Does creatine increase cognitive performance? Maybe for vegetarians but probably not.
2013-09-06–2019-01-29
finished
certainty: unlikely
importance: 5
I attempt to meta-analyze conflicting studies about the cognitive benefits of creatine supplementation. The wide variety of psychological measures by uniformly small studies hampers any aggregation. 3 studies measured IQ and turn in a positive result, but suggestive of vegetarianism causing half the benefit. Discussions indicate that publication bias is at work. Given the variety of measures, small sample sizes, publication bias, possible moderators, and small-study biases, any future creatine studies should use the most standard measures of cognitive function like RAPM in a reasonably large pre-registered experiment.
Creatine is a chemical found throughout the body in a number of roles; it is most famous for its presence in muscles and enabling greater exertion, but it also plays a role in the nervous system. Some small psychology experiments in healthy adults have found cognitive benefits to supplementation but others disagree (Wikipedia, Examine.com), and these differences may be due to covariates like being vegetarian & hence creatine-deficient.
When small studies conflict, one way to get answers is to try to meta-analyze them into a single more robust summary. In particular, I am interested in whether creatine supplementation increases IQ. One problem here is that the studies may not use enough of the same measures to include in the same meta-analysis; besides that, the studies are likely severely underpowered to detect plausible effects: IQ increases have been often claimed, but have rarely panned out (see, for example, dual n-back) and “extraordinary claims require extraordinary proof”.
Background
While creatine is famous for its athletic uses1, there is also biological evidence suggesting creatine is involved in mental performance, serving as a fast source of energy, creatine-related retardation & disability, correlates between meat-eating and performance etc. For one survey, and a more detailed discussion of the rationale for expecting creatine to help, see Littleton 2013; for discussion of the neuroprotective effects, see Cunha 2017. An interesting longitudinal correlation between creatine levels and later increased salary is found in Böckerman et al 2014. And Smith et al 2014 reviews some animal experiments suggesting potential benefits in neurodegenerative diseases like aging.
Experimentally, creatine turns out to boost mental performance in some circumstances (eg. Ling et al 2009 saw the creatine group post-score 4 points higher than controls, or Watanabe 2002’s less oxygen use during mental arithmetic; Jonathan Toomim recommends it highly, claiming that “I’m more confident that I’ve noticed effects [on mental performance] of creatine than of DnB.”)
These results are a little mixed. There are studies showing benefits in:
- Vegetarians (Rae 2003)
- the sleep-deprived (McMorris 2006; McMorris 2007)
- the elderly (McMorris et al 2007)
However, Rawson et al 2008 is a broad null result for healthy omnivores, who are probably most of the readers of this FAQ. (Jonathan Toomim has criticized Rawson et al 2008 as statistically weak and using a possibly not sensitive test of mental performance; others have pointed out Rawson et al 2008 administered a total of creatine, which is less than half that of Rae 2003 and 16% less than Ling et al 2009.)
A 2018 meta-analysis/
Search
Besides the studies I already knew about through discussion, my own research, Wikipedia, or Examine, I also did several searches for additional studies modeled on the search query creatine AND (IQ OR intelligence OR "Raven's") -mutagen
(‘IQ’ turns out to be the name of a mutagen which appears in many contexts with creatine kinase):
- Google: up to pg10 of results
- Google Scholar: up to pg41
- Pubmed: 129 results, reviewed all
- APA PsycNET: for just
creatine
(more complex queries are apparently not supported), 4 hits (none relevant) - ProQuest Dissertations & Theses Full Text and ERIC
all(creatine) AND (all(intelligence) OR all(IQ))
: 2 hits
I then set up a Google Alert, a Google Scholar alert, and a Pubmed alert for those searches in case any new studies come out.
Overview
The searches & alerts yielded the following potentially useful studies:
- Watanabe 2002
- Rae 2003
- McMorris 2006
- McMorris 2007
- McMorris et al 2007
- Gastner et al 2007
- Rawson et al 2008
- Ling et al 2009
- Hammett et al 2010
- Benton & Donohoe 2011
- Alves et al 2013a
- Alves et al 2013b
- Turner et al 2015 (supplement; while creatine was apparently beneficial, not useful because only pre-supplementation baseline cognitive performance and hypoxia+supplementation cognitive performance was collected, according to the flowchart and supplement, with no supplementation+normal-breathing condition)
- Merege-Filho et al 2016
- Cook et al 2011
We are looking for studies of the effects of creatine on cognitive performance in normal healthy populations under normal conditions (ie no diseases, no genetic disorders, no exotic conditions like hypoxia).
Usable studies turn out to employ a wide variety of psychological measures:
Study | Test |
---|---|
Watanabe 2002 | Uchida-Kraepelin serial calculation test |
Rae 2003 | Raven’s Advanced Progressive Matrices; Backward Digit Span |
McMorris 2006 | Random movement generation test; forward verbal recall; backwards verbal recall; 4-choice visual reaction time test; Hemmings mood state inventory |
McMorris 2007 | Random number generation task; number recall test; four-choice visual reaction time test; Hemmings mood state inventory; NASA-TLX effort sub-scale |
McMorris et al 2007 | Random number generation task; forward verbal recall; backwards verbal recall; forward Corsi Block Tapping test; backward Corsi Block Tapping test; long-term memory test |
Gastner et al 2007 | Raven’s Advanced Progressive Matrices; Uchida-Kraepelin serial calculation test; Backward Digit Span |
Rawson et al 2008 | Simple reaction time; code substitution; code substitution delayed; logical reasoning symbolic; mathematical processing; running memory; Sternberg memory recall |
Ling et al 2009 | Raven’s Advanced Progressive Matrices; Memory Scanning task; Number-Pair Matching task; Sustained Attention task; Arrow Flanker task |
Hammett et al 2010 | Raven’s Advanced Progressive Matrices; Backward Digit Span |
Benton & Donohoe 2011 | Word recall; reaction-time; vigilance rapid information processing task; Controlled Oral Word Association Test |
Alves et al 2013 | Forward Digit Span; Backward Digit Span; Mini-Mental State Examination; Stroop Test; Trail Making Test; Delay Recall Test |
Merege-Filho et al 2016 | Stroop Test; Rey Auditory Verbal Learning Test; Raven Progressive Matrices; Trail Making Test |
Cook et al 2011 | Rugby ball passing |
In total, these studies use ~33 distinct measures of cognitive functioning; this heterogeneity renders any summary difficult as most measures were used in only one experiment, and encourages selective reporting. The Hemmings mood state inventory, random number generation task, forward verbal recall, & Uchida-Kraepelin serial calculation test are used in 2 experiments each, but the backward digit span is used in 4 experiments, and the RAPM is used in 4 experiments - so it would be best to analyze those two.
RAPM
Data
I decided to code multiple relevant variables:
diet: if no diet was specified, assume omnivorousness since as little as 5% of Western population are vegetarians
- 0: omnivore
- 1: vegan or vegetarian
sleep:
- 0: no mention is made of sleep deprivation
- 1: if sleep deprivation in the experimental as opposed to control group
IQ:
- 0: RAPM
dose: total amount of creatine administered, in grams; average is total amount of creatine divided by number of days on which creatine is taken by a subject
age: average mean of all subjects’ age; medians were treated as means if that was provided instead, and means given of range endpoints if only that was provided
type: creatine can be consumed in multiple forms.
Creatine monohydrate (CM) is the most common, but also used in a study is creatine ethyl ester (CEE). While CEE was developed to allow smaller doses than CM, Katseres et al 2009 suggests it breaks down far too fast to be effective and so CEE doses may not be 1:1 equivalent with CM.
year | study | n.e | mean.e | sd.e | n.c | mean.c | sd.c | type | dose total | dose average | age | diet | sleep |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
2003 | Rae | 25 | 13.7 | 4.1 | 25 | 9.7 | 3.8 | monohydrate | 210 | 5 | 25.59 | 1 | 0 |
2009 | Ling | 17 | 120.3 | 5.945 | 17 | 116.1 | 9.086 | ethyl ester | 75 | 5 | 21 | 0 | 0 |
2010 | Hammett | 11 | 13.45 | 2.25 | 11 | 11.45 | 3.8 | monohydrate | 110 | 15.7 | 27.59 | 0 | 0 |
2016 | Merege-Filho | 35 | 30.4 | 4.6 | 32 | 31.8 | 3.8 | monohydrate | 13.74 | 1.96 | 11.5 | 0 | 0 |
Results
The 4 studies do not turn in a statistically-significant positive result in the random-effects meta-analysis:
Random-Effects Model (k = 4; tau^2 estimator: REML)
tau^2 (estimated amount of total heterogeneity): 0.2731 (SE = 0.3128)
tau (square root of estimated tau^2 value): 0.5226
I^2 (total heterogeneity / total variability): 72.62%
H^2 (total variability / sampling variability): 3.65
Test for Heterogeneity:
Q(df = 3) = 12.8147, p-val = 0.0051
Model Results:
estimate se zval pval ci.lb ci.ub
0.4259 0.3095 1.3761 0.1688 -0.1807 1.0325

When vegetarianism is used as a covariate (this applies only to Rae 2003), it is not statistically-significant either but does lower the estimate further (given that Rae 2003 was also the largest effect):
Mixed-Effects Model (k = 4; tau^2 estimator: REML)
tau^2 (estimated amount of residual heterogeneity): 0.2034 (SE = 0.3213)
tau (square root of estimated tau^2 value): 0.4510
I^2 (residual heterogeneity / unaccounted variability): 64.29%
H^2 (unaccounted variability / sampling variability): 2.80
R^2 (amount of heterogeneity accounted for): 25.52%
Test for Residual Heterogeneity:
QE(df = 2) = 5.9274, p-val = 0.0516
Test of Moderators (coefficient(s) 2):
QM(df = 1) = 1.5477, p-val = 0.2135
Model Results:
estimate se zval pval ci.lb ci.ub
intrcpt 0.2095 0.3261 0.6423 0.5207 -0.4297 0.8487
diet 0.7865 0.6322 1.2441 0.2135 -0.4526 2.0257
Unfortunately, with so few studies I can’t investigate dose meaningfully
Publication bias
The common publication bias checks like the funnel plot are useless with 3 studies. As it happens, there is no need to do any hypothesis-testing here: Ling (personal communication 2013) mentions that 2 student theses were done involving creatine supplementation & cognition with apparently uninteresting results, but did not have any copies and the university library had not retained any; this is prima facie publication bias. Hence, we know that the meta-analytic results are biased upwards by publication bias.
Backward Digit Span
Data
year | study | n.e | mean.e | sd.e | n.c | mean.c | sd.c | type | dose total | dose average | age | diet |
---|---|---|---|---|---|---|---|---|---|---|---|---|
2010 | Hammett | 11 | 11 | Monohydrate | 110 | 15.7 | 27.59 | 0 | ||||
2003 | Rae | 25 | 8.5 | 1.76 | 25 | 7.05 | 1.19 | Monohydrate | 210 | 5 | 25.59 | 1 |
2013 | Alves | 25 | 3.75 | 1.0 | 22 | 3.25 | 0.76 | Monohydrate | 25 | 4.17 | 66.8 | 0 |
Results
Source
set.seed(7777) # for reproducible numbers
# TODO: factor out common parts of `png` (& make less square), and `rma` calls
library(XML)
creatine <- readHTMLTable(colClasses = c("integer", "factor", rep("numeric", 6), "factor", rep("numeric", 5)),
"https://www.gwern.net/Creatine")[[2]]
# install.packages("metafor") # if not installed
library(metafor)
cat("Basic random-effects meta-analysis of all studies:\n")
res1 <- rma(measure="SMD", m1i = mean.e, m2i = mean.c, sd1i = sd.e, sd2i = sd.c, n1i = n.e, n2i = n.c,
data = creatine); res1
png(file="~/wiki/images/creatine/forest.png", width = 580, height = 580)
forest(res1, slab = paste(creatine$study, creatine$year, sep = ", "))
invisible(dev.off())
cat("Random-effects with vegetarian covariate:\n")
rma(measure="SMD", m1i = mean.e, m2i = mean.c, sd1i = sd.e, sd2i = sd.c, n1i = n.e, n2i = n.c,
data=creatine, mods = ~ diet)
system(paste('cd ~/wiki/images/creatine/ &&',
'for f in *.png; do convert "$f" -crop',
'`nice convert "$f" -virtual-pixel edge -blur 0x5 -fuzz 10% -trim -format',
'\'%wx%h%O\' info:` +repage "$f"; done'))
system("optipng -o9 -fix ~/wiki/images/creatine/*.png", ignore.stdout = TRUE)
Study details
- Watanabe 2002, McMorris 2006, McMorris et al 2007, McMorris 2007, Rawson et al 2008, Benton & Donohoe 2011: excluded for not using a measure of intelligence.
- Gastner et al 2007: excluded for lack of necessary details.
Rae 2003
In this work, we tested the hypothesis that oral creatine supplementation (5g daily for six weeks) would enhance intelligence test scores and working memory performance in 45 young adult, vegetarian subjects in a double-blind, placebo-controlled, cross-over design. Creatine supplementation had a significant positive effect (p = 0.0001) on both working memory (backward digit span) and intelligence (Raven’s Advanced Progressive Matrices), both tasks that require speed of processing.
Forty-five vegan or vegetarian subjects (12 males (median age of 27.5, range of 19-37 years), 33 females (median age of 24.9, range of 18-40 years); 18 vegan (median duration of 4.6 years, range of 0.7-17 years) and 27 vegetarian (median duration of 14.3, range of 1-23 years)) were recruited with informed consent from among the student population of The University of Sydney
The study followed a double-blind, placebo-controlled, cross-over design. Subjects were seen on four separate occasions, at six-week intervals, following an overnight fast to minimize any fluctuations in blood glucose.
A cognitive test battery was also administered. At the end of the first and third test sessions, subjects were given an envelope marked with their study number and containing 5 g doses of supplement (creatine monohydrate ((2-methylguanido)acetic acid); Pan Pharmaceuticals, Australia) or placebo (maltodextrin; Manildra Starches, Australia) in plastic vials. Subjects were asked to consume this supplement at the same time each day for the next six weeks and received advice on how best to take this supplement to ensure maximum solubility and absorption. Subjects returned the envelope with unused vials at the end of each six-week period and the number of vials remaining was used to assess compliance, validated against increases in red cell (tissue) creatine. Between visits 2 and 3, the subjects consumed no supplement. Note: six weeks has been shown to be an adequate ‘wash-out’ period (Harris et al. 1992).
Subjects completed timed (10 min) parallel versions of Raven’s Advanced Progressive Matrices (RAPMs) constructed to have equal levels of difficulty based on the published normative performance data and verified by us on an independent sample of 20 subjects.
Supplementation with oral creatine monohydrate significantly increased intelligence (as measured by RAPMs done under time pressure, figure 1a) compared with placebo (F3 ,33 = 32.3, p , 0.0001; repeated-measures ANOVA). There was no significant effect of treatment order (F1 ,33 = 1.62, p = 0.21), although there was a significant interaction with treatment order (F3 ,99 = 6.7, p = 0.0004). The mean RAPMs raw score under placebo was 9.7 (s.d. = 3.8) items correct in 10 min versus 13.7 (s.d. = 4.1) items correct under the experimental treatment. Supplementation with oral creatine monohydrate (figure 1b) significantly affected performance on BDS (F3 ,34 = 29.0, p , 0.0001), with no effect of order (F3 ,10 2 = 0.98, p = 0.40). Mean BDS under the placebo was 7.05 items (s.d. = 1.19), compared with a mean of 8.5 items under creatine treatment (s.d. = 1.76).
Gastner et al 2007
“Use of creatine containing preparation e.g. for improving memory, retentivity, long-term memory and for preventing mental fatigue condition, comprising e.g. Ginkgo biloba, ginseng and niacin” (English translation, original): German patent filed in June 2007 by Dr. Thomas Gastner, Frauke Selzer, Dr. Hans-Peter, Dr. Bendikt Hammer, for Alzchem Trostberg Gmbh:
Use of a creatine containing preparation for improving memory, retentivity, long-term memory and for preventing mental fatigue conditions, comprising e.g. at least a further physiologically effective component of the series Ginkgo biloba, ginseng, taiga root, yam root, lecithin, choline, phosphatidylserine, dimethylamino ethanol, acetyl choline, acetyl-L-carnitine, glutathione, glutamine, cysteine, vitamin A, E, B1, B2, B6, B12, folic acid, pantothenic acid and/
or zinc, is claimed. Use of a creatine-component containing preparation for improving memory, retentivity, long-term memory and for preventing mental fatigue conditions, comprising at least a further physiologically effective component of the series Ginkgo biloba, ginseng, taiga root, yam root, lecithin, choline, phosphatidylserine, dimethylamino ethanol, acetyl choline, acetyl-L-carnitine, glutathione, glutamine, cysteine, vitamin A, E, B1, B2, B6, B12, E, niacin, biotin, folic acid, pantothenic acid, zinc, manganese, selenium, magnesium, coenzyme Q10, glucose, colostrum, synephrine, octopamine, caffeine, theophylline, alpha -linolenic acid, eicosapentaenoic acid, omega-3-fatty acid, piracetam, aniracetam, memantine, pyritinol, galantamine, vinpocetin, pangamic acid and/ or optionally organic or inorganic salts and/ or optionally esters, is claimed.
Section 2, “Effectiveness”:
Subjects were divided randomly into four groups of 25 people each. The age of the subjects varied between 18 and 64 years. The four groups (a-d) were given twice per day for six weeks following each test substances in softgel capsules:
- placebo (1500 mg maltodextrin)
- creatine monohydrate (1500 mg)
- Ginkgo biloba leaves dry extract (120 mg)
- creatine monohydrate (1500 mg) and Ginkgo biloba leaves dry extract (120 mg)
It measured:
Backward Digit Span
The number of correctly repeated numbers before supplementation and the number of correctly repeated numbers after six weeks of supplementation are shown in the table. To better compare the results, the difference between the numerical values is further illustrated.
0 weeks 6 weeks Difference Placebo (maltodextrin) 6.4 6.8 0.4 Creatine monohydrate 6.2 7.9 1.7 Ginkgo biloba 6.7 7.5 0.8 Creatine monohydrate + Ginkgo biloba 6.5 9.2 2.7 Test Method: Wechsler, D .: Adult Intelligence Scale manual. (1955) New York: Psychological Corporation.
Raven’s Advanced Progressive Matrices
0 weeks 6 weeks Difference Placebo (maltodextrin) 8.7 10.2 1.5 Creatine monohydrate 8.1 12.7 4.6 Ginkgo biloba 9.8 12.9 3.1 Creatine monohydrate + Ginkgo biloba 9.3 17.2 7.9 Test Method: Rauen, JC et al .: Manual for Raven’s progressive matrices and vocabulary scales. (1988) London: HK Lewis.
Uchida-Kraepelin test
The test subjects a computational test was performed, which measures the mental fatigue. They were given simple computing tasks with an interval of 5 minutes twice 15 minutes. In the second 15 minutes, the number of solved problems per minute were determined. The test was performed before taking supplementation and after 6 weeks. By linear regression analysis can be inferred from the measured data on mental fatigue. In Table 3, the regression coefficient a is given (). An enlargement of the regression coefficient is a direct measure of a reduced mental fatigue.
0 weeks 6 weeks Difference Placebo (maltodextrin) -0.0076 -0.0089 -0.0013 Creatine monohydrate -0.0088 -0.0046 0.0042 Ginkgo biloba -0.0105 -0.0081 0.0024 Creatine monohydrate + Ginkgo biloba -0.0097 -0.0021 0.0075 Test Method: Watanabe, A. et al .: Neuroscience Research (Oxford, United Kingdom) (2002), 42 (4), 279-285
But Gastner et al reported only pre and post-test scores, and not standard deviations; nor was any kind of statistical test reported, making it difficult to infer anything about the results.
It is unclear where this experiment was done, by whom, or whether it was ever published. (The “in press” citation to Mielcarz et al 2007 turns out to refer to McMorris et al 2007.) Nothing in the English translation indicates that it was published anywhere else; searches failed to find anything related to this but the patent itself; the Uchida-Kraepelin test is unusual and I tried searching for anything relating to it and creatine in Google/
On 2013-09-23, I attempted to reach Gastner via the Alzchem contact form. (Gastner knows English, as demonstrated by co-authoring “Creatine - its chemical synthesis, chemistry, and legal status” in Creatine and Creatine Kinase in Health and Disease.) 3 months later on 2013-12-14, I mailed a physical letter to the Trostberg, Germany address listed in Creatine and Creatine Kinase (“Degussa AG, Dr. Albert-Frank-Straße 32, D-83308 Trostberg, Germany”). As of 2015-01-08, I have received no responses to any of my attempts.
Ling 2009
Ling et al 2009 saw the creatine group post-score 4 points higher than controls
There were 34 participants (including 12 females) who completed the study, with a mean age of 21 years (SD: 1.38; range: 18-24). Participants were excluded, if they presented with a medical history of drug and/
or alcohol abuse, diagnosed psychiatric disorders, diabetes, renal insufficiency (kidney dysfunction) or had recently or were currently supplementing with a creatine-based substance. None of the participants was vegetarian.
The final task participants undertook was a modified version of Raven’s Advanced Progressive Matrices (e.g. Raven et al., 1998) presented on a PC using Macromedia Flash Player. The difficulty of the 39 questions gradually increased and was constrained by a 40-min time limit.
The cited iqtest.dk
online IQ test contains only one set of questions and does not randomize or vary the selection, implying that subjects answered the same questions twice, which is not good (usually IQ tests will come split in equivalent halves, so one can do pre-tests with the A questions and post-tests with new B questions). This may invalidate the apparent improvement.
At the end of the first testing phase, participants were given a large envelope that contained 15 plastic vials of either 5 g doses of CEE (obtained through the online store Discount Supplements) or a placebo, maltodextrin (obtained from the manufacturer Chemical Nutrition; http:/
/ www.cnpprofessional.co.uk).
There was a significant effect of test phase on performance in the IQ test [F(1,32) = 88.98, P < 0.01] with participants scoring a mean of 112 (SD: 9.44) at baseline, and 118 (7.89) at the end of the study. There was no significant main effect of supplement condition [F(1,32) = 0.56, NS]. However, the interaction was significant [F(1,32) = 81.18, P < 0.01]. Pairwise comparisons indicated that participants in the creatine condition performed worse than the placebo group in the first phase of testing, with baseline means for creatine group of 108 (SD: 7.42) and for placebo, 116 (SD: 9.60) (Tukey HSD, P < 0.01). Performance of the creatine group also improved significantly over the supplementation period, with the mean of 108 at baseline increasing to 120 (SD: 5.95) at the end of study (Tukey HSD, P < 0.01). Further pairwise comparisons indicated that there was no significant improvement in the performance of the placebo group over the supplementation period (P > 0.05).
Performance of the creatine group also improved significantly over the supplementation period, with the mean of 108 at baseline increasing to 120 (SD: 5.95) at the end of study
Using the spreadsheet of data Ling provided me:
# ling <- read.csv(stdin(),header=TRUE)
Creatine,IQ
1,120
1,118
1,126
1,121
1,119
1,118
1,125
1,117
1,133
1,116
1,124
1,114
1,110
1,130
1,123
1,116
1,115
2,110
2,112
2,105
2,106
2,115
2,105
2,112
2,124
2,119
2,133
2,116
2,123
2,122
2,110
2,125
2,105
2,131
summary(ling)
# Creatine IQ
# Min. :1.0 Min. :105
# 1st Qu.:1.0 1st Qu.:112
# Median :1.5 Median :118
# Mean :1.5 Mean :118
# 3rd Qu.:2.0 3rd Qu.:124
# Max. :2.0 Max. :133
i <- ling[ling$Creatine==1,]$IQ; mean(i); sd(i)
# [1] 120.3
# [1] 5.945
i <- ling[ling$Creatine==2,]$IQ; mean(i); sd(i)
# [1] 116.1
# [1] 9.086
# we use a _t_-test rather than a Wilcoxon to replicate Ling's probable analysis
t.test(IQ ~ Creatine, data=ling)
# Welch Two Sample t-test
#
# data: IQ by Creatine
# t = 1.608, df = 27.58, p-value = 0.1192
# alternative hypothesis: true difference in means is not equal to 0
# 95% confidence interval:
# -1.163 9.634
# sample estimates:
# mean in group 1 mean in group 2
# 120.3 116.1
Hammett 2010
“Dietary supplementation of creatine monohydrate reduces the human fMRI BOLD signal”, Hammett et al 2010; quotes relevant for calculating the variables:
To establish whether the magnitude of the BOLD response is influenced by Cr levels, we have measured responses to visual stimuli in the primary visual cortex (V1) of 22 healthy human volunteers using fMRI, before and after oral administration of Cr or a placebo (11 in the Cr group and 11 in the placebo group).
The mean and median age of the Cr group was 30.18 and 27 years (SD = 8.37) respectively and the mean and median age of the placebo group was 25 years (SD = 4.82).
Creatine supplementation (Sci-Mx: Gloucestershire, UK) was provided at a dose of 20 g/
day for five days, followed by two additional days at a dose of 5 g/ day.
In order to verify previous reports of cognitive enhancement following Cr supplementation we also measured performance on the Backwards Digit Span (BDS) [28] and Raven’s Advanced Progressive Matrices (RAPM) [24] prior to each scan. The BDS comprises a set of number sequences of increasing length with two different sequences of each length. Subjects were required to repeat each sequence backwards. The test was terminated when the subject failed to repeat two sequences of the same length. Different number sequences were used for the two testing sessions. Subjects were required to complete as many items of the RAPM as possible in 5 min. Since the RAPM tests are ordered in terms of difficulty, odd-numbered and even-numbered tests were administered on weeks 1 and 2 respectively.
Performance on the RAPM increased non-significantly by 9.6% following Cr (t = 1.882, df = 10, p = 0.0745) and reduced non-significantly by 4.5% (t = 0.7733, df = 10, p = 0.4572) following placebo. A Group × Week ANOVA revealed a main effect of week (F(1, 20) = 5.75, p = 0.026, two-tailed) and a significant interaction between week and compound (F(1, 20) = 8.58, p = 0.008, two-tailed) for BDS performance. No significant effects were found for RAPM performance.
What’s the standard deviation which produces a p-value of 0.0745 on an increase of 9.6% & a sample size of 11 in each group? Hard to tell, but Hammett provided me the pre/
pre | post | ||
---|---|---|---|
creatine | mean | 12.27 | 13.45 |
SD | 3.31 | 2.25 | |
placebo | mean | 12 | 11.45 |
SD | 3.52 | 3.8 |
Alves et al 2013
The CR and CR+ST groups received 20 g of creatine monohydrate (4 × 5 g/
d) for five days followed by 5 g/ d as a single dose throughout the trial.
Alves et al 2013: combined the placebo & placebo+strength-training groups, and the creatine & creatine+strength-training groups
External links
Link Bibliography
Bibliography of page links in reading order (with annotations when available):
“Creatine”, (2021-01-02):
Creatine ( or ) is an organic compound with the nominal formula (H2N)(HN)CN(CH3)CH2CO2H. This species exists in various modifications (tautomers) in solution. Creatine is found in vertebrates where it facilitates recycling of adenosine triphosphate (ATP), the energy currency of the cell, primarily in muscle and brain tissue. Recycling is achieved by converting adenosine diphosphate (ADP) back to ATP via donation of phosphate groups. Creatine also acts as a buffer.
“Creatine”, (2021-01-02):
Creatine ( or ) is an organic compound with the nominal formula (H2N)(HN)CN(CH3)CH2CO2H. This species exists in various modifications (tautomers) in solution. Creatine is found in vertebrates where it facilitates recycling of adenosine triphosphate (ATP), the energy currency of the cell, primarily in muscle and brain tissue. Recycling is achieved by converting adenosine diphosphate (ADP) back to ATP via donation of phosphate groups. Creatine also acts as a buffer.
“Dual N-Back Meta-Analysis”, (2012-05-20):
I meta-analyze the >19 studies up to 2016 which measure IQ after an n-back intervention, finding (over all studies) a net gain (medium-sized) on the post-training IQ tests.
The size of this increase on IQ test score correlates highly with the methodological concern of whether a study used active or passive control groups. This indicates that the medium effect size is due to methodological problems and that n-back training does not increase subjects’ underlying fluid intelligence but the gains are due to the motivational effect of passive control groups (who did not train on anything) not trying as hard as the n-back-trained experimental groups on the post-tests. The remaining studies using active control groups find a small positive effect (but this may be due to matrix-test-specific training, undetected publication bias, smaller motivational effects, etc.)
I also investigate several other n-back claims, criticisms, and indicators of bias, finding:
- payment reducing performance claim: possible
- dose-response relationship of n-back training time & IQ gains claim: not found
- kind of n-back matters: not found
- publication bias criticism: not found
- speeding of IQ tests criticism: not found
“A review of creatine supplementation in age-related diseases: more than a supplement for athletes.”, (2014):
Creatine is an endogenous compound synthesized from arginine, glycine and methionine. This dietary supplement can be acquired from food sources such as meat and fish, along with athlete supplement powders. Since the majority of creatine is stored in skeletal muscle, dietary creatine supplementation has traditionally been important for athletes and bodybuilders to increase the power, strength, and mass of the skeletal muscle. However, new uses for creatine have emerged suggesting that it may be important in preventing or delaying the onset of neurodegenerative diseases associated with aging. On average, 30% of muscle mass is lost by age 80, while muscular weakness remains a vital cause for loss of independence in the elderly population. In light of these new roles of creatine, the dietary supplement's usage has been studied to determine its efficacy in treating congestive heart failure, gyrate atrophy, insulin insensitivity, cancer, and high cholesterol. In relation to the brain, creatine has been shown to have antioxidant properties, reduce mental fatigue, protect the brain from neurotoxicity, and improve facets/components of neurological disorders like depression and bipolar disorder. The combination of these benefits has made creatine a leading candidate in the fight against age-related diseases, such as Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, long-term memory impairments associated with the progression of Alzheimer's disease, and stroke. In this review, we explore the normal mechanisms by which creatine is produced and its necessary physiology, while paying special attention to the importance of creatine supplementation in improving diseases and disorders associated with brain aging and outlining the clinical trials involving creatine to treat these diseases.
https:/
/ groups.google.com/ group/ brain-training/ msg/ 5d5ca4de825f7187 “Creatine kinase”, (2021-01-02):
Creatine kinase (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and uses adenosine triphosphate (ATP) to create phosphocreatine (PCr) and adenosine diphosphate (ADP). This CK enzyme reaction is reversible and thus ATP can be generated from PCr and ADP.
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/ www.plosone.org/ article/ info%3Adoi%2F10.1371%2Fjournal.pone.0076301 -
We investigated the effects of sleep deprivation with or without acute supplementation of caffeine or creatine on the execution of a repeated rugby passing skill. Ten elite rugby players completed 10 trials on a simple rugby passing skill test (20 repeats per trial), following a period of familiarisation. The players had between 7-9 h sleep on 5 of these trials and between 3-5 h sleep (deprivation) on the other 5. At a time of 1.5 h before each trial, they undertook administration of either: placebo tablets, 50 or 100 mg/kg creatine, 1 or 5 mg/kg caffeine. Saliva was collected before each trial and assayed for salivary free cortisol and testosterone. Sleep deprivation with placebo application resulted in a significant fall in skill performance accuracy on both the dominant and non-dominant passing sides (p < 0.001). No fall in skill performance was seen with caffeine doses of 1 or 5 mg/kg, and the two doses were not significantly different in effect. Similarly, no deficit was seen with creatine administration at 50 or 100 mg/kg and the performance effects were not significantly different. Salivary testosterone was not affected by sleep deprivation, but trended higher with the 100 mg/kg creatine dose, compared to the placebo treatment (p = 0.067). Salivary cortisol was elevated (p = 0.001) with the 5 mg/kg dose of caffeine (vs. placebo). Acute sleep deprivation affects performance of a simple repeat skill in elite athletes and this was ameliorated by a single dose of either caffeine or creatine. Acute creatine use may help to alleviate decrements in skill performance in situations of sleep deprivation, such as transmeridian travel, and caffeine at low doses appears as efficacious as higher doses, at alleviating sleep deprivation deficits in athletes with a history of low caffeine use. Both options are without the side effects of higher dose caffeine use.
“Creatine”, (2021-01-02):
Creatine ( or ) is an organic compound with the nominal formula (H2N)(HN)CN(CH3)CH2CO2H. This species exists in various modifications (tautomers) in solution. Creatine is found in vertebrates where it facilitates recycling of adenosine triphosphate (ATP), the energy currency of the cell, primarily in muscle and brain tissue. Recycling is achieved by converting adenosine diphosphate (ADP) back to ATP via donation of phosphate groups. Creatine also acts as a buffer.
“Creatine”, (2021-01-02):
Creatine ( or ) is an organic compound with the nominal formula (H2N)(HN)CN(CH3)CH2CO2H. This species exists in various modifications (tautomers) in solution. Creatine is found in vertebrates where it facilitates recycling of adenosine triphosphate (ATP), the energy currency of the cell, primarily in muscle and brain tissue. Recycling is achieved by converting adenosine diphosphate (ADP) back to ATP via donation of phosphate groups. Creatine also acts as a buffer.
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Creatine supplementation is in widespread use to enhance sports-fitness performance, and has been trialled successfully in the treatment of neurological, neuromuscular and atherosclerotic disease. Creatine plays a pivotal role in brain energy homeostasis, being a temporal and spatial buffer for cytosolic and mitochondrial pools of the cellular energy currency, adenosine triphosphate and its regulator, adenosine diphosphate. In this work, we tested the hypothesis that oral creatine supplementation (5 g d(-1) for six weeks) would enhance intelligence test scores and working memory performance in 45 young adult, vegetarian subjects in a double-blind, placebo-controlled, cross-over design. Creatine supplementation had a significant positive effect (p < 0.0001) on both working memory (backward digit span) and intelligence (Raven's Advanced Progressive Matrices), both tasks that require speed of processing. These findings underline a dynamic and significant role of brain energy capacity in influencing brain performance.
“Cognitive effects of creatine ethyl ester supplementation”, (2009-12):
Supplementation with creatine-based substances as a means of enhancing athletic performance has become widespread. Until recently, however, the effects of creatine supplementation on cognitive performance has been given little attention. This study used a new form of creatine—creatine ethyl ester—to investigate whether supplementation would improve performance in 5 cognitive tasks, using a double-blind, placebo-controlled study. Creatine dosing led to an improvement over the placebo condition on several measures. Although creatine seems to facilitate cognition on some tasks, these results require replication using objective measures of compliance. The improvement is discussed in the context of research examining the influence of brain energy capacity on cognitive performance.
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Creatine monohydrate is a nutritional supplement often consumed by athletes in anaerobic sports. Creatine is naturally found in most meat products; therefore, vegetarians have reduced creatine stores and may benefit from supplementation. to determine the effects of creatine supplementation on vegetarians. PubMed and SPORTDiscus. Eligibility criteria: Randomized controlled trials (parallel group, cross-over studies) or prospective studies. Vegetarians. Creatine supplementation. Study appraisal and synthesis: A total of 64 records were identified, and eleven full-text articles (covering nine studies) were included in this systematic review. Creatine supplementation in vegetarians increased total creatine, creatine, and phosphocreatine concentrations in vastus lateralis and gastrocnemius muscle, plasma, and red blood cells, often to levels greater than omnivores. Creatine supplementation had no effect on brain levels of phosphocreatine. Creatine supplementation increased lean tissue mass, type II fiber area, insulin-like growth factor-1, muscular strength, muscular endurance, Wingate mean power output, and brain function (memory and intelligence) in vegetarian participants. Studies were mixed on whether creatine supplementation improved exercise performance in vegetarians to a greater extent compared to omnivores. Studies that were reviewed had moderate-high risk of bias. Overall, it appears vegetarian athletes are likely to benefit from creatine supplementation.
“Dual N-Back FAQ”, (2009-03-25):
A compendium of DNB, WM, IQ information up to 2015