Creatine is a nonprotein compound which plays an important role in supplying our tissues with energy during periods of increased demand. It is not an essential nutrient: the human body can make creatine using the amino acids glycine, arginine and methionine as building blocks.
Because creatine (in non-negligible quantities) is only found in animal flesh, vegetarians and vegans rely solely on their body's ability to synthesise this compound. Consequently, they typically have lower stores 9, 10, 11, 12. Does this this means that vegetarians/vegans are at a disadvantage in relation to physical and cognitive function? and if so, might supplementing with creatine correct for this? I have attempted to answer these questions in this blog.
Creatine supplementation is being studied for various other potential therapeutic applications e.g., mental health, pregnancy, vascular health, metabolic health15. However, the science in support of these applications is weak. I've focused solely on the potential benefits of creatine in relation to sports performance and cognitive function because these interventions are supported by high-quality evidence.
The Ergogenic Benefits of Creatine
It has been established beyond reasonable doubt that creatine supplementation improves high-intensity exercise performance (e.g., resistance training and sprinting) and increases muscle mass (in conjunction with resistance training)1,2. Ostensibly, creatine facilitates muscle gain by enabling individuals to perform more work (more reps/sets/weight) than they otherwise would have been able to (although there are other potential mechanisms). Creatine supplementation most likely improves exercise performance through improved muscle availability of creatine (more accurately phosphocreatine), which is in turn used for ATP production – a form of energy that can be released quickly, especially during reduced oxygen availability.
Creatine may enhance performance in various sporting activities, particularly those that involve power and strength. The ergogenic benefits of creatine have been observed in adolescents, younger adults and older adults1. However, it appears that men respond to creatine more robustly and consistently3, 4.
While there is a strong consensus in relation to the ergogenic benefits of creatine supplementation, most of the research has been based on non-vegan participants. As such, only a limited number of studies can help to inform whether creatine might benefit vegans/vegetations more than meat-eaters. To the best of my knowledge only three studies have investigated the impact of creatine supplementation on muscle mass and/or strength in vegetarians compared to meat-eaters:
Watt et al.12 observed that vegetarians and omnivores on creatine performed similarly well at sprint cycling. However, total creatine levels in the vegetarians did not return to baseline which may have distorted the results.
Shomrat et al.9 tested the impact of 6 days of creatine supplementation (7g per day) on maximal cycling capacity in vegetarians and non-vegetarians. Maximal cycling capacity did not significantly differ at baseline. Creatine improved exercise performance in both vegetarians and non-vegetarians to a similar extent compared to the non-vegetarian control group.
Burke et al.10 randomly assigned vegetarians and non-vegetarians to either an intervention group (creatine) or placebo (maltodextrin) for eight weeks. All subjects participated in supervised, intense, heavy-load training. At baseline there were no significant differences between groups in terms of: 1) lean mass, 2) muscle fibre area, 3) 1-rep max leg press or 4) 1-rep max bench press. However, at baseline vegetarians had significantly lower total creatine stores and consumed less protein and calories.
After eight weeks the vegetarians that were given creatine had significantly higher phosphocreatine and total creatine compared to all other groups.
Lean tissue mass increased in both the vegetarian and non-vegetarian intervention groups compared to placebo. However, the vegetarians on creatine experienced significantly greater gains (2.4kg vs 1.9kg). Moreover, changes in lean tissue mass correlated with changes in total creatine in muscle.
Upon completion of training, all groups improved their leg press 1-rep max, with no differences between groups. The intervention groups gained more strength in relation to chest press 1-rep max compared to placebo (with apparently no significant differences between the vegetarian and non-vegetarian intervention groups).
Since the vegetarians on creatine experienced greater increases in lean tissue mass (which seemed to scale with greater increases in total creatine concentrations), this study provides some support for the idea vegetarians may stand to benefit more from creatine supplementation.
Do vegetarians/vegans exhibit lower levels of lean mass and strength?
Vegetarians and vegans have been observed to display lower levels of lean tissue mass and grip strength compared to meat eaters in a large cross-sectional study13. In my estimation this may be entirely explained by the fact that vegan and vegetarian diets are associated with lower BMI14: one can't reasonably expect slimmer people to have equivalent amounts of lean mass and strength compared to larger individuals. What's more, the above-mentioned cross-sectional analysis13 found that vegans/vegetarians had comparable strength per kilogram of lean mass (a measure of muscle quality).
Other cross-sectional studies suggest strength and muscle are similar between vegans and omnivores of similar bodyweight5, 6, 8. Moreover, a recent interventional study found no significant differences in lean mass and strength between habitual vegans & omnivores at baseline and observed similar improvements in terms of lean mass and strength after 12-weeks of resistance training in conjunction with a high protein diet7. In light of this, it seems to me that if there are differences between vegetarians and meat-eaters in terms of muscle and strength adaptations to exercise, they are likely to be rather small.
Exercise “unlocks” the ergogenic benefits of creatine
As previously mentioned, creatine supplementation only increases strength and muscle if it is combined with exercise. Thus, we have no cause to expect sedentary vegans to lack muscle/strength compared to sedentary omnivores due to a “creatine deficiency”. Whether one is vegan/vegetarian or not, creatine will not increase muscle mass or strength without an anabolic stimulus in the form of strength or high-intensity training.
Vegans/vegetarians MAY get more exercise performance benefits from creatine supplementation
Firstly, it is mechanistically plausible that vegans may benefit more from creatine. Creatine plays an established role in making energy available during high intensity physical activity and is scientifically proven to enhance muscle and strength adaptations to exercise. Vegans/vegetarians have lower stores at baseline and upon supplementation exhibit greater increases of creatine concentrations in muscles.
Secondly and more importantly, Burke et al.10 observed that vegans on creatine gained significantly more lean mass in response to strength training (compared to omnivores on creatine). This is only one study, however. More studies are needed before we can be certain that vegans/vegetarians stand to benefit more from creatine in terms of sports performance.
Regardless, vegans and vegetarians that are interested in gaining strength/power/muscle (in response to exercise) may wish to consider supplementing with creatine. Creatine monohydrate is the form of creatine most widely studied; it's also the cheapest. Creatine monohydrate has been studied extensively over several decades and does not appear to pose any risks to health1.
Creatine and cognitive function
A number of randomized controlled trials have investigated the effect of creatine on various measures of cognitive function. The results have been mixed for most cognitive domains, but the evidence in relation to memory and intelligence is promising16. A recent meta-analysis of clinical trials found creatine supplementation to be associated with large improvements in memory among healthy older adults17,18. However, the number of studies were limited and most of them were judged to be at high risk of bias.
The above-mentioned meta-analysis16 excluded studies with vegetarian/vegan participants. Furthermore, it was not possible to determine whether baseline serum/brain creatine is related to responsiveness (as none of the included studies assessed this). Sidenote: I think it's interesting that there's evidence that brain creatine levels are comparable between vegetarians and meat-eaters19, 20.
To the best of my knowledge only two studies have investigated the impact of creatine supplementation in vegetarians; both are double-blind placebo-controlled randomised trials. I will briefly describe these studies below.
Rae et al.21 found that creatine significantly improved working memory and intelligence of young adult vegetarians. This suggests that vegetarians/vegans may benefit cognitively from supplementation; but it does not shed any light on the question of whether they may benefit more than meat-eaters (they used a crossover design; all participants were vegetarian).
Benton et al.22 investigated the impact of 20g of creatine (or a placebo) for 5 days on various cognitive tasks in vegetarians and non-vegetarians.
• The vegetarians did comparably well at baseline & thus this study provides no evidence that a putative "creatine deficiency" impairs memory in vegetarians.
• In those that received creatine (as opposed to the placebo), the vegetarians outperformed the non-vegetarians. But both did worse compared to baseline (?second memory test more difficult; ?were the participants less motivated).
It's challenging to interpret these results, I think. Arguably, it's suggestive of vegans being more responsive to creatine supplementation. But given that 1) everyone did worse on the second test & 2) The non-vegetarians performed less well compared to placebo, I'd say we can't conclude much from this.
Where does the evidence point?
Creatine supplementation may have cognitive benefits, especially for older adults. However, I would describe the evidence as promising. More trials (ideally longer, larger ones) are required before we can be confident about creatine improving memory and intelligence.
It is unclear whether vegetarians/vegans stand to benefit more from creatine supplementation in relation to cognitive performance. But I am not aware of any decent quality evidence suggesting that vegetarian/vegan diets lead to worse cognitive function or outcomes (due to a lack of dietary creatine or otherwise).
Summary
- Creatine is an effective ergogenic aid (for vegans and non-vegans alike).
- One trial provides some support for the idea that vegans/vegetarians may benefit more from creatine supplementation in relation to muscle adaptations to exercise. But more studies are required to confirm this finding.
- But vegans/vegetarians DO NOT need to supplement with creatine to obtain similar muscle and strength gains (versus non-supplementing meat-eaters).
- A lack of dietary creatine does not appear to negatively impact cognitive function in vegetarians/vegans.
- Limited evidence (based on non-vegetarian/non-vegan populations) suggests that creatine may enhance cognitive function (especially in older adults).
References
1. Kreider, R.B., Kalman, D.S., Antonio, J., Ziegenfuss, T.N., Wildman, R., Collins, R., Candow, D.G., Kleiner, S.M., Almada, A.L. and Lopez, H.L., 2017. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14(1), p.18.
2. Kerksick, C.M., Wilborn, C.D., Roberts, M.D., Smith-Ryan, A., Kleiner, S.M., Jäger, R., Collins, R., Cooke, M., Davis, J.N., Galvan, E. and Greenwood, M., 2018. ISSN exercise & sports nutrition review update: research & recommendations. Journal of the international society of sports nutrition, 15(1), p.38.
3. Delpino, F.M., Figueiredo, L.M., Forbes, S.C., Candow, D.G. and Santos, H.O., 2022. The Influence of Age, Sex, and Type of Exercise on the Efficacy of Creatine Supplementation on Lean Body Mass: A Systematic Review and Meta-analysis of Randomized Clinical Trials. Nutrition, p.111791.
4. Antonio, J., Candow, D.G., Forbes, S.C., Gualano, B., Jagim, A.R., Kreider, R.B., Rawson, E.S., Smith-Ryan, A.E., VanDusseldorp, T.A., Willoughby, D.S. and Ziegenfuss, T.N., 2021. Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?. Journal of the International Society of Sports Nutrition, 18(1), p.13.
5. Page, J., Erskine, R.M. and Hopkins, N.D., 2022. Skeletal muscle properties and vascular function do not differ between healthy, young vegan and omnivorous men. European Journal of Sport Science, 22(4), pp.559-568.
6. Boutros, G.H., Landry-Duval, M.A., Garzon, M. and Karelis, A.D., 2020. Is a vegan diet detrimental to endurance and muscle strength?. European journal of clinical nutrition, 74(11), pp.1550-1555.
7. Hevia-Larraín, V., Gualano, B., Longobardi, I., Gil, S., Fernandes, A.L., Costa, L.A., Pereira, R.M., Artioli, G.G., Phillips, S.M. and Roschel, H., 2021. High-protein plant-based diet versus a protein-matched omnivorous diet to support resistance training adaptations: a comparison between habitual vegans and omnivores. Sports Medicine, 51, pp.1317-1330.
8. Pohl, A., Schünemann, F., Bersiner, K. and Gehlert, S., 2021. The impact of vegan and vegetarian diets on physical performance and molecular signaling in skeletal muscle. Nutrients, 13(11), p.3884.
9. Shomrat, A., Weinstein, Y. and Katz, A., 2000. Effect of creatine feeding on maximal exercise performance in vegetarians. European journal of applied physiology, 82, pp.321-325.
10. Burke, D.G., Chilibeck, P.D., Parise, G.I.A.N.N.I., Candow, D.G., Mahoney, D.O.U.G.L.A.S. and Tarnopolsky, M., 2003. Effect of creatine and weight training on muscle creatine and performance in vegetarians. Medicine & Science in Sports & Exercise, 35(11), pp.1946-1955.
11. Delanghe, J., De Slypere, J.P., De Buyzere, M., Robbrecht, J., Wieme, R. and Vermeulen, A., 1989. Normal reference values for creatine, creatinine, and carnitine are lower in vegetarians. Clinical chemistry, 35(8), pp.1802-1803.
12. Watt, K.K., Garnham, A.P. and Snow, R.J., 2004. Skeletal muscle total creatine content and creatine transporter gene expression in vegetarians prior to and following creatine supplementation. International journal of sport nutrition and exercise metabolism, 14(5), pp.517-531.
13. Tong, T.Y., Key, T.J., Sobiecki, J.G. and Bradbury, K.E., 2018. Anthropometric and physiologic characteristics in white and British Indian vegetarians and nonvegetarians in the UK Biobank. The American journal of clinical nutrition, 107(6), pp.909-920.
14. Fontes, T., Rodrigues, L.M. and Ferreira-Pêgo, C., 2022. Comparison between different groups of vegetarianism and its associations with body composition: A literature review from 2015 to 2021. Nutrients, 14(9), p.1853.
15. Kreider, R.B. and Stout, J.R., 2021. Creatine in health and disease. Nutrients, 13(2), p.447.
16. Avgerinos, K.I., Spyrou, N., Bougioukas, K.I. and Kapogiannis, D., 2018. Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Experimental gerontology, 108, pp.166-173.
17. Prokopidis, K., Giannos, P., Triantafyllidis, K.K., Kechagias, K.S., Forbes, S.C. and Candow, D.G., 2022. Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials. Nutrition Reviews.
18. Prokopidis, K., Giannos, P., Triantafyllidis, K.K., Kechagias, K.S., Forbes, S.C. and Candow, D.G., 2023. Author's reply: Letter to the Editor: Double counting due to inadequate statistics leads to false-positive findings in “Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials”. Nutrition Reviews.
19. Solis, M.Y., Artioli, G.G., Otaduy, M.C.G., Leite, C.D.C., Arruda, W., Veiga, R.R. and Gualano, B., 2017. Effect of age, diet, and tissue type on PCr response to creatine supplementation. Journal of Applied Physiology, 123(2), pp.407-414.
20. Solis, M.Y., de Salles Painelli, V., Artioli, G.G., Roschel, H., Otaduy, M.C. and Gualano, B., 2014. Brain creatine depletion in vegetarians? A cross-sectional 1H-magnetic resonance spectroscopy (1H-MRS) study. British journal of nutrition, 111(7), pp.1272-1274.
21. Rae, C., Digney, A.L., McEwan, S.R. and Bates, T.C., 2003. Oral creatine monohydrate supplementation improves brain performance: a double–blind, placebo–controlled, cross–over trial. Proceedings of the Royal Society of London. Series B: Biological Sciences, 270(1529), pp.2147-2150.
22. Benton, D. and Donohoe, R., 2011. The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. British journal of nutrition, 105(7), pp.1100-1105.
