The aim of this systematic review was to investigate the relationship between legal dietary supplements and cognitive performance in healthy young adults. Specifically, we sought to determine whether the intake of any such supplements could preserve or enhance cognitive performance with a view to optimising such performance during deployment for the modern war fighter. Our review extended previous reviews in two important ways. First, it included studies of healthy young adult samples more generally, as the results have wider applicability beyond the military. Second, our review included a wide range of dietary supplements, such as various macronutrients and micronutrients, as well as biologically active non-nutrients. Studies included in the current review covered a range of cognitive areas. Individual studies generally focused on one or more of the following cognitive domains: psychomotor, information processing speed, attention/vigilance, memory, and executive function.

For the majority of dietary supplements included in this review, findings were inconsistent across studies. While some studies showed positive effects of supplementation on psychomotor, information processing speed, attention/vigilance, memory, and/or executive function, others did not. This was notably the case for tyrosine [ 66 73 ], caffeine [ 40 46 ] and guarana [ 58 61 ]. By contrast, several supplements, namely omega-3 [ 64 ], B vitamins [ 74 ], and nitrates [ 62 63 ] showed very little, if any effect on cognitive performance in healthy young adults. However, in terms of military specific tasks, supplementation with beta-alanine was shown to improve marksmanship [ 39 ].

However, as shown in Table 5 , these beneficial effects were not observed either across all cognitive domains or for all aspects of a particular cognitive domain. For example, Veasey et al. [ 61 ] found no effect of guarana on visual information processing speed but they did for recognition memory. In addition, the single study on prebiotics found positive effects only for episodic memory but not semantic memory [ 65 ]. Furthermore, Hoffman et al. [ 39 ] found that beta-alanine enhanced psychomotor performance, but not working memory. Likewise, flavonoids enhanced information processing speed [ 47 ], but not executive function [ 47 50 ].

Overall there appears to be some evidence of cognitive enhancement from dietary supplements in healthy young adults. Several studies reported beneficial effects on information processing speed, in particular from supplementation with flavonoids [ 47 ] and guarana [ 60 ]. Others showed positive effects on memory following supplementation with tyrosine [ 66 73 ], caffeine [ 43 ], flavonoids [ 48 ], gingko biloba [ 54 56 ], ginseng [ 57 ], and prebiotics [ 65 ]. In addition, enhanced effects on attention were observed in some studies that supplemented with tyrosine [ 69 70 ], caffeine [ 44 ] or ginseng [ 57 ], and a handful of studies showed improved executive function with tyrosine [ 67 71 ], omega-3 [ 28 ], or caffeine supplementation [ 43 44 ].

Interestingly, several studies showed enhanced cognitive performance from supplementation under specific conditions. In particular, when macronutrient manipulations involving carbohydrates yielded beneficial effects, this occurred specifically under high cognitive task demand [ 77 ]. Furthermore, supplementation with tyrosine improved some aspects of memory and executive function following exposure to a cognitive stressor, but had no impact on the effect of a physical stressor (see Table 5 ) [ 66 71 ]. However, [ 69 ] did find that tyrosine improved vigilance during physical exercise in the heat. Thus, unless a certain threshold of physiological stress is reached, tyrosine by itself does not improve cognition. In addition, flavonoid supplementation produced stronger cognitive effects in the two studies that induced cognitive demand [ 48 49 ]. Although Kennedy et al. [ 60 ] observed stronger cognitive effects from guarana supplementation administered under cognitive demands, Veasey et al. [ 61 ] did not when participants also exercised; however, the cognitive load in the latter study may have been insufficient to induce mental fatigue. Likewise, a number of studies found that caffeine mitigated the effects of sleep deprivation on reaction time, recognition, vigilance and overall executive functioning, including in military samples [ 40 45 ]. In addition, some recent studies showed improvements in memory and executive function from caffeine consumption in well-rested individuals [ 43 ]; however, others did not [ 42 ].

4.4. Limitations

The studies included in the review are subject to various limitations. First, there was substantial variability in sample size and composition across studies. Sample sizes ranged from as few as 11 participants to more than 200 participants, with small sample size a frequent occurrence, yielding insufficient power to detect enhanced cognitive effects. Military samples were predominantly made up of men, whereas samples of healthy young adults typically included roughly equal gender ratios, or slightly more women.

48,49,48, Second, the quality, purity, ratio, duration, dose, and timing of the supplements varied widely across studies. In terms of quality, some studies did not administer the supplement in its pure form; it also contained other active ingredients, which could have been responsible for, or have contributed to, any enhanced cognitive effects. For example, the guarana extract can also naturally contain up to four times the amount of caffeine as found in coffee beans [ 109 ], with some studies also combining it with B vitamins [ 60 61 ], while the nitrate-rich beetroot juice not only contained nitrate but also flavonoids and flavonols [ 63 ]. Relatedly, different sub-classes of flavonoids were used across flavonoid supplementation studies [ 47 50 ], while omega-3 supplementation studies have been found to suffer from varied EPA to DHA ratios [ 88 ], as well as the use of oxidised supplements in some studies [ 110 ]; all of these could have contributed to the current state of mixed findings. In addition, potential cognitive effects could have been masked by (a) under-dosing, both in terms of low dosages, and (b) short supplementation periods. Doses considered to be low were used in several omega-3 [ 28 ], flavonoid [ 47 50 ], and ginseng [ 111 ] studies, whilst the short supplementation period in Lamport et al. [ 47 ] resulted in insufficient absorption time, as the cognitive effects of flavonone-infused citrus juice were evaluated only two hours after supplementation. Finally, although the majority of included studies did use a placebo-control group or a crossover design, the timing of supplementation (i.e., time of day of administration) was not always mentioned, and thus variations in circadian rhythms could have minimised or amplified any cognitive effects. As the gastrointestinal system and metabolism are regulated by circadian rhythms [ 112 113 ], it is important to control for the impact of the circadian system on the absorption and metabolism of the ingested supplement.

Third, studies varied in terms of the cognitive domains that were assessed, with limited or no investigation of executive function following supplementation with beta-alanine, gingko biloba, ginseng and guarana. Relatedly, different tasks were used to measure a particular cognitive function across studies.

Fourth, study designs did not consistently control for practice effects (ginseng) [ 57 ] or pre-existing baseline differences between the supplementation and placebo groups (gingko biloba) [ 51 ], or did not include a placebo-control group altogether (omega-3) [ 28 ].

Finally, SIGN50 scoring identified a substantial number of included papers of low quality (see Table 2 ). To make firm recommendations about the use of dietary supplements for cognitive enhancement, it is crucial that researchers are aware of the need to provide full information on their methodology, especially randomization and blinding techniques, to ensure papers are of high quality and reduce liability of risk and bias. Teo et al. [ 88 ] made a similar recommendation in their review on the effect of omega-3 on cognition and highlighted the importance of researchers following agreed reporting guidelines.

These methodological limitations could account for some of the conflicting results regarding cognitive effects from dietary supplementation. Methodological variations among studies also make it difficult to directly compare them, and thus draw firm conclusions. Moreover, the risk of bias assessment deemed the risk of the majority of studies to be unclear. In addition, the quality assessment indicated considerable variability in the quality of studies, with very few studies of high quality.