Flavokawain B

Flavokawain B at a Glance

Flavokawain B (FKB) is a chalcone — a small, open-chain flavonoid — and one of three flavokawains (A, B and C) that occur as minor constituents of kava (Piper methysticum), far below the kavalactones that carry kava’s anxiolytic activity ^{7,20Reference 7Lebot V et al. · 2014Detection of flavokavins (A, B, C) in cultivars of kava (Piper methysticum) using high performance thin layer chromatography (HPTLC)View study →Reference 20Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →}.

Its pharmacology is genuinely two-sided. On one side, isolated FKB is pro-apoptotic and cytotoxic to a range of cancer cell lines — prostate, colon, lung and gastric among them — killing tumour cells through mitochondrial, death-receptor and stress-kinase pathways while sparing some normal cells, a preclinical anticancer signal shared with its sibling flavokawain A ^{9,10,11,12Reference 9Tang Y et al. · 2010Flavokawain B, a kava chalcone, induces apoptosis via up-regulation of death-receptor 5 and Bim expression in androgen receptor negative, hormonal refractory prostate cancer cell lines and reduces tumor growthView study →Reference 10Palko-Łabuz A et al. · 2020Cyclization of flavokawain B reduces its activity against human colon cancer cellsView study →Reference 11An J et al. · 2012Flavokawain B induces apoptosis of non-small cell lung cancer H460 cells via Bax-initiated mitochondrial and JNK pathwayView study →Reference 12Hseu YC et al. · 2020Flavokawain B and doxorubicin work synergistically to impede the propagation of gastric cancer cells via ROS-mediated apoptosis and autophagy pathwaysView study →}.

On the other side, FKB is the leading chemical candidate for kava-associated liver injury. It is the most cytotoxic of the kava chalcones to human hepatocytes in vitro, kills them by depleting glutathione and driving oxidative stress, and — with flavokawain A but not the kavalactone dihydromethysticin — potentiates acetaminophen (paracetamol) hepatotoxicity in mice ^{1,2,5Reference 1Zhou P et al. · 2010Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathwaysView study →Reference 2Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →Reference 5Pinner KD et al. · 2016Flavokawains A and B from kava (Piper methysticum) activate heat shock and antioxidant responses and protect against hydrogen peroxide-induced cell death in HepG2 hepatocytesView study →}. That hazard is real but conditional: traditional aqueous, peeled-root (“noble”) kava extracts very little FKB, and its handled honestly below, set against the good safety record of the traditional beverage.

Flavokawain B & Kava Hepatotoxicity

This is the reason the molecule matters beyond oncology, and it deserves careful, unhyped handling. Kava products have occasionally been linked to rare but severe hepatotoxicity — enough that regulators in Europe and the US restricted sales in the early 2000s — and FKB is the most-implicated single compound ^{1,4Reference 1Zhou P et al. · 2010Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathwaysView study →Reference 4Teschke R · 2011Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}.

Why FKB is the prime suspect. In bioassay-guided fractionation of kava by the US National Center for Toxicological Research, the compound responsible for the cytotoxicity of the active (organic-solvent) fraction, on human HepG2 hepatocytes, was identified as flavokawain B ^{3Reference 3Jhoo JW et al. · 2006In vitroIn vitro cytotoxicity of nonpolar constituents from different parts of kava plant (Piper methysticum)View study →}. A dedicated mechanistic study then showed FKB is a potent hepatocellular toxin (LD₅₀ ≈ 15 µM in HepG2, ≈ 32 µM in the L-02 hepatocyte line) that kills liver cells by inducing oxidative stress and depleting reduced glutathione (GSH), inhibiting IKK/NF-κB survival signalling and constitutively activating the ERK, p38 and JNK MAP kinases; oral FKB produced severe liver damage in vivo, and — tellingly — replenishing GSH rescued the hepatocytes ^{1Reference 1Zhou P et al. · 2010Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathwaysView study →}. Among the flavokawains, FKB is the most damaging: in a direct comparison FKA (≤100 µM) was not toxic to HepG2 while FKB killed them (IC₅₀ ≈ 23 µM) ^{5Reference 5Pinner KD et al. · 2016Flavokawains A and B from kava (Piper methysticum) activate heat shock and antioxidant responses and protect against hydrogen peroxide-induced cell death in HepG2 hepatocytesView study →}.

A revealing animal model. Kava alone caused no liver injury in mice even at 500 mg/kg long-term. But a three-day kava pre-treatment potentiated acetaminophen-induced hepatotoxicity (higher serum ALT/AST, worse liver lesions), and flavokawains A and B reproduced that synergism while the kavalactone dihydromethysticin did not — implicating a herb–drug interaction as one plausible route to the rare human cases ^{2Reference 2Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →}. This is why dihydromethysticin is treated as the exonerated kavalactone contrast here, and why FKB (with pipermethystine, the other aerial-part candidate) carries the safety flag.

The nuance that matters — not all kava is equal. The hazard tracks which kava and how it is made, not kava as a category:

• Cultivar drives the FKB load. Across 172 samples, the FKB/kavalactone ratio was much higher in two-day (tudei) and wichmannii kava (~0.39 in tudei) than in noble cultivars, and that ratio is genetically controlled — it does not vary much between roots, stumps and basal stems of the same clone ^{7Reference 7Lebot V et al. · 2014Detection of flavokavins (A, B, C) in cultivars of kava (Piper methysticum) using high performance thin layer chromatography (HPTLC)View study →}. So the dominant lever is cultivar, not simply “root vs leaf”.
• Extraction method drives how much reaches you. FKB is lipophilic. Aqueous extractions of noble kava root had no measurable toxicity to HepG2 cells, whereas organic-solvent (acetone/ethanol) and some supercritical-CO₂ extracts concentrate more of the cytotoxic chalcone ^{6Reference 6Petersen GE et al. · 2019In vitroChemical and in vitro toxicity analysis of a supercritical fluid extract of Kava kava (Piper methysticum)View study →}. The traditional Pacific beverage — cold-water maceration of peeled root — is the low-FKB, low-toxicity end of the spectrum; the European capsule extracts associated with the case reports sat at the higher end.
• Plant part still counts — but chiefly through pipermethystine, a leaf/stem-peeling alkaloid cytotoxic to HepG2, rather than through FKB ^{8Reference 8Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →}.

How strong is the case? It is strong mechanistically and in animals, not a closed case in humans: the clinical hepatotoxicity is rare, idiosyncratic and multifactorial, and reviews list FKB alongside pipermethystine and mould-derived hepatotoxins as assumed rather than proven culprits ^{4Reference 4Teschke R · 2011Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}. The honest summary is that FKB is the best-characterised chemical driver of kava liver toxicity, that its levels should be monitored and minimised in commercial kava ^{1Reference 1Zhou P et al. · 2010Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathwaysView study →}, and that choosing noble-cultivar, aqueous, peeled-root preparations is the evidence-aligned way to stay near the safe end.

What It's Used For

Beyond the hepatotoxicity story, FKB’s researched activity is anticancer and anti-inflammatory — and almost entirely preclinical. The load-bearing caveat for a compound page applies in full: this is isolated-molecule work in cell lines and mice, with no human efficacy trials.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Every row here is preclinical (cell line ± mouse), so scores stay modest by design; there are no human efficacy data.

01Anticancer / Pro-ApoptoticShaky42%Isolate apoptosis across prostate/colon/lung/gastric lines + xenograft tumour reduction ^{9,10,11,12Reference 9Tang Y et al. · 2010Flavokawain B, a kava chalcone, induces apoptosis via up-regulation of death-receptor 5 and Bim expression in androgen receptor negative, hormonal refractory prostate cancer cell lines and reduces tumor growthView study →Reference 10Palko-Łabuz A et al. · 2020Cyclization of flavokawain B reduces its activity against human colon cancer cellsView study →Reference 11An J et al. · 2012Flavokawain B induces apoptosis of non-small cell lung cancer H460 cells via Bax-initiated mitochondrial and JNK pathwayView study →Reference 12Hseu YC et al. · 2020Flavokawain B and doxorubicin work synergistically to impede the propagation of gastric cancer cells via ROS-mediated apoptosis and autophagy pathwaysView study →}

02Chemo-Sensitisation / SynergyShaky32%Synergy with doxorubicin, gemcitabine, bortezomib, TRAIL — preclinical ^{10,12,13,14Reference 10Palko-Łabuz A et al. · 2020Cyclization of flavokawain B reduces its activity against human colon cancer cellsView study →Reference 12Hseu YC et al. · 2020Flavokawain B and doxorubicin work synergistically to impede the propagation of gastric cancer cells via ROS-mediated apoptosis and autophagy pathwaysView study →Reference 13Hua R et al. · 2020Antitumor effects of flavokawain-B in gemcitabine-resistant lung cancer cells are mediated via mitochondrial-mediated apoptosis, ROS production and blocking of PI3K/AKT signalingView study →Reference 14Li X et al. · 2019Flavokawain B targets protein neddylation for enhancing the anti-prostate cancer effect of Bortezomib via Skp2 degradationView study →}

03Anti-Inflammatory (Preclinical)Shaky26%NF-κB suppression via TLR2 (colitis) and MD-2 (acute lung injury), rodent/in vitro ^{15,16Reference 15Chen Y et al. · 2024Flavokawain B inhibits NF-κB inflammatory signaling pathway activation in inflammatory bowel disease by targeting TLR2View study →Reference 16Luo W et al. · 2022Flavokawain B alleviates LPS-induced acute lung injury via targeting myeloid differentiation factor 2View study →}

Mechanisms

The through-line is a pro-oxidant, pro-apoptotic chemistry: the GSH-depleting, ROS-generating, mitochondrial-priming action that kills cancer cells is the same action that injures hepatocytes when the antioxidant reserve is overwhelmed ^{1,5,12Reference 1Zhou P et al. · 2010Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathwaysView study →Reference 5Pinner KD et al. · 2016Flavokawains A and B from kava (Piper methysticum) activate heat shock and antioxidant responses and protect against hydrogen peroxide-induced cell death in HepG2 hepatocytesView study →Reference 12Hseu YC et al. · 2020Flavokawain B and doxorubicin work synergistically to impede the propagation of gastric cancer cells via ROS-mediated apoptosis and autophagy pathwaysView study →}.

Pharmacokinetics

Dedicated human ADME for FKB (oral bioavailability, Cmax, half-life) is not established — a real hole for a molecule whose safety is at issue. What is characterised is hepatic metabolism: in human liver microsomes FKB undergoes Phase I O-demethylation (yielding flavokawain C) and hydroxylation, and, more extensively, Phase II glucuronidation to FKB-2′-O-glucuronide ^{17Reference 17Zenger K et al. · 2015Biotransformation of flavokawains A, B, and C, chalcones from kava (Piper methysticum), by human liver microsomesView study →}. Two implications follow. First, glucuronidation dominates, so conjugation capacity may modulate exposure to the reactive parent — relevant to why toxicity appears idiosyncratic. Second, the fact that FKB is metabolically interconverted with the other flavokawains means “flavokawain” exposure is best considered as a set, not a single molecule ^{17Reference 17Zenger K et al. · 2015Biotransformation of flavokawains A, B, and C, chalcones from kava (Piper methysticum), by human liver microsomesView study →}. Its lipophilicity is also why aqueous extraction leaves most of it behind while organic solvents carry it through ^{6Reference 6Petersen GE et al. · 2019In vitroChemical and in vitro toxicity analysis of a supercritical fluid extract of Kava kava (Piper methysticum)View study →}.

Clinical Trials

There are no clinical trials of isolated flavokawain B for any indication — neither efficacy (anticancer/anti-inflammatory) nor a controlled human toxicity study. The human relevance is inferential: from case reports of kava hepatotoxicity, from the compound’s in-vitro/mouse toxicology, and from analytical surveys of FKB content in commercial kava ^{1,4,6,7Reference 1Zhou P et al. · 2010Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathwaysView study →Reference 4Teschke R · 2011Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →Reference 6Petersen GE et al. · 2019In vitroChemical and in vitro toxicity analysis of a supercritical fluid extract of Kava kava (Piper methysticum)View study →Reference 7Lebot V et al. · 2014Detection of flavokavins (A, B, C) in cultivars of kava (Piper methysticum) using high performance thin layer chromatography (HPTLC)View study →}.

Last checked: July 2026.

Isolate vs. Plant Studies

FKB is a case where isolate data and whole-plant experience point in opposite directions, and reconciling them is the whole point. The therapeutic (anticancer) and toxic (hepatocyte) findings are almost all on the isolated molecule at defined micromolar concentrations ^{1,5,9Reference 1Zhou P et al. · 2010Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathwaysView study →Reference 5Pinner KD et al. · 2016Flavokawains A and B from kava (Piper methysticum) activate heat shock and antioxidant responses and protect against hydrogen peroxide-induced cell death in HepG2 hepatocytesView study →Reference 9Tang Y et al. · 2010Flavokawain B, a kava chalcone, induces apoptosis via up-regulation of death-receptor 5 and Bim expression in androgen receptor negative, hormonal refractory prostate cancer cell lines and reduces tumor growthView study →} — clean pharmacology, but far from ordinary dietary exposure. The whole-plant picture is reassuring at the traditional end: aqueous noble-root kava is low in FKB and non-cytotoxic in vitro, and kava alone was not hepatotoxic in mice ^{2,6Reference 2Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →Reference 6Petersen GE et al. · 2019In vitroChemical and in vitro toxicity analysis of a supercritical fluid extract of Kava kava (Piper methysticum)View study →}. The isolate’s hazard becomes plant-relevant only when the matrix concentrates it — tudei/wichmannii cultivars and organic-solvent or supercritical extracts ^{6,7Reference 6Petersen GE et al. · 2019In vitroChemical and in vitro toxicity analysis of a supercritical fluid extract of Kava kava (Piper methysticum)View study →Reference 7Lebot V et al. · 2014Detection of flavokavins (A, B, C) in cultivars of kava (Piper methysticum) using high performance thin layer chromatography (HPTLC)View study →}.

A genuinely interesting wrinkle sits between the two: at sub-lethal doses FKB (and FKA) activate Nrf2 and heat-shock responses, transiently raising hepatocyte glutathione and protecting against a later oxidative challenge — a hormetic, adaptive response ^{5Reference 5Pinner KD et al. · 2016Flavokawains A and B from kava (Piper methysticum) activate heat shock and antioxidant responses and protect against hydrogen peroxide-induced cell death in HepG2 hepatocytesView study →}. This does not license the molecule (higher or repeated exposure still depletes GSH and kills cells), but it explains why low-level exposure and outright toxicity can both be reported, and it cautions against reading any single dose in isolation.

Prevalence in Nature

Flavokawain B is a minor constituent of kava (Piper methysticum), present at a small fraction of the kavalactone content ^{20Reference 20Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →}. Its abundance is governed less by plant part than by cultivar/chemotype: analytical surveys find the FKB-to-kavalactone ratio is genetically controlled and much higher in two-day (tudei) and wichmannii kava (≈0.39 in tudei) than in the noble cultivars used for the traditional beverage, and it varies little between roots, stumps and basal stems of a given clone ^{7Reference 7Lebot V et al. · 2014Detection of flavokavins (A, B, C) in cultivars of kava (Piper methysticum) using high performance thin layer chromatography (HPTLC)View study →}. Because FKB is lipophilic, the amount that ends up in a product also depends heavily on extraction — organic solvents and supercritical CO₂ recover more of it than cold-water maceration of peeled root ^{6Reference 6Petersen GE et al. · 2019In vitroChemical and in vitro toxicity analysis of a supercritical fluid extract of Kava kava (Piper methysticum)View study →}.

Outside kava, flavokawain B has been isolated from other Zingiberaceae, notably the rhizomes of Alpinia mutica and Alpinia pricei, where it likewise shows cytotoxic/apoptotic activity — so it is a genus-crossing chalcone, not unique to Piper ^{18Reference 18Malami I et al. · 2017Crude extracts, flavokawain B and alpinetin compounds from the rhizome of Alpinia mutica induce cell death via UCK2 enzyme inhibition and in turn reduce 18S rRNA biosynthesis in HT-29 cellsView study →}.

Discovery & Synthesis

Flavokawain B was characterised as one of the “flavokawains” (A, B and C) — chalcone pigments of kava — during phytochemical study of Piper methysticum; a precise first-isolation date and author are not cleanly documented in the accessible literature (logged to the gaps tracker). Chemically it is 2′-hydroxy-4′,6′-dimethoxychalcone, a simple methoxylated chalcone, and like most chalcones it is readily accessible by Claisen–Schmidt condensation of the appropriate acetophenone and benzaldehyde — the route by which research quantities are made and by which structural analogues (e.g. its cyclised flavanone) are prepared to probe structure–activity relationships ^{10Reference 10Palko-Łabuz A et al. · 2020Cyclization of flavokawain B reduces its activity against human colon cancer cellsView study →}. Interest in the molecule grew from two directions at once: the anticancer programme built around its sibling flavokawain A ^{19Reference 19Zi X · 2005AnimalFlavokawain A, a novel chalcone from kava extract, induces apoptosis in bladder cancer cells by involvement of Bax protein-dependent and mitochondria-dependent apoptotic pathway and suppresses tumor growth in miceView study →}, and the hepatotoxicity investigations that followed the kava liver-injury reports ^{1,3Reference 1Zhou P et al. · 2010Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathwaysView study →Reference 3Jhoo JW et al. · 2006In vitroIn vitro cytotoxicity of nonpolar constituents from different parts of kava plant (Piper methysticum)View study →}.

Patents: not yet researched.

Toxicity & Safety

FKB carries a moderate flag — above a typical minor plant chalcone — because of a well-characterised hepatocyte cytotoxicity in vitro and in-vivo liver injury / acetaminophen potentiation in mice, even though confirmed human harm is rare, conditional and tied to particular kava preparations rather than to dietary exposure at large ^{1,2,3Reference 1Zhou P et al. · 2010Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathwaysView study →Reference 2Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →Reference 3Jhoo JW et al. · 2006In vitroIn vitro cytotoxicity of nonpolar constituents from different parts of kava plant (Piper methysticum)View study →}.

Safety at a Glance

⚠️ Moderate toxicity

• Traditional aqueous noble-root kava is the low-FKB, low-toxicity end. Cold-water peeled-root preparations extract little of this lipophilic chalcone and were non-cytotoxic to hepatocytes in vitro ^{6,7Reference 6Petersen GE et al. · 2019In vitroChemical and in vitro toxicity analysis of a supercritical fluid extract of Kava kava (Piper methysticum)View study →Reference 7Lebot V et al. · 2014Detection of flavokavins (A, B, C) in cultivars of kava (Piper methysticum) using high performance thin layer chromatography (HPTLC)View study →}.
• A glutathione-depleting hepatocyte toxin in vitro. FKB is the most cytotoxic kava chalcone to human liver cells (IC₅₀ ≈ 15–23 µM), killing them via GSH depletion and oxidative stress; GSH replenishment reverses it ^{1,5Reference 1Zhou P et al. · 2010Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathwaysView study →Reference 5Pinner KD et al. · 2016Flavokawains A and B from kava (Piper methysticum) activate heat shock and antioxidant responses and protect against hydrogen peroxide-induced cell death in HepG2 hepatocytesView study →}.
• Potentiates acetaminophen liver injury in mice. FKB (with FKA, unlike dihydromethysticin) worsened acetaminophen hepatotoxicity — a plausible herb–drug interaction; caution combining kava with acetaminophen or other hepatotoxic drugs ^{2Reference 2Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →}.
• Product type matters more than “kava” as a category. Tudei/wichmannii cultivars and organic-solvent/supercritical extracts carry far more FKB than noble aqueous root; prefer noble, aqueous, peeled-root preparations ^{6,7Reference 6Petersen GE et al. · 2019In vitroChemical and in vitro toxicity analysis of a supercritical fluid extract of Kava kava (Piper methysticum)View study →Reference 7Lebot V et al. · 2014Detection of flavokavins (A, B, C) in cultivars of kava (Piper methysticum) using high performance thin layer chromatography (HPTLC)View study →}.
• A prime suspect, not a closed case. Human kava hepatotoxicity is rare, idiosyncratic and multifactorial; FKB is assumed alongside pipermethystine and mould toxins rather than proven as the sole cause ^{4Reference 4Teschke R · 2011Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}.
• Pregnancy/lactation and drug-interaction specifics are decided on the kava herb/product page, where intake is chosen — not adjudicated at the molecule level. Human ADME for isolated FKB is not established.

Dosage

There is no established or recommended human dose for isolated flavokawain B, and none should be inferred. The concentrations in the literature are in-vitro cytotoxic values — single-digit to tens of micromolar against hepatocytes and cancer cells ^{1,5,9Reference 1Zhou P et al. · 2010Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathwaysView study →Reference 5Pinner KD et al. · 2016Flavokawains A and B from kava (Piper methysticum) activate heat shock and antioxidant responses and protect against hydrogen peroxide-induced cell death in HepG2 hepatocytesView study →Reference 9Tang Y et al. · 2010Flavokawain B, a kava chalcone, induces apoptosis via up-regulation of death-receptor 5 and Bim expression in androgen receptor negative, hormonal refractory prostate cancer cell lines and reduces tumor growthView study →} — and rodent research doses, neither of which converts to human intake. In practice, human exposure to FKB is incidental to kava use, and the only lever a consumer has is product choice: noble cultivar over tudei/wichmannii, and aqueous peeled-root preparations over organic-solvent extracts, both of which lower FKB exposure ^{6,7Reference 6Petersen GE et al. · 2019In vitroChemical and in vitro toxicity analysis of a supercritical fluid extract of Kava kava (Piper methysticum)View study →Reference 7Lebot V et al. · 2014Detection of flavokavins (A, B, C) in cultivars of kava (Piper methysticum) using high performance thin layer chromatography (HPTLC)View study →}. These are research figures and quality-selection principles, not a personal recommendation.

References

1. Zhou P, et al. (2010). Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathways. FASEB Journal. https://pubmed.ncbi.nlm.nih.gov/20696856/
2. Narayanapillai SC, et al. (2014). Flavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 mice. Chemical Research in Toxicology. https://pubmed.ncbi.nlm.nih.gov/25185080/
3. Jhoo JW, et al. (2006). In vitro cytotoxicity of nonpolar constituents from different parts of kava plant (Piper methysticum). Journal of Agricultural and Food Chemistry. https://pubmed.ncbi.nlm.nih.gov/16608246/
4. Teschke R (2011). Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culprits. Digestive and Liver Disease. https://pubmed.ncbi.nlm.nih.gov/21377431/
5. Pinner KD, et al. (2016). Flavokawains A and B from kava (Piper methysticum) activate heat shock and antioxidant responses and protect against hydrogen peroxide-induced cell death in HepG2 hepatocytes. Pharmaceutical Biology. https://pubmed.ncbi.nlm.nih.gov/26789234/
6. Petersen GE, Tang Y, Fields C (2019). Chemical and in vitro toxicity analysis of a supercritical fluid extract of Kava kava (Piper methysticum). Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/30710733/
7. Lebot V, Do TK, Legendre L (2014). Detection of flavokavins (A, B, C) in cultivars of kava (Piper methysticum) using high performance thin layer chromatography (HPTLC). Food Chemistry. https://pubmed.ncbi.nlm.nih.gov/24423570/
8. Nerurkar PV, et al. (2004). In vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactones. Toxicological Sciences. https://pubmed.ncbi.nlm.nih.gov/14737001/
9. Tang Y, et al. (2010). Flavokawain B, a kava chalcone, induces apoptosis via up-regulation of death-receptor 5 and Bim expression in androgen receptor negative, hormonal refractory prostate cancer cell lines and reduces tumor growth. International Journal of Cancer. https://pubmed.ncbi.nlm.nih.gov/20112340/
10. Palko-Łabuz A, et al. (2020). Cyclization of flavokawain B reduces its activity against human colon cancer cells. Human & Experimental Toxicology. https://pubmed.ncbi.nlm.nih.gov/31640425/
11. An J, et al. (2012). Flavokawain B induces apoptosis of non-small cell lung cancer H460 cells via Bax-initiated mitochondrial and JNK pathway. Biotechnology Letters. https://pubmed.ncbi.nlm.nih.gov/22729748/
12. Hseu YC, et al. (2020). Flavokawain B and doxorubicin work synergistically to impede the propagation of gastric cancer cells via ROS-mediated apoptosis and autophagy pathways. Cancers (Basel). https://pubmed.ncbi.nlm.nih.gov/32882870/
13. Hua R, et al. (2020). Antitumor effects of flavokawain-B in gemcitabine-resistant lung cancer cells are mediated via mitochondrial-mediated apoptosis, ROS production and blocking of PI3K/AKT signaling. Journal of B.U.ON. https://pubmed.ncbi.nlm.nih.gov/32277640/
14. Li X, et al. (2019). Flavokawain B targets protein neddylation for enhancing the anti-prostate cancer effect of Bortezomib via Skp2 degradation. Cell Communication and Signaling. https://pubmed.ncbi.nlm.nih.gov/30885218/
15. Chen Y, et al. (2024). Flavokawain B inhibits NF-κB inflammatory signaling pathway activation in inflammatory bowel disease by targeting TLR2. Toxicology and Applied Pharmacology. https://pubmed.ncbi.nlm.nih.gov/38583725/
16. Luo W, et al. (2022). Flavokawain B alleviates LPS-induced acute lung injury via targeting myeloid differentiation factor 2. Acta Pharmacologica Sinica. https://pubmed.ncbi.nlm.nih.gov/34737421/
17. Zenger K, et al. (2015). Biotransformation of flavokawains A, B, and C, chalcones from kava (Piper methysticum), by human liver microsomes. Journal of Agricultural and Food Chemistry. https://pubmed.ncbi.nlm.nih.gov/26123050/
18. Malami I, et al. (2017). Crude extracts, flavokawain B and alpinetin compounds from the rhizome of Alpinia mutica induce cell death via UCK2 enzyme inhibition and in turn reduce 18S rRNA biosynthesis in HT-29 cells. PLoS One. https://pubmed.ncbi.nlm.nih.gov/28103302/
19. Zi X, Simoneau AR (2005). Flavokawain A, a novel chalcone from kava extract, induces apoptosis in bladder cancer cells by involvement of Bax protein-dependent and mitochondria-dependent apoptotic pathway and suppresses tumor growth in mice. Cancer Research. https://pubmed.ncbi.nlm.nih.gov/15833884/
20. Wang J, et al. (2015). Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solvents. Journal of Food Science and Technology. https://pubmed.ncbi.nlm.nih.gov/25694734/

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