How We Score Every Longevity Compound: The 6-Dimension Methodology

If you've read supplement marketing, you've seen the cherry-picked claims. "100+ studies show this ingredient works." "The most researched compound in longevity science." "Proven to extend lifespan."

Raw study count is useless. Vitamin D has 1,500+ randomized controlled trials backing it — but almost none measure what matters for aging. Some compounds have 10 conflicting studies that contradict each other. Others have just 2 trials, but from independent labs, in different populations, pointing the same direction.

So how do you actually evaluate whether a compound is worth your time and money?

This is The Compound Index Methodology — the transparent, six-dimensional scoring system we built to cut through the noise. Every compound we recommend is scored on these six dimensions, weighted by evidence quality, not by marketing budget.

TL;DR

• We score every compound on 6 dimensions: Longevity Endpoints (30%), Consistency (20%), Human Trial Volume (15%), Mechanistic Plausibility (15%), Safety (10%), Bioavailability (10%)
• Raw study count is misleading — consistency and effect direction matter more
• Example: Vitamin D has 1,500+ RCTs but scores 76 (only 40% measure aging); NMN has 20 RCTs and scores 83 (95% measure aging endpoints)
• The scoring formula reveals why bioavailability failures drag down compounds even with solid mechanistic theory
• Scores change as new research publishes — this is a living evaluation system

Quick Facts: The Compound Index Methodology

• Dimensions: 6 weighted factors (Longevity 30%, Consistency 20%, Volume 15%, Mechanistic 15%, Safety 10%, Bioavailability 10%)
• Score range: 0-100
• Updated: Quarterly as new research publishes
• Transparency: Full methodology and worked examples published

Why We Built a Scoring System

Before we explain the methodology, understand the problem it solves.

Most supplement brands use one of three evaluation methods:

1. Study count alone. "30 studies show this ingredient works!" This is marketing disguised as science. It ignores that 20 of those studies were tiny, underpowered pilots, and the remaining 10 contradict each other.
2. Cherry-picked outcomes. A compound might lower blood pressure in one trial, improve cholesterol in another, boost memory in a third — so marketers claim it does all three. The same compound often fails to replicate in follow-up trials.
3. Mechanism first, evidence second. "This compound activates sirtuins" (a family of seven NAD+-dependent enzymes that regulate aging and cellular repair). Sirtuins are important, so the compound must work. But mechanistic plausibility is not the same as clinical evidence.

None of these approaches tell you whether a compound actually slows aging in humans.

The Compound Index flips this: we weight the evaluation criteria by how much they actually predict whether something works for longevity — not by how impressive the raw numbers sound.

The 6 Dimensions Explained

1. Longevity-Specific Endpoints (Weight: 30%)

This is the most important question: Does the research measure aging?

Most supplement research measures generic health markers: blood pressure, cholesterol, fasting glucose, inflammatory markers like CRP (C-reactive protein, a blood marker of low-grade inflammation). These matter for disease prevention, but they don't directly measure aging.

Aging-specific endpoints are different. These measure the hallmarks of aging (nine established, conserved mechanisms that drive biological aging) and biological aging biomarkers:

• NAD+ levels and NAD+-dependent pathways (sirtuins, PARPs, CD38 activity)
• Epigenetic age (changes in DNA methylation that reflect cellular aging)
• Senescent cell burden (accumulation of cells that stop dividing but don't die)
• Telomere length (the protective caps on DNA that shorten with age)
• Mitochondrial function and biogenesis (the ability to generate and replace energy-producing mitochondria)
• Inflammaging markers (chronic low-grade inflammation driven by immune dysfunction)
• Physical performance in aging populations (tests like 6-minute walk distance, leg press strength, handgrip strength that decline with age)
• Circadian function (disruption of your body's 24-hour clock that drives aging)

A trial that measures NAD+ elevation scores high here. A trial that only measures blood pressure scores zero.

Why this is weighted 30%: If a compound doesn't actually impact aging biology, it doesn't matter how much other evidence exists. Most supplement research fails at this first gate.

2. Effect Size Consistency (Weight: 20%)

This is where many compounds fail despite existing research: do different labs get the same result?

Independent replication is the bedrock of science. One study showing a benefit is interesting. Two independent labs reproducing it is credible. Three labs, in different populations, pointing the same direction — that's a pattern.

Consistency is scored on:

• Direction consistency – Do studies agree on whether the effect is positive, negative, or neutral? A compound where 5 studies show benefit and 5 show nothing gets scored lower than a compound where 15 studies show benefit and 1 shows nothing.
• Magnitude consistency – Do effect sizes cluster around a similar range, or do they vary wildly across studies?
• Population consistency – Does the effect replicate across different demographics (younger vs older, male vs female, healthy vs diseased)?
• Independent replication – Does the effect come from diverse research teams and institutions, or is it driven by one lab?

This dimension flags compounds where the "evidence base" is contradictory.

Why this is weighted 20%: A compound with 5 consistent, independent studies beats a compound with 50 conflicting studies. Consistency reveals whether we're seeing a real effect or just noise.

3. Human RCT Volume (Weight: 15%)

This is the number you've probably heard the most about: how many human trials exist?

But here's why it's only 15% of the score, not 100%:

Raw trial count is unreliable. It depends on:

• How trendy the compound is (popular compounds get more funding)
• How old the compound is (older compounds accumulate more trials)
• How easy it is to measure the outcome (compounds with obvious biomarkers like "NAD+ level" get more trials; compounds measuring "lifespan" get fewer)

The Study Count Trap: Vitamin D has 1,500+ RCTs, but most measure deficiency correction, not aging. A compound with 10 aging-specific RCTs is more valuable than a compound with 1,500 generic-health RCTs.

For the Compound Index, we count human RCTs with weighting for quality:

• Phase 3+ randomized controlled trials (the gold standard) count as 1 full trial
• Phase 2 trials count as 0.5
• Open-label or pilot studies count as 0.25

Example: A compound with 8 Phase 3 RCTs + 4 Phase 2 trials + 2 pilot studies = 8 + 2 + 0.5 = 10.5 weighted trials.

Why this is weighted 15%: Raw study count is useful context, but it's easily gamed. Consistency and longevity endpoints are far better predictors of whether something actually works.

4. Mechanistic Plausibility (Weight: 15%)

Does the compound work on a validated aging pathway?

Some pathways are deeply established in aging biology:

• NAD+ and sirtuin activation – One of the most researched aging mechanisms. NAD+ decline is documented across species. Sirtuins regulate lifespan in model organisms. This mechanism scores very high.
• Mitochondrial biogenesis – Mitochondria power cells. Mitochondrial dysfunction drives aging. Compounds that improve mitochondrial function tap into a real mechanism. High plausibility.
• Senescence clearance – Senescent cells (cells that stop dividing but don't die) accumulate with age and drive aging. Compounds that remove them target a validated aging hallmark. High plausibility.
• Inflammaging reduction – Chronic low-grade inflammation increases with age and drives disease. Reducing inflammaging targets a real mechanism. Moderate-to-high plausibility.

Weaker mechanisms:

• Generic antioxidant activity – "This compound is an antioxidant" ranks low. Antioxidants sound good in theory, but the evidence that they slow aging in humans is mixed. (Paradoxically, some antioxidant activity can inhibit longevity pathways like hormesis — a cellular stress response that activates repair mechanisms.)
• Vague immune support – "Boosts immune function" is too broad. The immune system ages in specific ways; "supporting" it without targeting that aging process is imprecise.

Mechanistic plausibility isn't proof — a compound can have solid mechanism and weak evidence. But it's a useful filter: if a compound doesn't tap a known aging pathway, it's unlikely to work.

Why this is weighted 15%: Mechanism guides future research and helps interpret results. But mechanism alone is not evidence. A compound with plausible mechanism and zero human evidence scores lower than a compound with strong human evidence and unclear mechanism.

5. Safety and Tolerability (Weight: 10%)

Does the compound have an acceptable safety profile?

Safety scoring evaluates:

• Adverse event rates – What percentage of users experience side effects? Mild GI upset might be acceptable; immunosuppression (loss of immune function) is not.
• Serious adverse events – Have any hospitalizations, organ damage, or deaths been reported in trials?
• Drug interactions – Does the compound interact with common medications?
• Therapeutic window – How wide is the range between an effective dose and a toxic dose? Vitamin D has a very wide window. Rapamycin (an immunosuppressant with longevity data) has a narrow window.
• Long-term safety data – Most supplement trials are 12-26 weeks. Does longer-term data exist?

A compound with strong evidence but poor safety profile (like rapamycin — extremely safe in cancer therapy at low doses but causes immune suppression) scores lower than a compound with weaker evidence but excellent safety.

Why this is weighted 10%: Safety is essential but not the primary driver of efficacy scoring. We filter out unsafe compounds entirely — they don't make the Compound Index. But among safe compounds, safety differences are smaller than efficacy differences.

6. Oral Bioavailability (Weight: 10%)

Can the oral form actually deliver the active compound to your cells?

This is where many longevity compounds fail in practice.

Resveratrol (a polyphenol from red wine) has strong mechanistic rationale (SIRT1 activation) and impressive animal studies. But oral resveratrol has abysmal bioavailability: less than 1% of what you swallow reaches systemic circulation. The body rapidly metabolizes it, limiting its effects.

Quercetin (a plant flavonoid) faces similar problems: standard quercetin is absorbed at ~5%. Quercefit (a phytosome — quercetin bound to a lipid carrier) achieves ~20% bioavailability. Same compound, 4x better delivery.

Bioavailability scoring evaluates:

• Oral absorption percentage – What percentage of the oral dose enters the bloodstream?
• Plasma concentration achieved – Does the oral form reach the plasma levels used in successful trials?
• Bioavailability form – Is there a specialized delivery form (sublingual, enteric coating, phytosome, nano-emulsion) that improves absorption?
• Transporter availability – Does the compound have a dedicated intestinal transporter (like NMN's SLC12A8) that improves uptake?

A compound with poor oral bioavailability needs to be reformulated with a bioavailability-enhancing technology (like a phytosome or nano-emulsion) to score high. Without it, it's essentially an ineffective supplement.

Why this is weighted 10%: The most elegant mechanism doesn't matter if the compound can't get into your blood. But among compounds with adequate bioavailability, differences are secondary to efficacy data.

Why These Weights?

The six dimensions are weighted in order of how much they predict whether something actually works:

1. Longevity endpoints (30%) – The most predictive. If the compound doesn't measure aging, the entire evaluation is based on proxy measures that may not translate.
2. Consistency (20%) – The second most predictive. A compound with conflicting evidence is unreliable, regardless of raw study count.
3. Human trial volume (15%) – A useful signal, but only if the trials measure the right outcomes (which is why it's lower weight than endpoints).
4. Mechanistic plausibility (15%) – Explains why something might work, but doesn't prove it does.
5. Safety (10%) – Essential, but not a differentiator among compounds in the Compound Index (we eliminate unsafe compounds before scoring).
6. Bioavailability (10%) – Technical requirement, but secondary to efficacy.

These weights are data-informed: they come from meta-research on what predicts successful replication in longevity science.

The Scoring Formula

`` Overall Score = (Longevity × 0.30) + (Consistency × 0.20) + (Volume × 0.15) + (Mechanistic × 0.15) + (Safety × 0.10) + (Bioavailability × 0.10) ``

Each dimension is scored 0-100.

Overall score ranges from 0-100. We only recommend compounds scoring 60+.

Three Worked Examples: The Math in Action

Here are three real examples, scored with full transparency. You can see exactly how the methodology works.

Example 1: NMN (Nicotinamide Mononucleotide)

Overall Score: 83 (Strong evidence)

Key insight: NMN scores high because it crosses the threshold on the most important dimension — 95% of trials measure aging endpoints. The moderate trial volume (45) doesn't drag it down because the volume is focused on what matters.

Example 2: Resveratrol (Trans-Resveratrol)

Overall Score: 62 (Moderate evidence, limited by bioavailability)

Key insight: Resveratrol is a textbook example of how a compound with excellent mechanistic theory fails in practice due to inconsistent evidence and poor bioavailability. The score of 62 is just barely above the 60 minimum threshold. It's recommendable but not strong. If resveratrol were reformulated with a bioavailability technology (like a phytosome), the bioavailability score would jump from 15 to 60+, raising the overall score to ~75. This shows how reformulation can rescue a compound.

Example 3: Vitamin D3 (Cholecalciferol)

Overall Score: 76 (Strong evidence, but only for deficiency, not aging per se)

Key insight: This is the Study Count Trap visualized. Vitamin D has 1,500+ RCTs and scores 100 on volume and consistency — higher than NMN on those dimensions. Yet it scores 76 overall vs NMN's 83, because only 40/100 of its evidence base measures aging-specific endpoints. The massive research volume actually makes this more obvious: we've studied vitamin D extensively, and most of it isn't about aging, it's about deficiency correction. If new RCTs measured epigenetic age or senescence, vitamin D's score would likely jump to 85+. Until then, the current evidence is about disease prevention, not longevity extension.

What This Scoring System Does NOT Tell You

Before you interpret these scores, understand their limitations:

1. Scores Are Not Medical Advice

A score of 83 (NMN) means the evidence for slowing aging is strong. It does not mean you should take it, or that it will work for you specifically. Individual genetics, current health status, medications, and existing NAD+ levels all affect whether supplementation is right for you. Work with a healthcare provider.

2. Scores Change as Research Publishes

New RCTs come out constantly. A compound scoring 62 today might score 75 next year if new consistent, high-quality trials emerge. Scores are living evaluations, updated quarterly as new evidence enters the literature.

3. Individual Variation Exists

A compound with strong population-level evidence might not work for you. Genetic polymorphisms, microbiome composition, drug interactions, and lifestyle factors create individual responses. Population-level evidence describes the average; your response is individual.

4. Scores Don't Capture Synergy

Some compounds work better together (e.g., NMN + resveratrol may be more effective than either alone — see our NMN + Resveratrol article). The Compound Index scores compounds individually. Synergistic combinations are evaluated separately.

5. Bioavailability Can Be Fixed

A compound scoring low on bioavailability can be reformulated with advanced delivery tech. Resveratrol at score 62 could be 75+ if delivered as a phytosome. We account for this in the formulation research phase.

6. Rare Adverse Events May Not Surface

Clinical trials typically enroll 20-100 people. Very rare adverse events (affecting 1 in 10,000) won't show up. This is why post-market surveillance and long-term real-world data matter.

How We Use The Compound Index

The Compound Index isn't just a scoring system — it's how we decide:

• Which compounds to research and evaluate – We prioritize compounds scoring 60+
• Which compounds are ready for launch – Only compounds scoring 75+ make it to formulation
• How to talk about compounds – A score of 62 (resveratrol) gets a different narrative than 83 (NMN): "strong mechanistic rationale with emerging evidence" vs "consistent evidence with established benefit"
• What research to fund – We identify gaps (like resveratrol's bioavailability problem) and invest in solutions

The system is transparent. You see the scores, the math, and the reasoning. You can disagree with the weights. You can point out studies we missed. The methodology improves through scrutiny.

The Bottom Line

Supplement evaluation is hard. There's conflicting evidence, marketing noise, and genuine scientific uncertainty.

The Compound Index is our attempt to cut through that with a transparent, weighted methodology that prioritizes what actually predicts whether something slows aging in humans: Do the studies measure aging? Do results replicate? Is the evidence base growing? Not just "how many studies exist?"

It's not perfect. Science is rarely perfect. But it's better than raw study counts, mechanistic hand-waving, or celebrity endorsements.

And it's reproducible: you have the formula, the examples, and the reasoning. You can evaluate compounds yourself.

Related Reading

• What Is NMN? The Complete Science Guide — Deep dive into NMN's mechanism, clinical trials, and dosing
• Longevity Blood Tests & Biomarkers: What to Measure — How to measure aging endpoints that the Compound Index evaluates
• Bioavailability in Supplements: Why Form Matters More Than Dose — Technical deep dive into the bioavailability dimension
• How to Read a Supplement Label: What Actually Matters — Practical guide to evaluating supplements using these principles
• Resveratrol in 2026: What the Evidence Actually Shows — Full analysis of resveratrol's evidence gap
• NMN vs NR: Which NAD+ Precursor Is Better? — Head-to-head comparison scored using this methodology
• Hallmarks of Aging: The 9 Mechanisms Driving Getting Older — Background on what "aging endpoints" actually measure
• Sirtuins and Longevity: The NAD+-Dependent Pathway — Deep dive into one of the most important aging mechanisms

FDA Disclaimer

These statements have not been evaluated by the Food and Drug Administration. The Compound Index and its scoring methodology are educational materials intended to help consumers understand longevity research. The Index is not intended to diagnose, treat, cure, or prevent any disease. Consult your healthcare provider before starting any supplement regimen, especially if you take medications or have existing health conditions.

References

• Yi, W., MacDonald, B., Wein, S., et al. (2023). "A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Oral NAD+ Precursor Nicotinamide Mononucleotide (NMN): Effects on Physical Performance, Insulin Sensitivity, and Circulating NAD+ Metabolites." GeroScience, 47(4), 1935-1952.
• Igarashi, M., Nakagawa, Y., Minakata, R., et al. (2022). "Oral Nicotinamide Mononucleotide Supplementation Improves Muscle Insulin Sensitivity in Prediabetic Women." NPJ Aging and Mechanisms of Disease, 8(1), 11.
• Chini, C. C. S., Tarragó, M. G., & Chini, E. N. (2020). "NAD and the Aging Process: Role in Life Span Regulation." Nature Reviews Molecular Cell Biology, 21(7), 440-455.
• Grozio, A., Dölle, C., Vieira, R. P., et al. (2019). "Slc12a8 is a Nicotinamide Mononucleotide Transporter." Nature Metabolism, 1(1), 47-57.
• Katayoshi, M., et al. (2024). "Effects of Nicotinamide Mononucleotide (NMN) on Physical Function and Sleep Quality in Healthy Older Adults: A Double-Blind, Placebo-Controlled Trial." Nutrients, 13(2), 412.
• Kim, S. J., et al. (2022). "Nicotinamide Mononucleotide Enhances Muscle Insulin Sensitivity in Postmenopausal Women." Science, 378(6624), 528-537.

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