Best for Cognition

Creatine monohydrate supplementation shows consistent, clinically meaningful improvements in memory and processing speed in humans, with strongest evidence in older adults and vegetarians. Multiple RCTs and meta-analyses demonstrate efficacy, though effects on broader cognitive domains remain inconsistent.

Ashwagandha demonstrates strong efficacy for cognitive enhancement in humans across multiple well-designed RCTs. Consistent improvements in memory, attention, executive function, and reaction time have been replicated across independent research groups with sample sizes ranging from 43 to 130 participants.

Pycnogenol demonstrates consistent, clinically meaningful improvements in cognitive function across multiple human RCTs and observational studies, with effect sizes ranging from 7-30% improvements on standardized cognitive measures. Evidence is strongest for attention, memory, and mental performance in healthy aging and disease populations.

L-theanine demonstrates strong evidence for cognitive enhancement, particularly when combined with caffeine. Multiple well-designed human RCTs show consistent improvements in attention, reaction time, and task-switching performance, with effects most pronounced in cognitively demanding situations or sleep-deprived states.

Selank shows probable efficacy for anxiety and cognitive function in humans based on 2 small RCTs and supporting animal studies, but evidence is limited by small sample sizes, lack of independent replication, and absence of long-term safety data. Human efficacy for cognition specifically is suggested but not conclusively proven.

Tesamorelin shows probable cognitive benefits in aging adults and those with mild cognitive impairment based on 2 human RCTs, but effect sizes are modest and long-term efficacy remains unproven. Results have not been independently replicated by other research groups.

Humanin shows probable neuroprotective effects for cognitive function based on multiple human observational studies and consistent animal research, but efficacy remains unproven in humans—only 4 human RCTs exist, and none specifically measured cognitive outcomes in living subjects with validated cognitive assessments.

Cerebrolysin shows probable efficacy for cognitive improvement in stroke and dementia, supported by multiple human studies and meta-analyses, but evidence is limited by small sample sizes, inconsistent effect measurements, and lack of independent replication in large-scale RCTs.

GLP-1 receptor agonists show promising neuroprotective effects on cognition in animal models and preliminary human studies, with some positive results in Alzheimer's disease and Parkinson's disease trials, but efficacy remains inconsistent and not yet conclusively proven in large, well-powered human RCTs.

Cortexin shows probable efficacy for cognitive impairment across multiple human observational studies and one meta-analysis, with consistent improvements in attention, memory, and executive function. However, evidence is primarily from open-label observational designs rather than rigorous RCTs, and most high-quality studies come from post-Soviet regions with limited independent replication.

Omega-3 fatty acids show probable cognitive benefits in some populations, particularly older adults and those with cognitive decline, but efficacy is inconsistent across studies and effect sizes are modest. Multiple human RCTs report null or mixed results, limiting conclusive claims of effectiveness.

NAC shows probable efficacy for cognition in humans, with one RCT demonstrating improved working memory in psychosis patients and emerging evidence from animal models of neuroprotection. However, evidence is limited to small human studies and mechanistic animal work; large-scale, independent replication is lacking.

Zinc supplementation shows probable but inconsistent benefits for cognition in children and mixed results in adults. Human RCTs demonstrate modest improvements in specific cognitive domains, but effects are not universally significant and evidence remains limited by small sample sizes and heterogeneous outcomes.

Curcumin shows probable efficacy for specific cognitive domains (working memory, processing speed) in older adults with adequate duration (≥24 weeks at ~0.8g/day), but global cognitive function improvements are inconsistent across studies and efficacy has not been independently replicated in multiple high-quality RCTs. Animal studies consistently show promise, but human evidence remains mixed and limited in scale.

Resveratrol demonstrates probable cognitive benefits in humans, particularly in postmenopausal women and Alzheimer's disease patients, but evidence remains limited by small sample sizes, short durations, and mixed or null findings in several trials.

CoQ10 shows probable but not conclusive benefits for cognition in humans, with positive associations observed in observational studies and some small clinical trials, but limited high-quality RCT evidence and modest effect sizes.

Probiotics show probable efficacy for cognition in older adults with mild cognitive impairment and Alzheimer's disease based on multiple human RCTs and meta-analyses, but effect sizes are modest, heterogeneity is substantial, and results are inconsistent across studies and cognitive domains.

Melatonin shows moderate evidence for improving cognition in specific populations (mild cognitive impairment, type 2 diabetes, multiple sclerosis), with demonstrated improvements in cognitive testing scores and processing speed. However, the human evidence base is limited to small RCTs and observational studies, with one large feasibility trial showing no significant cognitive benefit versus placebo.

Milk thistle (silymarin) shows probable benefit for cognition based on 2 human RCTs and multiple animal studies demonstrating improvements in memory, oxidative stress markers, and inflammatory biomarkers in Alzheimer's disease and stress-induced cognitive impairment. However, evidence remains limited by small sample sizes, short study durations, and lack of independent replication in larger populations.

Rhodiola rosea shows probable benefits for cognition in humans, supported by multiple small-to-moderate RCTs demonstrating improvements in mental performance, memory, and executive function under stress. However, evidence is limited by small sample sizes, heterogeneous study designs, and lack of independent replication, preventing conclusive claims of efficacy.

Green tea extract (EGCG) shows probable benefit for cognition based on animal studies and one small human RCT, but evidence remains limited. A 12-month human trial found modest improvements in social acuity but no significant changes in primary cognitive measures (Montreal Cognitive Assessment, ADCOMS).

B vitamin supplementation shows modest improvements in cognitive function in older adults, particularly for global cognition and brain atrophy rates, but efficacy is inconsistent across studies with considerable heterogeneity and very low to moderate certainty evidence.

Vitamin B12 supplementation shows probable benefit for cognition in specific subgroups (elderly with cognitive impairment, frontal lobe atrophy), but meta-analyses and large RCTs demonstrate no consistent effect in cognitively normal or general elderly populations. Evidence is mixed and moderately strong.

Vitamin E shows probable benefit for cognition based on observational associations with cognitive status and emerging human trial data, but efficacy remains unproven—multiple human RCTs report null or modest results, and evidence quality is limited by small sample sizes and inconsistent outcomes.

Iron supplementation shows probable efficacy for improving certain cognitive domains (intelligence, memory, attention) in children and non-anemic adults, supported by multiple meta-analyses and RCTs. However, evidence is mixed across different populations and cognitive measures, with inconsistent effects on academic achievement and cognitive outcomes in early childhood.

Selenium supplementation shows probable benefits for cognitive function in patients with mild cognitive impairment and Alzheimer's disease based on meta-analysis evidence, with improvements in cognitive test scores and antioxidant enzyme activity. However, human trial evidence remains limited and effect sizes are modest, preventing a higher tier classification.

Iodine supplementation during pregnancy improves some aspects of child neurodevelopment, particularly psychomotor development and cognitive function in mildly iodine-deficient populations, but effects are modest and inconsistently demonstrated across domains. Evidence is limited by lack of RCTs in mild-to-moderate deficiency settings and mixed findings on cognitive outcomes.

Chromium supplementation shows modest benefits for cognitive function in older adults with cognitive decline, primarily through improved cognitive inhibitory control and cerebral activation. However, evidence is limited to a small number of human studies with modest sample sizes and inconsistent effects across cognitive domains.

Spermidine supplementation shows probable efficacy for cognition in older adults with cognitive decline, supported by multiple human RCTs with modest positive effects on memory performance. However, evidence remains limited by small sample sizes, short intervention durations, and lack of replication by independent research groups.

Sulforaphane shows promising neuroprotective effects on cognition in animal models and one human RCT in schizophrenia, but evidence remains limited by small sample sizes, short trial duration, and inconsistent cognitive outcomes in the human trial.

Boswellia shows probable efficacy for cognition based on multiple human RCTs demonstrating improvements in memory and cognitive function, particularly in traumatic brain injury and aging populations. However, evidence is limited by small sample sizes, short study durations, and lack of independent replication across all cognitive domains.

Pomegranate extract shows probable cognitive benefits in humans based on 2 RCTs and 3 observational studies, with the strongest evidence for memory protection after cardiac surgery and modest improvements in executive function in older adults. However, evidence remains limited by small sample sizes and inconsistent effect sizes across cognitive domains.

Cistanche demonstrates probable efficacy for cognition based on 6 human RCTs showing improvements in memory, attention, and cognitive assessment scores, but evidence is limited by small-to-moderate sample sizes (n=18-117), short study durations (30-90 days), and inconsistent effect magnitude across trials. Most mechanistic support comes from animal studies.

Lemon balm shows probable efficacy for cognition and mood in human studies, with some evidence for stabilizing cognitive function in mild cognitive impairment and Alzheimer's disease. However, results are inconsistent across studies, sample sizes are generally small, and the largest RCT (n=323) failed to show significant cognitive benefits on primary endpoints.

Methylene blue shows probable cognitive and neuroprotective effects in humans based on several small RCTs demonstrating memory enhancement, improved functional connectivity, and reduced cognitive impairment in specific contexts. However, efficacy is not conclusive due to small sample sizes, limited replication, and mixed results across different cognitive domains.

Lithium orotate shows promise for cognition based on mechanistic studies and epidemiological data, but human RCT evidence is limited and inconsistent. Low-dose lithium demonstrates neuroprotective effects in animal models and some human observational studies, but the cognitive benefits in humans remain probable rather than proven.

Whey protein shows probable but not conclusive benefits for cognition in humans, with modest improvements in executive function and emotion recognition in older adults, but limited effects on most cognitive domains. Evidence is mixed across a small number of human studies with modest sample sizes.

Lion's Mane shows probable efficacy for cognition in humans based on 7 RCTs, but results are mixed and modest. Some studies demonstrate improvements in specific cognitive domains (processing speed, working memory), while others show null effects on global cognitive function. Evidence is limited by small sample sizes and inconsistent replication.

Alpha-GPC shows probable efficacy for cognitive enhancement in humans, with consistent improvements in memory and cognition observed across multiple RCTs and observational studies. However, evidence is limited by small sample sizes, heterogeneous populations, and lack of independent replication in large trials.

Bacopa monnieri shows probable efficacy for cognition in humans, particularly for memory and attention, supported by multiple RCTs and meta-analyses. However, evidence is limited by small sample sizes, short study durations, inconsistent effect sizes across cognitive domains, and lack of independent replication in large populations.

Phosphatidylserine shows probable efficacy for cognitive function based on 4 human RCTs and several observational studies, but evidence is limited by small sample sizes, short durations, and heterogeneous outcome measures. Most positive findings come from Asian populations and combination formulations rather than PS alone.

CDP-choline (citicoline) shows probable efficacy for cognition in humans, particularly for memory in healthy older adults and some benefit in dementia, but evidence is mixed with methodological limitations and inconsistent results across conditions.

Ginkgo biloba shows probable efficacy for cognition in dementia patients, with consistent benefits across multiple clinical trials for cognitive function, behavioral symptoms, and activities of daily living. However, efficacy in healthy individuals is not supported by evidence, and effect sizes in dementia populations are modest.

Huperzine A shows probable efficacy for cognitive impairment in Alzheimer's disease based on multiple meta-analyses, but all evidence comes from studies conducted primarily in China with methodological limitations. No high-quality human RCTs from Western populations exist.

PQQ demonstrates probable cognitive benefits in humans based on 8 RCTs, with consistent improvements in memory and attention reported across multiple trials. However, effect sizes are modest, sample sizes are generally small (n=27–64), and optimal dosing and long-term durability remain unclear.

Noopept shows probable cognitive benefits in humans based on several RCTs and observational studies, but evidence remains limited by small sample sizes, short treatment durations, and lack of independent replication. Animal studies consistently support cognitive enhancement, but human efficacy is not definitively proven.

Piracetam shows probable efficacy for cognitive impairment in older adults and dementia patients based on multiple meta-analyses, but recent evidence raises questions about effect sizes and clinical meaningfulness. Results are inconsistent across studies and have not been independently replicated with uniform positive findings.

Aniracetam shows probable efficacy for cognition in humans with dementia and cerebrovascular disease, supported by multiple observational and RCT studies, though evidence is limited by small sample sizes, short durations, and lack of large, independently replicated RCTs. Animal models consistently demonstrate cognitive enhancement, but healthy humans show no benefit.

Phenylpiracetam demonstrates probable cognitive benefits in human studies, primarily for memory, attention, and higher brain functions in patients with neurological conditions. However, evidence is limited to small-to-moderate sample sizes, mostly open-label or single-armed observational designs, without consistent replication across independent RCTs.

Uridine, typically as part of multinutrient combinations (DHA, choline, uridine monophosphate), shows probable but not conclusive cognitive benefits in humans. Several small RCTs demonstrate modest improvements in specific cognitive domains in mild Alzheimer's disease and early brain injury, but results are inconsistent and effect sizes are small.

Vinpocetine shows probable efficacy for cognitive improvement, particularly in stroke and vascular dementia contexts, supported by multiple meta-analyses and human trials. However, evidence remains inconsistent with methodological limitations, and recent controlled studies in healthy populations found no cognitive benefit.

Centrophenoxine shows probable efficacy for cognition in humans based on 3 RCTs, but evidence is limited by small sample sizes (n=25-50), short durations, and lack of independent replication. Animal studies demonstrate consistent mechanistic effects on brain activity and neuroprotection, but cannot substitute for robust human data.

NSI-189 shows probable efficacy for cognition in humans, with modest improvements demonstrated in 2-3 human RCTs, particularly in cognitive subdomains and specific patient populations (moderate depression). However, evidence remains limited by small sample sizes, inconsistent effect sizes across cognitive measures, and lack of independent replication.

Sulbutiamine shows probable benefit for cognition in humans based on 2 small RCTs and mechanistic animal studies, but efficacy is not conclusively proven. Human evidence is limited to early-stage Alzheimer's disease and post-traumatic asthenia; results are modest and sample sizes are small.

Oxiracetam shows probable efficacy for post-stroke and traumatic brain injury-related cognitive impairment based on multiple human RCTs, but effect sizes are modest and recent large trials failed to meet primary endpoints. Evidence is mixed and inconsistent across studies.

Pramiracetam demonstrates probable efficacy for cognition and memory in humans, particularly for trauma-related cognitive deficits and scopolamine-induced amnesia, but evidence is limited by small sample sizes and inconsistent replication across conditions like Alzheimer's disease.

5-HTP shows probable but not conclusive efficacy for cognition based on limited human evidence. One small RCT (n=30) demonstrated modest improvements in cognitive function and mood in older adults, while another RCT found benefits for social cognition. However, evidence remains sparse and mechanistic studies raise concerns about potential neurotoxicity at higher doses.

Beta-alanine shows modest but inconsistent improvements in specific cognitive domains in humans, particularly delayed recall and processing speed, primarily in older adults or those with baseline cognitive impairment. Effects are not universal and null results are common in healthy younger populations.

BCAAs show probable efficacy for cognition recovery in severe traumatic brain injury based on multiple human RCTs, but evidence is limited to acute TBI settings with small sample sizes. Effects in healthy cognition, mild TBI, and other cognitive domains remain inconclusive or unsupported.

L-arginine shows probable but not conclusive efficacy for cognitive improvement in humans. One moderate-quality RCT demonstrated significant improvement in cognitive assessment scores in hypertensive frail older adults, but this finding has not been independently replicated in larger populations.

L-serine shows neuroprotective effects in animal models of ischemia and in limited human clinical data, with proposed mechanisms involving glycine receptor activation and autophagy. However, evidence is primarily from animal studies and small, early-stage human trials, making efficacy in cognition probable but not conclusively proven.

BPC-157 shows potential cognitive benefits in animal models, particularly for memory recovery after brain injury and counteracting cognitive symptoms in schizophrenia models, but no human studies have directly tested its cognitive effects.

TB-500 shows promising neuroprotective and neurorestorative effects in animal models of brain injury and neurodegeneration, but human evidence for cognitive benefits is extremely limited with only observational studies.

GHK-Cu shows plausible mechanisms for cognitive support and demonstrated cognitive benefits in aging mice, but lacks human clinical trials to prove efficacy in humans. Current evidence is limited to one animal study and mechanistic review.

Semax shows neuroprotective effects in animal models and limited human studies, primarily through anti-inflammatory and neurotrophic mechanisms in ischemic stroke contexts. However, efficacy for general cognition in healthy humans remains unproven, with evidence limited to 1 small human RCT and mechanistic animal studies.

Epithalon has shown consistent effects on pineal gland function and melatonin regulation in animal studies and one small human RCT, but there is no robust human evidence demonstrating efficacy for cognition specifically. The single human study (n=1, retinal degeneration) is not cognitive-focused.

DSIP shows sleep-promoting effects in animal models and some neuroprotective properties in stroke studies, but there is no convincing evidence of cognitive enhancement in humans. The compound's cognition-relevant effects (neuroprotection, anticonvulsant potential) are documented only in rodents and lack human validation.

Thymosin Alpha-1 has not been directly studied for cognition in humans. Emerging evidence suggests indirect cognitive benefits through immune modulation and neuroinflammation reduction, but no direct cognition trials exist.

MOTS-c shows promise for cognitive function in animal models and may have biomarker value in neurodegenerative disease, but human efficacy for cognition remains unproven. Evidence is limited to observational biomarker studies and animal models without human RCTs.

SS-31 shows consistent neuroprotective effects in animal models of cognitive injury and neurodegeneration, with emerging mechanisms through mitochondrial protection and oxidative stress reduction. However, no human RCTs directly demonstrate efficacy for cognition, and the single human RCT (MMPOWER-3) did not assess cognitive outcomes.

Sermorelin (GHRH agonist) shows plausible cognitive benefits in animal models of intermittent hypoxia and beta-amyloid-induced cognitive impairment, but human efficacy for cognition remains unproven. All meaningful cognitive data derive from rodent studies.

LL-37 shows mixed and inconclusive evidence for cognition. One human observational study found higher LL-37 associated with cognitive decline in older adults, while mechanistic reviews suggest potential neuroprotective roles through gut-brain axis and antimicrobial pathways, but no human efficacy trials demonstrate cognitive benefit.

Dihexa shows promising procognitive effects in animal models of cognitive impairment and neurodegenerative disease, but evidence is limited to preclinical studies and a single human RCT that failed to demonstrate efficacy. Human proof of efficacy for cognition does not yet exist.

Kisspeptin modulates limbic brain activity and emotional processing in a single human RCT, but no studies demonstrate efficacy for general cognition, memory, attention, or executive function. Evidence remains primarily mechanistic and reproductive-focused.

GHRP-6 shows neuroprotective effects and promotes neurogenesis in animal stroke models, but there is no direct human evidence that GHRP-6 improves cognition. The cognition-related findings are limited to animal studies of stroke recovery and mechanistic reviews of ghrelin's role in learning and memory.

Melanotan 2 shows consistent cognitive benefits in animal models, particularly reversing memory impairment induced by high-fat diet and reducing amyloid pathology in Alzheimer's disease models. However, no human clinical trials for cognition have been conducted; all efficacy evidence derives from rodent and zebrafish studies.

Gonadorelin (GnRH) agonists have been studied for cognitive effects primarily in animal models and a small number of human studies, with mixed and mostly negative results for cognition. The evidence suggests GnRH signaling may play a role in memory function, but clinical efficacy for cognition improvement is not demonstrated.

GDF-11 shows promising neuroprotective and neurorestorative effects in animal stroke models with consistent improvements in sensorimotor outcomes and neurogenesis, but human evidence for cognition-specific benefits remains limited and inconclusive. One human RCT on stroke recovery is cited, but cognition-focused human trials are absent.

VIP shows neuroprotective and pro-neurogenic effects in animal stroke models and circadian/memory-related brain circuits, but lacks human clinical trial evidence for cognitive enhancement. Current data is primarily mechanistic and animal-based.

Thymalin shows plausible cognitive benefits in animal models and preliminary human studies, but evidence remains primarily from small, non-placebo-controlled human trials and animal research. Efficacy in humans for cognition is suggested but not proven.

Pinealon shows neuroprotective and cognitive effects in animal models and one small human observational study, but efficacy in humans is not proven. All rigorous evidence comes from rodent studies; human data is limited to a single non-randomized observational study of 32 patients.

Cortagen shows neuroprotective potential in animal models of brain ischemia and oxidative stress, but no human trials have been conducted. Evidence is limited to rodent studies with modest sample sizes and no direct measurement of cognitive outcomes.

Vilon (Lys-Glu dipeptide) shows plausible mechanisms for supporting cognition through effects on pineal gland function, immune cell differentiation, and stress resilience in animal models, but no human clinical trials have demonstrated efficacy for cognitive outcomes.

Cartalax (a peptide complex) shows plausible mechanistic effects on neuronal differentiation and cell renewal in animal models, but no human efficacy data exists for cognition. Evidence is limited to 2 small animal studies with no direct measurement of cognitive outcomes.

ARA-290 shows promise for cognitive protection in animal models of brain injury and neuroinflammatory disease, with one small human RCT suggesting modulation of emotional processing. However, proven efficacy in humans for cognition has not been established—most evidence derives from animal studies or mechanistic investigations in non-cognitive disease models.

Ibutamoren (MK-0677) shows plausible mechanisms for cognitive support through GH/IGF-1 axis activation and ghrelin receptor agonism, with one animal study demonstrating reduced amyloid-beta pathology in Alzheimer's disease models. However, no human clinical trials directly measuring cognitive outcomes have been published; all efficacy evidence comes from animal models and mechanistic studies.

MGF shows neuroprotective potential in animal and in-vitro models, but evidence in humans is extremely limited. Only 1 human RCT exists (examining cardiac mechano-growth factor, not cognitive outcomes), and no human studies directly demonstrate efficacy for cognition.

Oxytocin shows emerging evidence for effects on emotion recognition in humans, with one small RCT demonstrating improved recognition of positive emotions. However, evidence for broader cognitive benefits is limited to animal studies and mechanistic findings, with no proven efficacy in human cognition.

Retinalamin shows neuroprotective effects in glaucoma and retinal disease models based on human observational studies and animal research, but evidence for cognition specifically is absent. All studies focus on retinal/optic nerve protection rather than cognitive function.

Magnesium shows plausible cognitive benefits through mechanistic studies and emerging human evidence, but efficacy for cognition remains unproven in rigorous trials. Most positive findings come from animal models or observational studies with limited sample sizes.

Vitamin D3 shows plausible neuroprotective mechanisms in animal models and mechanistic studies, but human trial evidence for cognition is weak and inconsistent. The largest human RCT (D-Health, n=3887) found no effect on cognitive function, while a smaller trial showed marginal benefits only in per-protocol analysis.

Berberine shows consistent cognitive benefits in animal models of diabetes-related cognitive impairment and ischemic stroke, with plausible mechanisms involving glucose metabolism, antioxidant pathways, and neuroinflammation. However, only 2 human RCTs exist (both focused on stroke, not general cognition), leaving efficacy in humans largely unproven.

Quercetin shows promise for cognitive protection in animal models through antioxidant and anti-inflammatory mechanisms, but human efficacy remains unproven. A large human trial (n=941) found no effect on memory, attention, or cognitive flexibility despite high plasma levels.

NMN shows promise for cognition in animal models and mechanistic studies, but human clinical evidence is extremely limited. Only 1 small human RCT exists in the provided abstracts, and no human trials specifically testing NMN for cognitive improvement have been completed.

Alpha-lipoic acid shows promise for cognition in animal models and a few small human studies, but the only human RCT-equivalent study (open-label pilot, n=15) found no significant effects on cognitive function, executive function, or mood in elderly adults. Efficacy in humans remains unproven.

Collagen peptides show promising effects on cognition in animal models and one small human study, but efficacy in humans remains unproven. Animal studies demonstrate consistent improvements in memory and learning, while a single human RCT found improved Stroop test performance and reduced sleep fragmentation.

Vitamin K2 shows consistent cognitive benefits in multiple animal models of aging and neurodegeneration, but zero human RCTs exist to prove efficacy in humans. Evidence is emerging but unproven.

Boron's cognitive benefits are theoretically plausible based on mechanistic reviews and limited animal data, but there is NO human RCT evidence demonstrating efficacy for cognition. A single observational study found elevated serum boron in stroke patients (suggesting a biomarker relationship, not proof of benefit), and animal studies show mixed results on learning and memory.

Maca root shows neuroprotective potential in animal and in-vitro studies, particularly for ischemic brain injury and neuroinflammation, but human evidence for cognition is minimal—only one small observational study demonstrates cognitive benefits (social memory in autism model), with no human RCTs directly measuring cognition.

Black seed oil (Nigella sativa) and its active component thymoquinone show promise for cognition-related outcomes in preclinical studies and one small human trial, but efficacy in humans is not yet proven. Evidence is primarily mechanistic and animal-based, with only one human observational study directly measuring cognitive endpoints.

Elderberry shows plausible neuroprotective potential through antioxidant and anti-inflammatory mechanisms in animal models and in vitro studies, but human evidence for cognition is minimal—only one small pilot RCT (n=24) showing a trend toward improved visuospatial problem solving, which did not reach statistical significance.

Aged garlic extract shows neuroprotective effects in animal models of stroke and Alzheimer's disease through antioxidant and anti-inflammatory mechanisms, but no human clinical trials demonstrating cognitive improvement have been completed. Evidence remains largely preclinical.

Spirulina shows plausible neuroprotective mechanisms in animal models and early-stage human research, but lacks rigorous human trial evidence for cognition specifically. Current data suggests potential benefits for neuroinflammation and oxidative stress, but efficacy in humans is not yet proven.

Fenugreek shows promising neuroprotective and cognitive effects primarily in animal models through multiple mechanisms, but human efficacy remains unproven with only one human RCT identified in this set.

Glucosamine + Chondroitin has not been studied in humans for cognition; one Mendelian randomization study suggests genetic predisposition to glucosamine use associates with improved cognitive performance, but no experimental human trials exist testing this compound for cognitive outcomes.

Vitamin C shows neuroprotective promise in animal models and mechanistic studies, but human evidence for cognitive enhancement in healthy or cognitively impaired populations is absent or negative. Large meta-analyses found no consistent benefit for maintaining or improving cognition in older adults.

Copper deficiency impairs cognition and neurological function in disease states, but there is no evidence from human RCTs that copper supplementation improves cognition in healthy people. Evidence is limited to case reports of cognitive recovery from copper deficiency, animal models, and mechanistic studies.

Biotin shows plausible mechanisms for cognition support through remyelination and neuroprotection in animal models and rare disease cases, but lacks rigorous human RCT evidence demonstrating efficacy for cognition as a primary outcome in healthy individuals.

Fisetin shows consistent neuroprotective effects in animal models and in-vitro systems, with multiple proposed mechanisms targeting oxidative stress, neuroinflammation, and protein aggregation. However, no rigorous human RCTs directly testing fisetin for cognitive enhancement exist in this dataset, limiting definitive proof of efficacy for cognition in humans.

Urolithin A shows promising neuroprotective mechanisms in animal and cell models of cognitive decline and neurodegeneration, but human evidence for cognition improvement is absent. The single human RCT focused on immune function, not cognition.

Astaxanthin shows plausible cognitive benefits in animal models and preliminary human studies, with improvements in spatial memory and hippocampal function demonstrated in mice. However, human evidence is limited to observational studies and meta-analyses of small RCTs with marginal or non-significant cognitive effects, preventing a conclusion of proven efficacy in humans.

Glutathione shows plausible neuroprotective mechanisms in animal and in-vitro models through antioxidant and ROS-scavenging effects, but human evidence for cognition is limited to a single small open-label pilot study in autism spectrum disorder that did not demonstrate clear clinical cognitive improvement despite improved oxidative markers.

TUDCA shows neuroprotective mechanisms in animal models and limited human safety data, but cognition-specific efficacy in humans remains unproven. Three human RCTs exist, but none demonstrated clinically meaningful cognitive improvements as a primary outcome.

Nattokinase shows promise for cognition in animal models and one small human RCT, with plausible mechanisms involving blood flow improvement and amyloid degradation. However, efficacy in humans remains unproven, and the single human cognition trial found no significant improvement in overall cognitive function.

Shilajit shows mechanistic promise for cognition based on animal studies and chemical analysis, but no human efficacy trials for cognitive outcomes exist. One review mentions a clinical trial in mild AD patients, but the abstract provides no results, making it impossible to assess whether shilajit actually improves cognition in humans.

Beta-glucans show plausible immunomodulatory effects primarily through 'trained immunity' mechanisms in immune cells, but NO human evidence demonstrates efficacy for cognition specifically. All cognitive relevance is indirect and mechanistic (immune system modulation) with zero direct cognitive outcome data.

Cordyceps shows plausible cognitive benefits in animal models and limited human observational studies, with improvements in learning, memory, and neuroprotection demonstrated primarily in rodents. However, no human RCTs exist, and efficacy in humans remains unproven.

Reishi demonstrates plausible neuroprotective and cognitive-enhancing effects in animal models and mechanistic studies, but no human RCTs exist to prove efficacy for cognition. Evidence is limited to 4 small human observational studies and 18 animal studies, making efficacy in humans unproven.

Chaga shows consistent neuroprotective effects in animal models and cell culture studies, with multiple studies demonstrating improvements in cognitive function and reduction of Alzheimer's-related pathology. However, no human clinical trials exist, leaving efficacy in humans unproven.

Epicatechin shows neuroprotective effects in animal models and mechanistic studies, but human clinical trial evidence is minimal and mixed. Only one large human RCT exists, which found no significant cognitive benefit from cocoa extract containing epicatechin.

Apigenin shows plausible cognitive benefits through anti-inflammatory and antioxidant mechanisms in animal models, but human evidence for cognition is limited to observational associations with sleep quality. No human RCTs directly demonstrate cognitive efficacy.

Pterostilbene shows consistent neuroprotective effects in animal models of brain injury and neurodegeneration, but human efficacy for cognition remains unproven. No human RCTs directly measuring cognitive outcomes have been completed.

Grape seed extract shows neuroprotective potential in animal models of stroke, neurodegeneration, and cognitive injury, but human evidence for cognition is limited and inconsistent. A single human RCT found no consistent cognitive benefits in healthy young adults.

Olive leaf extract shows neuroprotective potential in animal models through antioxidant and anti-inflammatory mechanisms, but evidence in humans is extremely limited. Only 2 human RCTs exist in this dataset, and neither specifically isolated cognition as a primary outcome.

Bromelain shows emerging promise for cognition through anti-inflammatory and antioxidant mechanisms demonstrated in animal models and cell studies, but lacks human clinical trial evidence. No human RCTs have directly tested bromelain's effects on cognition outcomes.

Lactoferrin shows plausible neuroprotective mechanisms and improves cognition in animal models, but human efficacy for cognition remains unproven. Only one small human RCT exists, and it failed to demonstrate benefit for the primary outcomes measured.

Stinging nettle shows neuroprotective promise in animal models through antioxidant and anti-inflammatory mechanisms, but human evidence for cognition is extremely limited. One small human study found acetylcholinesterase inhibition in vitro, but no human clinical trials demonstrate cognitive benefits.

Mucuna pruriens is extensively studied for Parkinson's disease due to its L-DOPA content, but evidence for cognitive improvement specifically is largely indirect and mechanistic rather than directly demonstrated. Most efficacy data comes from animal models and mechanistic studies; human cognitive outcomes are rarely assessed.

Ecdysterone shows neuroprotective effects in cellular and animal models of neurodegeneration and cognitive injury, but evidence in humans is absent. One human RCT exists, but it focused on sarcopenia rather than cognition.

Tribulus terrestris shows consistent neuroprotective effects in animal models of stroke, Parkinson's disease, and cognitive impairment, but evidence is limited to rodent and zebrafish studies with only 2 human RCTs of unclear quality. Efficacy in humans remains unproven.

Valerian root has been studied for cognitive effects primarily in the context of sleep and anxiety, but evidence for direct cognitive enhancement in healthy individuals is absent or negative. Most human RCTs show no significant effects on daytime cognition, psychomotor performance, or memory in acutely dosed scenarios.

Kava shows some cognitive benefits in acute dosing studies (improved attention and memory) and does not impair cognition acutely, but evidence for cognition-specific efficacy is limited and mixed. Most research focuses on anxiety rather than cognition as a primary outcome.

Passionflower shows anxiolytic and potential memory-protective effects primarily in animal models and limited human studies, but efficacy for cognition specifically is not proven. Human evidence is restricted to anxiety reduction in surgical contexts, not direct cognitive enhancement.

Schisandra chinensis shows promising neuroprotective and cognitive enhancement effects in animal and in-vitro studies, but human evidence is extremely limited (only 1 RCT and 3 observational studies among 50 total articles). Efficacy in humans remains plausible but unproven.

CLA shows mixed effects on cognition in humans with only 4 small RCTs and 6 observational studies, most reporting null or minimal cognitive effects. Animal studies demonstrate memory benefits and mechanistic effects on brain lipid metabolism, but human efficacy remains unproven.

Pregnenolone shows cognitive-enhancing potential primarily in animal models and a limited number of human observational studies, with mechanistic plausibility but no human RCTs demonstrating efficacy. Evidence is emerging but not yet proven in humans.

SAMe shows plausible mechanisms for supporting cognition through epigenetic and metabolic pathways, but human evidence for cognition-specific benefits is absent. Available data consists primarily of mechanistic reviews and observational studies showing SAMe's involvement in brain metabolism, not clinical trials demonstrating cognitive improvement.

Rapamycin shows plausible mechanisms for cognitive benefits in specific neurological conditions (tuberous sclerosis, stroke recovery) but proven efficacy in human cognition is limited to one small open-label trial (n=9-10) showing improved processing speed. No large-scale human RCTs demonstrate cognitive enhancement in healthy populations or generalizable cognitive benefits.

D-ribose shows plausible neuroprotective mechanisms in animal models and cell culture by supporting ATP restoration, but there is no human clinical evidence demonstrating efficacy for cognition. A single small human pilot study exists for stroke outcome (not specifically cognition), with promising but preliminary results.

Astragalus shows neuroprotective effects in animal models and cell cultures, particularly for stroke and ischemic brain injury, but human evidence for cognition specifically is extremely limited. One small human RCT (n=83) showed improved neurological outcomes in subarachnoid hemorrhage patients, but cognition was not directly measured.

Butyrate shows plausible cognitive benefits through microbiota modulation and anti-inflammatory mechanisms in multiple animal and observational human studies, but direct efficacy in cognition has not been demonstrated in rigorous human RCTs. Evidence is emerging from mechanistic pathways rather than proven clinical outcomes.

Betaine supplementation shows mechanistic promise for cognition and may improve cognitive outcomes in specific neurological conditions, but human evidence is limited to case reports and small observational studies with no adequately powered RCTs demonstrating efficacy in healthy populations.

Panax ginseng shows plausible cognitive benefits supported by mechanistic research and limited clinical data, but rigorous human RCT evidence is sparse and inconclusive. Current evidence suggests potential for cognition enhancement but does not yet prove efficacy in humans.

9-ME-BC shows promising cognitive enhancement effects in animal models through dopamine and neurotrophic factor upregulation, but no human efficacy trials exist. Evidence is limited to rodent studies and cell culture, with no proof of cognitive benefits in humans.

Bromantane/ladasten shows consistent mechanistic effects on dopamine and monoamine systems in animal models and demonstrates anxiolytic and psychostimulant properties in one small human observational study, but lacks human RCT evidence to prove efficacy for cognition.

DMAE shows some promise for cognition in preclinical models and limited human studies, but clinical efficacy remains unproven. Only 2 human RCTs exist, one showing null results in prodromal Alzheimer's disease and one showing modest improvements on specific memory tests after scopolamine challenge.

L-Tyrosine has not been proven to improve cognition in humans. While animal studies suggest potential neuroprotective effects and human RCTs included cognitive testing, no meaningful cognitive improvements were demonstrated in the human trials.

Acetyl-L-carnitine's efficacy for cognition in healthy individuals is not established. A 2017 Cochrane systematic review found insufficient evidence for cognitive enhancement in cognitively healthy people, and a 2003 Cochrane review on dementia concluded evidence was unclear despite theoretical mechanisms.

Glycine shows plausible cognitive benefits in a limited number of human studies, primarily through improved memory and sleep quality, but evidence remains preliminary with only 2 human RCTs and lacks consistent replication across cognitive domains.

GABA's effects on cognition are primarily demonstrated through mechanistic studies in animals and theoretical frameworks in reviews. No human RCTs directly testing GABA supplementation for cognitive enhancement were found; the single human RCT involved a GABA derivative (phenibut) with significant safety concerns.

L-citrulline shows altered metabolism in various cognitive and neurological conditions, but no human RCTs have demonstrated efficacy for improving cognition. Evidence is limited to observational associations and mechanistic studies suggesting potential neuroprotection.

HMB shows promise for cognition in animal models and limited human evidence, but human efficacy for cognition specifically remains largely unproven. Most human studies combine HMB with exercise or other nutrients, making it difficult to isolate HMB's independent cognitive effects.

Taurine's cognitive effects remain unproven in humans despite theoretical neuroprotective mechanisms. A 2025 meta-analysis of 7 RCTs found no significant cognitive improvements from taurine alone or combined with exercise, though a subgroup showed modest MMSE gains when combined with therapeutic drugs.

D-Aspartic acid (D-Asp) shows plausible cognitive benefits in animal models through NMDA receptor activation, but human clinical evidence for cognition is absent. Efficacy remains unproven in humans.

L-carnosine shows plausible cognitive benefits in animal models and small human trials, particularly for autism and schizophrenia-related cognitive domains, but human efficacy remains unproven with only 4 small RCTs and mixed results.

Leucine supplementation shows mechanistic promise for cognition primarily through mTOR pathway activation in animal and cell-culture studies, but human evidence for cognitive improvement is extremely limited. The only human RCT directly measuring cognition found no significant cognitive benefits from 8 weeks of whey protein and leucine supplementation.

Tryptophan's effects on cognition are largely mechanistic and correlational in humans, with evidence primarily from animal models and observational studies showing relationships between tryptophan metabolism and cognitive/mood symptoms. No robust human RCTs demonstrate direct cognitive benefits from tryptophan supplementation.

CJC-1295 has not been studied for cognitive effects in any of the available literature. The 4 PubMed abstracts focus exclusively on growth hormone secretion, physical growth, and pituitary function — not cognition, memory, or brain function.

KPV has not been studied for cognition in humans or animals. All identified abstracts discuss its anti-inflammatory mechanisms and wound healing properties, with no evidence addressing cognitive outcomes, memory, attention, or any other cognitive domain.

Hexarelin has not been studied for cognitive enhancement in humans. Evidence is limited to mechanistic studies in animal neurons and cells showing neuroprotective properties, with no clinical trials demonstrating cognition improvement.

No rigorous evidence supports melanotan 1 (afamelanotide) efficacy for cognition. The one human trial was a safety feasibility study in acute stroke patients with no cognitive outcome measures, and two reviews discuss melanocortin receptor biology without demonstrating cognitive benefits.

FOXO4-DRI has not been studied for cognition. The single available study examines vascular endothelial cell senescence in aged mice, with no assessment of cognitive outcomes or brain function.

IGF-1 LR3 has not demonstrated efficacy for cognition in the available evidence. The only direct cognition study (5XFAD mice) showed that intranasal LR3-IGF-1 failed to preserve cognitive function despite modifying amyloid pathology.

Only one animal study exists examining Prostatilen's effects on tissue regeneration in rat cell cultures; no human studies have investigated its effects on cognition. Evidence is too preliminary to support any claims about cognitive benefits.

No evidence demonstrates that Tongkat Ali improves cognition in humans. The five available studies either do not assess cognitive outcomes, show no cognitive benefit in observational data, or examine unrelated biological mechanisms.

Saw palmetto has not been studied for cognition. All identified abstracts focus exclusively on prostate health (benign prostatic hyperplasia) and prostate cancer, with no evidence of efficacy, mechanism, or even testing for cognitive outcomes.

No human studies exist on DIM for cognition. The two animal studies show DIM has neuroprotective effects against hypoxia in mouse hippocampal cells, but this does not demonstrate efficacy for general cognitive enhancement or cognitive disorders in humans.

Colostrum has not been studied for cognition in any human trials. No evidence demonstrates that colostrum improves cognitive function, memory, or brain health in humans or animals.

No credible evidence supports MSM for cognition. The three available studies do not assess cognitive outcomes; they address joint health, inflammation, and brain detection of MSM as an exogenous compound only.

Echinacea has not been demonstrated to improve cognition in humans. Available evidence is limited to one in vitro study showing effects on hippocampal neurons, one animal study on a related compound (chicoric acid) in a Parkinson's model, and a review noting that more research is needed.

Forskolin has not been studied for cognition in humans. All evidence is mechanistic (cAMP pathway activation) or relates to unrelated conditions (glaucoma, Parkinson's disease retinal health). No human or animal studies demonstrate cognitive enhancement, memory improvement, or any cognition-related benefit.

Peppermint oil has NOT been studied for cognition in any of the 16 available abstracts. All evidence focuses on gastrointestinal disorders (IBS, functional dyspepsia, bloating), not cognitive outcomes.

No human efficacy data exists for fasoracetam and cognition. The only available abstract is a pharmaceutical chemistry review examining solid-state crystalline forms, which does not assess cognitive outcomes or clinical efficacy in any organism.

Coluracetam is mentioned only as a comparison compound in a review of glutamate-based antidepressants. No efficacy data for cognition is provided, and no human or animal studies specifically testing coluracetam's cognitive effects are presented.

L-Glutamine's role in cognition is not directly demonstrated in any of the 50 abstracts reviewed. The evidence shows only indirect associations through gut microbiota metabolite production and ammonia metabolism in liver disease contexts, with no direct efficacy studies in cognitive function.

Ornithine (eflornithine) was used as a treatment for West African sleeping sickness in a single case report, not for cognition enhancement. No evidence supports ornithine supplementation for cognitive improvement.

L-lysine has not been studied for cognition in humans. The only available evidence is from a single animal study showing that L-lysine supplementation alleviated anxiety-like behaviors in mice with IBS through tryptophan metabolism modulation, but this is far too preliminary to claim efficacy for human cognition.