Is The Lack Of Dietary Collagen A Problem For Animal-Free Diets?

Collagen is a fibre-like structural protein. It forms part of connective tissue, which is figuratively speaking the glue that holds us (and all other animals) together1. Collagen is present throughout the entire body, but accumulates in larger quantities in skin, tendons, bone, cartilage and ligaments. It therefore stands to reason then that collagen is found in animal products (particularly in connective tissue and flesh). But collagen is not present in animal-free foods and vegan-friendly synthetic collagen supplements are not commercially available.  

Fortunately, collagen is not an essential macronutrient; meaning that our bodies can manufacture it by combining various amino acids (mostly glycine, proline, alanine and hydroxyproline). But we can still wonder whether vegan diets might be improved with a source of dietary collagen. Perhaps, an external source would boost collagen synthesis and thereby improve the health of our joints and skin for example. 

Animal-free collagen for oral use is not commercially available. As far as I know, none of the vegan products which are designed to boost collagen production contain collagen. However, all the amino acids that make up this protein molecule can be synthesized without reliance on animal products. But collagen does provide something that animal-free supplements presently cannot: collagen specific peptides (peptides are amino acids that are bound together). Digestive processes do not break down all collagen to individual amino acids; it seems that dipeptides and tripeptides (couplets and triplets of bound amino acids respectively) are also absorbed to some extent5,6. Moreover, these collagen-derived peptides have been theorized to encourage tissue repair.   

Do collagen peptides provide unique benefits?  

It seems to me that the whole question of whether animal-free diets are disadvantaged due to a lack of dietary collagen, turns on whether collagen derived peptides provide unique benefits.

Now, in vitro studies have shown that certain collagen peptides stimulate fibroblasts (a type of cell contributes to the production of connective tissues) 2,3,4. But does this mechanism translate to better outcomes in vivo? For a few reasons, I think that some scepticism is warranted. Firstly, these in vitro experiments typically involve directly exposing fibroblasts in petri dishes with collagen peptides for days. Whereas following ingestion of collagen, blood levels of the relevant dipeptides and tripeptides would rise for a mere matter of hours15. Secondly, only a fraction is absorbed as peptides18. Thirdly, since the major components of collagen are non-essential amino acids, one would imagine that with sufficient intake of essential amino acids the body can manufacture all the collagen it needs.   

I suspect that the last point is especially important. In my opinion, to establish that collagen has special benefits for our connective tissues, this would need to be shown in isonitrogenous (viz, protein-matched) randomised controlled studies in humans. Since there is a lack of experiments of this nature, I remain somewhat sceptical.   

Dietary collagen and muscle mass  

Compared to placebo, collagen peptides may improve training adaptations to exercise, in terms of increasing fat-free mass and strength16,17.  

But how does collagen perform relative to other isolated sources of protein? Compared to the same amount of whey protein, collagen very much appears to be an inferior product for muscle protein synthesis 7,8,9. Arguably, this result is explained by the fact that collagen is mostly composed of non-essential amino acids and what’s more it lacks certain essential amino acids (it’s low in methionine and is devoid of tryptophan)10. In light of this, I think it’s safe to assume that collagen is less anabolic compared to many other sources of concentrated protein, including those that are animal-free (such as soy and pea protein isolates).  

Dietary collagen and musculoskeletal connective tissue  

Short-term studies have failed to show that protein supplementation per se increases collagen synthesis in musculoskeletal connective tissue15. It’s been hypothesized that collagen in particular holds promise for increasing muscle connective tissue protein synthesis (which is mostly dependent on increased collagen synthesis)20. However, I am not aware of a published human clinical trial that has put this to the test.  
 
Interestingly, two small, short clinical trials observed no significant difference between 30g of collagen peptides and the same amount of whey protein in terms of intramuscular collagen synthesis7,30. To me, this substantiates the case for scepticism in relation to purported upregulation of collagen synthesis in other tissues in response to dietary collagen. 

However, a handful of placebo-controlled trials suggest that oral collagen supplements may help with symptoms of osteoarthritis, such as joint stiffness23 as well as (in the short-term at least) pain and physical function24. This is arguably a promising research program, but I suspect that more research is needed before definitive conclusions can be made. At present, no medical guidelines endorse collagen as a therapeutic or supportive option for patients with osteoarthritis. 

Several studies suggest that collagen supplementation may relieve exercise-related joint pain and promote recovery from injury compared to placebo26. However, the largest study on this topic to date failed to replicate these findings28.

Unfortunately, I’ve been unable to identify any studies that investigated the impact of other protein sources on these endpoints. However, a recent double-blind placebo controlled study showed that a blend of non-essential amino acids (found in collagen) also seemed to improve joint pain and function27. This is only a single study, but it opens up the possibility that it’s the amino acid profile of collagen – rather than collagen peptides – that promotes better joint health. 

Dietary collagen and skin appearance  

Numerous randomized controlled trials indicate that hydrolysed collagen improves skin hydration11,14, skin elasticity11,14, mean wrinkle value11 and cutaneous density11 compared to a similarly administered placebo.  

Despite the consistency of these results, I am not convinced that collagen is uniquely beneficial for skin appearance.  Firstly, nearly all studies pitted collagen against a placebo (usually maltodextrin), rather than another protein supplement. Secondly, in most studies the intervention group was given other active ingredients (e.g., co-enzyme Q10, vitamins, zinc, L-carnitine etc.) and as such we should be less confident that the observed results are solely an effect of collagen.   

Vegan diets and wound healing  

Two studies have shown that vegans display poorer skin healing abilities in comparison to omnivores 12,13. Since wound healing depends on collagen synthesis and collagen remodelling, one might speculate that this is due to a lack of dietary collagen.  

However, while these results should be taken seriously, I don’t believe we should conclude that this is the result of a putative dietary collagen deficiency. There are other potentially important dietary variables to consider. For instance, vegans are consistently shown to consume lower amounts of protein21, 22 and zinc22; both of which are recognised as being important for building collagen and wound repair.  Additionally, vegans typically have lower iron status22 – another nutrient relevant to collagen production. Moreover, the bioavailability of animal-free sources of these nutrients are typically lower compared to those found in animal-based foods.   

Summary and recommendations  

As things stand, I am unconvinced that a lack of dietary collagen is an issue for animal-free diets. The hypothesis that dietary collagen stimulates collagen synthesis in connective tissue more than other proteins is not well supported. While there is evidence that oral collagen supplements may confer benefits (particularly for skin and joints), virtually all studies did not use an active control group. Moreover, it’s worth bearing in mind that most studies were industry funded and used small sample sizes. 

Future studies that compare collagen to other protein sources may change my mind; but for now I tend to think that well-planned high protein animal-free diets facilitate sufficient endogenous collagen production.  Regardless, the following practical tips may help to improve the quality of connective tissue in those that choose to avoid animal products: 


Eat more protein  

I recommend aiming for 1.2-1.6g of protein per kilogram of bodyweight per day – this will supply an abundance of essential amino acids. For those that opt to eat lower protein diets, it may be prudent to include animal-free foods which are similar in protein quality to animal protein (e.g., soy, mycoprotein).   

Hit nutrient targets 

Vitamin C, iron and zinc are thought to be particularly important for collagen production. But be aware of nutrients of focus. 

Exercise regularly and frequently 

Exercise is the most important stimulus for remodelling musculoskeletal connective tissue. 

Follow sun safety guidelines

Protect your skin from the sun via shade, clothing and sunscreen. 

Vegan collagen “boosters”

Some vegans may wish to use an animal-free supplement which purportedly boosts collagen production. To be clear, these products have very little scientific backing. But for those that want to try one of these supplements – in the hope of benefits – I would suggest choosing one that has an amino acid profile similar to collagen or one that provides a lot of glycine29
 

References 

1. Shoulders, M.D. and Raines, R.T., 2009. Collagen structure and stability. Annual review of biochemistry, 78, pp.929-958. 

2. Postlethwaite, A.E., Seyer, J.M. and Kang, A.H., 1978. Chemotactic attraction of human fibroblasts to type I, II, and III collagens and collagen-derived peptides. Proceedings of the National Academy of Sciences, 75(2), pp.871-875. 
 
3. Ohara, H., Ichikawa, S., Matsumoto, H., Akiyama, M., Fujimoto, N., Kobayashi, T. and Tajima, S., 2010. Collagen?derived dipeptide, proline?hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblasts. The Journal of dermatology, 37(4), pp.330-338. 

4. Sato, K., Asai, T.T. and Jimi, S., 2020. Collagen-derived di-peptide, prolylhydroxyproline (Pro-Hyp): a new low molecular weight growth-initiating factor for specific fibroblasts associated with wound healing. Frontiers in Cell and Developmental Biology, 8, p.548975. 

5. Iwasaki, Y., Nakatogawa, M., Shimizu, A., Sato, Y. and Shigemura, Y., 2022. Comparison of gelatin and low-molecular weight gelatin hydrolysate ingestion on hydroxyproline (Hyp), Pro-Hyp and Hyp-Gly concentrations in human blood. Food Chemistry, 369, p.130869. 

6. Iwasaki, Y., Taga, Y., Suzuki, A., Kurokawa, M., Sato, Y. and Shigemura, Y., 2020. Effect of co-ingestion of collagen peptides with yogurt on blood absorption of short chain hydroxyproline peptides. Applied Sciences, 10(12), p.4066. 
 
7. Oikawa, S.Y., Kamal, M.J., Webb, E.K., McGlory, C., Baker, S.K. and Phillips, S.M., 2020. Whey protein but not collagen peptides stimulate acute and longer-term muscle protein synthesis with and without resistance exercise in healthy older women: a randomized controlled trial. The American journal of clinical nutrition, 111(3), pp.708-718. 
 
8. Oikawa, S.Y., Macinnis, M.J., Tripp, T.R., McGlory, C., Baker, S.K. and Phillips, S.M., 2020. Lactalbumin, Not Collagen, Augments Muscle Protein Synthesis with Aerobic Exercise. Medicine and Science in Sports and Exercise, 52(6), pp.1394-1403. 
 
9. Oikawa, S.Y., McGlory, C., D’Souza, L.K., Morgan, A.K., Saddler, N.I., Baker, S.K., Parise, G. and Phillips, S.M., 2018. A randomized controlled trial of the impact of protein supplementation on leg lean mass and integrated muscle protein synthesis during inactivity and energy restriction in older persons. The American journal of clinical nutrition, 108(5), pp.1060-1068. 
 
10. Phillips, S.M., 2017. Current concepts and unresolved questions in dietary protein requirements and supplements in adults. Frontiers in nutrition, p.13. 

11. de Miranda, R.B., Weimer, P. and Rossi, R.C., 2021. Effects of hydrolyzed collagen supplementation on skin aging: a systematic review and meta?analysis. International Journal of Dermatology, 60(12), pp.1449-1461. 

12. Fusano, M., Fusano, I., Galimberti, M.G., Bencini, M. and Bencini, P.L., 2020. Comparison of postsurgical scars between vegan and omnivore patients. Dermatologic Surgery, 46(12), pp.1572-1576. 
 
13. Fusano, M., Zane, C., Calzavara-Pinton, P. and Bencini, P.L., 2021. Photodynamic therapy for actinic keratosis in vegan and omnivore patients: The role of diet on skin healing. Journal of Dermatological Treatment, 32(1), pp.78-83. 
 
14. Pu, S.Y., Huang, Y.L., Pu, C.M., Kang, Y.N., Hoang, K.D., Chen, K.H. and Chen, C., 2023. Effects of Oral Collagen for Skin Anti-Aging: A Systematic Review and Meta-Analysis. Nutrients, 15(9), p.2080. 

15. Holwerda, A.M. and van Loon, L.J., 2022. The impact of collagen protein ingestion on musculoskeletal connective tissue remodeling: a narrative review. Nutrition Reviews, 80(6), pp.1497-1514. 

16. Zdzieblik, D., Oesser, S., Baumstark, M.W., Gollhofer, A. and König, D., 2015. Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: a randomised controlled trial. British Journal of Nutrition, 114(8), pp.1237-1245. 

17. Oertzen-Hagemann, V., Kirmse, M., Eggers, B., Pfeiffer, K., Marcus, K., de Marées, M. and Platen, P., 2019. Effects of 12 weeks of hypertrophy resistance exercise training combined with collagen peptide supplementation on the skeletal muscle proteome in recreationally active men. Nutrients, 11(5), p.1072. 
 
18. Taga, Y., Iwasaki, Y., Shigemura, Y. and Mizuno, K., 2019. Improved in vivo tracking of orally administered collagen hydrolysate using stable isotope labeling and LC–MS techniques. Journal of agricultural and food chemistry, 67(16), pp.4671-4678. 

19. Phillips, S.M., Tipton, K.D., Van Loon, L.J., Verdijk, L.B., Paddon-Jones, D. and Close, G.L., 2016. Exceptional body composition changes attributed to collagen peptide supplementation and resistance training in older sarcopenic men. British Journal of Nutrition, 116(3), pp.569-570. 

20. Holwerda, A.M., Trommelen, J., Kouw, I.W., Senden, J.M., Goessens, J.P., van Kranenburg, J., Gijsen, A.P., Verdijk, L.B. and van Loon, L.J., 2021. Exercise plus presleep protein ingestion increases overnight muscle connective tissue protein synthesis rates in healthy older men. International journal of sport nutrition and exercise metabolism, 31(3), pp.217-226. 

21. Sam West, Alistair J. Monteyne, Ino van der Heijden, Francis B. Stephens, Benjamin T. Wall,Nutritional considerations for the vegan athlete.,Advances in Nutrition, 2023, 

22. Bakaloudi, D.R., Halloran, A., Rippin, H.L., Oikonomidou, A.C., Dardavesis, T.I., Williams, J., Wickramasinghe, K., Breda, J. and Chourdakis, M., 2021. Intake and adequacy of the vegan diet. A systematic review of the evidence. Clinical nutrition, 40(5), pp.3503-3521. 

23. García-Coronado, J.M., Martínez-Olvera, L., Elizondo-Omaña, R.E., Acosta-Olivo, C.A., Vilchez-Cavazos, F., Simental-Mendía, L.E. and Simental-Mendía, M., 2019. Effect of collagen supplementation on osteoarthritis symptoms: a meta-analysis of randomized placebo-controlled trials. International orthopaedics, 43, pp.531-53 

24. Liu, X., Machado, G.C., Eyles, J.P., Ravi, V. and Hunter, D.J., 2018. Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. British journal of sports medicine, 52(3), pp.167-175. 

25. Honvo, G., Lengelé, L., Charles, A., Reginster, J.Y. and Bruyère, O., 2020. Role of collagen derivatives in osteoarthritis and cartilage repair: a systematic scoping review with evidence mapping. Rheumatology and therapy, 7, pp.703-740. 

26. Khatri, M., Naughton, R.J., Clifford, T., Harper, L.D. and Corr, L., 2021. The effects of collagen peptide supplementation on body composition, collagen synthesis, and recovery from joint injury and exercise: a systematic review. Amino acids, 53(10), pp.1493-1506.

27. Takeuchi, F., Takada, M., Kobuna, Y., Uchida, H. and Adachi, Y., 2022. Effects of Non-Essential Amino Acids on Knee Joint Conditions in Adults: A Randomised, Double-Blind, Placebo-Controlled Trial. Nutrients, 14(17), p.3628.

28. Bongers, C.C., Ten Haaf, D.S., Catoire, M., Kersten, B., Wouters, J.A., Eijsvogels, T.M. and Hopman, M.T., 2020. Effectiveness of collagen supplementation on pain scores in healthy individuals with self-reported knee pain: a randomized controlled trial. Applied Physiology, Nutrition, and Metabolism, 45(7), pp.793-800.

29. de Paz-Lugo, P., Lupiáñez, J.A. and Meléndez-Hevia, E., 2018. High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis. Amino Acids, 50(10), pp.1357-1365.

30. Aussieker, T., Hilkens, L., Holwerda, A.M., Fuchs, C.J., Houben, L.H.P., Senden, J.M., van Dijk, J.-W., Snijders, T. and van Loon, L.J.C. (n.d.). Collagen Protein Ingestion during Recovery from Exercise Does Not Increase Muscle Connective Protein Synthesis Rates. Medicine & Science in Sports & Exercise,

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