).
Can supplements affect soft tissue? The volume and quality of evidence is still in its infancy but the studies Eric cites point to a number of examples. Whey protein has been shown to improve tendon size when combined with resistance training,[9] and a study on rats (after malnutrition) using leucine (an amino acid which helps with protein synthesis) found a positive impact on tendon hypertrophy.[10] Additionally, there are studies discussed later which point to “indirect indicators” of effectiveness within humans.
Is there research showing an effect in humans? Studies on osteoarthritic populations have been completed since the 1980s. In 2017 a controlled study was carried out on a population with knee joint issues using collagen peptides.[11] Also in 2017, 8 subjects using a supplement were found to have double the amount of bone-specific collagen amino acids within the blood than placebo while a similar effect was seen in engineered sinew.[12]
A similar formula to PhysiVāntage’s Supercharged Collagen (Hydrolysate) was used in a study published in early 2019 on 20 runners with Achilles tendinopathy.[13] In the experiment, the researchers found the formula to be effective at improving “VISA-A” (satisfaction) scores well above a “minimum clinically important difference.” The study also indicated good results for return to their chosen sport, and showed a decrease in ‘microvascularity’, which is viewed as a positive indicator. It should be noted that funding for the study came from GELITA, whose product was evaluated in the study.
A more recent study looked at the effect of hydrolyzed collagen on muscle damage caused by the intensity of 150 countermovement, or plyometric, exercise jumps.[14] In a carefully-designed study of 24 males, the supplementation appeared to accelerate recovery after the exercise. The study used a twice daily, 7 day “pre-load” (prior to the muscle damage), as well as a 40 minutes prior dose. They made their determination based on a qualitative questionnaire of muscle soreness, blood sampling for inflammation and muscle damage, as well as blood markers thought to be helpful toward collagen synthesis.
More on how transfer from digestion to sinew may occur will be discussed later.
How similar is the formula PhysiVāntage is using to research? It’s similar but not exact. The 2019 study uses a product from a company in Germany that doesn’t appear to publish the exact formula, but it notes it includes glycine, proline, and hydroxyproline (and the studies note the importance of Vitamin C). PhysiVāntage’s Supercharged Collagen (Hydrolysate) formula includes Vitamin C, I-Leucine, glycine, proline, and hydroxyproline.
The human experiments either use gelatin (partially hydrolyzed – a chemical reaction which breaks the collagen down) or a fully hydrolyzed powder. PhysiVāntage’s formula is hydrolyzed collagen. PhysiVāntage also adds I-tryptophan, which means it includes all the “essential” (unable to be synthesized within the human body) amino acids and is therefore a “complete” protein – a label often important to vegetarians.[15]
Will the supplement alone give me stronger tendons? No one is making this claim. It is believed that the “mechanical loading” involved in exercise (and trauma) ‘signals’ immature tendon cells into fully developed tendon cells.[16] The supplement’s intent is to increase collagen synthesis in combination with exercise. The information provided by the “loading” helps create new collagen “turnover” and “crosslinks” collagen within the tendon, leading to an improvement in how well your sinew works.
What kind of frequency, intensity, or duration of exercise affects a change in sinew? Still unclear, but there’s laboratory evidence using engineered (from ACL, or knee ligaments) sinew which suggests that wide ranges of intensity (stretching) produce collagen similarly.[17] This ‘response’ peaked at 10 minutes of activity, and – notably – became resistant to additional production. It took a minimum of 3 hours before the cells which researchers were monitoring would respond to a second bout of stretching and 6 hours to reset the cells completely.[18] This information suggests that longer durations of exercise may break down tendon during a period when we have a limited ability to signal the formation of new collagen. There is a suggestion here that this could help us better understand why chronic tendon injury occurs.
How much intensity did the researchers put the engineered sinew through? The researchers opted for a 2.5% stretch intensity for their experiments since it simulated low impact. [19] The researchers note that as a general guide, stair climbing imparts 2.7% and bicycling about 1.2-2.1%.[20] This information (plus that from the previous question) indicated to the researchers that a regular, low intensity, short duration, intermittent training paradigm for tendon strengthening may be beneficial.
Are these recommendations made for injury rehabilitation or strengthening tendons and ligaments which are prone to injury? Interestingly, the author of research on engineered sinew and collagen amino acid digestion (Dr. Baar) recommends both.[21]
Will a supplement make it into the blood stream? Yes. However, it will take time. In a study of Vitamin-C infused gelatin, researchers found that the gelatin increased the circulation of amino acids (glycine, proline, hydroxyproline, and hydroxylysine) in blood and that it peaked at 1 hour after intake.[22]
Does that mean the supplement will make it to my injured or targeted sinew? This may be the biggest unknown. The peptides first have to make it from your small intestine to your blood stream. At least a small proportion do.[23] Additionally, researchers in the Shaw study found an indicator of increased collagen synthesis within subjects’ blood.[24]
Next, it needs to get to the damaged tissue. Preclinical trials suggest that a proportion of peptides does make it to the cartilage in joints.[25] All sinew has different levels of blood flow. In tendons, collagen fibers are surrounded by connective tissue which provide blood flow. Blood helps create a pathway for nutrients to transfer into your tissue but, strangely, soft tissue repair doesn’t necessarily occur just because blood vessels are present.[26] That’s because there’s another layer: as already mentioned, tendons rely on “synovial fluid diffusion” to receive nutrients – synovial fluid accounts for about 90% of tendon nutrition.[27] The “diffusion” (or movement) of fluid occurs from actively exercising.
So why is there controversy? Why can’t the researchers determine this 100%? Identifying a way of measuring whether nutrients have passed from digestion, into the mini-vessels for blood, and then into bands of connective tissue that transfer synovial fluid into the tendon sheath, remains a challenge for researchers.
The threshold for evidence accumulation is a really complex topic. The bottom line is that different minds will have different thresholds for when they believe the evidence is “sufficient” to be reported as “fact”.
How will future research affect these findings? It’s challenging to “biopsy” (remove “living” tissue and analyze it) sinew from human subjects.[28] A study using better indicators of strengthened human tendons remains to be completed.
How do animal studies and lab studies differ from human studies? They are indicative but not definitive. There are clear distinctions. For example, research suggests that rats have an accelerated healing pattern compared to humans.[29] Additionally, lab studies (such as those on engineered sinew) taken from a single donor would not take into account genetic and epigenetic variations between humans.
Has a meta-study been published that includes Hydrolyzed Collagen? Meta-studies are usually a sort of “state-of-the-field” because they review all the research they can find. Below are quick summaries of two. Though both are recent, the distinctions in their conclusions also show how fast this field is moving. The first is a 2018 meta-study whose summary writes:
“A small amount of literature exists that demonstrates a benefit of gelatin and/or collagen on connective tissue health. As adverse effects from gelatin/collagen supplements appear low, at worst, these supplements are just an inexpensive source of amino acids, so the benefits of supplementation outweigh the risks.”[30]
The 2016 meta-study was published before much of the research Eric cites. It’s on supplemental management of tendinopathy (chronically damaged tendons) and analyzed 40 pre-clinical studies and 6 clinical studies of the following supplements: Glucosamine/Chondroitin; Vitamin C; Hydrolyzed Collagen; L-arginine-alfa-keto-glutarate; Curcumin; Boswellic acid; Methylsulfonilmethane (MSM); and a formulation comprised of mucopolysaccharides, hydrolyzed type-1 collagen, and vitamin C. They assessed the clinical studies as being of fair-to-poor quality, but acknowledged that the preclinical results were encouraging.
[1] Screen et al, “Tendon Functional Extracellular Matrix,” J Orthop Res. 2015 Jun; 33(6): 793–799.
[2] Snedeker, Foolen, “Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy, Acta Biomaterialia, 63, 18-36 (2017)
[3] A. Subramanian, TF Schilling, “Tendon development and musculoskeletal assembly: emerging roles for the extracellular matrix,” Development 2015 142: 4191-4204
[4] Ibid Snedeker (2017)
[5] BA Zelle, FH Fu, “Pathogenesis of Soft Tissue and Bone Repair,” in Rehabilitation for the Postsurgical Orthopedic Patient (Third Edition), 2013
[6] Baar, “Minimizing Injury and Maximizing Return to Play: Lessons from Engineered Ligaments,” Sports Med. 2017; 47(Suppl 1): 5–11.
[7] M. Wu, JS Crane, “Biochemistry, Collagen Synthesis,” 2019
[8] Praet et al, “Oral Supplementation of Specific Collagen Peptides Combined with Calf-Strengthening Exercises Enhances Function and Reduces Pain in Achilles Tendinopathy Patients,” Nutrients, Jan 11(1): 76, 2019
[9] Ibid Baar (2017)
[10] Barbosa AW, Benevides GP, Alferes LM, et al. A leucine-rich diet and exercise affect the biomechanical characteristics of the digital flexor tendon in rats after nutritional recovery. Amino Acids. 2012;42:329–36.
[11] Zdzieblik et al, “Improvement of activity-related knee joint discomfort following supplementation of specific collagen peptides,” Applied Physiology, Nutrition, and Metabolism, 2017, 42(6): 588-595
[12] G. Shaw et al. “Vitamin C–enriched gelatin supplementation before intermittent activity augments collagen synthesis,” Am J Clin Nutr. 2017 Jan; 105(1): 136–143.
[13] Ibid Praet (2019)
[14] Clifford et al, “The effects of collagen peptides on muscle damage, inflammation and bone turnover following exercise: a randomized, controlled trial,” Amino Acids, 2019, 51(4), 691-704
[15] From the information provided, I could not determine a protein digestibility-corrected amino acid score (PDCAAS).
[16] K. Lipman, CC Wang, “Tendinopathy: injury, repair, and current exploration.” Drug Design, Development, and Therapy, Volume 12 (2018) 591-603
[17] Paxton JZ, Hagerty P, Andrick JJ, et al. Optimizing an intermittent stretch paradigm using ERK1/2 phosphorylation results in increased collagen synthesis in engineered ligaments. Tissue Eng Part A. 2012;18:277–84.
[18] Ibid Paxton (2012)
[19] Ibid Paxton (2012)
[20] Ibid Paxton (2012)
[21] Ibid Baar (2017)
[22] Ibid Shaw (2017)
[23] Ibid Zdzieblik (2017
[24] Ibid Shaw (2017)
[25] Ibid Snedeker (2017)
[26] Fenwick, Hazleman, and Riley, “The vasculature and its role in the damaged and healing tendon.” Arthritis Res. 2002; 4(4): 252-260
[27] Ibid Zelle (2013)
[28] Ibid Snedeker (2017)
[29] Ibid Snedeker (2017)
[30] ES Rawson, MP Miles, DE Larson-Meyer, “Dietary Supplements for Health, Adaptation, and Recovery in Athletes,” Human Kinetics Journals, 28 (2), 188-199
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