Kava (Piper methysticum) | Supplementopedia

Overview

Kava (Piper methysticum) is a perennial shrub native to the Pacific Islands.
Root extracts are traditionally used as a calming beverage.
Modern kava supplements primarily provide anxiolytic and mild sedative effects.
These effects are achieved without the intoxicating properties of alcohol or benzodiazepines.

Clinical trials and meta-analyses show standardized kava extracts (30%–70% kavalactones) reduce symptoms of generalized anxiety disorder and stress-related insomnia.
Effect sizes are comparable to low-dose benzodiazepines (e.g., 0.5–0.8 Hedges g).
Acute studies demonstrate modest improvements in subjective mood.
Kava reduces physiological stress markers (cortisol, heart-rate variability).
It enhances sleep efficiency (≥ 15% increase in total sleep time).
Some investigations suggest kava may attenuate neuro-inflammation and oxidative stress, potentially supporting cognitive resilience.
Kava does not enhance muscular performance or metabolic rate.
Its calming effect can indirectly improve adherence to exercise and dietary programs by reducing anxiety-driven eating.

Kava's activity derives from its kavalactones (kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, desmethoxy-kavalactone).
These lipophilic compounds cross the blood-brain barrier.
They modulate the central nervous system primarily by allosterically enhancing GABA-A receptor function, especially at the α1 and α5 subunits.
This increases chloride influx and neuronal inhibition.
Kavalactones also inhibit voltage-gated calcium channels.
They modulate the dopaminergic and serotonergic pathways, contributing to anxiolysis without significant sedation at low doses.
Kavalactones act as reversible inhibitors of monoamine oxidase-B, which may modestly raise dopamine and serotonin levels.
Their metabolism involves hepatic CYP2D6 and CYP3A4, producing hydroxy-kavalactone metabolites excreted in urine.

Standardized extracts (30%–70% kavalactones) are typically dosed at 70–250 mg kavalactones per day, divided into 2–3 administrations.
For acute anxiety, 150 mg (≈ 3 g of dried root) taken 30 minutes before the desired effect is common.
For chronic stress, 100 mg twice daily is often recommended.
“Full-strength” extracts (e.g., 30% kavalactones) allow a 50 mg dose to be equivalent to ~150 mg of root.
Users should start at the lower end (50–100 mg) for 1–2 weeks to assess tolerance.
Avoid exceeding 300 mg/day to reduce hepatotoxicity risk.
Timing should avoid bedtime if the dose produces marked sedation.
Athletes should consider timing 3–4 h before competition to allow any mild sedation to resolve.

Common, mild side effects include drowsiness, dry mouth, and mild gastrointestinal discomfort.
Rarely, hepatotoxicity has been reported, especially with high-dose, non-standardized extracts or concurrent alcohol use.
Contra-indications: pre-existing liver disease, pregnant or lactating women, and individuals on hepatotoxic drugs (e.g., acetaminophen, isoniazid, certain antiretrovirals).
Kava inhibits CYP2D6 and CYP3A4; therefore, it can increase plasma levels of benzodiazepines, antidepressants, and statins.
Alcohol, other sedatives, and opioids amplify CNS depression.
Children and adolescents should avoid use.
Regular liver function monitoring (ALT/AST) is advised for >4 weeks of use or in high-risk individuals.
Discontinue use if jaundice, fatigue, or dark urine appear.

Kavalactones share a 5-membered lactone ring fused to a 3-methyl-2-butenyl side chain.
The principal component, kavain, has the molecular formula C₁₁H₁₄O₃ and IUPAC name (5-hydroxy-2-prop-2-enyl-2-pyrone).
Yangonin contains an additional methoxy group (C₁₁H₁₂O₄, IUPAC: 4-methoxy-5-hydroxy-2-prop-2-enyl-2-pyrone).
Kavalactones are lipophilic (log P ≈ 2.5–3.2), non-volatile, and poorly soluble in water (≤ 0.2 mg/mL).
They readily dissolve in ethanol, acetone, and supercritical CO₂.
Their UV-visible absorption peaks near 260 nm (π→π* transition).
They are stable under acidic conditions.
They degrade under prolonged oxidative exposure, leading to potential quinone formation linked to hepatotoxicity.

Kava is cultivated primarily in Vanuatu, Fiji, and Tonga.
The root is harvested from mature (3–5-year-old) plants.
Commercial supplements usually use the “noble” varieties (e.g., P. methysticum ‘Taveuni’, ‘Vula’, ‘Nambawan’).
Noble varieties contain higher ratios of kavalactones to flavokavains (the latter are more hepatotoxic).
Extraction is typically performed with 70% ethanol or super-critical CO₂ to preserve kavalactone integrity.
The resultant powder or tincture is then standardized to a specific kavalactone content.
Quality-grade products are assayed by HPLC-UV for kavalactone profile.
They are screened for heavy metals, pesticides, and microbial contamination.
Certified “Noble” kava with ≥ 30% kavalactones and < 0.5% flavokavain is considered the safest source for dietary supplements.