Search outcomes and included articles overview
Our search led to 850 related studies. After duplicates removing (n = 27), a wide screening range of the titles and abstracts and careful assessment was conducted on 823 related studies. Of these, 29 studies remained after considering the inclusion and exclusion criteria for the eligibility. Finally, 9 studies, including, 30 effect sizes for CK and 24 effect sizes for LDH, which studied a total of 630 and 420 participants respectively and aged 19.9 – 37.5 years, were identified in the current review. This numbers is inclusive of individuals who were dropouts in some experiments. Participants tended to be young, but one study evaluated creatine effects on CK and LDH concentration for middle-aged men in addition to youth (29). Moreover, all participants were men, except in one study which women participated (n = 15) (30), and in one study both men and women participated (n = 49) (31).
Two studies were not randomized (32, 33) and data from two studies was not directly accessible from the published papers, and we sent email and request the raw data but we did not receive information from the studies authors (34, 35). Figure 1 shows the selection procedure and causes for excluding the studies and the data inTable 1 illustrates the basic characteristics of the articles in our systematic review and meta-analysis.
In brief, the studies were published between 1998 and 2018. The total number of individuals who completed the studies in inclusion criteria was 319 and 311 individuals in the intervention and placebo groups respectively for CK and 211 and 209 individuals in the intervention and placebo groups respectively for LDH. The dose of creatine supplementation was 2 to 40 g/day among these studies and the duration of these trials ranged between 5 to 56 days. All studies used a randomized parallel design, and all of them had the design of double-blind except two studies (36, 37). The effect of creatine on CK and LDH concentration together was examined in 5 studies (29, 38-41) and 4 studies only reported CK (30, 31, 37, 42).
Some of the articles undertook multiple follow-up (e.g., muscle damage indices for intervention and placebo immediately, 0.5, 1, 2, 4, 24, 48, 72, and 96 hour and 7, 10, 14, 21 days after exercise). We focused on results reported immediately post exercise (<24 hours) and subsequent hours (24, 48, 72 and 96 hours). Eight trials in 4 studies reported <24 hours follow-up times (30, 31, 39, 42); Five trials in 4 studies had 24 hours follow-up times (38-40, 42); Seven trials in 6 studies reported 48 hours follow-up times (29, 37-40, 42); Four trials in 4 studies reported follow-ups at 72 hours after exercise (29, 38-40) and four trials in 4 studies reported follow-ups at 96 hours after exercise (37-40).