Condition
Cognitive Function
Cognitive function is the brain's ability to remember, focus, plan, and think quickly, all relying on nerve cells communicating well. The best-supported options are tesamorelin and sermorelin, and trials found that months of treatment improved executive function and tests of working memory, planning, attention, and processing speed in older adults. Those trials were small, though, and most other research, including on humanin and semax, came from animals or lab studies.
Sources: PMID 22869065; PMID 23750326
- Updated
- How we grade
- 100 studies cited
- Supplements studied
- 9
- Medicines and peptides
- 7
- Graded outcomes
- 21
Evidence by supplement
- Strong
- Moderate
- Limited
- Very limited
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cognitive Function in Alzheimer's Clinical study (48 weeks, 300mg/day): Improved cognitive function in patients with moderate Alzheimer's disease. No exacerbation of symptoms. Preclinical review (20 studies): Strong neuroprotective evidence. | Improves (the measure goes up) | Moderate effect |
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Memory Performance Improved memory performance especially in those with mild cognitive impairment | Improves (the measure goes up) | Moderate effect | 85 people | |||
| Dementia Risk 26% lower dementia risk with higher dietary intake (epidemiological) | Improves (the measure goes down) | Moderate effect | 800 people |
Fisetin
- Neuroprotective Markers: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Neuroprotective Markers Small neuroprotective effect observed | Improves (the measure goes up) | Small effect | 65 people |
American Ginseng
- Working Memory: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Working Memory Modest cognitive enhancement in some studies | Improves (the measure goes up) | Small effect | 80 people |
Theacrine
- Cognitive Performance: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cognitive Performance Improved cognition when combined with caffeine (150mg each) | Improves (the measure goes up) | Small effect | 90 people |
Centrophenoxine
- Cognitive Performance: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cognitive Performance Older clinical studies (1960s-1980s) in elderly with cognitive decline showed improvements in memory, attention, and mental clarity. Study quality limited by modern standards. | Improves (the measure goes up) | Moderate effect | 400 people |
Tryptophan
- Memory: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Memory Memory improvements mainly in populations with serotonergic disturbances | Improves (the measure goes up) | Small effect | 200 people |
Bromantane
- Cognitive/Psychomotor Performance: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cognitive/Psychomotor Performance Limited human experimental data suggest bromantane may improve selected psychophysiological or operator-performance measures under fatigue (PMID: 10998997) and modulate EEG rhythms consistent with CNS activation (PMID: 19642584). Evidence is preliminary and not based on large cognitive endpoint trials. | Improves (the measure goes up) | Small effect | 2 studies | |||
Studies that measured cognitive/psychomotor performance | ||||||
Multivitamin
- Cognitive Decline
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cognitive Decline COSMOS-Mind (n=2,262): No slowing of cognitive decline over 3 years. | NoneNo effect | 5,000 people |
Prescription medicines and peptides studied, for context
Semax
- BDNF Levels: improves
- Memory Performance: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| BDNF Levels Moderate Increase | Improves (the measure goes up) | Moderate effect | 8 studies | 95 people | ||
| Memory Performance Moderate Increase | Improves (the measure goes up) | Moderate effect | 7 studies | 180 people |
Humanin
- Cognitive Function: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cognitive Function Humanin administration improved cognition in aged mice. In humans, a specific SNP in the humanin gene is associated with accelerated cognitive aging, and centenarians' offspring have higher circulating levels. | Improves (the measure goes up) | Moderate effect | 8 studies |
Tesamorelin
- Executive Function: improves
- Cognitive Function in MCI: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Executive Function A 20-week RCT showed tesamorelin improved executive function (P=0.005) as measured by Task Switching, Stroop Color-Word Interference, Self-Ordered Pointing Test, and Word Fluency. | Improves (the measure goes up) | Moderate effect | 6 studies | |||
| Cognitive Function in MCI Treatment attenuated the expected functional decline in individuals with mild cognitive impairment and improved cognitive function in healthy older adults. | Improves (the measure goes up) | Small effect | 6 studies |
Sermorelin
- Cognitive Function: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cognitive Function Six months of GHRH treatment improved performance on tests of fluid intelligence including working memory, planning, selective attention, and processing speed in healthy older adults. | Improves (the measure goes up) | Small effect | 2 studies |
Pinealon
- Cognitive Performance: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cognitive Performance Small Increase | Improves (the measure goes up) | Small effect | 48 studies | 85 people |
Dihexa (PNB-0408)
- Cognitive Enhancement: improves
- Neuroprotection: improves
- Synaptogenesis: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cognitive Enhancement Preclinical: Restored spatial learning and memory in aged rats and APP/PS1 Alzheimer's mice. 7 orders of magnitude more potent than BDNF for spinogenesis. Reversed scopolamine-induced deficits. No human trial data available. | Improves (the measure goes up) | Large effect | 37 studies | |||
| Neuroprotection Preclinical: Protected against neurodegeneration in Alzheimer's mouse models. Reduced amyloid-related cognitive decline. Enhanced neuronal survival via c-Met signaling. | Improves (the measure goes up) | Moderate effect | 33 studies | |||
| Synaptogenesis Preclinical: Promoted new dendritic spine formation in hippocampal neurons at picomolar concentrations. Enhanced synaptic connectivity and plasticity via HGF/c-Met/PI3K pathway activation. | Improves (the measure goes up) | Large effect | 31 studies |
Selank
- Memory Performance: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Memory Performance Small Increase | Improves (the measure goes up) | Small effect | 6 studies | 110 people |
What the published studies found
2 automated readings
Creatine: cognitive function
The studies disagree. The best available review (2024, 16 studies, 492 people) found little or no difference in cognitive function, while 6 of the 10 studies read found an improvement. The evidence is very weak.
10 studies counted of 11 read: 4 reviews and 6 trials (233 people in the trials).
- Systematic review, 2024; 16 studies, 492 people; adults aged 20.8-76.4 years, healthy and diseased: no clear difference (the review the verdict rests on).
no significant improvements were found on overall cognitive function
The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis - Systematic review, 2025; 7 studies, 275 people; individuals with bipolar disorder: improves. Lifestyle-based interventions targeting neurocognition in bipolar disorders - a systematic review of randomized controlled trials
- Systematic review, 2024; vegans, vegetarians, elderly, sleep deprived, hypoxic individuals: unclear: evidence too weak to tell.
demonstrated somewhat equivocal results for effects on cognition
Creatine supplementation research fails to support the theoretical basis for an effect on cognition: Evidence from a systematic review - Meta-analysis, 2023; 8 studies; healthy individuals: improves.
creatine supplementation improved measures of memory compared with placebo
Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials - Randomised trial, 2026; 40 people; young healthy active omnivorous males and females: no clear difference.
no effects of Cr on any of the cognitive tasks
Creatine monohydrate improved cycling Wingate performance but not cognitive function in young active males and females - Randomised trial, 2026; 36 people; perimenopausal and menopausal women: improves.
superior to placebo in enhancing reaction time
The Effects of 8-Week Creatine Hydrochloride and Creatine Ethyl Ester Supplementation on Cognition, Clinical Outcomes, and Brain Creatine Levels in Perimenopausal and Menopausal Women (CONCRET-MENOPA): A Randomized Controlled Trial - Crossover trial, 2025; 14 people; physically active men: improves.
improved cognitive performance on the DCT
Effects of Creatine Monohydrate Loading on Sleep Metrics, Physical Performance, Cognitive Function, and Recovery in Physically Active Men: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial - Crossover trial, 2015; 15 people; healthy young adults: improves.
decrements in cognitive performance, specifically attentional capacity, were restored
Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation - Randomised trial, 2011; 128 people; young adult females: mixed results.
creatine supplementation resulted in better memory
The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores - Randomised trial, 2009: improves.
improvement over the placebo condition on several measures
Cognitive effects of creatine ethyl ester supplementation
- Systematic review, 2024; 16 studies, 492 people; adults aged 20.8-76.4 years, healthy and diseased: no clear difference (the review the verdict rests on).
Phosphatidylserine: cognitive function
The best available review (2026, 11 studies) found little or no difference in cognitive function. That review studied children, adolescents, and adults with mental disorders. 3 of the 6 studies read agree; 3 found an improvement. The evidence is moderate.
6 studies counted of 9 read: 1 review and 5 trials (710 people in the trials).
- Systematic review, 2026; 11 studies; children, adolescents, and adults with mental disorders: no clear difference (the review the verdict rests on).
findings were heterogeneous and inconsistent across diagnostic groups
The Impact of Citicoline/Phosphatidylserine Supplementation on Cognitive Performance and Executive Functions in Mental Disorders: A Systematic Review of Controlled Trials - Crossover trial, 2013; recreationally trained individuals: no clear difference.
does not affect CF or RT
Phosphatidylserine and caffeine attenuate postexercise mood disturbance and perception of fatigue in humans - Crossover trial, 2011; 18 people; lower body resistance trained college aged males: improves.
significantly reduced the time needed for a correct calculation
The effects of IQPLUS Focus on cognitive function, mood and endocrine response before and following acute exercise - Randomised trial, 2010; 78 people: improves.
memory scores in PS treated groups were significantly increased
Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints - Randomised trial, 2001; 120 people: no clear difference.
No significant differences were found in any of the outcome variables
The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment - Randomised trial, 1993; 494 people; elderly patients with moderate to severe cognitive decline: improves.
Statistically significant improvements in the phosphatidylserine-treated group
Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration
- Systematic review, 2026; 11 studies; children, adolescents, and adults with mental disorders: no clear difference (the review the verdict rests on).
Key findings
- Cognitive Function in Alzheimer'sImproves (the measure goes up)
- Memory PerformanceImproves (the measure goes up)
- Dementia RiskImproves (the measure goes down)
Safety notes in the studies
- 26% lower dementia risk with higher dietary intake (epidemiological)
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Studies cited
100 studies from PubMed
- Body composition, hepatic fat, metabolic, and safety outcomes of Tesamorelin, a GHRH analogue, in HIV-associated lipodystrophy: A meta-analysis of randomized controlled trials.
- Effects of Cistanche deserticola Y.C. Ma Supplementation on Muscle Strength and Recovery: A Randomized Controlled Trial
- Plasma Humanin and Non-Coding RNAs as Biomarkers of Endothelial Dysfunction in Rheumatoid Arthritis: A Pilot Study.
- Humanin attenuates metabolic, toxic, and traumatic neuropathic pain in mice by protecting against oxidative stress and increasing inflammatory cytokine.
- HUMANIN produced by human efferocytic macrophages promotes the resolution of inflammation.
- Hepatoprotective Effects of Thymogen Analogues in Hydrazine Hepatopathy in Rats.
- Genes That Associated with Action of ACTH-like Peptides with Neuroprotective Potential in Rat Brain Regions with Different Degrees of Ischemic Damage.
- The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease.
- Semax, a Copper Chelator Peptide, Decreases the Cu(II)-Catalyzed ROS Production and Cytotoxicity of aβ by Metal Ion Stripping and Redox Silencing.
- Growth Hormone-Releasing Hormone Antagonists Increase Radiosensitivity in Non-Small Cell Lung Cancer Cells.
- Effects of Tesamorelin on Neurocognitive Impairment in Persons With HIV and Abdominal Obesity
- Metabolic dysfunction-associated steatotic liver disease in people with HIV.
- The Effects of Fisetin on Reducing Biological Aging: A Pilot Study
- Senolytics To slOw Progression of Sepsis (STOP-Sepsis) in elderly patients: Study protocol for a multicenter, randomized, adaptive allocation clinical trial
- [Gly14]-Humanin ameliorates high glucose-induced endothelial senescence via SIRT6.
- Impaired Expression of Humanin during Adrenocortical Carcinoma.
- Humanin ameliorates TBI-related cognitive impairment by attenuating mitochondrial dysfunction and inflammation.
- Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4-induced brain pathology.
- Humanin-G Ameliorates Hemorrhage-Induced Acute Lung Injury in Mice Through AMPKα1-Dependent and -Independent Mechanisms.
- Humanin's impact on pain markers and neuronal viability in diabetic neuropathy model.
- Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress.
- Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors.
- Humanin and Its Pathophysiological Roles in Aging: A Systematic Review
- A novel link between chronic inflammation and humanin regulation in children.
- Mitochondrial stress and mitokines in aging.
- Humanin and Its Pathophysiological Roles in Aging: A Systematic Review.
- S14G-humanin confers cardioprotective effects against chronic adrenergic and pressure overload-induced heart failure in mice.
- S14G-humanin alleviates acute lung injury by inhibiting the activation of NF-κB.
- Increase in False-Positive Fourth-Generation Human Immunodeficiency Virus Tests in Patients With Coronavirus Disease 2019.
- Growth hormone-releasing hormone receptor antagonist MIA-602 attenuates cardiopulmonary injury induced by BSL-2 rVSV-SARS-CoV-2 in hACE2 mice.
- Growth hormone-releasing hormone antagonist MIA-602 inhibits inflammation induced by SARS-CoV-2 spike protein and bacterial lipopolysaccharide synergism in macrophages and human peripheral blood mononuclear cells.
- GHRH agonist MR-409 protects β-cells from streptozotocin-induced diabetes.
- Echinacoside Improves Cognitive Impairment by Inhibiting Aβ Deposition Through the PI3K/AKT/Nrf2/PPARγ Signaling Pathways in APP/PS1 Mice
- Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy.
- The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress
- Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection
- Humanin and diabetes mellitus: A review of in vitro and in vivo studies.
- The protective effects of S14G-humanin on gestational diabetes mellitus symptoms.
- Humanin vivoliver and tumor bioimpedance measured with biopsy needle.
- An evidence of Humanin-like peptide and Humanin mediated cryosurvival of spermatozoa in buffalo bulls.
- Effect of Humanin G (HNG) on inflammation in age-related macular degeneration (AMD).
- [Gly14]-Humanin inhibits an angiotensin II-induced vascular smooth muscle cell phenotypic switch via ameliorating intracellular oxidative stress.
- Circulating humanin is lower in coronary artery disease and is a prognostic biomarker for major cardiac events in humans.
- Cardio-protective role of Humanin in myocardial ischemia-reperfusion.
- Humanin-induced autophagy plays important roles in skeletal muscle function and lifespan extension.
- Long-term Survival of Adhesively Luted Post-endodontic Restorations.
- RISK OF HOSPITAL MORTALITY IN CRITICALLY ILL PATIENTS WITH TRANSIENT AND PERSISTENT THROMBOCYTOPENIA: A RETROSPECTIVE STUDY.
- Synthesis of potent antagonists of receptors for growth hormone-releasing hormone with antitumor and anti-inflammatory activity.
- Impact of growth hormone-releasing hormone antagonist on decidual stromal cell growth and apoptosis in vitro†.
- Causes and outcomes of hepatic fibrosis in persons living with HIV.
- A Botanical Product Containing Cistanche and Ginkgo Extracts Potentially Improves Chronic Fatigue Syndrome Symptoms in Adults: A Randomized, Double-Blind, and Placebo-Controlled Study
- Dihexa Improves Cognitive Deficits in Aged Rats by Promoting Hippocampal Synaptogenesis
- Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era
- Neuroprotective Effect of Fisetin Against the Cerebral Ischemia-Reperfusion Damage via Suppression of Oxidative Stress and Inflammatory Parameters
- Humanin and Alzheimer's Disease: The Beginning of a New Field
- Protective Mechanism of Humanin Against Oxidative Stress in Aging-Related Cardiovascular Diseases
- Humanin Alleviates Insulin Resistance in Polycystic Ovary Syndrome: A Human and Rat Model-Based Study.
- Humanin: A mitochondrial-derived peptide in the treatment of apoptosis-related diseases.
- Humanin regulates oxidative stress in the ovaries of polycystic ovary syndrome patients via the Keap1/Nrf2 pathway.
- Protective Mechanism of Humanin Against Oxidative Stress in Aging-Related Cardiovascular Diseases.
- Mitochondrial humanin peptide acts as a cytoprotective factor in granulosa cell survival.
- Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer's Disease
- Optimization of Jiuzao protein hydrolysis conditions and antioxidant activity in vivo of Jiuzao tetrapeptide Asp-Arg-Glu-Leu by elevating the Nrf2/Keap1-p38/PI3K-MafK signaling pathway.
- The Influence of Selank on the Level of Cytokines Under the Conditions of "Social" Stress.
- Morphofunctional State of the Large Intestine in Rats under Conditions of Restraint Stress and Administration of Peptide ACTH((4-7))-PGP (Semax).
- Investigation of the effect of a modified fragment of neuropeptide Y on memory phases and extrapolation escape of animals.
- Growth hormone-releasing hormone agonists ameliorate chronic kidney disease-induced heart failure with preserved ejection fraction.
- Effects of growth hormone-releasing hormone agonistic analog MR-409 on insulin-secreting cells under cyclopiazonic acid-induced endoplasmic reticulum stress.
- Clinical Predictors of Liver Fibrosis Presence and Progression in Human Immunodeficiency Virus-Associated Nonalcoholic Fatty Liver Disease.
- Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-infection and Nonalcoholic Fatty Liver Disease.
- Non-Alcoholic Steatohepatitis (NASH) - A Review of a Crowded Clinical Landscape, Driven by a Complex Disease.
- Senolytic drugs: from discovery to translation
- The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan
- Humanin Promotes Tumor Progression in Experimental Triple Negative Breast Cancer.
- Humanin Ameliorates Free Fatty Acid-Induced Endothelial Inflammation by Suppressing the NLRP3 Inflammasome.
- EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer's Disease
- Functional Connectomic Approach to Studying Selank and Semax Effects
- The occurrence of putative cognitive enhancing research peptides in seized pharmaceutical preparations: An incentive for controlling agencies to prepare for future encounters of the kind.
- Correction of Lipid Metabolism Disorders in Diabetes Mellitus with Peptide Drugs.
- Growth hormone secretagogues: history, mechanism of action, and clinical development
- Antinflammatory, antioxidant, and behavioral effects induced by administration of growth hormone-releasing hormone analogs in mice.
- Signaling mechanisms of growth hormone-releasing hormone receptor in LPS-induced acute ocular inflammation.
- Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD
- Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD.
- Preclinical Evidence and Possible Mechanisms of Extracts or Compounds from Cistanches for Alzheimer's Disease
- Mitochondrial-derived peptide humanin as therapeutic target in cancer and degenerative diseases.
- Humanin levels in human seminal plasma and spermatozoa are related to sperm quality.
- Potent humanin analogue (HNG) protects human sperm from freeze-thaw-induced damage.
- Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content in the Hippocampus and Prefrontal Cortex in Rats
- Effect of Selank on Morphological Parameters of Rat Liver in Chronic Foot-Shock Stress.
- Experimental Substantiation of Application of Semax as a Modulator of Immune Reaction on the Model of "Social" Stress.
- Growth Hormone-Releasing Hormone Receptor Antagonist Modulates Lung Inflammation and Fibrosis due to Bleomycin.
- Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial
- Tesamorelin, liver fat, and NAFLD in the setting of HIV.
- Effect of Cistanche Tubulosa Extracts on Male Reproductive Function in Streptozotocin-Nicotinamide-Induced Diabetic Rats
- Echinacoside, an Inestimable Natural Product in Treatment of Neurological and other Disorders
- Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies.
- Fisetin is a senotherapeutic that extends health and lifespan
- Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration
- Fisetin Exerts Antioxidant and Neuroprotective Effects in Multiple Mutant hSOD1 Models of Amyotrophic Lateral Sclerosis by Activating ERK