What each letter means.

Replicated The same finding reproduced by a separate research group. A result seen once can be chance or bias; a replicated one is harder to explain away. randomized human trials showing benefit on a qualifying endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score.. A randomized controlled trial People are assigned to the treatment or a comparison by chance, so the groups differ only in what they received. It is the design that can show cause and effect. means real people randomly assigned to treatment or placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received., which is what makes the comparison worth anything. Three kinds of endpoint qualify: a hard clinical outcome such as mortality, major adverse cardiovascular events or fractures; an objectively measured function recorded by an instrument rather than reported by a person, such as dynamometer grip strength, measured VO2max The most oxygen the body can use during all-out exercise, a standard measure of aerobic fitness., or polysomnography sleep latency; or a validated outcome scale scored by a clinician blinded to treatment, such as the Hamilton or Montgomery-Asberg depression scales or a clinician-assigned mucositis grade, because the person scoring it does not know which treatment the patient received. The effect must replicate across independent research groups. Self-reported and surrogate biomarker A measurable sign in the body, such as a blood test value, used to track a condition or the effect of a treatment. endpoints cap a record at Grade B however large or well-run the trial, and observational Research that watches what people already do rather than assigning a treatment. It can show that two things travel together, not that one causes the other. data may inform context but never carries a grade.

Creatine Monohydrate

At least one well-designed human randomized trial showing a meaningful effect, supported by further trials rather than standing alone. These are typically trials on validated biomarkers, HbA1c A blood test that reflects average blood sugar over the previous two to three months., LDL Low-density lipoprotein cholesterol, the cholesterol fraction most closely tied to plaque in the arteries., blood pressure, which move in the right direction without yet being the clinical outcome anyone cares about. The form and the dose must be the ones the trials used and must be obtainable, because a grade attaches to what was studied, not to the ingredient name. A biomarker qualifies only when it is an established stand-in for a clinical outcome, such as HbA1c, LDL, blood pressure or bone density; a blood level of the supplement itself, or of what the body makes from it, shows that it was absorbed and qualifies for nothing above C. B is where the endpoint ceiling bites: a surrogate or self-reported endpoint caps a record here regardless of trial size or quality.

EGCG, Zinc, Amla, Omega-3

Human randomized evidence exists but is thin: small trials, mixed results, a single positive trial nobody has independently repeated, or a replication that failed. Grade C moves in both directions: an entry rises to B when a good trial replicates, and falls from B when a closer look finds the supporting trials never tested the thing being claimed. Nicotinamide riboside was Grade B until August 2026 and is Grade C today for exactly that reason.

NR, NMN, NAC, TMG

No human RCT Randomized controlled trial: people are assigned to the treatment or a comparison by chance, so the groups differ only in what they received. It is the design that can show cause and effect. demonstrates benefit. Entries reach D by one of two routes. Route 1 No human randomized trial has been run, so the record rests on animal or mechanistic evidence only. One of the two routes to the lowest letter on EBL's scale., no human randomized trial has been run; mechanistic or animal data only, which fails in more than 90% of drug development transitions. Route 2 Human randomized trials have been run and did not show benefit on the stated outcome. One of the two routes to the lowest letter on EBL's scale.. Human randomized trials have been run and did not show benefit on the stated endpoint. Route 2 records report one of two findings, and they are not the same news. Where the trial was simply null, the record carries the TESTED, NO BENEFIT badge. Where the treated arm did worse than placebo on the stated endpoint, the record carries the TESTED, HARM FOUND badge. Both badges name the endpoint, the population, and the certainty of the finding. The routes are not equivalent either: a Route 1 entry may still turn out to work once someone tests it. A Route 2 entry has been tested and did not.

15 of the 25 are Route 1, where no qualifying human trial has been run. 9 are Route 2, where trials were run and did not show benefit. 1 is graded by use, and declares a route on each graded use rather than one route for the record.

C60, NAD+ Nicotinamide adenine dinucleotide, a molecule cells use in energy metabolism. Its level falls with age in some tissues., Boron, Niacin

The five tiers of evidence quality

The letters above grade what a supplement has been shown to do. This grades the studies themselves. A letter can only be as good as the design underneath it.

1. Tier 1 Systematic Reviews A review that searches for every study on a question using a method set in advance, then assesses them together. & Meta-analyses A study that pools the numbers from several trials into one combined estimate. Strongest · EBL Grade A/B

   The highest level of clinical evidence. Combines data from multiple independent randomized controlled trials (RCTs) using pre-registered protocols. Hard endpoints An outcome that matters directly to a person and is counted without judgment, such as death, heart attack, stroke or fracture.: mortality, cardiovascular events, hospitalization. EBL grades A and B are built on Tier 1 and Tier 2 evidence only.

2. Tier 2 Randomized Controlled Trials (RCTs) Grade A/B eligible

   People are randomly assigned to treatment or placebo, the design that isolates cause and effect. A well-designed RCT with biomarker endpoints, supported by further trials, can earn Grade B; a single positive trial nobody has repeated is Grade C. Multiple independent RCTs with hard endpoints can earn Grade A. This is the minimum bar for any grade above D.

3. Tier 3 Observational & Cohort Studies An observational study that follows a group of people over time and compares what happens to them. Context only · never raises a grade

   Follows groups of people over time without any intervention. Can show association but not causation. Observational data never earns a letter above D on this site, at any tier: where no randomized human trial exists the record is Grade D by Route 1, however strong the mechanism or the cohort signal. Tier 3 evidence is published as context beside a letter, never as the basis for one.

4. Tier 4 Case Reports & Expert Opinion Never enters a grade

   Individual patient reports or clinical opinion, even from respected authorities. Highly susceptible to selection bias and confirmation bias. EBL does not cite expert opinion as evidence for any grade. If a supplement's primary evidence is a recommendation, it does not appear on this platform.

5. Tier 5 Animal & In-vitro Studies Tier 5 · never graded

   Mice, cultured cells, and petri dishes. Biologically interesting but mice are not humans, most longevity findings in rodents do not replicate in human trials. EBL labels Tier 5 data wherever it appears and never uses it to support a grade. If a supplement's only evidence is a mouse study, it grades D.