Hops (Humulus lupulus) | Supplementopedia

Overview

Hops (Humulus lupulus) is a perennial climbing plant in the Cannabaceae family, cultivated primarily for its female inflorescences (“cones”). These cones contain a rich mixture of essential oils, bitter acids, and flavonoids. Historically used as a bittering, flavoring, and preservative agent in beer, modern research has identified several bioactive compounds that support human health, particularly through modulation of neurotransmission, inflammation, and hormonal pathways.

Benefits

Sleep and anxiety: α‑Acid and hop-derived flavonoids (e.g., xanthohumol) improve sleep latency and reduce anxiety scores in randomized trials, likely via GABA‑ergic modulation and cortisol reduction.
Menopausal symptoms: A 12‑week double‑blind study showed a 30 % reduction in hot‑flash frequency with standardized hop extracts, comparable to low‑dose estrogen.
Cognitive function: Acute dosing improves psychomotor speed and reduces mental fatigue, possibly through enhanced dopaminergic signaling.
Metabolic health: Xanthohumol reduces hepatic lipid accumulation and improves insulin sensitivity in rodent models; limited human data suggest modest reductions in fasting glucose and triglycerides.
Anti‑inflammatory & antioxidant: In vitro and animal data demonstrate inhibition of NF‑κB and reduction of oxidative markers, supporting cardiovascular and immune health.

How It Works

Process: The primary bioactive groups in hops are α‑acids (humulone, lupulone), β‑acids (lupulone, humulone derivatives), and prenylflavonoids (xanthohumol, isoxanthohumol).
α‑Acids: Act as positive allosteric modulators of GABA(_A) receptors, promoting inhibitory neurotransmission and producing anxiolytic and sedative effects.
Xanthohumol: Activates Nrf2 pathways, up‑regulating antioxidant enzymes (e.g., HO‑1, NQO1) and suppressing NF‑κB‑mediated inflammation.
Bitter acids: Engage PPAR‑α/γ receptors, modulating lipid metabolism and improving insulin sensitivity.
Phytoestrogenic flavonoids: Bind estrogen receptors α/β with modest affinity, mitigating menopausal vasomotor symptoms.
Overall effect: Collectively, these mechanisms produce the observed sleep‑enhancing, mood‑stabilizing, metabolic, and anti‑inflammatory outcomes.

Dosage

Standardized extracts: Typically contain 0.5–1 % α‑acids and 0.2–0.5 % xanthohumol.
Sleep-related benefits: 200–500 mg of extract (≈ 30–80 mg α‑acid) taken 30 minutes before bedtime.
Menopausal relief: 300–600 mg of a 0.5 % xanthohumol extract taken twice daily (morning and evening).
Anxiety: 150–300 mg of a 50 % α‑acid‑standardized extract was administered twice daily in clinical trials.
Split dosing: May reduce gastrointestinal discomfort.
Menopausal symptoms trial: A 12‑week trial used 500 mg of a 0.4 % xanthohumol extract twice daily.
Metabolic support: 300 mg of a 4 % xanthohumol extract once daily has been explored.
Recommendation: Always start with the lowest effective dose and increase gradually under professional guidance.

Safety & Side Effects

General tolerance: Hops is generally well‑tolerated.
Mild side effects: Include drowsiness, dry mouth, and gastrointestinal upset (e.g., nausea, bloating) at higher doses (> 1 g).
Contraindications:
- Pregnancy and lactation (due to estrogenic activity)
- Severe liver disease (potential for cholestatic effects)
- Hypotension (possible additive effect with antihypertensives)
Drug interactions:
- Potentiation of sedative/benzodiazepine effects
- Possible CYP450‑2C9 inhibition (affecting warfarin, phenytoin)
Cautions:
- Children
- Elderly with impaired cognition
- Patients on hormonal therapy
Discontinuation: Discontinue if excessive sedation or allergic skin reactions occur.

Chemistry

α‑Acids:
- Humulone, cohumulone, adhumulone (C({21})H() for humulone; molecular weight 354 g mol⁻¹).})O(_{5
- IUPAC: (3R,6R,8S)-3,5‑dimethyl‑7‑(1‑hydroxy‑3‑methyl‑but-2‑enyl)‑2‑(3‑methylbut‑2‑enyl)‑6‑propyl‑2,4‑dihydro‑3‑pyrone‑5‑carboxylic acid.
β‑Acids: Lupulone (C({21})H() similar scaffold, more acidic).})O(_{5
Prenylflavonoids:
- Xanthohumol (C({21})H(), MW 354 g mol⁻¹) with a 6‑prenyl‑substituted chalcone structure; isoxanthohumol is the demethylated metabolite.})O(_{5
Properties:
- Lipophilic, soluble in ethanol, CO₂, and supercritical fluids.
- Display moderate water solubility (≈ 0.1 g L⁻¹)
- Stable at pH 3–5.
Structure-activity relationship: The α‑acid lactone ring is critical for GABA(_A) modulation, while the prenyl side‑chain confers strong antioxidant activity.

Sources & Quality

Cultivation: Commercial hops are cultivated in temperate regions.
Major growers: United States (Pacific Northwest, especially Washington and Oregon), Germany, Czech Republic, and Slovenia.
Processing: Harvested cones are dried, pelletized, or milled, then extracted using ethanol, CO₂, or super‑critical CO₂ to preserve volatile oils and bitter acids.
Standardized extracts: Produced by solvent‑recovery processes that remove residual solvents to < 10 ppm per USP.
Quality control:
- HPLC quantification of humulone and xanthohumol.
- Verification of microbial limits (≤ 1 × 10⁴ CFU g⁻¹).
- Absence of pesticide residues (per EU/US limits).
Recommendations: For research‑grade material, USDA‑certified organic hops and GMP‑certified manufacturers are recommended to ensure consistency and minimal contaminants.