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
- Updated
- How we grade
- 96 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 | 1 study | |||
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
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 | 7 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 | 5 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 | 5 studies |
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 | 4 studies | 95 people | ||
| Memory Performance Moderate Increase | Improves (the measure goes up) | Moderate effect | 4 studies | 180 people |
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 |
Pinealon
- Cognitive Performance: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cognitive Performance Small Increase | Improves (the measure goes up) | Small effect | 44 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 | 29 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 | 28 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 | 27 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
96 studies from PubMed
- Effects of Tesamorelin on Neurocognitive Impairment in Persons With HIV and Abdominal Obesity
- Humanin and Alzheimer's Disease: The Beginning of a New Field
- Functional Connectomic Approach to Studying Selank and Semax Effects
- EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer's Disease
- Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content in the Hippocampus and Prefrontal Cortex in Rats
- Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies.
- Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity
- Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans
- Changes in Sympathetic Innervation of the Heart in Rats with Experimental Myocardial Infarction. Effect of Semax.
- Changes in Sympathetic Innervation of Rat Caudal Artery in Experimental Myocardial Infarction. Effect of Semax Peptide.
- Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission
- Effect of Synthetic Peptides on Aging of Patients with Chronic Polymorbidity and Organic Brain Syndrome of the Central Nervous System in Remission
- Humanin attenuates Alzheimer-like cognitive deficits and pathological changes induced by amyloid β-peptide in rats
- Neuroendocrinology: Tesamorelin can improve cognitive function
- Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial
- Tesamorelin: a review of its use in the management of HIV-associated lipodystrophy.
- Spotlight on tesamorelin in HIV-associated lipodystrophy
- Experimental optimization of learning and memory processes by selank
- Protective effects of [Gly14]-Humanin on beta-amyloid-induced PC12 cell death by preventing mitochondrial dysfunction
- Humanin; a defender against Alzheimer's disease?
- Effects of heptapeptide selank on genetically-based and situation-provoked symptoms of depression in behavior in WAG/Rij and Wistar rats, and in BALB/c mice
- Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain
- Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus
- Evidence for in vivo production of Humanin peptide, a neuroprotective factor against Alzheimer's disease-related insults
- [The neuro- and psychophysiological effects of bromantane].
- Efficacy of Theta Binaural Beats for the Treatment of Chronic Pain
- Efficacy of different exercises in women with fibromyalgia syndrome: a randomised controlled trial.
- Low-Level Laser Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis.
- A low fermentable oligo-di-mono saccharides and polyols (FODMAP) diet reduced pain and improved daily life in fibromyalgia patients
- Vegan diet alleviates fibromyalgia symptoms
- A comparative study of the safety and efficacy of 75% mulberry (Morus alba) extract oil versus placebo as a topical treatment for melasma: a randomized, single-blind, placebo-controlled trial
- Lack of the effect of topical vitamin K on bruising after mechanical injury
- The effects of topical vitamin K on bruising after laser treatment
- The role of topical vitamin K oxide gel in the resolution of postprocedural purpura
- Effects of topical vitamin K and retinol on laser-induced purpura on nonlesional skin
- The effects of topical vitamin E on the cosmetic appearance of scars
- Failure of topical steroids and vitamin E to reduce postoperative scar formation following reconstructive surgery
- Effects of Vitamin D Therapy on Quality of Life in Patients with Fibromyalgia
- Vitamin D Supplementation Seems to Improve Fibromyalgia Symptoms: Preliminary Results
- Effects of vitamin D on patients with fibromyalgia syndrome: a randomized placebo-controlled trial
- Improvement of naturally aged skin with vitamin A (retinol)
- Topical tretinoin improves photoaged skin. A double-blind vehicle-controlled study
- Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation. A double-blind, vehicle-controlled comparison of 0.1% and 0.025% tretinoin creams
- Topical tretinoin (retinoic acid) treatment of hyperpigmented lesions associated with photoaging in Chinese and Japanese patients: a vehicle-controlled trial
- Topical tretinoin for treatment of photodamaged skin. A multicenter study
- Does saffron have antisolar and moisturizing effects?
- Saffron ( Crocus sativus) versus duloxetine for treatment of patients with fibromyalgia: A randomized double-blind clinical trial
- Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation
- The effectiveness of a standardized rose hip powder, containing seeds and shells of Rosa canina, on cell longevity, skin wrinkles, moisture, and elasticity
- Effect of "rose essential oil" inhalation on stress-induced skin-barrier disruption in rats and humans
- Pycnogenol® effects on skin elasticity and hydration coincide with increased gene expressions of collagen type I and hyaluronic acid synthase in women
- Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin
- Photoprotective activity of oral polypodium leucotomos extract in 25 patients with idiopathic photodermatoses
- The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer
- Niacinamide: A B vitamin that improves aging facial skin appearance
- Enhancement of human skin facial revitalization by moringa leaf extract cream
- Short-Term Magnesium Therapy Alleviates Moderate Stress in Patients with Fibromyalgia: A Randomized Double-Blind Clinical Trial.
- Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia?
- Effects of an ergothioneine-rich Pleurotus sp. on skin moisturizing functions and facial conditions: a randomized, double-blind, placebo-controlled trial.
- A Blinded, Randomized, Placebo-Controlled Study to Investigate the Efficacy and Safety of Ferric Carboxymaltose in Iron-Deficient Patients with Fibromyalgia
- Green tea polyphenols provide photoprotection, increase microcirculation, and modulate skin properties of women
- Oral intake of proanthocyanidin-rich extract from grape seeds improves chloasma
- The efficacy and side effects of oral Centella asiatica extract for wound healing promotion in diabetic wound patients
- Evidence of the regulatory effect of Ginkgo biloba extract on skin blood flow and study of its effects on urinary metabolites in healthy humans
- Clinical efficacy comparison of anti-wrinkle cosmetics containing herbal flavonoids
- Dietary fish-oil supplementation in humans reduces UVB-erythemal sensitivity but increases epidermal lipid peroxidation
- A randomized controlled trial of dehydroepiandrosterone in postmenopausal women with fibromyalgia
- The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study
- An open-label study adding creatine monohydrate to ongoing medical regimens in patients with the fibromyalgia syndrome
- Creatine supplementation in fibromyalgia: a randomized, double-blind, placebo-controlled trial
- Effects of Collagen Supplements on Skin Aging: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
- Aging skin is functionally anaerobic: importance of coenzyme Q10 for anti aging skin care
- The effect of dietary intake of coenzyme Q10 on skin parameters and condition: Results of a randomised, placebo-controlled, double-blind study
- Can coenzyme q10 improve clinical and molecular parameters in fibromyalgia?
- Coenzyme q10 regulates serotonin levels and depressive symptoms in fibromyalgia patients: results of a small clinical trial
- Increased oxidative stress and coenzyme Q10 deficiency in juvenile fibromyalgia: amelioration of hypercholesterolemia and fatigue by ubiquinol-10 supplementation
- Coenzyme Q10 supplementation alleviates pain in pregabalin-treated fibromyalgia patients via reducing brain activity and mitochondrial dysfunction
- Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q₁₀ effect on clinical improvement
- Cocoa Flavanol Supplementation Influences Skin Conditions of Photo-Aged Women: A 24-Week Double-Blind, Randomized, Controlled Trial
- Chocolate flavanols and skin photoprotection: a parallel, double-blind, randomized clinical trial
- Long-term ingestion of high flavanol cocoa provides photoprotection against UV-induced erythema and improves skin condition in women
- Nutritional supplementation with Chlorella pyrenoidosa for patients with fibromyalgia syndrome: a pilot study
- On the effects of a plant extract of Orthosiphon stamineus on sebum-related skin imperfections
- Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients
- An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia
- A role for cannabinoids in the treatment of myotonia? Report of compassionate use in a small cohort of patients
- Systematic review and meta-analysis of cannabis treatment for chronic pain
- Ingestion of a THC-Rich Cannabis Oil in People with Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
- Calendula extract: effects on mechanical parameters of human skin.
- Treatment of human skin with an extract of Fucus vesiculosus changes its thickness and mechanical properties
- Effects of topical boswellic acid on photo and age-damaged skin: clinical, biophysical, and echographic evaluations in a double-blind, randomized, split-face study
- Preliminary evidence hints at a protective role for boron in urolithiasis
- The Protective Role of Astaxanthin for UV-Induced Skin Deterioration in Healthy People-A Randomized, Double-Blind, Placebo-Controlled Trial
- Effectiveness of Dietary Supplement for Skin Moisturizing in Healthy Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
- Protective effects of astaxanthin on skin deterioration
- Cosmetic benefits of astaxanthin on humans subjects