Methodology

The Evidence Standard.

Every A, B, C, and Emerging grade on this site is assigned against one rubric, applied the same way whether an ingredient ends up in Signal State Core or gets graded out. This page is that rubric, made public — not a claim about any ingredient's effect, and not a claim about the unlaunched product.

Educational, methodology content — not medical advice and not a product or efficacy claim. Evidence grades describe our conservative reading of the published human research for an ingredient's studied role. They are unrelated to whether Signal State Core, once launched, will carry any specific claim, which depends on separate regulatory review.

Who does the review: every grade and ingredient/article page is written and checked in-house against this published rubric by the Signal State Labs editorial team, and re-checked when a page's "Updated" date changes. This is an editorial process, not a credentialed clinical review — we have not yet engaged a registered dietitian, pharmacist, or physician to sign off on this content, and we say so plainly rather than imply otherwise.

The five statuses

What actually separates an A from Graded Out.

A, B, C, and Emerging are ordered by strength of human evidence, not by how promising an ingredient's story sounds. Graded Out is different in kind, not just in strength — it sits off that scale entirely. Here is what each one actually requires.

Grade A

Strong — multiple human trials and consistent effects0 of 52 ingredients currently carry this status.

Multiple independent human RCTs — not one trial run several ways.
Evidence sits in the actual target population (healthy, replete adults), not a deficient, older, or clinical group.
Consistent direction of effect across independent research teams, with no major null meta-analysis or Cochrane review contradicting it.
Studied dose matches what a real label can deliver in one or two servings.
No unresolved safety signal and no reliance on sponsor- or developer-funded trials alone.

Grade B

Moderate — several human trials, some mixed results11 of 52 ingredients currently carry this status.

Several human RCTs, generally in the right population, generally pointing the same direction.
Effect sizes are real but modest, or benefit is reliably tied to a specific context (e.g. stress, fatigue, sleep loss) rather than a universal baseline lift.
Some mixed results or dose/design variability across the trial set — enough to keep it short of A, not enough to disqualify it.
No material safety flag for the population it's positioned for.

Grade C

Limited — early or small human trials30 of 52 ingredients currently carry this status.

Human trials exist, but at least one honest discount applies: an independent systematic review or Cochrane analysis finds the effect null or unconvincing; the strongest data sits in an older, deficient, or clinical population rather than healthy adults; the well-evidenced benefit is for a different endpoint than the one being discussed; or a single sponsor-linked trial hasn't been independently replicated.
Where a safety signal exists (even an unresolved, associative one), it holds the grade down regardless of how the efficacy data reads.

Emerging

Emerging — mostly preclinical or preliminary human data6 of 52 ingredients currently carry this status.

Mechanism is established mainly in preclinical or animal work.
Human data is limited to one or a small handful of small trials, sometimes developer-linked, with no independent replication yet.
Directionally interesting, but not yet evidence you'd build a same-day claim on.

Graded Out

Graded out — evaluated and not featured (failed replication or a safety signal)5 of 52 ingredients currently carry this status.

Not a passing grade, and not on the A–Emerging strength scale at all — evaluated to the same standard as everything else, then excluded outright.
Applies when the dominant evidence is a failed or null result (a replication attempt or independent systematic review contradicts the original positive finding), OR
A safety signal exists that vetoes inclusion regardless of how the efficacy data reads — mechanism plausibility and dose don't matter if the ingredient fails on safety.
Distinct from a low grade: a Grade C or Emerging ingredient can still have a real, if limited, positive signal. A Graded Out ingredient does not.

Why nothing is a Grade A

A is defined by a bar, not by marketing.

Most stimulant-free cognitive ingredients simply don't have the multi-trial, right-population, consistent-effect evidence base that a caffeine-grade claim would need. Rather than lower the bar to fill the top grade, we leave it empty.

Right now every active ingredient under consideration for Signal State Core v1 clears Grade C or better — no lower grade is used for a cognitive active in the formula. Grade C and Emerging ingredients in the library are either excluded from v1 entirely, or included only for a separate, well-established non-cognitive role (see the foundational layer on the Ingredient Library).

We grade ingredients out

Honesty about what didn't make the cut is the differentiator.

A brand that only shows you what it sells can't be second-guessed. We publish the ingredients we researched and chose not to use, with the same evidence note we'd give anything else.

DMAE: Graded Out.

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, which — while not a clear-cut signal on its own — 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.

Read the full DMAE breakdown

Graded Out isn't the same as grading low. Some Grade C and Emerging ingredients stay in the library for education and comparison — they still have a real, if limited, positive signal. DMAE carries the Graded Out status specifically because the acetylcholine mechanism it's marketed on is poorly substantiated, its strongest positive human data is decades-old pediatric research since abandoned, a Cochrane review of the related cholinergic approach found no evidence of benefit, and a modern developmental-toxicity signal argues for avoidance rather than inclusion — a failed efficacy picture plus a safety veto, which fails the standard outright, not just the grade.

See every researched ingredient, in or out, in the Evidence Explorer, filtered by Graded out.

Claim-specific grading

A grade attaches to a claim, not to the whole ingredient.

The same ingredient can honestly score differently depending on what it's being asked to do — the trial base often supports one use far better than another. Rather than invent B+ or C− notation, we keep the letters simple and scope each grade explicitly to its claim.

Ashwagandha

Stress and cortisol evidence is roughly Grade B — 60-day RCTs of standardized extract lowered perceived stress and serum cortisol versus placebo. The direct-cognition evidence is thinner and smaller, so the cognition claim doesn't inherit the stress grade.

Ginkgo Biloba

Evidence is more consistent for symptomatic mild cognitive impairment than for healthy adults, where controlled trials are mixed and large prevention trials were negative — so the healthy-adult use case can't borrow the clinical signal.

Alpha-GPC

Most positive cognition trials are in dementia or post-stroke recovery populations, and a large observational cohort flagged a stroke-risk association — an association, not proven causation, but enough to grade the healthy-adult use case conservatively.

Phosphatidylserine

The persuasive trials used a bovine-cortex source in memory-impaired older adults; a direct RCT of the soy-derived form actually used in modern supplements failed to beat placebo at 300 or 600 mg/day. Wrong source, wrong population — an honest Grade C. We held PS to that grade, and it's the reason we cut it from the Core formula rather than carry a below-B active for appearances.

The split can run even within a genus: an independent Cochrane review found no convincing cognitive effect for Asian Panax ginseng, which grades C for cognition here — while American ginseng (Panax quinquefolius) carries a separate, narrower mental-fatigue signal and grades B on its own page. Reading one grade across to the other would be dishonest, so we don't.

Studied dose vs. label dose

A grade only means something at the dose it was earned at.

Every ingredient page states a studied dose range — what human research actually used — separately from any dose a real product might carry. A high grade at 500 mg says nothing about a product carrying 50 mg.

“Fairy dusting” — including an ingredient at a fraction of its studied dose so it can appear on a label without meaningfully contributing — is the most common way a legitimate evidence grade gets borrowed for a formula that doesn't deserve it. We treat studied dose as part of the grade, not a footnote: check the dose transparency breakdown in Ingredient count vs. studied dose, and check any ingredient's own studied range on its library page.

FAQ

Common questions about the standard.

What does an evidence grade mean on this site?

A grade from A to Emerging is our own conservative reading of the published human research behind a single ingredient, for the specific claim we're discussing — not a product claim, a promise of effect, or a regulatory approval.

Why doesn't any ingredient in the library have a Grade A yet?

A is reserved for multiple independent human trials, in the right population, with a consistent effect and no safety flags — a bar nothing in our current library clears. Right now the library tops out at Grade B (11 ingredients), with most entries at C or Emerging.

What does "Graded Out" mean?

Graded Out is its own evidence status, not just a low grade. It means we researched an ingredient to the same standard as everything else and it actively failed that standard — either the dominant evidence is a failed replication or a null result on independent review, or a safety signal vetoes it regardless of how the efficacy data reads. It doesn't sit on the A–Emerging strength scale at all. DMAE is the clearest example: a poorly substantiated mechanism, no adequate positive human data in healthy adults, and an animal developmental-toxicity signal.

What's the difference between a studied dose and a label dose?

A studied dose is the amount used in the actual research behind an ingredient. A label dose is what a product actually delivers per serving. If the label dose is well below the studied dose, the ingredient's evidence grade doesn't transfer to the product — that's why every ingredient page states a studied dose range, not a recommendation.

Do grades change over time?

Yes. Each ingredient page carries an updated date, and a grade is revisited as new trials, meta-analyses, or safety data appear — it isn't a one-time label.

See the standard applied to every ingredient in the Evidence Explorer, read the full Ingredient Library, or see how grading connects to what we will and won't claim in the Claims Policy.