Evidence Updates
What changed, and why.
A grade that never moves isn't rigorous — it's just old. This is the dated, public record of every change we've made to an ingredient's evidence status, with the reasoning attached. Downgrades included; especially downgrades.
July 12, 2026
10 changesNew profile at Grade C, with explicit serotonergic-interaction cautions.
Review context: Added while expanding our sleep and recovery coverage.
New profile at Grade C for sleep/relaxation, on limited human data.
Review context: Added while expanding our sleep and recovery coverage.
New profile at Grade C for sleep/mood-adjacent roles, with conservative interaction cautions.
Review context: Added while expanding our sleep and recovery coverage.
New profile at Grade C — a well-tolerated, well-absorbed magnesium form with limited direct human cognition/sleep trials at this specific form.
Review context: Added while expanding our sleep, recovery, and micronutrient coverage.
New profile, published at Grade B on independent (non-sponsor) evidence: a meta-analysis of 19 randomized trials found melatonin reduced sleep-onset latency and modestly increased total sleep time. Graded for sleep onset specifically — not as a daytime nootropic.
Review context: Added while expanding our sleep and recovery coverage and introducing the Hormone category.
New profile at Grade C for sleep/relaxation, on limited human data.
Review context: Added while expanding our sleep and recovery coverage.
Published straight into Graded Out on a safety-and-null-evidence basis. Randomized trials in replete older adults show no cognitive or dementia-prevention benefit (SELECT, PREADViSE), and the window between adequate and excessive intake is narrow.
Review context: Part of a broader review of our micronutrient coverage.
New profile at Grade C for sleep; trials are mixed and heterogeneous in preparation.
Review context: Added while expanding our sleep and recovery coverage.
Published straight into Graded Out on a safety veto. In replete adults the cognitive-prevention evidence is null (PREADViSE), and high-dose supplementation carries a documented safety signal — repletion of a true deficiency is not a nootropic effect.
Review context: Part of a broader review of our micronutrient coverage.
New profile at Grade C — essential for cognition when deficient, but supplementation in replete adults is a repletion story, not a nootropic one.
Review context: Part of a broader review of our micronutrient coverage.
July 11, 2026
6 changesDowngraded from B to C. Acute cognitive effects appear in small trials but do not replicate consistently enough across doses and populations to hold a B.
Review context: Reassessed during a full-library evidence and data refresh.
Downgraded from B to C. The cognition signal comes from a small number of trials with a specific bioavailable form; the broader, independent replication needed for a B is not there yet.
Review context: Reassessed during a full-library evidence and data refresh.
Downgraded from B to C. Cognitive-benefit trials are promising but limited in number and largely in specific populations, short of the consistent replication a B requires.
Review context: Reassessed during a full-library evidence and data refresh.
Downgraded from B to C. Acute dosing raises cerebral blood flow but did not improve cognition in healthy adults; the only positive cognition data come from a narrower postmenopausal-women population.
Review context: Reassessed during a full-library evidence and data refresh.
Downgraded from B to C. The working-memory effect is real in the trials that exist but rests on a single branded extract with limited independent replication.
Review context: Reassessed during a full-library evidence and data refresh.
Downgraded from B to C. The attention/memory result rests on a single acute-dose trial in healthy adults; a B needs independent replication that does not yet exist.
Review context: Reassessed during a full-library evidence and data refresh.
July 8, 2026
2 changesInitial profile published at Grade C for cognition specifically: a 24-trial meta-analysis found only a small effect concentrated in deficient groups, with no cognitive lift in replete adults; its bone, calcium, and immune roles grade stronger separately.
Initial profile published at Grade C: a 16-RCT meta-analysis supports bone and works-with-D roles in postmenopausal women, but the trial base is still limited and mixed.
July 7, 2026
19 changesInitial profile published at Grade C: most positive cognition trials are in dementia or post-stroke populations with sparse healthy-adult data; the profile carries a stroke-risk association caveat.
Initial profile published straight into Graded Out: the sponsor-run Madison Memory Study failed its pre-specified primary endpoints, and an orally-digested protein has little plausible route to the brain.
Initial profile published at Grade C: 60-day RCTs lower perceived stress and cortisol, but direct healthy-adult cognition signals remain thin; the profile carries a liver-safety caution.
Initial profile published at Grade B (qualified): acute cerebral-blood-flow and attention effects are demonstrated, while the large chronic trial (COSMOS) was null on its primary global-cognition endpoint.
Graded out, not merely low-graded. The strongest human data are 1960s–70s pediatric 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.
Review context: Reassessed during our full-library evidence audit.
Initial profile published at Grade Emerging: a replicated pre-sleep sleep-quality and next-day-alertness signal, held below B because the trial base is concentrated with a single amino-acid manufacturer.
Initial profile published at Grade B: stress and cortisol RCTs replicate across more than one manufacturer's standardized extract — cross-sponsor replication rather than repeated single-sponsor trials.
Initial profile published at Grade B (conditional): the cognition benefit is specific to correcting iron deficiency or iron-deficiency anemia, not a general enhancer in replete adults.
Initial profile published at Grade B: multiple small human trials show acute calm and attention effects, often studied alongside caffeine, with modest and variable effect sizes.
Initial profile published at Grade B: five or more double-blind RCTs plus independent meta-analyses support the Silexan extract on anxiety-scale endpoints, with no sedation or dependence signal on its studied endpoints.
Initial profile published at Grade B: replicated acute calm-under-load findings, extended beyond single-dose use by a 2023 subchronic RCT from a different sponsor.
Downgraded from B to C. Acute cognitive effects appear in some trials but replicate inconsistently across doses and extracts, so the evidence is limited rather than moderate.
Review context: Reassessed during our full-library evidence audit.
Downgraded from B to C. The stronger data sit in age-related decline and soy-derived PS trials; the healthy-adult, focus-specific evidence at label-realistic doses is thinner than a B implies.
Review context: Reassessed during our full-library evidence audit.
Initial profile published at Grade Emerging: positive human trials are all single-sponsor on one branded ingredient, with no independent replication published yet.
Downgraded from B to C. The human trials are mostly small, short, and heterogeneous in outcome measure, and several are sponsor-linked — not enough consistent, independent replication to hold a B.
Review context: Reassessed during our full-library evidence audit, when we introduced the Graded Out status.
Initial profile published at Grade Emerging: small, sponsor-linked Zembrin trials with limited independent replication.
Initial profile published at Grade Emerging: human data is biomarker-level (brain phospholipid precursors on 31P-MRS), not a cognition-outcome trial in healthy adults.
Initial profile published straight into Graded Out on legal and safety grounds: the FDA has stated vinpocetine is not a lawful dietary ingredient and flagged a reproductive-harm risk.
Initial profile published at Grade B: a status-correction story — benefit is tied to correcting an inadequate baseline rather than a universal cognitive lift in already-replete adults.
July 5, 2026
10 changesInitial profile published at Grade C: the only Cochrane cognition review is in a dementia population, with no dedicated evidence base in healthy, unimpaired adults.
Initial profile published at Grade C: benefit is concentrated in older adults with elevated homocysteine (VITACOG), while a ~22,000-person meta-analysis found no cognitive effect in unselected adults.
Initial profile published at Grade C: a 6-RCT systematic review suggests short-term memory and reasoning gains concentrated in stressed or low-baseline states.
Initial profile published at Grade C: healthy-adult enhancement trials are mixed and large prevention trials (GEM, GuidAge) were negative; the evidence is more consistent only for symptomatic mild cognitive impairment.
Initial profile published at Grade C: positive RCTs cluster in dementia patients and high-risk-of-bias student cohorts, and the signal largely disappears in healthy adults.
Initial profile published at Grade B: acute-dose RCTs improve working memory and cognitive flexibility mainly when catecholamines are depleted by stress or demand, not at rested baseline.
Initial profile published at Grade Emerging: the mechanism rests on rodent work (Slutsky 2010), with only a small developer-linked human trial to date.
Initial profile published at Grade C for cognition in healthy adults: a Cochrane review and AREDS2 found no cognitive benefit; its cardiovascular and triglyceride roles grade stronger separately.
Initial profile published at Grade C: RCTs support mood, stress, and sleep at 28 mg/day affron, but direct healthy-adult cognition data are thin and mostly extrapolated from clinical populations.
Initial profile published at Grade C: small acute trials show recall and attention effects via cholinesterase inhibition, with the strongest branded trial sponsor-funded.
July 4, 2026
5 changesInitial profile published at Grade C: a growing but still limited human evidence base on cognitive endpoints specifically.
Initial profile published at Grade B: multiple 8–12 week human trials report memory and learning gains, with a characteristically cumulative (not acute) time course.
Initial profile published at Grade B: several human trials report attention and memory measures, though both principal supporting trials are tied to the branded-form manufacturer — a sponsor-dependence caveat behind the grade.
Initial profile published at Grade Emerging: some small human pilot trials plus considerable preclinical work, short of the consistent healthy-adult replication a higher grade needs.
Initial profile published at Grade C: human cognition trials are concentrated in one branded extract and largely one research group, so the results do not automatically generalize.
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