Evidence Explorer
Filter, sort, and compare the evidence itself.
Every ingredient we've researched, graded to the same conservative standard, including the ones that aren't candidates for 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.
How it works
- FilterNarrow by evidence grade, goal, category, or v1 candidacy.
- CompareTick up to three ingredients to see them side by side.
- Go deeperOpen any profile for studied doses, cautions, and citations.
Please note
Educational content, not medical advice. Filtering by a goal or grade below groups ingredients by what the research studied. It is not a personalized recommendation. Talk to a qualified clinician before starting any supplement.
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
- mostly preclinical or preliminary human data
- 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.
54 of 54 ingredients
- NootropicEvidence: Grade B
Bacopa Monnieri
Signal State Core candidate
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 and why this grade
Studied dose: 300–600 mg daily of a standardized extract (commonly ~50% bacosides).
Multiple human trials over 8–12 weeks, from several independent research groups, report memory and learning improvements, with benefits that are cumulative rather than acute. That is the basis for B. Held at B on 2026-09-14 but now under monitoring: the most recent adequately sized trial at 300 mg (Lopresti & Smith 2025; 12 weeks; adults aged 40–70 with memory or attention complaints) found no difference from placebo on verbal learning, attention or working memory, and more adverse reactions, mostly digestive complaints and headache. A 2026 network meta-analysis (Tiemtad et al., 29 RCTs) placed the clearest working-memory gains at 600 mg/day or more, above Health Canada's 300 mg/day figure for standardized extract, though its pooled effect sizes are large enough to suggest small-study inflation. Another adequately powered null result at 300 mg would move the grade to C.
- AdaptogenEvidence: Grade B
Holy Basil
Researched, 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 and why this grade
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.
- Amino acidEvidence: Grade B
L-Theanine
Signal State Core candidate
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 and why this grade
Studied dose: 50–250 mg per serving across the trials cited here (Nobre 50 mg; Haskell 250 mg), most commonly 100–200 mg.
Held at B on 2026-09-14; with Bacopa, it is one of the two B-graded actives in the Signal State Core concept formula. A 2026 meta-analysis of 31 randomized trials (Gerolymos et al.) found a single 200 mg dose improved attention and reaction-time measures versus placebo (SMD 0.51); its acute-stress effect was smaller and leaned on higher-risk-of-bias studies, and it found no effect on fatigue. A 2025 meta-analysis of sleep trials (Bulman et al.) found better self-rated sleep quality and daytime functioning, but no change on objective sleep measures. What keeps it short of A: the attention signal shows up mainly on reaction-time tasks rather than as a broad, all-day calm-focus effect, most trials are small, several are industry-linked, and a smaller 2025 meta-analysis of five trials in 148 healthy adults (Mátyus et al.) splits: it found a dose-dependent improvement in rapid visual information processing and recognition reaction time (−15.20 ms), but no effect on simple reaction time or Stroop performance. Positive acute trials cluster in the 100–250 mg range; Health Canada's monograph permits a relaxation claim only, at 200–250 mg/day.
- Amino acidEvidence: Grade B
L-Tyrosine
Researched, 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 and why this grade
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)
Researched, not in v1
An oral lavender-oil softgel studied in double-blind trials for easing occasional nervous tension and supporting calm, with no sedation or dependence signal in its trials. Not the same as aromatherapy lavender.
Studied dose and why this grade
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 meaningful reductions in anxiety-scale scores versus placebo and no sedation or dependence signal on its own studied endpoints. 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
Researched, 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 and why this grade
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.
- HormoneEvidence: Grade B
Melatonin
Researched, not in v1
The body's own sleep-timing hormone, taken as a low-dose evening supplement. Its best evidence is for shortening how long it takes to fall asleep and for re-aligning a shifted body clock (jet lag, shift work, delayed sleep phase), not as a general sedative or a cure for chronic insomnia. An evening, sleep-slot ingredient, not a daytime cognitive active.
Studied dose and why this grade
Studied dose: 0.5–5 mg taken 30–60 minutes before the target bedtime (Health Canada permits up to 10 mg/dose for adults). More is not better: low doses (0.5–1 mg) are often as effective as higher ones with less next-morning grogginess. For circadian shifting, the timing of the dose matters more than its size.
Claim-specific B, and, unlike several branded ingredients in this library, it rests on independent, non-sponsor evidence. A meta-analysis of 19 randomized trials in 1,683 people (Ferracioli-Oda 2013) found melatonin reduced sleep-onset latency and modestly increased total sleep time and sleep quality versus placebo. The honest caveats that keep it at B rather than higher: the effect sizes are small (sleep onset shortened by roughly 7 minutes on average), and the American Academy of Sleep Medicine's 2017 guideline (Sateia et al.) issued a weak recommendation *against* melatonin for chronic sleep-onset or sleep-maintenance insomnia, citing low-quality evidence. Read together, the fair reading is a real, well-replicated but modest effect: strongest for sleep-onset timing and circadian realignment, weakest as a treatment for chronic insomnia. Monitoring since 2026-09-14: a conference abstract presented at the American Heart Association's 2025 Scientific Sessions (TriNetX health records; 65,414 adults prescribed melatonin for at least a year, propensity-matched against 65,414 others with insomnia) reported roughly 89% higher hazard of incident heart failure and about double the all-cause mortality over five years. We treat this as information to monitor rather than a safety signal that caps the grade, and the distinction is deliberate: it is a preliminary conference abstract rather than a peer-reviewed publication; it sees only prescribed melatonin, so over-the-counter users sit in the comparison group; and confounding by insomnia severity is likely. The safety signals that do hold grades down in this library (alpha-GPC's stroke cohort, ashwagandha's LiverTox rating) are peer-reviewed or regulator-issued. A peer-reviewed publication that survives those criticisms would trigger a grade review. Re-checked 2026-09-17: the abstract still has no peer-reviewed full publication, and the peer-reviewed work that has appeared since points the other way. A survey-weighted NHANES analysis (Khan & Lima 2026) found no significant association between recent melatonin use and prevalent cardiovascular disease or heart failure once baseline differences were accounted for, and a meta-analysis of 14 randomized trials in cardiovascular patients (Ang 2026) found no harm signal. Neither settles the question; together they make the abstract weaker rather than stronger evidence. B holds, and it remains a reason to use the lowest effective dose and to raise long-term nightly use with a clinician.
- Amino acidEvidence: Grade C
5-HTP
Researched, not in v1
The immediate serotonin precursor, extracted from Griffonia simplicifolia seed, that crosses into the brain more readily than tryptophan. Small trials suggest benefit for mood and sleep, but quality is low and it carries the same serious serotonin-syndrome interaction with antidepressants. An evening/mood-slot ingredient requiring conservative dosing.
Studied dose and why this grade
Studied dose: 100–300 mg/day typical (Health Canada: mood 150–300 mg/day; sleep 100–200 mg/day; maximum 300 mg per single dose). Start low and titrate over ~2 weeks to limit nausea.
Limited. 5-HTP crosses the blood-brain barrier without the transport competition tryptophan faces, and small double-blind trials suggest benefit for mood and for fibromyalgia symptoms (Caruso 1990), but the Cochrane review and a follow-up meta-analysis (Shaw 2001; Shaw 2002) judged the overall evidence insufficient to recommend routine use: the trials are small, old, and largely unreplicated at modern standards. Graded C, with a prominent drug-interaction caution.
- Amino acidEvidence: Grade C
Acetyl-L-Carnitine
Researched, 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 and why this grade
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
Researched, 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. That is an association, not a proven cause, but it is enough that citicoline is the more defensible choline pick for a healthy-adult stimulant-free product.
Studied dose and why this grade
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.
- AdaptogenEvidence: Grade C
American Ginseng
Researched, 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 and why this grade
Studied dose: 200 mg of standardized extract, single dose in the studied trials.
Downgraded from B to C on 2026-07-11 under the house replication-over-recency + sponsor-dependence standard (the same basis used for Rhodiola and Panax). All three supporting acute trials (Scholey 2010, PMC2952762; Ossoukhova 2015; and White 2020, PMID 32896022, with two Naturex-employee authors) were funded by Naturex, the Cereboost developer, and the one chronic-dosing trial (Bell 2022, doi:10.1007/s00394-021-02654-5) was largely null. A single sponsor's repeated trials are self-replication, not independent replication, so the honest grade is C. This is a different species from Asian Panax ginseng; the signals should not be read across.
- PolyphenolEvidence: Grade C
Anthocyanins
Researched, 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 and why this grade
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, and antioxidant and circulation mechanisms are better characterized. Under monitoring since 2026-09-14: a 2025 meta-analysis of 59 randomized trials (Micek et al.) reported improved global cognition with anthocyanins and anthocyanin-rich foods (SMD 0.46), with smaller effects on individual domains. We have not moved the grade: the pooled trials mix whole berries, juices and extracts across very different populations, effects that large from small, heterogeneous trials often shrink, and a six-month blueberry trial in adults with metabolic syndrome found no cognitive effect. A 2026 meta-analysis restricted to healthy participants (He et al., 14 RCTs, 632 people) is the clearest counterweight: blueberry intake improved flow-mediated dilation but produced no significant change in executive function or mood. The vascular mechanism is better supported than the cognitive endpoint.
- AdaptogenEvidence: Grade C
Ashwagandha
Researched, 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 and why this grade
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. Re-examined 2026-09-17: an independent GRADE-assessed meta-analysis of 20 RCTs in 1,249 adults (Zhu 2026) now reports consistent gains across memory, attention and processing speed, executive function and visuospatial ability, with low heterogeneity, a stronger cognition base than this profile previously had. It does not move the grade, because the cap here is a safety signal, not the efficacy data. A liver-safety signal caps the grade regardless of the stress-efficacy data: NIH LiverTox classifies ashwagandha as a "likely" cause of clinically apparent liver injury (likelihood score B), 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. A 1,002-person, 8-week randomized safety trial published in 2026 (Pakhale et al.) found no change in liver-function tests and fewer adverse events than placebo, which is reassuring about ordinary short-term use but does not test the rare, idiosyncratic injury the LiverTox rating and the TGA alert describe.
- VitaminEvidence: Grade C
B-Complex (B6, B9, B12)
Core candidate: 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 and why this grade
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. Separately, a meta-analysis of B-vitamin trials in healthy and at-risk adults (Young 2019) found a small reduction in perceived stress (SMD 0.23) but no significant effect on anxiety or depressive symptoms, a stress signal noted here without raising the cognition grade.
- BotanicalEvidence: Grade C
Chamomile
Researched, not in v1
A gentle, well-tolerated evening botanical studied for mild anxiety and sleep quality, plausibly via the flavone apigenin acting on GABA pathways. The effect is genuine but small, and the sleep data are early: a calm-slot ingredient, not a sedative.
Studied dose and why this grade
Studied dose: 220–1500 mg/day of a standardized extract (often 500 mg of a 1.2% apigenin extract, 1–3× daily); tea is the traditional, lower-and-more-variable-dose form.
Limited. Chamomile has the cleanest evidence of the common calm botanicals because its core trials are NIH-funded rather than sponsor-run: an 8-week RCT improved generalized-anxiety scores versus placebo (Amsterdam 2009), and a 2024 meta-analysis found a small improvement in sleep quality (Kazemi 2024), but the sleep trials are methodologically weak, and a standardized chronic-insomnia pilot missed its primary sleep-diary endpoints (Zick 2011). A longer-term anxiety trial (Mao 2016) missed its primary relapse-prevention endpoint while showing positive secondary outcomes. Real but small and early: a C.
- Choline sourceEvidence: Grade C
Citicoline
Signal State Core candidate
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 and why this grade
Studied dose: 250–500 mg daily in the branded-form trials; other trials used single 500–1000 mg doses in healthy volunteers, and 1–2 g daily in an older-adult memory trial.
Downgraded from B to C on 2026-09-14, on three grounds. First, the trials behind the branded form's attention claim are all tied to Cognizin's manufacturer, Kyowa Hakko Bio, through funding or co-authorship: McGlade 2012 (women, 28 days), McGlade 2019 (adolescent boys, 28 days) and Nakazaki 2021 (older adults, 12 weeks; Kyowa funded it and took part in its design, though the paper reports Kyowa was not involved in the intervention, data collection or statistical analysis). That is sponsor dependence rather than independent confirmation. Second, the healthy-adult evidence from outside those trials points to a narrower effect than the marketing does: an academically funded crossover trial (Knott 2015, n=24, single 500 or 1,000 mg doses) improved cognition only in people who started as low performers, found nothing in medium performers, and reduced performance in high performers. An older trial in adults aged 50–85 (Spiers 1996) improved memory mainly in participants whose recall was inefficient to begin with (a subgroup identified after the initial analysis), and while it carried NIH grant support, the journal later published a correction supplying a financial-disclosure statement the paper had omitted, setting out authors' financial ties to Interneuron and Ferrer, companies with commercial interests in citicoline, so it is not independent of commercial interest in the compound either. Third, independent review and large trials have gone against the compound: EFSA's 2024 health-claim opinion found no cause-and-effect relationship between citicoline and memory, and two large citicoline RCTs were both null: ICTUS in acute stroke (n=2,298), funded by the citicoline manufacturer Ferrer, and COBRIT in traumatic brain injury (n=1,213), sponsored by the US National Institutes of Health. Those are clinical populations rather than healthy adults, but they are large, well-powered tests of the compound. Two completed healthy-adult trials, one testing 250 mg and one in adults aged 18–35, had no posted results when we checked on 2026-09-14. A well-conducted independent trial showing a benefit at label doses in healthy adults would move this back toward B. Health Canada's sustained-attention monograph claim is unaffected; a permitted claim is not the same as a strong evidence grade.
- PolyphenolEvidence: Grade C
Cocoa Flavanols
Researched, not in v1
A de-theobrominated cocoa extract studied for cerebral blood flow and attention. Single doses raise cerebral blood flow, but the large multi-year COSMOS trials found no overall cognitive benefit, with a memory signal only in people whose diets were lowest in flavanols.
Studied dose and why this grade
Studied dose: ~500 mg cocoa flavanols/day (roughly 80 mg epicatechin).
Downgraded from B to C on 2026-09-14. Acute cerebral-blood-flow RCTs (Scientific Reports, 2020) found a single dose improved blood flow and attention measures, and that acute signal is real. But the COSMOS program (the large, multi-year parent trial and its cognitive sub-studies, the most substantial test of cocoa flavanols to date) found no overall cognitive benefit from 500 mg/day: no effect on global cognition in COSMOS-Mind (doi:10.1002/alz.12767) or the COSMOS clinic sub-cohort, and no overall effect on the primary memory outcome in COSMOS-Web, where memory improved only in participants with the lowest baseline diet quality or habitual flavanol intake (Brickman 2023). That is a repletion effect in a subgroup, not a general one. Under our standard, null results in the most substantial trial program hold the grade at C, the same basis used for resveratrol, where blood flow rose and cognition did not. Funding transparency: COSMOS ran on an investigator-initiated grant from Mars Edge, with study pills and packaging donated by Mars and partly by Pfizer Consumer Healthcare (now Haleon), and NIH grants supported parts of the program including the COSMOS-Mind cognitive sub-study. Much other cocoa-flavanol research, and the CocoaVia-branded material, is also tied to Mars. The null results therefore come from trials the ingredient's maker helped fund, which cuts against the ingredient rather than for it. Re-examined 2026-09-17 against a newer GRADE-assessed meta-analysis (Arabpour 2026) that reports faster Trail Making Test times and better verbal fluency with chronic cocoa intake, strongest at 500 mg flavanols/day or more for eight weeks or longer, at moderate-to-high certainty. It is the strongest positive synthesis this ingredient has, and it is the reason this grade is now flagged for monitoring rather than settled. What it does not do is answer COSMOS: the paper is paywalled, so we could not read its list of included trials, and we do not know whether the COSMOS cognitive sub-studies are among its 16. C holds on COSMOS's own result either way. A positive pooled estimate does not displace a null finding in the largest and longest trial programme, and if COSMOS is inside the pool then the pooled estimate is being carried by the smaller trials.
- Amino acidEvidence: Grade C
Creatine Monohydrate
Researched, not in v1
Best known for muscle, creatine is also a brain energy-buffer. Its cognition evidence is modest and contested: the positive signals come from high acute doses during sleep deprivation and from older adults, while the largest trial in rested adults was borderline and EFSA's 2024 review found no established cognitive effect. Extremely cheap with a strong safety record.
Studied dose and why this grade
Studied dose: 3–5 g/day maintenance in most trials. The sleep-deprivation studies used one-off doses of about 0.2–0.35 g/kg (roughly 14–25 g for a 70 kg adult), a research context, not a daily-use recommendation.
Held at C on 2026-09-14, and a proposed upgrade was rejected. EFSA's 2024 review of a creatine cognition claim found no cause-and-effect relationship in any cognitive domain at 3 g/day: working-memory effects appeared only at 20 g/day for 5–7 days, not with 5 g/day for six weeks, and the applicant's meta-analysis counted the same participants more than once. When a widely cited 2023 memory meta-analysis was re-analysed without that double counting, the overall benefit was no longer significant except in adults aged roughly 66–76 (Eckert & Pascher 2023). The largest trial in healthy adults (Sandkühler 2023, n=123, 5 g/day for six weeks) found only a borderline effect on backward digit span, and vegetarians did not benefit more. An earlier systematic review (Avgerinos 2018) had suggested memory gains concentrated in stressed or older groups. Single doses of about 0.2–0.35 g/kg improved performance during sleep deprivation in two small studies from one research group (Gordji-Nejad 2024 and 2026). These were acute research doses, not a daily-use effect. Reviewed 2026-09-17: a 2026 trial in young active adults found creatine improved Wingate cycling performance but not cognition (Silva et al.), and a 2026 scoping review looking for creatine trials in dementia found no randomized controlled trials at all. Honestly C.
- BotanicalEvidence: Grade C
Curcumin (lipidated)
Researched, 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 and why this grade
Studied dose: 400 mg/day of Longvida (delivering roughly 80 mg curcuminoids).
Cox 2015 and a 2020 follow-up found modest working-memory and mood/fatigue benefits with the Longvida lipidated formulation versus placebo. Downgraded from B to C on 2026-07-11: both trials are the same research group (Swinburne) using Longvida material (internal, same-group replication, not the independent cross-sponsor replication a B requires), and the studied population skews 50+ rather than a broad healthy-adult range.
- PolyphenolEvidence: Grade C
Ginkgo Biloba
Researched, 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 and why this grade
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. Reviewed 2026-09-17 against a new Cochrane review (Wieland 2026; 82 studies, 10,613 participants), which changes what we can say about the mild-cognitive-impairment case: in MCI, ginkgo probably has little or no effect at six months on global status, cognition or activities of daily living (moderate-certainty evidence). In people with a dementia diagnosis it may bring small-to-moderate benefits, but that estimate is low-certainty with very high heterogeneity, and in people with subjective cognitive complaints the review found the effect uncertain and the risk of adverse events possibly higher than placebo at three months. C holds for a healthy-adult use case, now on a stronger footing.
- NootropicEvidence: Grade C
Huperzine-A
Researched, 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 and why this grade
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.
- MineralEvidence: Grade C
Iron
Researched, 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 and why this grade
Studied dose: 18–65 mg elemental iron/day as bisglycinate, dependent on documented deficiency. Note the adult tolerable upper intake level is 45 mg/day elemental iron; the top of this range is defensible only under clinician-guided treatment of confirmed deficiency, not general use.
Moved from a conditional B to C on 2026-09-17, on our own rubric rather than on new evidence: the rubric puts evidence concentrated in a deficient population under C, and that is exactly what this is. 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 C
L-Tryptophan
Researched, not in v1
The dietary amino-acid precursor to serotonin and melatonin, studied mainly for sleep onset and mood. Small trials show modest, inconsistent benefits for falling asleep. It carries a serious serotonin-syndrome interaction with antidepressants and a manufacturing-safety history worth understanding. It is an evening/mood-slot ingredient, not a daytime active.
Studied dose and why this grade
Studied dose: Sleep trials used ~1–2 g at night. Regulatory note: Health Canada classifies oral L-tryptophan as a natural health product only up to 220 mg per dose/day; above that it is regulated as a drug.
Limited. Small double-blind trials report modest reductions in sleep-onset time (Demisch 1987; Wang 2016), and the Cochrane review of tryptophan and 5-HTP for depression found a signal versus placebo but judged only 2 of 108 trials high enough quality to include (Shaw 2001), which is insufficient to be conclusive. There are no modern large RCTs. The 1989–90 eosinophilia-myalgia syndrome (EMS) outbreak was traced to a contaminant from one manufacturer's process (Belongia 1990), not to tryptophan itself: a purity lesson, not a property of the molecule. Graded C.
- CarotenoidEvidence: Grade C
Lutein + Zeaxanthin
Researched, 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 and why this grade
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; separate Hammond-group work has linked macular pigment density to faster visual processing speed. Downgraded from B to C on 2026-07-11: the positive human cognition base is OmniActive-funded (the Lutemax maker) and concentrated in a single research group (Hammond), and the "processing speed" endpoint is partly a visual-processing measure rather than a pure cognition-only outcome. Sponsor plus single-group dependence caps this at C. (Eye-health evidence is stronger, but that is a different claim.)
- MineralEvidence: Grade C
Magnesium Glycinate
Researched, not in v1
A well-absorbed, low-laxative form of an essential mineral, used as an evening calm/sleep foundation. Its human evidence for sleep and stress is real but modest and concentrated in people who are low to begin with: a mild, mainly-if-you're-deficient effect, not a sedative. This is the everyday repletion form; the CNS-targeted cognition pitch belongs to magnesium L-threonate, a different form graded C on small, commercially funded trials.
Studied dose and why this grade
Studied dose: ~200–350 mg elemental magnesium/day (the key sleep RCT used 250 mg). Watch the compound-weight trap: bisglycinate is only ~14% elemental magnesium, so ~250 mg elemental is ~1,800 mg of the salt. Studies and labels must state elemental. The supplemental upper limit is 350 mg/day elemental (food magnesium is not counted).
Limited but real. A 2025 RCT of magnesium bisglycinate in adults with poor sleep (Schuster 2025, n=155) found a statistically significant but small reduction in insomnia severity (larger in people with low dietary intake), and one author is tied to a nutraceutical-funded CRO, so it is sponsor-adjacent. A meta-analysis of oral magnesium for insomnia in older adults (Mah 2021) found sleep onset roughly 17 minutes shorter than placebo but rated the evidence low-to-very-low quality, and a systematic review of magnesium for anxiety/stress (Boyle 2017) found only a suggestive benefit in anxiety-prone groups on poor-quality trials. Reviewed 2026-09-17 against a systematic review of every randomized trial of magnesium as a stand-alone sleep intervention (Lopresti 2026, 12 trials): findings were inconsistent across subjective scales, EEG, actigraphy and wearables, certainty was low to very low, and the authors conclude the evidence does not support magnesium as a routine treatment for insomnia. Graded C. General-magnesium cognition evidence is weaker still. The crisp line versus L-threonate is claim architecture, not magnesium content.
- MineralEvidence: Grade C
Magnesium L-Threonate
Researched, not in v1
A magnesium salt marketed specifically for the brain because it raised brain magnesium in rodents. Small, commercially funded human trials report modest cognition and self-rated sleep improvements, while a publicly funded trial in patients after breast-cancer surgery found no significant difference from placebo in sleep or cognition, so the marketing still runs ahead of the evidence. Magnesium as a general mineral has separate, better-established roles.
Studied dose and why this grade
Studied dose: 1–2 g/day of magnesium L-threonate in the trials that tested it without other actives (delivering a relatively small amount of elemental magnesium).
Upgraded from Emerging to C on 2026-09-14. The mechanism rests on rodent work (Slutsky 2010, Neuron). Three small trials built around magnesium L-threonate report benefits, and all three were commercially funded. Liu 2016 (~44 completers, older adults with cognitive complaints) tested MMFS-01, which contains magnesium L-threonate (a salt the authors say they developed), and reported an improvement in overall cognitive ability versus placebo (p = 0.003); Neurocentria funded it, designed it jointly with the contract research site that ran it, analysed the cognitive outcomes and wrote the paper, and the authors report that effects on sleep and anxiety could not be determined. Hausenblas 2024 (80 adults with self-reported sleep problems) reported better sleep quality and daytime functioning; AIDP commissioned and funded it, three of its six authors are paid by AIDP, and a 2025 corrigendum disclosed that the trial was registered retrospectively. Lopresti & Smith 2026 (100 adults aged 18–45 with poor sleep), funded by the ingredient's owner, reported a modest improvement on an overall cognition composite (p = 0.043) and reaction time and better self-rated sleep, but no change on objective sleep measures. Two further trials qualify that picture. Zhang 2022 (109 healthy adults, 30 days) reported memory-test scores significantly higher than placebo (p < 0.001), but it tested a combination formula that also contained phosphatidylserine and vitamins, funded by Wu-xi Magtein Bioscience, so it cannot isolate this ingredient. Ni 2023 randomized 109 patients after breast-cancer surgery to 1.2 g/day magnesium L-threonate (48) or placebo (61) for 12 weeks and found no significant between-group differences in pain, anxiety, depression, sleep or cognition; it reports public funding and no conflicts of interest. That is a clinical population, but the null result comes from outside the commercially funded research. That is enough human signal for C, not B: the positive trials are small and commercially funded, the 2026 trial's results are borderline (p = 0.043 and 0.031), the stronger results come from a developer-funded trial of about 44 people and a formula that cannot isolate the ingredient, the sleep findings are not consistent, and no independent group has replicated the benefits. General magnesium status remains a separate, better-founded topic.
- PolyphenolEvidence: Grade C
Maritime Pine Bark
Researched, 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 and why this grade
Studied dose: 50–150 mg daily of a standardized extract in many studies.
Human cognition trials exist but are heavily concentrated in one branded extract (Pycnogenol, Horphag Research) and largely one research group (Belcaro and colleagues), so results do not automatically generalize to all pine bark products and the manufacturer's own "39 trials" tally reflects volume, not independent replication. Graded C accordingly.
- VitaminEvidence: Grade C
Multivitamin-Mineral
Researched, not in v1
A single daily tablet covering a broad set of vitamins and minerals at roughly recommended intakes. Its cognition evidence comes from one large trial program in older adults, where the effect was small, which is why the grade is claim-specific and conservative.
Studied dose and why this grade
Studied dose: One daily tablet providing roughly 100% of recommended intakes for most vitamins and minerals, as in COSMOS (Centrum Silver).
Claim-specific C for cognition in healthy adults, with the supporting evidence sitting just outside that population. A 2024 meta-analysis of three cognitive sub-studies of the COSMOS trial (Vyas et al.; 5,203 adults aged 60 and older, followed for 2–3 years) found a daily multivitamin-mineral produced slightly better change in global cognition (0.07 standard deviations) and episodic memory (0.06 standard deviations) than placebo, which the investigators equated to about two years of cognitive aging. It holds C rather than A or B for two reasons our standard names explicitly: the evidence sits in older adults rather than the general healthy-adult population, and the three analyses share one parent trial, so they are not independent replications. Trials in younger, nonclinical adults have mainly measured stress and mood rather than cognition (Long & Benton 2013). The effect is small, and this is a formula rather than a single ingredient. A 228-person, 12-week trial in adults over 70 (Docherty 2025) missed its primary wellbeing outcome, with the positive findings confined to sex-split secondary measures, a further reason to read this grade as C.
- Fatty acidEvidence: Grade C
Omega-3 (EPA/DHA)
Researched, 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 and why this grade
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
Researched, 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 and why this grade
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.
- BotanicalEvidence: Grade C
Passionflower
Researched, not in v1
A traditional calming botanical studied in small trials for anxiety and subjective sleep, with a consistent direction of benefit but no large confirmatory trial. A gentle evening/as-needed calm-slot option rather than a proven sleep aid.
Studied dose and why this grade
Studied dose: Studied as ~45 drops/day of a standardized tincture, roughly 500 mg of a dry extract, or passionflower tea; extracts are often standardized to flavonoids/vitexin.
Limited but consistent. Several small double-blind RCTs and a systematic review point the same way: a 36-patient double-blind pilot in an anxiety-trial population reported meaningful reductions in anxiety scores over four weeks with little daytime performance impairment (Akhondzadeh 2001), a tea RCT improved subjective sleep quality (Ngan 2011, though polysomnography was not significant), and a 2020 systematic review found most trials reported reduced anxiety (Janda 2020). The evidence is capped by very small samples, short durations, and heterogeneous preparations: a plausible-but-early C.
- PhospholipidEvidence: Grade C
Phosphatidylserine
Researched, not in v1
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 every current supplement actually contains) has not cleared that same bar.
Studied dose and why this grade
Studied dose: 100 mg two to three times daily (≈200–300 mg total) in most studies; Jorissen tested up to 600 mg daily.
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.
- PolyphenolEvidence: Grade C
Resveratrol
Researched, 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 and why this grade
Studied dose: 150 mg/day (commonly split as 75 mg twice daily) of trans-resveratrol.
Kennedy 2010 (PMID 20357044) found an acute single dose improved cerebral blood flow in healthy adults but did NOT improve cognitive performance. The blood-flow effect is real, the acute cognition benefit is not. The only positive cognition data come from postmenopausal-women RCTs (including a 24-month trial) run by a single research group (RESHAW). Downgraded from B to C on 2026-07-11: for a broad healthy-adult cognition claim, the load-bearing acute trial was cognition-null and the memory signal exists only in one group studying one narrow, non-generalizable population, and a single-group base does not support a B.
- AdaptogenEvidence: Grade C
Rhodiola Rosea
Signal State Core candidate
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 and why this grade
Studied dose: 100–170 mg daily of the SHR-5 standardized extract in the trials cited here; the wider literature spans roughly 100–600 mg daily.
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. Reviewed 2026-09-17: a 2025 crossover trial in 27 resistance-trained adults (Koozehchian et al.) reported better Stroop performance, but the cognitive comparisons are reported against a no-capsule condition rather than against the placebo, so they are not blinded comparisons and do not lift the grade.
- AdaptogenEvidence: Grade C
Saffron
Researched, not in v1
A well-tolerated botanical with a large body of human trials on mood and stress, plus secondary sleep findings, 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 and why this grade
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 pooling the mood trials report improvements in low-mood and stress scores versus placebo with good tolerability. Reviewed 2026-09-14: effects are smaller in newer, larger trials than in the early, mostly single-centre studies. A 12-week affron trial in 202 adults, co-authored by staff of the extract's manufacturer, found a modest improvement in low-mood scores (Cohen's d 0.39) but no effect on anxiety, stress, or restorative sleep (Lopresti 2025), and a publicly funded 6-week trial in 51 adults did not improve its primary mood composite. Reviewed again 2026-09-17 against a GRADE-assessed meta-analysis of 34 trials in 1,769 adults (Mahmoudi 2026), which sharpens where the mood evidence sits: self-rated depression and anxiety scores improved, but the clinician-rated scales (HDRS, HARS) and the POMS did not, and heterogeneity was above 90% on both pooled outcomes. Mood evidence is roughly B on self-report and weaker on clinician-rated measures, not A; direct healthy-adult cognition data are thin and mostly extrapolated from clinical populations, so the cognition grade is honestly C.
- PolyphenolEvidence: Grade C
Sage
Researched, 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 and why this grade
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.
- BotanicalEvidence: Grade C
Spearmint Extract
Researched, 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 and why this grade
Studied dose: 900 mg/day of standardized extract.
Downgraded from B to C on 2026-07-11 for sponsor-dependence. Both supporting trials are Kemin-funded (the Neumentix developer): Herrlinger 2018 (J Altern Complement Med), a 90-day RCT in adults with age-associated memory impairment (not a broad healthy-adult population), and the Falcone 2018 follow-up acute-attention trial (PMC6291964). With no manufacturer-independent replication, a pivotal trial in the wrong population, and effect sizes near the threshold of clinical meaningfulness, the honest grade is C.
- BotanicalEvidence: Grade C
Valerian
Researched, not in v1
A traditional evening sedative herb. Despite centuries of use, the best systematic reviews find its efficacy for sleep genuinely unproven: a weak subjective "slept better" signal that objective sleep measures do not confirm, built on low-quality, non-standardized trials. Included for transparency and traditional-use context, not on a strong efficacy claim.
Studied dose and why this grade
Studied dose: 225–1215 mg/day of extract; most commonly 300–600 mg taken 30–120 minutes before bed.
Limited and genuinely borderline: graded C only because there is no safety or legal veto to justify Graded Out, not because the evidence is convincing. The strongest systematic reviews conclude the evidence is inconclusive (Stevinson 2000) and that the only positive result is a dichotomous self-reported "slept better" that disappears on objective measures, with documented publication bias (Bent 2006). A more favorable 2020 review (Shinjyo 2020) reports benefit but pools 60 heterogeneous studies and blames inconsistent results on variable extract quality. Under a replication-over-recency standard, the honest read is "traditional use, efficacy unproven," and we would not headline an efficacy claim on valerian.
- VitaminEvidence: Grade C
Vitamin C
Researched, 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 and why this grade
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. Moved from B to C on 2026-09-17, on our own rubric rather than on new evidence. The rubric places evidence that sits in a deficient population under C, and reserves B for effects tied to a context such as stress, fatigue or sleep loss. This is the first case: the supporting review is largely observational (5 RCTs among 50 studies), and the cleanest supporting trial (Sim 2022) enrolled only adults whose serum vitamin C was already below 50 µmol/L. That is a real, useful effect, but it is repletion, and the grade should say so.
- VitaminEvidence: Grade C
Vitamin D3
Core candidate: 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 and why this grade
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.
- VitaminEvidence: Grade C
Vitamin K2 (MK-7)
Researched, not in v1
A fat-soluble vitamin that activates the proteins directing calcium into bone rather than soft tissue. It is a foundational cofactor for vitamin D, not a cognitive ingredient, and it carries one significant caution: it directly interacts with warfarin and other vitamin K antagonists.
Studied dose and why this grade
Studied dose: 90–180 mcg/day of MK-7, typically taken alongside vitamin D3 and with a fat-containing meal for absorption.
Claim-specific grading: for bone/working-with-D, a 2022 meta-analysis of 16 RCTs (Ma 2022, Frontiers in Public Health, PMID 36033779) found MK-7 supplementation has a positive effect on lumbar-spine bone mineral density in postmenopausal women, particularly combined with vitamin D or calcium. The evidence is real but the trial base is still limited and mixed, so this is graded C, not B. For the arterial-calcification/cardiovascular angle, the evidence is Emerging: a 2023 meta-analysis of 14 RCTs (Li 2023, Frontiers in Nutrition, PMID 37252246) found vitamin K supplementation slowed coronary-artery-calcification progression, and a 2023 RCT in older men (Hasific 2023, JACC Advances, PMID 38938724; the AVADEC trial, MK-7 720 mcg/day + vitamin D3) found no significant difference in the full study population but did find significantly slower CAC progression in a higher-risk subgroup with baseline CAC ≥400. That is a real, hypothesis-generating signal from one higher-risk-population RCT, not a confirmed effect. Replication in broader populations is needed before this claim could move past Emerging.
- MineralEvidence: Grade C
Zinc
Researched, not in v1
An essential mineral for immune function, taste, and brain signaling. Its cognition and mood benefit is real but largely confined to correcting a deficiency or augmenting antidepressants. For a well-nourished adult it is best understood as deficiency insurance, not a focus or mood enhancer, and chronic high doses carry a real copper-depletion downside.
Studied dose and why this grade
Studied dose: Everyday supplements ~8–15 mg elemental zinc/day; antidepressant-adjunct trials used ~25 mg/day. The tolerable upper limit is 40 mg/day elemental (set by copper-absorption interference). Declare elemental zinc; salts differ in elemental content.
Claim-specific. Deficiency correction is well established, but the consumer-relevant claim (mood or cognition in generally-nourished adults) is limited. A meta-analysis found serum zinc is lower in depressed than non-depressed people (Swardfager 2013), which supports a deficiency-correction rationale but is an association, not a supplementation result. Supplementation trials show a modest antidepressant effect mainly as an add-on to medication and in people who are low (Lai 2012; Donig 2022, called "preliminary"). Graded C: a foundational nutrient whose felt effect in replete adults is weak.
- BotanicalEvidence: Grade C
Zynamite
Researched, 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 and why this grade
Studied dose: 100–300 mg/day; 300 mg is the most-studied acute dose.
Wightman 2020 (Nutrients 12(8):2194, PMC7468873) gave 70 healthy adults a single 300 mg Zynamite dose and found improved attention accuracy and episodic memory versus placebo, without the cardiovascular activation seen with stimulants. Downgraded from B to C on 2026-07-11: this rests on one Nektium-sponsored acute trial (two manufacturer-affiliated authors) with no independent replication, and a single sponsor-funded trial does not meet the bar for B. Chronic daily use remains a separate, weaker (Emerging-level) question, not yet supported by repeated-dosing human trials.
- Amino acidEvidence: Emerging
Ergothioneine
Researched, not in v1
A sulfur-containing compound made by fungi and some bacteria, which people get from food, mushrooms especially. It is marketed as a longevity antioxidant; the human cognition evidence is two small trials, one sponsor-funded in adults with memory complaints, whose primary outcome did not separate from placebo, and a 19-person pilot in mild cognitive impairment.
Studied dose and why this grade
Studied dose: 10–25 mg daily across the two small human cognition trials.
Emerging. Most of the case is observational or preclinical: lower blood ergothioneine was associated with faster cognitive decline in older adults attending memory clinics (Wu 2022), and oral ergothioneine improved object-recognition memory in mice (Nakamichi 2021). The larger randomized trial (Zajac 2025; 147 adults aged 55–79 with subjective memory complaints; 10 or 25 mg/day for 16 weeks) raised blood ergothioneine but did not demonstrate a between-group benefit on its primary composite-memory outcome: the 25 mg group improved within-group at week 4 and did not sustain it. Reaction time showed a treatment-by-time interaction, but no pairwise between-group comparison reached significance, so the improvements differed by dose and time rather than cleanly favouring ergothioneine over placebo. Self-rated prospective memory and sleep onset improved dose-dependently, reaching significance at 25 mg. That trial was funded by Phyto Tech Corp (Blue California), which also employs one of its authors. A separate, publicly funded pilot in 19 people with mild cognitive impairment (Yau 2024, 25 mg/day for a year) reported better performance on a learning measure and steadier plasma neurofilament light. Two small trials, one without a between-group primary result and one at pilot scale in a clinical population, is Emerging territory. Reviewed 2026-09-17: a 12-week trial in 80 healthy adults aged 60–80 (Cha 2026) reported better delayed word recall and lower negative mood, but it fed participants oyster mushrooms rather than ergothioneine, so the result cannot be attributed to this compound; and a 2025 systematic review (Takhor & Phan) covering 19 studies found the case still resting mainly on observational and preclinical work.
- Amino acidEvidence: Emerging
Glycine
Researched, 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 and why this grade
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
Researched, 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 and why this grade
Studied dose: Recent trials used 2 g/day of fruiting body plus mycelium (2026 preprint) or a single 3 g dose of a 10:1 fruiting-body extract (Surendran 2025); many capsule products provide 500–1000 mg, well below those amounts.
Held at Emerging on 2026-09-17 after a second, deeper review that went looking for every human trial rather than the headline ones. More human trials exist than this profile used to cite, but the trials reporting a benefit each use a different preparation, dose and outcome measure, so none of them replicates another. On the positive side: an early trial in mild cognitive impairment (Mori 2009); a 31-person Japanese trial of fruiting body over 12 weeks (Saitsu 2019); an acute crossover of 1 g run by a contract research organisation that improved reaction-time measures (La Monica 2023); and a 33-person pilot of an erinacine-A-enriched extract (Černelič Bizjak 2024) in which cognition was a secondary outcome and the gain reached significance only in a model adjusting for baseline score, age, sex and a biomarker. Against them: a 2023 pilot in 41 young adults (Docherty) found faster Stroop performance an hour after a dose, with mostly null results over 28 days; a 2025 crossover in 18 healthy young adults found no effect of a single 3 g extract dose on global cognition or mood; and 10 g/day for four weeks in 24 college-age adults changed nothing (Grozier 2022). The strongest new result is still a 2026 preprint, which had not been peer-reviewed when we re-checked on 2026-09-17, funded by an ingredient supplier that employs two of its lead authors: 2 g/day for 8 weeks improved one visual attention and working-memory task in adults aged 40–75, but not the memory tasks or the composite score, and more than a quarter of randomized participants were not analysed. Three further trials have completed without posting results, one of them university-led. Studied amounts are far above typical capsule doses. Peer-reviewed publication plus an independent replication with a defined extract would support a C.
- MitochondrialEvidence: Emerging
PQQ
Researched, 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 and why this grade
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
Researched, 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 and why this grade
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
Researched, 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 and why this grade
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
Researched, 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 and why this grade
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 showed no statistically significant improvement over placebo on any of its nine pre-specified cognitive endpoints. In January 2017 the FTC and the New York State Attorney General jointly brought a deceptive-advertising action 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
Researched, 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 and why this grade
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. An NTP prenatal study (DART-04) reported equivocal evidence of developmental toxicity in rats. That is not a clear-cut signal on its own, but it adds a precautionary reason against use on top of the null-efficacy picture, 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 precautionary developmental-safety flag and a regulatory withdrawal for unproven efficacy) is what "Graded Out" means on this site.
- MineralGraded Out
Selenium
Researched, not in v1
An essential mineral for antioxidant selenoproteins and thyroid function. Low status is linked to cognitive decline in observational data, but that reflects deficiency correction, not a nootropic effect, and North American diets are generally selenium-sufficient. Graded out as a featured cognitive active on a safety veto: it has one of the narrowest therapeutic windows of any micronutrient, and supplementation RCTs are null for cognition.
Studied dose and why this grade
Studied dose: Not recommended as a cognitive supplement. For reference: RDA is 55 mcg/day and typical North American intake already meets it; the tolerable upper limit is just 400 mcg/day, one of the narrowest windows of any micronutrient. Cognition/prevention trials used ~200 mcg/day.
Graded out on a safety-and-null-evidence basis. Observational data link low selenium to cognitive decline, but randomized supplementation trials in replete older adults show no cognitive or dementia-prevention benefit (SELECT, Lippman 2009; PREADViSE, Kryscio 2017), while the gap between the RDA (55 mcg) and the upper limit (400 mcg) is dangerously narrow: chronic excess causes selenosis, and high supplemental intake carries a type-2-diabetes-risk signal. For a largely selenium-replete population, the risk/benefit does not support featuring it as a cognitive active.
- Semi-syntheticGraded Out
Vinpocetine
Researched, 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 and why this grade
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.
- VitaminGraded Out
Vitamin E
Researched, not in v1
An essential lipid-membrane antioxidant that is legitimate for correcting a (rare) deficiency, but graded out as a featured cognitive active on a safety signal: the supplemental doses studied for brain and heart benefit are associated with increased all-cause mortality and, in men, increased prostate cancer risk, while healthy-adult cognitive prevention is null.
Studied dose and why this grade
Studied dose: Not recommended as a cognitive supplement. For reference: RDA is 15 mg/day; the tolerable upper limit is 1,000 mg/day of any supplemental alpha-tocopherol form, and the harm signals cluster at ≥400 IU/day, at or below the doses studied for brain benefit, so there is no clean therapeutic window for cognition.
Graded out on a safety veto, not an evidence-strength judgment about the nutrient itself. Frank vitamin E deficiency (rare outside malabsorption) does cause neurological harm, but that is repletion, not a nootropic effect. In replete adults the cognitive-prevention evidence is null (PREADViSE, Kryscio 2017), and the supplemental doses historically tested for brain and cardiovascular benefit carry documented safety signals: a dose-response meta-analysis linked ≥400 IU/day to increased all-cause mortality (Miller 2005), and the SELECT trial linked 400 IU/day to increased prostate cancer risk in healthy men (Klein 2011). A transparency-first brand cannot feature, as a cognitive active, a supplement whose studied "benefit" doses raise mortality and cancer risk.