Evidence Explorer
Filter, sort, and compare the evidence itself.
Every ingredient we've researched, graded to the same conservative standard — including the ones that didn't make Signal State Core v1, and why. This is a research tool, not a shopping list: nothing here is a recommendation to take or combine anything.
What do the grades mean?
- Grade A
- Strong — multiple human trials and consistent effects
- Grade B
- Moderate — several human trials, some mixed results
- Grade C
- Limited — early or small human trials
- Emerging
- Emerging — mostly preclinical or preliminary human data
- Graded Out
- Graded out — evaluated and not featured (failed replication or a safety signal)
Grades are our own conservative reading of the human research for an ingredient's studied role — not product claims, and not a promise of effect. See The Evidence Standard for the full rubric.
41 of 41 ingredients
- AdaptogenEvidence: Grade B
American Ginseng
Graded out — not in v1
A caffeine-free adaptogen, botanically distinct from Asian Panax ginseng, studied for acute working-memory support. The signal is real for a single dose; chronic daily use has not held up as well.
Studied dose: 200 mg of standardized extract, single dose in the studied trials.
Graded B for the acute working-memory claim specifically, not for chronic use or for cognition broadly. Scholey 2010 (PMC2952762) and Ossoukhova 2015 found the Cereboost extract improved working-memory measures after a single dose in healthy adults. A chronic-dosing trial (Bell 2022, doi:10.1007/s00394-021-02654-5) was largely null — that gap between acute and chronic results is the honest caveat behind the grade. This is a different species from Asian Panax ginseng; its fatigue/working-memory signal should not be read across to that entry, and vice versa.
- NootropicEvidence: Grade B
Bacopa Monnieri
In Signal State Core
A traditional herb standardized for compounds called bacosides. It is studied mainly for memory and learning over sustained daily use, not for same-day effects.
Studied dose: 300–600 mg daily of a standardized extract (commonly ~50% bacosides).
Multiple human trials over 8–12 weeks report memory and learning measures. Benefits are cumulative rather than acute.
- Choline sourceEvidence: Grade B
Citicoline
In Signal State Core
A choline-donating compound the body uses in cell-membrane and neurotransmitter pathways. It is studied as a focus and mental-energy ingredient.
Studied dose: 250–500 mg per serving in many studies.
Several human trials in various populations report attention and memory measures. Dose and population differences make direct comparison difficult.
- PolyphenolEvidence: Grade B
Cocoa Flavanols
Graded out — not in v1
A de-theobrominated cocoa extract studied for acute cerebral blood flow and attention. A large chronic trial on global cognition was honestly null, so the qualified acute claim is what the grade rests on.
Studied dose: ~500 mg cocoa flavanols/day (roughly 80 mg epicatechin).
Qualified B. Acute cerebral-blood-flow RCTs (Scientific Reports, 2020) found a single dose improved blood flow and attention measures. But the large chronic COSMOS trial (2023, doi:10.1002/alz.12767) — a multi-year trial in older adults — was null on its primary global-cognition endpoint. We state that plainly: the acute signal is real, the chronic global-cognition claim is not supported by the best available trial.
- BotanicalEvidence: Grade B
Curcumin (lipidated)
Graded out — not in v1
A bioavailability-enhanced curcumin extract studied in healthy older adults for modest working-memory and mood support. The trial base is real but narrow — same-group replication and an older-adult skew.
Studied dose: 400 mg/day of Longvida (delivering roughly 80 mg curcuminoids).
Cox 2015 and a 2020 follow-up (same research group, healthy older adults) found modest working-memory and mood/fatigue benefits with the Longvida lipidated formulation versus placebo. Capped at B because the positive trial base is internal (same-group) replication rather than independent cross-sponsor replication, and the studied population skews 50+ rather than a broad healthy-adult range.
- AdaptogenEvidence: Grade B
Holy Basil
Graded out — not in v1
An adaptogenic herb studied across multiple independent manufacturers for supporting a healthy stress response and cortisol balance — the multi-sponsor replication is what earns it a B rather than a C.
Studied dose: 125 mg twice daily, up to roughly 1200 mg/day of standardized extract.
Multiple double-blind, placebo-controlled stress/cortisol RCTs exist across more than one manufacturer's standardized extract (including Holixer and OciBest), which is the specific reason this clears B rather than the single-sponsor C ceiling that applies to many adaptogens — independent replication across sponsors, not just repeated trials from one.
- MineralEvidence: Grade B
Iron
Graded out — not in v1
An essential mineral whose cognition, energy, and mood benefit is real but conditional: it applies specifically to iron-deficient individuals, most often menstruating women, not to iron-replete adults, who should not blanket-dose it.
Studied dose: 18–65 mg elemental iron/day as bisglycinate, dependent on documented deficiency.
Conditional B. The benefit is limited to iron-deficient individuals — do not blanket-dose iron-replete men or post-menopausal women, since excess iron carries a pro-oxidant and iron-overload risk rather than a cognitive benefit. This ingredient should be screened for (e.g. serum ferritin) before use, not included by default in a general-population formula.
- Amino acidEvidence: Grade B
L-Theanine
In Signal State Core
An amino acid found in tea leaves. It is studied for promoting a calm, settled kind of attention without sedation, which fits a stimulant-free focus direction.
Studied dose: 100–200 mg per serving, up to ~400 mg daily in studies.
Multiple small human trials report changes in subjective calm and attention, often studied alongside caffeine. Effect sizes are modest and study designs vary. The strongest, most consistent signal is for acute attention and choice-reaction-time measures — not a broad, all-day calm-focus claim — and positive results cluster around the 200 mg dose specifically.
- Amino acidEvidence: Grade B
L-Tyrosine
Graded out — not in v1
An amino acid the body uses to make dopamine and norepinephrine. It is studied for protecting focus and working memory when the brain is taxed by stress, sleep loss, or cold — not as an everyday enhancer for well-rested people.
Studied dose: ~2 g acutely in cognition studies; 100–150 mg/kg (~7–12 g) in sleep-deprivation and cold-stress paradigms.
A systematic review (Jongkees 2015) and several acute-dose RCTs show ~2 g improves working memory and cognitive flexibility, but mainly when catecholamines are depleted by stress or demand; it does not reliably lift baseline in rested adults. Graded B for the stress/depletion use case, closer to C for baseline enhancement.
- BotanicalEvidence: Grade B
Lavender (oral)
Graded out — not in v1
An oral lavender-oil softgel studied in double-blind trials for easing occasional nervous tension and supporting calm, without the sedation or dependence risk of a benzodiazepine. Not the same as aromatherapy lavender.
Studied dose: 80–160 mg/day as a softgel.
Five or more double-blind RCTs plus independent meta-analyses support the Silexan (WS 1265) extract, with trials showing it performs comparably to paroxetine or lorazepam in anxiety-trial populations without their sedation or dependence profile. Capped at B because the pivotal trials were largely run in subthreshold or clinical-anxiety populations rather than healthy adults under everyday stress, and the key trials are Schwabe-sponsored (the extract's developer).
- BotanicalEvidence: Grade B
Lemon Balm
Graded out — not in v1
An herb studied in replicated, independent trials for supporting acute calm under cognitive load — a narrower and better-evidenced claim than a general anti-anxiety one.
Studied dose: 300–600 mg/day of standardized extract.
The Kennedy research group's acute calm-under-load findings have been replicated, and a 2023 subchronic RCT extended the signal beyond single-dose use. Graded on the acute-calm claim specifically. An open-label, uncontrolled n=20 Cyracos study on insomnia is sometimes cited for lemon balm but is not adequate evidence on its own — it is not the basis for this grade and should not be treated as an efficacy claim.
- CarotenoidEvidence: Grade B
Lutein + Zeaxanthin
Graded out — not in v1
A pair of dietary carotenoids that accumulate in neural tissue, not just the eye, and are studied for supporting processing speed and sustained attention. Well-tolerated and well-studied for eye health; the cognitive-processing-speed angle is real but younger and narrower.
Studied dose: 10–14 mg lutein + 2–3 mg zeaxanthin/day (the Lutemax 2020 studied ratio).
Stringham 2019 (Physiol Behav) gave Lutemax 2020 to healthy adults aged 18–25 and found improved processing speed and attention along with higher serum BDNF versus placebo; Bovier & Hammond 2015 (PMC4176961) separately linked macular pigment density to faster visual processing speed. Capped at B for two honest reasons: most of the positive human trial base is OmniActive-funded (the branded-ingredient maker), and "processing speed" in these trials is partly a visual-processing measure, not a pure cognition-only endpoint.
- PolyphenolEvidence: Grade B
Resveratrol
Graded out — not in v1
A grape-skin polyphenol studied for supporting cerebral blood flow and verbal memory. The strongest human trial base is concentrated in postmenopausal women from a single research group.
Studied dose: 150 mg/day (commonly split as 75 mg twice daily) of trans-resveratrol.
Kennedy 2010 found an acute single dose improved cerebral blood flow in healthy adults, and postmenopausal-women RCTs — including a 24-month trial — extended the signal to memory measures over time. Capped at B because the strongest and longest human trials are concentrated in postmenopausal women studied by one research group, which limits how confidently the finding generalizes to a broader healthy-adult population.
- BotanicalEvidence: Grade B
Spearmint Extract
Graded out — not in v1
A phenolic-rich spearmint extract studied for supporting working memory and attention, with its pivotal trial run in adults with age-associated memory concerns rather than a broad healthy-adult population.
Studied dose: 900 mg/day of standardized extract.
Herrlinger 2018 (J Altern Complement Med) ran a 90-day RCT of Neumentix in adults with age-associated memory impairment and found improved working memory, with a follow-up acute-attention trial extending the signal. Capped at B: the pivotal data sits in a memory-impaired rather than broad healthy-adult population, the trials are Kemin-funded (the extract's developer), and effect sizes sit near the threshold of clinical meaningfulness.
- VitaminEvidence: Grade B
Vitamin C
Graded out — not in v1
An essential vitamin that supports attention and processing specifically by correcting inadequate status — a common but often-overlooked gap, not a stimulant or a cognitive enhancer above and beyond replete levels.
Studied dose: 500 mg/day.
The cognitive-support case for vitamin C is a status-correction story: benefit is tied to correcting an inadequate baseline, which is common even in developed-world diets, rather than a universal cognitive lift in adults who are already replete. Graded B on that specific, honest framing.
- BotanicalEvidence: Grade B
Zynamite
Graded out — not in v1
A caffeine-free mango-leaf extract studied for acute alertness and attention through COMT inhibition, without the blood-pressure or heart-rate activation a stimulant would carry. Human data is acute and single-dose so far.
Studied dose: 100–300 mg/day; 300 mg is the most-studied acute dose.
Graded B for the acute-use claim specifically; chronic daily use is Emerging, not yet supported by repeated-dosing human trials. Gutiérrez-Hellín 2020 (Nutrients, PMC7468873) gave 70 healthy adults 300 mg Zynamite and found improved attention accuracy and episodic memory versus placebo, without the cardiovascular activation seen with stimulants.
- Amino acidEvidence: Grade C
Acetyl-L-Carnitine
Graded out — not in v1
An acetylated form of the amino acid carnitine, studied for cellular energy and age-related cognitive support. Its benefit in healthy, high-functioning adults is largely unproven, so it is positioned honestly as a mitochondrial-energy ingredient rather than a same-day focus booster.
Studied dose: 1.5–3 g daily in trials, usually split into two doses (Health Canada permits up to 4 g/day).
The only Cochrane review of acetyl-L-carnitine and cognition is in a dementia population and found insufficient evidence to recommend it; there is no dedicated Cochrane review in healthy, unimpaired adults. Most positive human data is in older adults and mild cognitive impairment (1.5–3 g/day over 12–24 weeks), where effects are modest — so the grade is honest for a healthy-adult use case.
- Choline sourceEvidence: Grade C
Alpha-GPC
Graded out — not in v1
A highly bioavailable choline source studied mainly in older or impaired populations, not healthy high-performers. Healthy-adult cognition data is limited, and a very large 2021 observational study flagged an association with higher stroke risk — an association, not a proven cause, but enough that citicoline is the more defensible choline pick for a healthy-adult stimulant-free product.
Studied dose: 300–600 mg/day in studies; dose-conscious given the safety discussion.
Most positive cognition trials are in dementia or post-stroke recovery populations, with sparse healthy-adult data. The key honest caveat is Lee et al. 2021 (JAMA Network Open), a South Korean cohort of roughly 12 million adults aged 50 and older, which found alpha-GPC use associated with a dose-responsive ~43% higher 10-year stroke risk (adjusted HR ≈1.43) — an association that persisted in a 4-year lag analysis meant to rule out reverse causation. A 2025 Korean cohort study did not fully replicate the association; both studies are observational, so this is a safety signal, not proven causation, but it's large and holds the grade down regardless of the efficacy data. Citicoline has cleaner healthy-adult attention data and no comparable signal.
- PolyphenolEvidence: Grade C
Anthocyanins
Graded out — not in v1
Colorful plant polyphenols found in berries. They are studied for antioxidant activity and circulation, with interest in longer-term cognitive-health positioning.
Studied dose: Varies widely by source and standardization; look for a stated anthocyanin content.
Human data is growing but still limited for cognitive endpoints specifically. Antioxidant and circulation mechanisms are better characterized.
- AdaptogenEvidence: Grade C
Ashwagandha
Graded out — not in v1
A calming adaptogen with solid human evidence for reducing stress, anxiety, and cortisol at 300–600 mg/day of standardized extract. Any cognitive benefit is mostly downstream of stress relief and is still emerging in healthy adults.
Studied dose: 300–600 mg/day standardized root extract (KSM-66 ≥5% withanolides; Sensoril 125–250 mg at ≥10% withanolide glycosides).
60-day RCTs of 240–600 mg/day KSM-66 lowered perceived stress and serum cortisol versus placebo (Salve 2019; Lopresti 2019); direct cognition signals come from smaller trials and are not yet robust in healthy adults. Stress evidence is roughly B; the cognition grade is honestly C. A liver-safety signal caps the grade regardless of the stress-efficacy data: NIH LiverTox classifies ashwagandha as a "probable" cause of clinically apparent liver injury (likelihood score C), a 2023 case series documented ashwagandha-related liver injury — including deaths — in patients with underlying liver disease, and Australia's TGA issued a liver-safety alert in February 2024.
- VitaminEvidence: Grade C
B-Complex (B6, B9, B12)
Core — foundational base
The nervous-system B vitamins — B6, folate, and B12 — support normal neurological and psychological function and normal nutrient metabolism. Measurable cognitive benefit is strongest where baseline status is low or homocysteine is elevated (typically older adults); it is limited in young, well-nourished people.
Studied dose: Studied ranges: B6 ~10–20 mg/day (keep low — neuropathy risk), folate 400–800 mcg DFE/day, B12 5–500 mcg/day.
The VITACOG trial (Smith 2010) found high-dose B6/B9/B12 slowed brain atrophy in older adults with mild cognitive impairment and elevated homocysteine, but a ~22,000-person meta-analysis (Clarke 2014) found no cognitive effect in unselected older adults. Honest grade is C for young replete adults (closer to B in deficient/high-homocysteine groups); no acute effect.
- Amino acidEvidence: Grade C
Creatine Monohydrate
Graded out — not in v1
Best known for muscle, creatine is also a brain energy-buffer. The cognition evidence is emerging and modest, and it is clearest exactly when the brain is energy-stressed — sleep deprivation and low dietary baseline (vegetarians) — rather than in rested, omnivorous, healthy adults. Extremely cheap with a strong safety record.
Studied dose: 3–5 g/day maintenance (standard). The sleep-deprivation study used a one-off ~0.35 g/kg dose, which is a research context, not a daily-use recommendation.
A systematic review (Avgerinos 2018, 6 RCTs / 281 people) found short-term memory and reasoning may improve, with effects concentrated in stressed or low-baseline states. A small crossover study (Gordji-Nejad 2024, n=15) found a single high dose improved cognition and sustained brain phosphocreatine during 21-hour sleep deprivation. In rested, well-fed adults the effect is small and inconsistent — honestly C, not an A/B cognition ingredient.
- PolyphenolEvidence: Grade C
Ginkgo Biloba
Graded out — not in v1
A well-characterized stimulant-free botanical with a dedicated Health Canada monograph that allows a cognition/memory claim. Its best human evidence is in older adults with cognitive symptoms; in healthy adults the benefit is small and inconsistent.
Studied dose: 120–240 mg/day of leaf extract standardized to 22–27% flavonoid glycosides and 5–7% terpene lactones, with ginkgolic acids ≤5 ppm.
Controlled trials in healthy adults are mixed and reviews generally find it no better than placebo for enhancement, while large prevention trials (GEM 2009; GuidAge 2012) were negative; evidence is more consistent for symptomatic mild cognitive impairment at 240 mg/day. Graded C for a healthy-adult use case.
- NootropicEvidence: Grade C
Huperzine-A
Graded out — not in v1
A plant-derived compound that strongly and selectively blocks the enzyme that breaks down acetylcholine — the same mechanism as some prescription memory drugs. That drug-like potency, thin healthy-adult evidence, and cholinergic side-effect profile make it a serious ingredient to handle carefully, not a casual add.
Studied dose: 50–200 mcg daily (micrograms). Health Canada caps total Huperzine A at 200 mcg/day — at or below the studied-effective range.
Positive RCTs are concentrated in dementia patients and Chinese adolescent-student cohorts with high risk of bias; in healthy adults the signal largely disappears (e.g. a randomized crossover trial in healthy adults found no cognitive benefit). Honest grade for a healthy-adult use case is C.
- PolyphenolEvidence: Grade C
Maritime Pine Bark
Graded out — not in v1
A polyphenol-rich extract studied for circulation and antioxidant activity, with some interest in attention endpoints. Evidence quality varies by extract.
Studied dose: 50–150 mg daily of a standardized extract in many studies.
Human trials exist, several using a specific branded extract, so results do not automatically generalize to all pine bark products.
- Fatty acidEvidence: Grade C
Omega-3 (EPA/DHA)
Graded out — not in v1
A foundational dietary fat (EPA and DHA) that most people under-consume; DHA is a major structural lipid in the brain. It earns its place as a baseline-nutrition layer, not a same-day focus ingredient — controlled trials in already-healthy adults have generally not shown a cognitive-enhancement effect.
Studied dose: 250–500 mg combined EPA+DHA daily as a general baseline; Health Canada's cognitive-support window is 150–5,000 mg EPA+DHA with ≥100 mg DHA/day.
For its own roles (cardiovascular, triglycerides) the evidence is strong, but for cognition in already-healthy adults it is weak: a Cochrane review (Sydenham 2012) found no cognitive benefit in cognitively healthy older adults, and the AREDS2 RCT (Chew 2015) found no significant cognitive effect. Graded C for the healthy-adult cognition angle, positioned honestly as a foundational nutrient rather than an enhancer.
- AdaptogenEvidence: Grade C
Panax Ginseng
Graded out — not in v1
A well-tolerated adaptogen whose cognition evidence is genuinely weak on independent review, though single-dose trials show a milder mental-fatigue signal. This is claim-specific grading: Asian Panax ginseng for cognition grades C; a stronger fatigue signal exists but belongs to American ginseng, a different species, not this one.
Studied dose: 200–400 mg daily of extract standardized to 4–7% total ginsenosides (Health Canada permits 200–600 mg/day).
Claim-specific grading: for cognition, the largest independent review (Geng 2010, Cochrane, PMID 21154383) found no convincing evidence of a cognitive-enhancing effect in healthy people — grade C. Single-dose trials of the G115 extract (Reay 2005/2006) did reduce subjective mental fatigue and improve mental-arithmetic performance, but that mental-fatigue signal is graded B only for American ginseng (Panax quinquefolius) fatigue endpoints — a different species — not for this Asian Panax ginseng cognition claim. Do not read the American-ginseng fatigue grade across to this entry.
- PhospholipidEvidence: Grade C
Phosphatidylserine
In Signal State Core
A phospholipid that is part of cell membranes, including in the brain. Its most persuasive memory trials used a bovine-cortex source in memory-impaired older adults; modern soy- and sunflower-derived PS — what this and every current supplement actually contains — has not cleared that same bar.
Studied dose: 100 mg two to three times daily (≈200–300 mg total) in many studies.
This is a wrong-source, wrong-population discount. The classic positive trials (Crook 1991, bovine-cortex PS; Kato-Kataoka 2010, soy-PS with a positive result only in a low-baseline subgroup) don't match what a modern label delivers to a healthy adult: a direct RCT of soy-derived PS at both 300 mg and 600 mg/day (Jorissen et al. 2001) failed to beat placebo on the primary cognitive measures in the target population. The FDA's own qualified health claim review for PS and cognitive function/dementia concluded there is "little scientific evidence" supporting the claim. Still a reasonable, well-tolerated inclusion, but the honest grade for soy/sunflower PS in a healthy adult is C, not B.
- AdaptogenEvidence: Grade C
Rhodiola Rosea
In Signal State Core
An adaptogenic herb standardized for rosavins and salidroside. Its studied benefit is narrow: reducing stress-related mental fatigue and helping sustain output during genuinely demanding stretches (night shifts, exam load) — not lifting baseline performance in a rested, unstressed adult.
Studied dose: 200–400 mg daily of a standardized extract (commonly 3% rosavins, 1% salidroside).
Real but under-replicated. The two founding trials (Darbinyan 2000; Spasov 2000) are small and sponsor-clustered — both run through the Swedish Herbal Institute — and a 2012 systematic review (Ishaque et al.) flagged high risk of bias across the Rhodiola literature and a lack of independent replication. Under a replication-over-recency standard, that trial base is a C, not a B, even though the direction of effect is consistent. Graded for the specific claim it's actually tied to — stress-related fatigue and sustained output under load — not as a general-purpose baseline enhancer, which the evidence does not support.
- AdaptogenEvidence: Grade C
Saffron
Graded out — not in v1
A well-tolerated botanical with strong human evidence for mood and stress and secondary sleep benefits, standardized as branded extracts. Its role in a cognitive stack is as a mood- and stress-resilience component, not a proven direct cognition enhancer.
Studied dose: 28 mg/day of a standardized extract (28 mg once or 14 mg twice daily), e.g. affron at ≥3.5% Lepticrosalides.
Double-blind RCTs support mood, stress, and sleep at 28 mg/day affron (Lopresti 2021) and meta-analyses find saffron comparable to some antidepressants with fewer adverse events, but direct healthy-adult cognition data are thin and mostly extrapolated from clinical populations. Mood evidence is roughly B; the cognition grade is honestly C.
- PolyphenolEvidence: Grade C
Sage
Graded out — not in v1
Standardized sage extracts show a modest, mostly same-day boost to memory and attention in healthy adults, plausibly by slowing the breakdown of acetylcholine. The evidence is early-stage and dominated by small or industry-funded trials.
Studied dose: ~150–333 mg of a branded standardized extract (studied acute range 150–1332 mg; one chronic trial used 600 mg/day).
Tildesley 2003 (sage oil) improved immediate recall in healthy young adults and Scholey 2008 improved memory/attention in older adults via cholinesterase inhibition; a 2021 branded trial showed acute and some chronic gains but was sponsor-funded. Samples are small and chronic data thin — honestly C.
- VitaminEvidence: Grade C
Vitamin D3
Core — foundational base
A foundational fat-soluble nutrient, not a same-day nootropic. There is no reliable evidence it sharpens focus in people who already have adequate levels, but low vitamin D status is common at Canadian latitudes in winter and is associated with poorer cognition — so it fits as foundational "status insurance," not a cognitive active.
Studied dose: 1,000–2,000 IU (25–50 mcg) daily for maintenance; up to the 4,000 IU (100 mcg) adult upper limit under guidance. Canadian non-prescription monograph routes cap lower — see label tips.
For its own roles (bone, calcium, immune) the evidence is strong, but for cognition specifically it is weak: a 24-trial meta-analysis found only a small global-cognition effect concentrated in deficient groups, and RCTs in replete healthy adults show no cognitive benefit. Graded C for the cognition angle only.
- Amino acidEvidence: Emerging
Glycine
Graded out — not in v1
A simple amino acid taken before sleep, studied for supporting sleep quality and next-day alertness. It belongs in an evening slot, not a daytime stack, and the trial base is concentrated with one manufacturer.
Studied dose: 3 g, taken shortly before sleep.
Leans toward a B-minus on the strength of a replicated sleep-quality and next-day-alertness signal, but the trial base is concentrated with Ajinomoto (the amino-acid manufacturer funding most of the research), so it's held at Emerging pending more independent replication. Positioned for an evening slot, not daytime — this is not a daytime cognitive active.
- NootropicEvidence: Emerging
Lion's Mane
Graded out — not in v1
An edible mushroom studied for long-term cognitive support. Human evidence is still limited, so it is positioned as an emerging ingredient with sourcing and extract-quality considerations.
Studied dose: 500–1000 mg of extract in some studies; varies widely by preparation.
Some small human trials and considerable preclinical work. Human evidence remains limited and preliminary.
- MineralEvidence: Emerging
Magnesium L-Threonate
Graded out — not in v1
A magnesium salt marketed specifically for the brain because it raised brain magnesium in rodents. The cognition story is mostly preclinical plus a couple of small, largely developer-linked human trials — it is the most over-marketed relative to its human evidence in this library. Magnesium as a general mineral has separate, better-established roles.
Studied dose: ~1.5–2 g/day of magnesium L-threonate (delivering a relatively small amount of elemental magnesium) as used in the human trial.
The foundational work (Slutsky 2010, Neuron) is a rodent study showing raised brain magnesium improved learning and memory. Human data is thin: the MMFS-01 trial (Liu 2016, ~44 completers, developer-linked) reported cognitive improvement in older adults with complaints. This is single-small-trial and preclinical territory, not established human cognition benefit — general magnesium status is a separate, better-founded topic.
- MitochondrialEvidence: Emerging
PQQ
Graded out — not in v1
A mitochondrial-biogenesis cofactor studied for cognition and fatigue. The positive human trials all come from one branded-ingredient sponsor, with no independent replication yet.
Studied dose: 20 mg/day.
Positive human trials exist but are single-sponsor: all run on the BioPQQ branded ingredient, funded by its developer, with no independent replication published yet. Mechanistically plausible as a mitochondrial-biogenesis cofactor, but the human evidence base is too narrow and too concentrated to grade higher.
- BotanicalEvidence: Emerging
Sceletium Tortuosum
Graded out — not in v1
A South African succulent extract studied in small trials for mood and cognitive flexibility. The trial base is small and sponsor-linked, and it carries a specific interaction caution with serotonergic and MAOI medications.
Studied dose: 25 mg/day of standardized extract (Zembrin).
Human trials of the Zembrin extract are small and sponsor-linked, with limited independent replication. Directionally interesting for mood and cognitive flexibility, but not yet a trial base to build a confident claim on.
- NucleotideEvidence: Emerging
Uridine
Graded out — not in v1
A nucleotide that supplies a synaptic-membrane building block, mechanistically paired with choline sources and DHA. Human cognition evidence in healthy adults doesn't exist yet — what exists is biomarker data and a prodromal-Alzheimer's stack trial, not this population.
Studied dose: ~500 mg–2 g/day in available human research.
Human data is biomarker-level: 31P-MRS studies show increased brain phospholipid precursors with uridine supplementation. The cognition data that exists comes from animal studies or from the Souvenaid stack (uridine + DHA + choline) trialed in prodromal Alzheimer's patients — not from healthy adults, and not from uridine alone. Worth tracking: this is the most common ingredient serious competitor formulas carry that this brand currently doesn't, but the healthy-adult evidence isn't there yet.
- ProteinGraded Out
Apoaequorin
Graded out — not in v1
A jellyfish-derived calcium-binding protein marketed for memory, best known as the active ingredient in Prevagen. It failed its own sponsor-run trial on primary endpoints, was the subject of an FTC deceptive-advertising action, and is mechanistically implausible as an oral supplement.
Studied dose: Not applicable — not a candidate for inclusion.
Graded out on both efficacy and plausibility grounds. Apoaequorin's own sponsor-run Madison Memory Study failed its pre-specified primary endpoints. The FTC and multiple state attorneys general pursued deceptive-advertising actions against Prevagen's marketing claims. Mechanistically, apoaequorin is an orally ingested protein: it is digested in the gastrointestinal tract like any other dietary protein and has no established route to reach or act on the brain intact. Do not feature.
- NootropicGraded Out
DMAE
Graded out — not in v1
A small choline-related molecule marketed on the theory that it raises acetylcholine. That mechanism is poorly confirmed, healthy-adult cognition evidence is weak and dated, and animal studies show developmental-toxicity signals — so for a conservative, review-ready brand it is best understood as a flagged ingredient rather than a candidate.
Studied dose: ~100–500 mg/day of DMAE bitartrate on supplement labels; no validated healthy-adult cognitive dose exists.
Graded out, not merely low-graded. The strongest human data is 1960s–70s pediatric hyperactivity trials, since abandoned; there are essentially no adequate positive RCTs for memory or focus in healthy adults, and the acetylcholine mechanism is not well substantiated. A Cochrane review of the related cholinergic approach (Tammenmaa-Aho 2018) found no evidence of benefit. Animal developmental-toxicity studies (NTP DART-04) show a safety signal that vetoes inclusion regardless of any efficacy question, and the related prescription compound Deanol was withdrawn from the U.S. market over unproven efficacy. That combination — a null/failed efficacy picture plus a safety signal — is what "Graded Out" means on this site.
- Semi-syntheticGraded Out
Vinpocetine
Graded out — not in v1
A semi-synthetic compound derived from a periwinkle-plant alkaloid, marketed as a nootropic. The FDA has stated it does not meet the legal definition of a dietary ingredient, and issued a 2019 safety alert over reproductive-harm risk.
Studied dose: Not applicable — not a candidate for inclusion.
Excluded on legal and safety grounds, not just an evidence-strength judgment. The FDA has stated that vinpocetine does not meet the definition of a dietary ingredient under U.S. law, meaning it is not lawfully marketable as a supplement ingredient, and separately issued a 2019 consumer safety alert regarding reproductive harm and possible miscarriage risk. Do not feature.