Atlas chapter 21 · Immune biomarker

Sanghuang

Sanghuang (traditional medicinal category) / Sanghuangporus (modern genus of particular importance) / Sanghuangporus sanghuang (frequently invoked modern species) / Phellinus linteus (historical research identity under which the controlled human material was labelled). Historical P. linteus-labelled material does not automatically map to modern authenticated S. sanghuang; reassignment must be earned through preserved cultures, vouchers, sequence data or host/provenance evidence.

E3+ for the biomarker proposition+ — Supports the tested propositionR1. Why R1: exactly one research programme currently provides a VERIFIED positive placebo-relative controlled NK-cytotoxicity signal — the 2022 main randomized, double-blind, placebo-controlled trial, in which the 12.5:1 effector-to-target comparison is a genuine between-group comparison. The 2006 Eom programme (randomized, double-blind, placebo-controlled; 62 participants, 31/31; 3.3 g/day Keumsa sangwhang extract; 8 weeks; Jurkat target-cell assay) remains important controlled human evidence. It establishes a statistically significant PRE-VS-POST increase in NK-cytotoxic activity within the active arm with no corresponding change in placebo, and no significant between-group difference in CD56+ NK-cell NUMBER. However, an explicit placebo-relative treatment effect has NOT been verified from the currently recoverable record: no explicit treatment-versus-placebo NK-cytotoxicity test is reported in the recoverable material, and the full text is NOT RECOVERABLE in the present audit. It is therefore NOT classified as a verified positive placebo-relative programme, and it is NOT classified as a negative trial. Atlas rule applied: within-group significance is not a between-group treatment effect. Absence of recoverable evidence is not evidence that the analysis was absent from the inaccessible full text; if the Eom full text is later recovered and establishes a valid explicit between-group effect, replication may be reassessed. The 2022 randomized pilot is a distinct participant cohort but belongs to the same broader Ku/Kang research programme as the main trial (same investigators, same site, same funding stream, main trial powered from pilot variance). Its reported per-protocol analysis did NOT establish a significant between-group NK-cell activity effect: it is null/inconclusive for the narrow between-group NK proposition — neither a positive replication nor proof of no effect. Distinct cohorts within one programme do not constitute independent programme-level replication. Ratio-specificity and multiplicity qualification: NK-cell activity was the prespecified primary outcome of the main trial. Three effector-to-target ratios were analysed and only the 12.5:1 between-group comparison was significant; 25:1 and 50:1 were not. No multiplicity correction across the three ratios is reported in the verified main paper, and whether 12.5:1 specifically was prespecified as the confirmatory ratio is NOT REPORTED. The 12.5:1 placebo-relative result is genuine as reported, but its robustness as the uniquely positive result among multiple tested ratios requires qualification. This is not a basis for inferring the result is false, nor for inferring it would fail a correction that has not been performed. Therefore R2-qualified is not presently earned. This is an evidence-verification downgrade, not evidence that the 2006 result was false.

Proposition / claim: Defined Sanghuang-related preparations labelled Phellinus linteus have produced controlled human signals involving NK-cell cytotoxic activity. The proposition is owned by those specific preparations and by that biomarker; it is not a claim of generalised immune enhancement, infection prevention, cancer benefit, or species-wide S. sanghuang effect.
Evidence owner: Defined P. linteus-labelled / Sanghuang-related preparations
Dominant uncertainty: Two linked uncertainties, neither of which resolves the other. 1. CLINICAL TRANSLATION — does a reproducible NK-cell cytotoxicity change produce any patient-important benefit? A real biomarker movement is not a demonstrated clinical effect. 2. EVIDENCE OWNERSHIP — which authenticated fungal identity and which specific preparation owns each controlled result? Historical labelling and preparation heterogeneity mean the evidence is not yet attributable to one authenticated organism-plus-intervention pair.

Organism: Sanghuang
Tested intervention: Multiple distinct, defined Sanghuang-related preparations labelled Phellinus linteus, each owning its own controlled result: (1) 2006 — Keumsa sangwhang extract, 3.3 g/day, 8 weeks; (2) 2022 pilot — P. linteus extract, 1,000 mg/day or 2,000 mg/day versus placebo, 8 weeks; (3) 2022 main trial — defined fermented P. linteus mycelial extract, 1,000 mg/day, 8 weeks. These preparations are not established as chemically interchangeable and are not a single generic "Sanghuang supplement".
Evidence target: Standardized preparation
Intervention description: Preparation ownership boundary. Cultured mycelium, fruiting body, water extract, alcohol extract, isolated polysaccharide fraction and fermented products may differ chemically and pharmacologically and cannot be assumed equivalent. The 2022 main-trial intervention is specifically described as a fermented P. linteus mycelial extract; the 2006 programme used Keumsa sangwhang extract; the 2022 pilot used a P. linteus extract at two dose levels. Preparation characteristics not reported in the controlling chapter (batch chemistry, marker standardisation, extraction solvent where unstated) are not inferred here. The controlled programmes therefore do not establish equivalence of generic Sanghuang products sold to consumers.
Population: Distinct human programmes, not a single pooled population. 2006: 62 healthy volunteers. 2022 pilot: 30 randomized participants. 2022 main trial: 98 targeted (calculated sample size); 91 actually recruited/randomized (full analysis set 91 — P. linteus 45, placebo 46); 84 per-protocol (P. linteus 41, placebo 43), seven excluded from per-protocol (six with Visit-3 blood sampling not performed, one with compliance <80%). Eligibility criteria, ages and diagnoses beyond these descriptions are not established by the controlling chapter and are not inferred.
Comparator: Placebo. All three programmes are described as randomized, double-blind, placebo-controlled human trials; the 2022 pilot compared 1,000 mg/day and 2,000 mg/day arms against placebo. Placebo composition is not reported and is not inferred.
Outcome: 2006 (62 healthy volunteers, 3.3 g/day Keumsa sangwhang extract, 8 weeks): NK-cell cytotoxic activity against a Jurkat leukemia-cell line increased significantly; NK-cell NUMBER did not increase. 2022 pilot (30 randomized, 1,000 / 2,000 mg/day versus placebo, 8 weeks): the reported per-protocol analysis did NOT establish a significant between-group difference in NK-cell activity. 2022 main trial (98 targeted; 91 randomized / full analysis set; 84 per-protocol; fermented P. linteus mycelial extract 1,000 mg/day, 8 weeks): NK-cell cytotoxicity was tested at several effector-to-target ratios. Positive placebo-relative result at 12.5:1 — active change 5.62 +/- 8.24 versus placebo change 0.95 +/- 8.05, P = .008. Between-group comparisons at 25:1 and 50:1 were NOT significant. Reported secondary immune outcomes, including cytokines, white-cell measures and immunoglobulins, showed no significant placebo-relative improvement. Boundary: these are assay-level biomarker findings. They are not evidence of generalized immune enhancement or of any patient-important clinical outcome.
Evidence maturity (E): E3+ for the biomarker proposition
Direction: + — Supports the tested proposition
Historical flag (H): Not specified at dossier level
Replication (R): R1. Why R1: exactly one research programme currently provides a VERIFIED positive placebo-relative controlled NK-cytotoxicity signal — the 2022 main randomized, double-blind, placebo-controlled trial, in which the 12.5:1 effector-to-target comparison is a genuine between-group comparison. The 2006 Eom programme (randomized, double-blind, placebo-controlled; 62 participants, 31/31; 3.3 g/day Keumsa sangwhang extract; 8 weeks; Jurkat target-cell assay) remains important controlled human evidence. It establishes a statistically significant PRE-VS-POST increase in NK-cytotoxic activity within the active arm with no corresponding change in placebo, and no significant between-group difference in CD56+ NK-cell NUMBER. However, an explicit placebo-relative treatment effect has NOT been verified from the currently recoverable record: no explicit treatment-versus-placebo NK-cytotoxicity test is reported in the recoverable material, and the full text is NOT RECOVERABLE in the present audit. It is therefore NOT classified as a verified positive placebo-relative programme, and it is NOT classified as a negative trial. Atlas rule applied: within-group significance is not a between-group treatment effect. Absence of recoverable evidence is not evidence that the analysis was absent from the inaccessible full text; if the Eom full text is later recovered and establishes a valid explicit between-group effect, replication may be reassessed. The 2022 randomized pilot is a distinct participant cohort but belongs to the same broader Ku/Kang research programme as the main trial (same investigators, same site, same funding stream, main trial powered from pilot variance). Its reported per-protocol analysis did NOT establish a significant between-group NK-cell activity effect: it is null/inconclusive for the narrow between-group NK proposition — neither a positive replication nor proof of no effect. Distinct cohorts within one programme do not constitute independent programme-level replication. Ratio-specificity and multiplicity qualification: NK-cell activity was the prespecified primary outcome of the main trial. Three effector-to-target ratios were analysed and only the 12.5:1 between-group comparison was significant; 25:1 and 50:1 were not. No multiplicity correction across the three ratios is reported in the verified main paper, and whether 12.5:1 specifically was prespecified as the confirmatory ratio is NOT REPORTED. The 12.5:1 placebo-relative result is genuine as reported, but its robustness as the uniquely positive result among multiple tested ratios requires qualification. This is not a basis for inferring the result is false, nor for inferring it would fail a correction that has not been performed. Therefore R2-qualified is not presently earned. This is an evidence-verification downgrade, not evidence that the 2006 result was false.
Claim Gap (CG): CG0-1 — Controlled human studies have reported increased NK-cell cytotoxic activity from defined Sanghuang-related preparations labelled P. linteus. CG1 — Some defined Sanghuang-related preparations influence a measured component of human immune function. THIS IS THE DEFENSIBLE CLAIM CEILING. CG2 — Sanghuang supports immune function. CG3 — Sanghuang boosts immunity. CG4 — Sanghuangporus sanghuang prevents infections and/or cancer by boosting immunity. Each step above CG1 crosses at least one unearned boundary: taxonomic (historical P. linteus label to modern authenticated species), intervention (defined trial preparation to generic product), outcome (NK-cell assay to immune function as a whole), and clinical translation (biomarker to patient-important benefit).
Evidence Transfer Vector: Inflated claim audited: "S. sanghuang supplementation prevents infection by boosting NK-cell immunity". T — Taxon: historical / preparation-specific P. linteus-labelled material → modern S. sanghuang. I — Intervention: defined extracts (Keumsa sangwhang extract; fermented mycelial extract) → generic supplement. O — Outcome: NK-cell cytotoxicity → infection prevention. P — Population: studied participants → general consumers. R — Replication: related heterogeneous controlled programmes → established clinical effect. ETV: T / I / O / P / R
Taxonomic Transfer Confidence: Authenticated modern S. sanghuang → the same authenticated strain/material: HIGH. Historical P. linteus-labelled material → modern S. sanghuang: LOW-VARIABLE, unless preserved material, culture provenance or sequence evidence supports the reassignment. Specific Korean registered historical strains subsequently sequenced and clustering with S. sanghuang: HIGHER for those strains only. Generic "Sanghuang" → S. sanghuang: LOW without authentication. The existence of some successfully reassigned Korean strains does not license reassigning every historical P. linteus study to S. sanghuang.
Intervention Transfer Confidence: Defined preparation → the same sufficiently characterized preparation: potentially higher, conditional on demonstrated equivalence. Defined preparation → generic Sanghuang product: LOW. Cultured mycelium, fruiting body, water extract, alcohol extract, polysaccharide fraction and fermented products may differ chemically and pharmacologically. High TTC does not imply high ITC: correct species identity does not make two preparations the same intervention.
Safety: S1. Randomized human programmes provide direct short-term tolerability information for the tested preparations. The exposure database is limited and heterogeneous across preparations, doses and durations. The 2022 main trial did not identify a major safety signal sufficient to overturn the short-term programme. This does not establish species-wide or long-term safety for Sanghuang products generally.
Conservation: C1/C+. C1 is an Atlas sourcing caution, not a formal global threat classification: wild sourcing under uncertain species identity creates conservation-information uncertainty, because material cannot be reliably attributed to a named taxon. C+ reflects the value of authenticated cultivation and controlled production, which reduces dependence on uncertain wild collection and simultaneously improves research reproducibility.
Resolution zone: RZ-5 → RZ-3
Next best experiment: STAGE ONE — IDENTITY. Authenticate the evidence-owning strain or culture; preserve voucher or culture material; record provenance (host, origin, collection or registration history); use appropriate sequence data; chemically characterize the preparation; archive representative batches. Where historical cultures survive, perform evidence archaeology to determine what the historical P. linteus-labelled material actually was, rather than renaming it by assumption. STAGE TWO — CLINICAL MEANING. Choose a population in which the proposed immune pathway has plausible clinical relevance; use one patient-important primary endpoint; retain NK-cell cytotoxicity as a mechanistic secondary endpoint; test whether biomarker change predicts clinical benefit; where both clinical benefit and NK change occur, investigate mediation rather than assuming it.
Primary references: Eom SY, Zhang YW, Kim NS, et al. Effects of Keumsa Sangwhang (Phellinus linteus) Mushroom Extracts on the Natural Killer Cell Activity in Human. Korean Journal of Food Science and Technology. 2006;38(5):717-719. ROLE: PRIMARY / CONTROLLED HISTORICAL PROGRAMME / WITHIN-GROUP POSITIVE NK-CYTOTOXICITY SIGNAL / PLACEBO-RELATIVE CYTOTOXICITY EFFECT NOT VERIFIED FROM CURRENTLY RECOVERABLE RECORD / REPLICATION GENEALOGY
Ku YH, Kang JH. Efficacy of Phellinus linteus extract on immunity enhancement: A CONSORT-randomized, double-blind, placebo-controlled pilot trial. Medicine (Baltimore). 2022;101(40):e30829. doi:10.1097/MD.0000000000030829. PMID 36221338. ROLE: PRIMARY / CONTROLLED NULL-INCONCLUSIVE / PROGRAMME GENEALOGY
Ku YH, Kang JH, Lee H. Effects of Phellinus linteus extract on immunity improvement: A CONSORT-randomized, double-blinded, placebo-controlled trial. Medicine (Baltimore). 2022;101(34):e30226. doi:10.1097/MD.0000000000030226. PMID 36042633. PMCID PMC9410671. ROLE: GRADE-OWNING PRIMARY / CONTROLLED POSITIVE HUMAN BIOMARKER EVIDENCE
Ku YH, Lee H, Ryu HY, Kang JH. Clinical trial to analyze the effects of oral intake of Phellinus linteus (sanghuang) extract on immune function: a study protocol for a randomized, double-blind controlled trial. Trials. 2021;22:849. doi:10.1186/s13063-021-05740-5. ROLE: PROTOCOL / PRESPECIFICATION / INTERVENTION IDENTITY / PROGRAMME GENEALOGY / ANALYSIS CONTEXT
Han JG, Hyun MW, Kim CS, et al. Species identity of Phellinus linteus (sanghuang) extensively used as a medicinal mushroom in Korea. Journal of Microbiology. 2016;54(4):290-295. doi:10.1007/s12275-016-5520-2. PMID 27033204. ROLE: TAXONOMIC CROSSWALK / TTC
Lim YW, Cho Y, Kim D, Im JH, Woo SI. Taxonomic study of genus Sanghuangporus in Korea. Journal of Mushrooms. 2025;23(2):63-77. doi:10.14480/JM.2025.23.2.63. ROLE: MODERN TAXONOMIC CONTEXT / IDENTITY-CONSERVATION CONTEXT
Source chapter: Chapter 21, The Fungal Evidence Atlas