T-axis Adjuvant Urate-Target Mapping¶
The relevant gout weakness is the possibility that an androgen-active material could independently alter urate production or transport. The available evidence does not establish which material, if any, improves both axes in the same exposure.
COMP-015 cannot answer that question. It mixed purified compounds, botanical
extracts, related but non-identical quassinoids, animal studies, cell assays,
and a human safety table in one ordinal matrix. Its rankings,
GOUT-FAVORABLE verdicts, evidence-cell counts, exposure estimates, and
H-AN-02 interpretation are invalid and must not guide candidate selection.
The non-runnable retirement record is in the
COMP-015 directory.
Source-specific evidence that survives¶
| Exact material | Direct evidence | Exposure and claim boundary |
|---|---|---|
| Purified cordycepin | Oral cordycepin at 15, 30, and 60 mg/kg lowered serum urate and renal URAT1 mRNA and protein in hyperuricemic mice (Animal Model; PMID 29422889). | This supports a cordycepin–urate/URAT1 lead in that model. It does not establish human urate efficacy, useful oral exposure, or a simultaneous androgen effect. |
| 70% ethanol Eurycoma longifolia stem extract | The extract changed serum urate and renal transporter measures in hyperuricemic rodents (Animal Model; PMID 31920654). | The result belongs to that extract and cannot be transferred to Physta, purified eurycomanone, purified eurycomanol, or tongkat ali as a class. |
| Isolated E. longifolia quassinoids in the 2019 hURAT1 assay | Eurycomanol-type compounds 4–7 inhibited hURAT1-mediated urate uptake at 50 µM (In Vitro; PMID 31920654). Pure eurycomanone was compound 3 and had comparatively low activity in that assay. | The active compounds 4–7 are not interchangeable with eurycomanone. The assay does not establish oral exposure or in-vivo efficacy. |
| Purified eurycomanol | Oral eurycomanol at 5–20 mg/kg lowered serum urate, increased 24-hour urate clearance, decreased hepatic PRPS expression, and changed renal and intestinal transporter measures in hyperuricemic mice (Animal Model; PMID 34785103). | This is a source-specific eurycomanol lead. It does not establish direct PRPS binding, human efficacy, a Physta mechanism, or an eurycomanone effect. |
| Physta hot-water extract | In a 12-week randomized study of 105 men, serum urate appeared in the safety laboratory table. Week-12 comparisons with placebo were null at 100 mg/day (p=0.88) and 200 mg/day (p=0.52) (Clinical Trial — null urate outcome; PMC8254464). |
Within-arm changes are not evidence of urate efficacy. The trial supplies no mechanistic bridge to the animal extract or purified-quassinoid studies. |
Decision boundary¶
The source-specific leads remain worth testing, but they are unranked. A candidate advances only after its identity and exposure are measured and its androgen and urate effects are tested independently in a matched design. The wet-lab gate is validation §2.8; the underlying untested connection is preserved as a Research Conjecture on androgen-natural-modulation.md.