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How We Evaluate

Our position

Most supplement guidance fails in one of two ways: it's either uncritical cheerleading dressed up in scientific language, or reflexive dismissal that ignores a substantial body of legitimate clinical evidence. Simplemetry tries to occupy the narrow, less comfortable middle — taking the research seriously without pretending the field is cleaner than it is.

We make two distinct types of judgment on this site: does a supplement work, and which product is worth buying. These are separate questions with separate criteria, and we keep them separate.

Part 1: Evidence standards — does a supplement belong on the list?

The hierarchy we follow

We rank evidence in descending order of reliability:

Systematic reviews and meta-analyses are our primary reference point. A single positive RCT proves nothing on its own — it may be underpowered, unreplicated, or an outlier. When multiple independent trials are pooled and the effect survives, we take it seriously. Where possible, we look for trial-sequential analyses that confirm adequate statistical power has been reached across the evidence base.

Randomized controlled trials are the foundation. We prioritize large, multi-center, double-blind, placebo-controlled designs. A supplement supported by one small industry-sponsored trial does not meet our threshold for Tier 1. We note sample sizes, trial duration, and outcome measures — a 6-week trial measuring a biomarker proxy is not equivalent to a 3-year trial measuring clinical outcomes.

Mechanistic and animal data can inform plausibility, but cannot justify a recommendation on their own. A supplement must demonstrate benefit in humans to appear on this site.

What disqualifies a supplement

Poor replication. If a promising early trial has not been replicated by independent researchers, the supplement goes into Tier 2 at best, or does not appear at all.

Surrogate-only endpoints. Improving a blood marker is not the same as improving health. We note when evidence is limited to biomarker changes versus clinical outcomes.

Industry capture. We explicitly flag when the majority of a supplement's evidence base is funded by the manufacturer or a trade body with a financial stake in the result. Collagen peptides for skin is the canonical example — the effect sizes in industry-funded trials are systematically larger than in independent replications. This doesn't disqualify a supplement, but it adjusts our confidence level.

Dose mismatch. A supplement may have legitimate evidence at one dose and be sold at a fraction of that dose. We reference the doses used in the clinical trials that produced the results, not the doses that minimize manufacturing cost.

Tier 1 vs Tier 2: what the distinction means

Tier 1 — Essential Daily Stack contains supplements where:

  • Evidence comes from multiple independent RCTs or meta-analyses
  • Effect sizes are clinically meaningful, not just statistically significant
  • The safety profile in healthy adults is well-characterized
  • The majority of healthy adults in the target demographic have a plausible deficiency or suboptimal intake that supplementation can address

Tier 2 — Consider Adding contains supplements where:

  • Evidence is promising but less consistent, or the population benefiting is narrower
  • The supplement addresses a specific goal (stress resilience, cognitive performance, joint protection) rather than a widespread baseline gap
  • Benefits may depend on individual circumstances that we cannot assess universally

A supplement's tier is not fixed — the same compound can be a universal recommendation for one demographic and unnecessary (or potentially harmful) for another. Vitamin B12 sits in Tier 2 for omnivore adults under 50, where deficiency is rare, but moves to Tier 1 for vegans, adults over 50, and regular PPI or metformin users, where absorption is meaningfully impaired. Iron is Tier 2 with a mandatory ferritin test requirement — it causes harm in replete individuals, but addresses a documented deficiency in 17–30% of premenopausal women. Folate is Tier 2 for the general population but a USPSTF Grade A recommendation for all women of childbearing age regardless of pregnancy intent, given that 50% of pregnancies are unplanned and the neural tube closes before most pregnancies are detected. We document these conditional promotions and their rationale explicitly on each supplement page rather than treating a single tier assignment as the whole answer.

What we do not recommend

We do not recommend supplements where the primary evidence comes from:

  • In-vitro or cell culture studies only
  • Animal models without human RCT follow-up
  • Observational epidemiology without mechanistic plausibility and RCT support
  • A single industry-sponsored trial with no independent replication

Notable exclusions this rules out: collagen peptides for most claims, many nootropic stacks, testosterone-boosting blends, most "fat burners," and the majority of branded proprietary formulas where the individual ingredient doses are undisclosed.

Part 2: Product quality criteria — which product is worth buying

Evidence that a supplement works tells you nothing about whether a specific product delivers what's on the label. Third-party testing consistently finds that supplement products — even from major brands — frequently underdose active ingredients, contain unlisted contaminants, or use inferior forms with poor bioavailability.

Our product evaluation follows six criteria:

1. Active form, not just active ingredient

Many supplements are sold in forms with poor bioavailability when better-absorbed alternatives exist at similar cost. We specify the required form for each recommendation:

  • Magnesium as glycinate or bisglycinate, not oxide (oxide is ~4% absorbed vs ~80% for glycinate)
  • Vitamin D as D3 (cholecalciferol), not D2 (ergocalciferol) — D3 raises serum 25(OH)D 2–3× more effectively
  • B12 as methylcobalamin, not cyanocobalamin where relevant; folate as L-5-MTHF rather than folic acid, bypassing MTHFR polymorphisms
  • CoQ10 as ubiquinol rather than ubiquinone for adults over 40, where conversion efficiency declines
  • Iron as ferrous bisglycinate, not ferrous sulfate — equivalent efficacy with significantly fewer gastrointestinal side effects
  • Omega-3 in triglyceride (TG) or re-esterified triglyceride (rTG) form, not ethyl ester (EE), which has 50% lower bioavailability in the fasted state

2. Standardized, certified raw materials

Where a patented or certified ingredient form has a clinical evidence base attached to it, we specify it. These certifications are not marketing — they represent consistent composition across batches:

  • Creatine: Creapure® (99.99% pure creatine monohydrate, manufactured in Germany, tested for banned substances)
  • CoQ10: Kaneka Q10® or Kaneka QH® (the forms used in the majority of clinical trials)
  • L-Theanine: Suntheanine® (pure L-isomer; generic products may contain the less active D-isomer)
  • Lutein: FloraGLO® Lutein (the form used in AREDS2 and most major clinical trials)
  • K2: K2VITAL® DELTA (stabilized MK-7; unstabilized MK-7 degrades rapidly)
  • Collagen: UC-II® (undenatured type II collagen, 40 mg/day — works via oral immune tolerance, a different mechanism from hydrolyzed peptides)

3. Third-party testing and purity verification

We look for products that carry verification from independent testing bodies: NSF International, USP, Informed Sport, or IFOS (specifically for omega-3). For omega-3 products, we reference IFOS 5-star certification and a TOTOX score below 26 as minimum quality bars for oxidation.

4. Dose alignment with clinical evidence

We check that the amount of active ingredient per serving matches the doses used in the trials we cite. A product using a certified raw material but at 20% of the clinical dose is not a valid product recommendation.

5. Absence of unnecessary additives

We avoid products with proprietary blends (which obscure individual ingredient doses), excessive fillers, titanium dioxide, artificial dyes, or high-dose synthetic vitamins that exceed safe upper limits.

6. Geographic availability and value

We differentiate between EU-preferred and global brands where supply chains, labeling regulations, and import accessibility differ meaningfully.

Affiliate relationships: how they work and what they don't affect

Simplemetry earns a commission when readers purchase through our affiliate links. The brands linked on this site are selected exclusively based on the quality criteria above — they are not paying for placement, and they do not know in advance whether they will be included.

Two things our affiliate relationships do not influence:

  • Whether a supplement is recommended at all. The evidence assessment is conducted independently of any commercial consideration. If berberine has significant drug interaction risks, we say so prominently regardless of whether we earn a commission on berberine sales.
  • Safety information. We display warnings, contraindications, and cycling requirements in full, including for supplements where we link affiliate products.

One thing to be transparent about: we cannot affiliate every supplement we recommend. In some cases — particularly for EU pharmacy products like Dona® glucosamine or Prostaphane® sulforaphane — affiliate programs either do not exist or do not cover our readership geography. We recommend these products anyway.

What this methodology does not solve

We want to be direct about the limits of this approach.

We cannot assess your individual circumstances. The recommendations on this site are designed for healthy adults without diagnosed conditions and not taking prescription medications. If you have a health condition, take any medication (including common ones like statins, warfarin, or metformin, which have documented interactions with several supplements we discuss), or are pregnant, our general recommendations may not apply to you and in some cases may cause harm. We are not a substitute for a clinical assessment.

The evidence base for supplements is genuinely weaker than for pharmaceuticals. Most supplement RCTs are shorter, smaller, and less rigorously conducted than pharmaceutical trials. Where we say "evidence supports," we mean relative to the supplement research landscape — not relative to the standard required for drug approval.

Our recommendations will change. We update this site as new research is published. A supplement that is Tier 1 today may be downgraded if replications fail. We do not have a vested interest in maintaining a recommendation that the evidence no longer supports.

Last reviewed: 2026. If you identify an error in our evidence interpretation or a quality issue with a recommended product, contact us.