Since creatine and phosphocreatine concentrations may be lower in the muscle of vegetarians, there is good potential that supplementation with creatine might improve creatine and phosphocreatine concentrations, and potentially enhance exercise performance and recovery in vegetarians. It should be noted that although creatine is found mostly in animal products, the creatine in most supplements is synthesized from sarcosine and cyanamide [39
], does not contain any animal by-products, and is therefore “vegan-friendly”. The only precaution is that vegans should avoid creatine supplements delivered in capsule form because the capsules are often derived from gelatin and therefore could contain animal by-products. In our review of the literature, we found one systematic review on the effect of creatine supplementation in vegetarians [41
]; however, it included a review of only three manuscripts with two of the manuscripts derived from the same study. The conclusions from this systematic review were therefore limited. Our objective was to systematically review randomized and prospective parallel groups or cross-over studies on the effect of creatine supplementation (compared to placebo) in vegetarians (compared to omnivores where possible) for outcomes including body creatine stores and exercise performance. We hypothesized creatine supplementation would increase creatine concentrations in the blood and muscle of vegetarians (to a greater extent than omnivores) and this would lead to improvements in anaerobic exercise performance.
4.1. Systematic Review Methodology
Our systematic review was performed in accordance with the guidelines for the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The literature search was conducted in PubMed and SPORTDiscus, including all dates up until 18 April 2020. Key words and Boolean phrases searched included “creatine” AND “(vegetarian OR vegan OR vegetarianism OR veganism)”. There were no restrictions on language or date. Since creatine supplementation can have short-term effects on muscle function, we considered any length of follow up.
The following population, intervention, comparator, outcomes, and study types (PICOS) were included: The population was vegetarians. The intervention was creatine monohydrate supplementation. The comparator was either a placebo and/or participants who were omnivores. Outcomes included muscle, blood, or brain measurements of creatine or phosphocreatine, any exercise performance measure, lean tissue mass, muscle fiber area, anabolic hormones, creatine transporter levels, and cognitive performance. Study type included randomized controlled trials (parallel group and cross-over trials) and prospective trials.
Titles, abstracts, and full manuscripts were reviewed for inclusion by two reviewers. Data extraction and determination of risk of bias using the most recently revised Cochrane risk of bias tool [42
] was also performed by two reviewers. When there were disagreements, the reviewers either came to a consensus or consulted a third reviewer.
4.3. Systematic Review Discussion
Creatine supplementation in vegetarians is effective for increasing creatine and phosphocreatine levels to an extent that vegetarians may achieve higher levels of creatine and phosphocreatine after supplementation, compared to omnivores (i.e., it appears that the lower baseline levels in vegetarians might allow for “super compensation” of creatine or phosphocreatine levels with supplementation; see Table 1
). For example, five to seven days of creatine supplementation (at a dose of about 20–25 g/day) results in greater increases in plasma creatine [36
], vastus lateralis total creatine [37
], and gastrocnemius phosphocreatine [33
] concentrations in vegetarians versus omnivores, resulting in greater concentrations of creatine or phosphocreatine post-supplementation in vegetarians despite lower baseline levels. This leads to speculation that omnivores might be able to deplete their muscles of creatine (through meat abstinence) to achieve a super compensation of creatine and phosphocreatine levels with supplementation. Only one study has attempted this type of intervention. Lukaszuk et al. [17
] randomized 26 male omnivores to receive 26 days of their regular diet or a lacto–ovo vegetarian diet, and further randomized these participants to 0.3 g creatine/kg/day supplementation or placebo in the last five days (i.e., days 22–26). During these last five days, total creatine in the vastus lateralis increased in the vegetarian creatine-supplemented group by 20% and the omnivorous creatine-supplemented group by 10% [17
]. This was significantly greater than the placebo-supplemented groups, but because of low participant numbers and therefore lack of statistical power, the increases between the vegetarian-supplemented group and omnivorous-supplemented group were not statistically significant. Phosphocreatine concentrations were 22% higher at the end of the five days of creatine supplementation in the vegetarian compared to the omnivorous group, but again this was not statistically different, most likely due to low statistical power. One would expect, however, that a 22% difference in muscle phosphocreatine would lead to performance differences during short-term, high-intensity exercise, but this was not assessed in this study. This is an area open for future research to inform athletes involved in anaerobic sports: whether depleting the muscle of creatine (i.e., through adoption of a vegetarian diet) followed by creatine supplementation might lead to greater enhancements in sport performance compared to just supplementation alone.
With an apparently enhanced ability to take up and store creatine, one might expect the muscle creatine transporter to be enhanced with a vegetarian diet. This was assessed in one study where seven male vegetarians (with at least six months on a vegetarian diet) and seven male omnivores participated in a randomized cross-over study involving 0.4 g creatine/kg/day or placebo for five days [37
]. Baseline mRNA levels for the creatine transporter from biopsies of the vastus lateralis were not different between vegetarian and omnivore groups; they increased after one day of creatine supplementation (in vegetarian and omnivore groups combined) and then returned to baseline by day 5. Changes in mRNA levels do not always result in increased protein expression because further steps (i.e., translation) need to be activated for full protein synthesis. It would be of interest for future studies to assess protein levels of the creatine transporter in vegetarian versus omnivorous individuals.
The minimum level of creatine supplementation required in vegetarians to prevent decreased creatine stores is probably about 1 g/day (the amount found in 200 g of steak) [47
]. Blancquaert et al. [34
] randomized 40 female omnivores, with 10 continuing their normal diet, 15 going on a lacto–ovo vegetarian diet and supplementing with 1 g creatine/day, and 15 going on a lacto–ovo vegetarian diet and supplementing with placebo for six months. Vastus lateralis biopsies were collected at baseline and three months, and plasma at baseline, three months, and six months. After three months, total creatine in the vastus lateralis decreased 15% in the vegetarian + placebo group, and increased 9.7% in the vegetarian + creatine group and 6.8% in the control group. After six months, plasma creatine had decreased 46% in the vegetarian + placebo group, increased 195% in the vegetarian + creatine group, and did not change in the control group, compared to baseline. This indicates that just a small amount of creatine supplementation (i.e., 1 g/day) is required for vegetarians to prevent reductions in muscle creatine levels.
Since vegetarians respond better than omnivores to creatine supplementation, it might be expected that creatine would enhance exercise performance to a greater extent in vegetarians; however, studies are mixed (Table 1
). The study by Blancquaert et al. [34
] discussed in the previous paragraph assessed exercise performance during an incremental cycle ergometer test over six months in groups assigned to vegetarian diet, omnivorous diet, and vegetarian diet + 1 g creatine/day, but despite differences between groups for creatine levels in plasma and muscle, no differences were observed between groups for exercise performance. The performance test used, however, is more of a test of aerobic capacity, rather than a test that would stress anaerobic energy systems and muscular phosphocreatine usage; therefore, lack of effectiveness of creatine supplementation on this test is not surprising [24
]. Watt et al. [37
] assessed changes in performance during two repeats of a 30 s Wingate test, separated by four minutes rest during a cross-over study of 0.4 g creatine/kg/day or placebo for five days in seven vegetarian and omnivorous males. This type of test involves short-duration maximal cycling, largely depends on the usage of muscle phosphocreatine stores, and improves with creatine supplementation in studies of omnivorous participants [24
]. Despite a greater increase in vastus lateralis total creatine in vegetarians, both the vegetarians and omnivores equally increased mean power output during the second Wingate test with creatine supplementation. This could be due to a roughly equivalent (~31%) increase in vastus lateralis phosphocreatine in both groups (i.e., the greater total creatine in the vegetarian group would be due to greater increase in free creatine, whereas it is the phosphorylated creatine that is essential for re-phosphorylating adenosine diphosphate to re-synthesize adenosine triphosphate necessary for repeated high-force muscle contractions). A limitation discussed by Watt et al. [37
] is that the washout period of five weeks between creatine and placebo phases may not have been sufficient for the vegetarian participants. Of the three vegetarian participants who received creatine supplementation during the first phase of the cross-over, their vastus lateralis total creatine levels were still elevated at the start of their placebo phase. This lack of sufficient washout of muscle creatine may have artificially enhanced performance during the placebo phase, therefore, attenuating any performance difference between creatine and placebo phases in the vegetarian participants. In contrast to what might be expected with vegetarians being more responsive to creatine supplementation, Shomrat et al. [35
] found that omnivores might have slightly better improvement in anaerobic performance than vegetarians with creatine supplementation. In their study, seven male vegetarians and nine omnivores received 3 × 7 g creatine/day for six days. Mean power output during 3 × 20 s Wingate cycle tests (with four-minute recovery between bouts) was increased in both supplemented groups by about 5%, but only the omnivores had an increase in peak power output during the test (by about 5%).
A limitation of the creatine supplement studies in vegetarians presented Table 1
is that most assessed non-athletic populations. Burke et al. [18
] were the only researchers to assess recreational athletes, who either walked, jogged, swam, or cycled on a regular basis, and also had one to five years of resistance training experience. This study randomized 18 male and female vegetarians and 24 male and female omnivores to creatine (0.25 g creatine/kg lean tissue mass/day for seven days + 0.0625 g creatine/kg lean tissue mass/day for 56 days) or placebo groups. During supplementation, they engaged in a high-volume resistance training program (involving a three-day split which trained all major muscle groups over the three days). Vegetarians on creatine had a greater increase in vastus lateralis total creatine and phosphocreatine than other groups during the intervention (Table 1
). This translated to a greater increase in lean tissue mass and greater ability to perform work during a muscular endurance task involving 50 repetitions of maximal knee extension/flexion exercise on an isokinetic dynamometer at a velocity of 180 degrees/s [18
]. The difference in this study compared to other studies for enhancement of exercise performance preferentially in vegetarians who supplemented with creatine could be due to the longer-term supplementation, the use of an athletic population (who would have less variation from day to day on exercise performance tests than a non-athletic population), and that creatine supplementation was combined with a resistance training program. The athletes in the Burke et al. [18
] study were described as “recreational” athletes. An area for future research would be to assess the effect of creatine supplementation on a more elite group of vegetarian athletes.
Although most creatine in the body is stored in muscle, the brain is also dependent on phosphocreatine as an energy source and therefore there is interest in the effects of creatine supplementation on brain function. Brain function is important for athletes because activation of the motor cortex is essential for recruiting spinal motor neurons and contraction of muscle fibers [48
]. As mentioned previously, it appears that unlike skeletal muscle, creatine and phosphocreatine levels in the brains of vegetarians are not lower compared to omnivores [19
]. Creatine supplementation (0.3 g/kg/day for seven days) in vegetarians and omnivores failed to increase phosphocreatine levels in the brain [33
]. One might therefore expect equal responsiveness to creatine supplementation in vegetarians and omnivores for effects on brain function, but this is not the case (Table 1
). Benton et al. [45
] randomized 70 female vegetarians and 51 omnivores to 20 g creatine/day or placebo for five days and found that memory was enhanced in vegetarians supplemented with creatine but not omnivores. Rae et al. [46
] supplemented 45 vegetarians with 5 g creatine/day or placebo for six weeks in a cross-over study and found working memory and intelligence were increased with creatine supplementation compared with placebo. These studies therefore show that memory and intelligence can be enhanced in vegetarians with creatine supplementation; this may translate to better sport performance (for example, a competitive vegetarian athlete on creatine might be better able to remember strategies used by an opponent during past competitions). This, however, remains to be tested in an athletic situation. It would be of interest to determine if creatine supplementation enhances the ability to activate the motor cortex during exercise to recruit motor units. This has been a mechanism proposed to explain the enhancement of exercise responses with creatine supplementation in omnivorous participants [49
], but has never been directly tested.