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SupplementScience

Evidence Grading System — A+ through F

What the Grades Mean

Every health claim on every ingredient page receives an independent evidence grade from A+ (strongest) to F (insufficient). Here is what each tier represents:

A range
A+ / A / A-
Strong

Multiple meta-analyses or systematic reviews with consistent findings.

B range
B+ / B / B-
Good

Multiple RCTs with positive results.

C range
C+ / C / C-
Mixed

Limited RCTs or observational data only.

D range
D+ / D / D-
Weak

Preliminary human data or pilot studies.

F
 
Insufficient

No human evidence or contradicted by research.

Grading Criteria

The table below details the specific evidence threshold for each grade:

GradeCriteria
A+Multiple concordant meta-analyses or Cochrane reviews; large clinically meaningful effect size; consistent across diverse populations
AAt least 1 high-quality meta-analysis with significant results + 3 or more RCTs confirming
A-Meta-analysis present but with moderate heterogeneity, OR 5+ concordant RCTs
B+3+ high-quality RCTs with consistent positive results
B2-3 RCTs with positive results; moderate sample sizes (n>50 each)
B-1-2 RCTs positive, but small samples or mixed effect sizes
C+1 positive RCT + supporting observational data
CMultiple observational studies with consistent results; no RCTs
C-Limited observational data; small cohorts
D+Pilot RCT or single small observational study with positive signal
DCase series, open-label trials, or epidemiological correlation only
D-Single case report or very preliminary human data
FNo human evidence; animal/in-vitro only; or contradicted by evidence

Study Type Hierarchy

We weight evidence according to the established research hierarchy. Higher-ranked study types carry more influence on the final grade:

  1. Systematic reviews and meta-analyses — highest level of evidence
  2. Randomized controlled trials (RCTs) — gold standard individual studies
  3. Observational studies — cohort, cross-sectional
  4. Case series and case reports — descriptive evidence
  5. Expert opinion and mechanistic reasoning — lowest level

Grade Modifiers

Within each letter grade, the + and - modifiers reflect additional quality considerations:

+ modifier (upgrade)

  • Results replicated across 2+ populations
  • Clinically meaningful effect size
  • High-quality study designs with low risk of bias

- modifier (downgrade)

  • Conflicting results across studies
  • Narrow population (e.g., only elderly or only athletes)
  • Industry-funded studies only
  • High heterogeneity in meta-analyses

Base letter (no modifier)

Standard assessment without significant upgrading or downgrading factors.

Our Hard Rules

  • When in doubt, grade DOWN — an honest D+ on a hyped supplement builds more authority than an inflated B
  • No animal-only or in-vitro evidence grades above D
  • F is reserved for claims actively contradicted by evidence or with zero human data
  • Grades are reviewed when new meta-analyses or large RCTs publish
  • All PubMed citations are verified — we never fabricate references

Worked Example: Magnesium for Sleep

To illustrate how the grading system works in practice, here is a step-by-step walkthrough for a specific health claim:

Claim:"Reduces sleep onset latency"
Evidence:2022 meta-analysis (8 RCTs, n=2,132) + individual RCTs
Effect:Average 17-minute reduction in sleep onset latency
Population:Primarily adults with mild insomnia or magnesium deficiency
Grade assigned:A- — Strong meta-analytic support, but most studies focus on deficient populations; downgraded from A due to population specificity

Relationship to SupplScore

Evidence grades and SupplScore are complementary systems that serve different purposes:

  • SupplScore (0–100) rates the whole ingredient across 4 dimensions: evidence level, safety profile, dose accessibility, and form bioavailability
  • Evidence grades (A–F) rate individual health claims — one ingredient can have different grades for different benefits
  • They complement each other — an ingredient with SupplScore 85 might have A+ claims for some benefits and C claims for others

Update Policy

  • Grades are reviewed when significant new research publishes
  • Changes are reflected in the dateModified timestamp on the ingredient page
  • We track publication of major meta-analyses and Cochrane reviews quarterly