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. 2022 Jan 18;10(2):186. doi: 10.3390/healthcare10020186

Table 3.

Impact of supplements on cognitive function [20,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153].

Factor Subjects and Methods Results Conclusion References
Caffeine Review Caffeine doses of around 0.5–4.0 mg/kg b.w. (~40–300 mg) improved cognitive function in well-rested individuals, while doses of 3–7 mg/kg b.w. (~200–500 mg) taken approximately 1 h before exercise improved physical performance. The dose–response exhibited high interindividual variability. Doses of 1–4 mg/kg b.w. improve alertness, concentration, and reaction time, but there is less consistent impact on memory and executive functions, such as assessing the situation and making decisions. [118]
International Olympic Committee consensus statement Doses of 3–6 mg/kg b.w. caffeine improved cognitive, motor skills, and exercise performance in many types of sports. Caffeine supplementation may improve cognitive, motor skills, and exercise performance. [117]
Randomized, double-blind, placebo-controlled crossover trial;
9 elite League of Legends (LoL)
esports players
The administration of a supplement (AI Reload (118 mL) that included 150 mg caffeine (1.9 ± 0.3 mg/kg b.w.) designed to improve performance demonstrated no ergogenic effects relative to the indices examined in this study (measures of attention, reaction time, working memory, and fatigue). Three LoL games do not accumulate mental fatigue in elite LoL players. The administration of a supplement containing caffeine does not have a positive effect on the cognitive functions of LoL players. [20]
Crossover,
double-blind study;
10 male subjects
Intake of 3 mg/kg of caffeine boosted performance on the Stroop task under both incongruent and congruent conditions and increased mean oxygenated hemoglobin under the congruent condition. Ingestion of 6 mg/kg of caffeine increased efficiency on the Stroop task under the incongruent condition. Low-dose caffeine intake proved to have greater effects on cognition and brain activation compared with midrange and high caffeine doses, implying that small doses of caffeine may be the supplement of choice in enhancing executive function and prefrontal activities. [119]
Double-blind, crossover, randomized experimental trial;
15 professional e-gamers (age = 22 ± 3 years).
The acute ingestion of 3 mg/kg of caffeine improved both reaction time and accuracy in hitting targets. Caffeine consumption (3 mg/kg b.w.) can be considered an ergogenic aid for esports players (in first person shooters) due to its effect on increasing accuracy and hit time. [152]
Systematic Review and Meta-Analysis;
13 studies, of which 5 studies were included in the meta-analysis
Caffeine showed beneficial effects in tasks requiring attention, accuracy, and speed (meta-analysis). Supplementation with a low/moderate dose of caffeine before and/or during exercise helped raise mood, energy, and attention, but also enhanced simple reaction and response time, as well as augmenting memory and easing fatigue, though this may have depended on test protocols (13 studies). Caffeine supplementation in sports requiring attention and focus may be considered, but more research is needed. [120]
Combination of caffeine and theanine Randomized, placebo-controlled, double-blind, balanced crossover study;
24 participants (9
male and 15 female, mean age 21.3 years)
A combination of 250 mg of L-theanine and 150 mg of caffeine improved reaction time, working memory, and accuracy of task verification. The combination of caffeine and L-theanine seems to be justified in sports that require quick response, memory, and accuracy. [121]
Systematic review and meta-analysis (11 randomized placebo-controlled human studies) The combination of L-theanine with caffeine increased alertness, increased the accuracy of switching attention, slightly increased the accuracy of non-sensory visual attention, and slightly increased the accuracy of non-sensory auditory attention. Caffeine in combination with L-theanine had a beneficial effect on the cognitive function and mood. [122]
Systematic review (49 studies) Caffeine in a dose of 40 mg improved performance in demanding long-term cognitive tasks as well as self-reported alertness, agitation, and vigor. L-Theanine alone improved relaxation, tension and calmness reported by patients themselves, starting with 200 mg. The combination of L-theanine and caffeine improved performance in attention-switching and alertness tasks, but to a lesser extent than caffeine itself. L-Theanine and caffeine both have apparent advantageous effects on continued alertness, memory, and improved attention.
L-Theanine helped to relax by curbing arousal stimulated by caffeine.
[123]
Systematic review of controlled trials, crossover studies cross-sectional studies, and cohort study (21 studies) Green tea influenced psychopathological symptoms (e.g., reduction in anxiety), cognition (e.g., benefits in memory and attention), and brain function (e.g., activation of working memory seen in functional MRI). Caffeine in combination with L-theanine has a beneficial effect on cognition, while the separate use of both substances has a smaller effect. [124]
Combination of caffeine, theanine, and tyrosine Randomized, double-blind, placebo-controlled crossover trial;
20 current or former male collegiate athletes (age: 20.5 ± 1.4 years)
The combination of a low dose of caffeine with theanine and tyrosine improved the accuracy of athletes’ movements and reaction time during a series of grueling exercises. Supplementation recommended in exercises demanding accurate movements and quick reaction time. [125]
Polyphenols Systematic review and meta-analysis;
18 studies
The acute consumption of polyphenols enhanced processing of fast-paced visual stimuli in young participants. Acute polyphenol consumption might improve speed in rapid visual information processing task, a higher order task with elements of vigilance, working memory, and executive function, in young participants [128]
Cocoa Randomized, double-blind, crossover study;
12 healthy men
At rest, cocoa flavanol intake increased cerebral oxygenation, but not brain-derived neurotrophic factor concentrations, and no impact on executive function was detected. Positive influence of cocoa flavanol on brain oxygenation during rest was revoked by a strong increase in perfusion and brain oxygenation caused by exertion. [126]
98 healthy young adults (n = 57 females) aged 18–24 years Dark chocolate consumption (70% cocoa) was associated with better verbal memory performance for several outcome measures of the Rey Auditory Verbal Learning Test relative to the white chocolate consumption; however, there were no effects on mood. 70% cocoa dark chocolate consumption can benefit verbal episodic memory two hours post consumption in healthy young adults relative to a white chocolate control. A daily serving (35 g) of dark chocolate can benefit the brain of healthy consumers. [127]
Review; 11 intervention studies that involved a total of 366 participants After acute consumption, these beneficial effects seemed to be accompanied by an increase in cerebral blood flow or cerebral blood oxygenation. After chronic intake of cocoa flavanols in young adults, a better cognitive performance was found, together with increased levels of neurotrophins. The beneficial effect of cocoa flavanols on cognitive function and neuroplasticity was supported and indicates that such benefits are possible in early adulthood. [129]
Review,
15 human studies
Regular consumption of flavanols had a neuroprotective effect and also improved cerebrovascular and metabolic functions. Consuming cocoa flavanols may have beneficial effects in maintaining cognitive performance by improving indicators of general cognition, attention, processing speed, and memory. [130]
Systematic Review;
18 studies
Consuming chocolate or cocoa products improved lipid (triglyceride) profiles. The effect of chocolate on all other outcome parameters did not differ significantly (including cognitive functions). There is no evidence that cocoa and cocoa-containing products may be beneficial for cognition. [131]
Beetroot juice (nitrate) Randomized, double-blind, crossover study, 16 male team-sport players The total work done during the sprints was greater in the nitrate-rich beetroot juice group compared with the placebo group. The response time to cognitive tasks in the second half of the sprint improved in the nitrate-containing beet juice group compared with the placebo group. Dietary NO3 enhances repeated sprint performance and may attenuate the decline in cognitive function (and specifically reaction time) that may occur during prolonged intermittent exercise. [132]
Randomized, double-blind, placebo-controlled trial, 40 healthy adults (18–27 years) Dietary nitrate modulated the hemodynamic response to task performance, with an initial increase in prefrontal cortex cerebral blood flow at the start of the task period, followed by consistent reductions during the least demanding of the three tasks utilized. Cognitive performance was improved on the serial 3 s subtraction task. Single doses of dietary nitrates may modulate the cerebral blood flow response to task performance and potentially improve cognitive performance. [133]
Double-blind, placebo controlled, crossover trial; thirteen younger (18–30 years) and 11 older (50–70 years) Response time improved in the Stroop test after beetroot juice supplementation for both groups. Acute BR supplementation increased plasma nitrite levels and to a greater extent reduced diastolic BP in the elderly; while systolic BP was lowered in both older and younger subjects. Acute supplementation with beetroot juice can reduce blood pressure and improve aspects of cognitive performance; thus, having potential health benefits for both younger and older adults. [134]
Creatine Double-blind placebo-controlled trial;
24 healthy volunteers (19 men and five women, 24.3 ± 9.1 years old)
After taking the creatine supplement, task-evoked increase in cerebral oxygenated hemoglobin in the brains of subjects measured by near infrared spectroscopy was significantly reduced, which is compatible with increased oxygen utilization in the brain. Dietary supplement of creatine (8 g/day for 5 days) reduces mental fatigue when subjects repeatedly perform a simple mathematical calculation. [136]
Double-blind, placebo-controlled, crossover trial;
25 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)
Oral creatine supplementation (5 g/day for six weeks) improved IQ scores and working memory performance in 45 young adult vegetarians. Creatine supplementation had a positive effect on both working memory (digit spread) and intelligence (Raven’s Advanced Progressive Matrices), both tasks requiring processing speed. These findings underline a dynamic and significant role of brain energy capacity in influencing brain performance. [137]
Clinical trial;
volunteer male (n = 17) and female (n = 3) sports science and adventure education majors (mean age: 21.11 years)
At 24 h, the creatine group (20 g/day for 7 days) demonstrated significantly less change in performance in random movement generation (RMG), choice reaction time, balance, and mood state. Following 24 h sleep deprivation, creatine supplementation had a positive effect on mood state and tasks that place a heavy stress on the prefrontal cortex. [138]
Double-blind, placebo-controlled study;
34 participants (including 12 females);
mean age of 21 years (SD:
1.38; range: 18–24).
Creatine ethyl ester supplementation (5 g/day for 15 days) improved cognition on some tasks. 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. [139]
Randomized, double-blind, placebo-controlled trial;
Female undergraduates (n = 121), mean age 20·3 (SE
2·1) years,
meat-eaters (n = 51) and vegan or vegetarian (n = 70).
Creatine supplementation (20 g of creatine supplement for 5 d) did not affect the indicators of verbal fluency and alertness. However, in vegetarians, supplementation with creatine resulted in better memory compared with the group consuming meat. For vegetarians, it is worth using creatine supplementation to improve memory. [140]
Systematic review of randomized controlled trials;
6 studies (281 individuals)
Short-term memory and intelligence/reasoning can be improved by administering creatine. Effect of creatine on other cognitive domains, i.e., long-term memory, spatial memory, memory scanning, attention, executive functions, reaction inhibition, word fluency, reaction time, and mental fatigue was not clear cut.
Vegetarians responded better than meat eaters to memory tasks, but no differences were observed for other cognitive domains.
Oral creatine administration may improve short-term memory and intelligence/reasoning of healthy individuals, but its effect on other cognitive domains remains unclear.
Findings suggest potential benefit for aging and stressed individuals.
[135]
Pilot trial in healthy men (n = 5) Guanidinoacetic acid (GAA, 3 g·day), a naturally occurring creatine precursor, was reported to have a superior influence on brain creatine content when compared with an equimolar dose of creatine. GAA as a preferred alternative to creatine for improved bioenergetics in energy-demanding tissues. [141]
Blinded, placebo-controlled crossover design; 10 rugby backs (mean ± SD, age; 20 ± 0.5 years) 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. Creatine can be used in stressful situations in which there may be a temporary decrease in creatine levels and may offset the negative cognitive effects of sleep deprivation. [142]
Review It appears that creatine was most likely to exert an influence in situations whereby cognitive processes were stressed, e.g., during sleep deprivation, experimental hypoxia, or during the performance of more complex, and thus more cognitively demanding tasks. In situations of sleep deprivation and performing more complex tasks, creatine supplementation may turn out to be beneficial. [143]
Review There was a potential for creatine supplementation to improve cognitive processing, especially under conditions characterized by brain creatine deficits, which could be induced by acute stressors (e.g., exercise, sleep deprivation) or chronic, pathologic conditions (e.g., creatine synthesis enzyme deficiencies, mild traumatic brain injury, aging, Alzheimer’s disease, depression). The optimal creatine protocol able to increase brain creatine levels is still to be determined. [144]
Prebiotics, probiotics and fermented food A meta-analysis of randomized controlled trials; 22 studies (n = 1551) Despite several individual studies (14 of 22) reporting significant improvements in specific cognitive domains, results of the pooled meta-analysis found no significant effect for any intervention for global cognition. These results do not support the use of probiotic, prebiotic, and fermented food interventions for cognitive outcomes. [147]
Prebiotics Narrative review; 14 studies, (5 randomized, crossover trials, 3 double-blind, and 2 nonblinded studies) Chronic prebiotic interventions (>28 d) improved affect and verbal episodic memory compared with a placebo. Acute prebiotic interventions (<24 h) were more efficient in improving cognitive variables (e.g., verbal episodic memory). Acute prebiotic interventions (<24 h) can be used to improve cognitive variables. However, more research is needed. [146]
Randomized, double-blind, crossover, controlled trial; 18 healthy female participants Polydextrose improved cognitive flexibility (reducing the number of errors made in the Intra-Extra Dimensional Set Shift task). Better performance in terms of retention of attention was observed due to the greater number of correct answers and rejections in the quickly processing visual information task. Although there was no change in microbial diversity, Ruminiclostridium 5 abundance increased significantly after polydextrose supplementation compared with placebo. Supplementation with the polydextrose resulted in a modest improvement in cognitive performance. The results indicate that polydextrose could benefit gut-to-brain communication and modulate behavioral responses. [148]
Probiotics Randomized controlled trial; healthy female subjects, (aged 18–40 years) Subjects with a higher increase in Ruminococcaceae_UCG-003 abundance after probiotics were also more protected from negative effects of stress on working memory after probiotic supplementation. Gut microbial alterations, modulated through probiotics use, are related to improved cognitive performance in acute stress circumstances. [149]
Randomized, double-blind, placebo-controlled trial, 45 right-handed healthy participants (aged 20–40 years) Functional connectivity changes were observed in the default mode network, salience network, and middle and superior frontal gyrus network in the probiotic group as compared with the placebo and control groups. The results demonstrated that there is a close relationship between the effects of probiotic intervention on behavioral and neuroimaging readouts. [145]
Lutein Review Dietary sources of lutein (avocado, spinach) had an influence of serum level of lutein and could lead to the accumulation of lutein in retinal neural tissue and may maintain eye and brain health. Dietary intake and supplementation of lutein can improve cognitive and vision abilities. [150]
Randomized controlled trial;
20 healthy subjects
In a study, the elderly (mean age 63) consumed avocados (high source of lutein), which increased MPOD (macular pigment optical density) and was associated with the improvement in cognitive functions. Dietary intake of lutein has significant impact on the improvement in cognitive functions. [151]
Randomized double blind, placebo-controlled trial; 37 healthy subjects (aged 22–30 years) Lutein supplementation for 12 weeks increased levels of serum lutein and improved contrast sensitivity in both groups. Higher intake of lutein may be beneficial for visual performance. [153]