Other Names
Gland. LupuliGlandulae LupuliGlandular powder of hopsGlandular trichomes of Humulus lupulusHop lupulinLupulinLupulin glandsLupulinaLupulinic GlandsLupulinic GrainsLupulinum (B.P.)Lupulinum (N.F.)Lupulinum (U.S.P.)Yellow Powder
Lupulinum (also written lupulin and referred to historically as Lupulinum, N.F. in the National Formulary of the United States) is the collective name for the granular, resinous powder mechanically separated from the female strobiles (cones) of the hop plant, Humulus lupulus L. In older botanical and pharmacopeial literature the terms "lupulinum" and "lupulin" are used interchangeably; modern scientific literature predominantly uses "lupulin" to describe both the intact glandular trichomes and the powdered concentrate derived from them.
Humulus lupulus L. is a perennial, dioecious herb belonging to the family Cannabaceae. The plant grows as a vine that dies at the end of each season and regenerates from rhizomes in spring. Its cone-like female flowers are the organs with the highest concentration of desired compounds such as bitter acids and volatile terpenoids.
The female inflorescences of the hop plant, known as cones, are particularly valuable due to the secretion of lupulin by glandular trichomes. Lupulin is composed of resins and essential oils, with α- and β-acids (bitter acids) being its major components. The hop plant produces several valuable secondary metabolites, including prenylflavonoids, bitter acids, and essential oils, which are biosynthesized in glandular trichomes (lupulin glands) and are endowed with pharmacological properties.
Lupulin is prepared by beating or rubbing the strobiles of hops and then sifting them, whereby a glandular powder is separated. The sifting is necessary to remove broken bracts and other vegetable matter. About 10 per cent of lupulin is thus obtained from dried hops.
Lupulin as a pharmaceutical material is described as a granular powder, bright yellow, becoming yellowish-brown with age; mixed with minute scale particles; resinous; with a peculiar aromatic odor like hops but stronger; and a bitter taste. Lupulin carries the odor and taste common to hops; gentle heat renders it tenacious; and when exposed to flame it burns. Owing to the presence of its essential oil, lupulin in quantity is liable to spontaneous combustion.
Europe, Asia, and North America are the principal cultivated regions for hop strobiles (Strobiles lupuli), which occur mainly in temperate regions of the world.
The German Commission E approved a monograph on hops for use in mood and sleep disturbances. Similar indications are described in an ESCOP (European Scientific Cooperative on Phytotherapy) monograph. Today, a wide range of preparations containing hop extracts or hop-derived products are available on the market, in particular for use in the phytotherapy of sleep disorders, pain relief, and in postmenopausal therapy.
The following preparations are described in historical and current scientific literature:
The use of hops as a mild sedative came from the observation of fatigue, tiredness, and sleepiness symptoms in hop pickers, apparently due to resin absorption during harvesting or processing hops. The tranquilizing and sleep-enhancing properties of H. lupulus were cited in old manuals of pharmacology and pharmacognosy, including Fluckiger and Hanbury (1879), Maisch (1892), Schleif and Galludet (1907), Greenish (1909), Culbreth (1927), and Gathercoal and Wirth (1936), as well as in modern textbooks of phytotherapy.
In Eclectic medical practice, lupulin or its tincture was used in delirium tremens and wakefulness in connection with nervous irritation, anxiety, or exhaustion; it was noted that it did not disorder the stomach nor cause constipation, as occurred with opium.
Medical uses of hops and lupulin historically include aiding digestion, mild sedation, diuresis, and treating menstrual problems.
Lupulin, described as the active principle of hops, was recognized in the mid-nineteenth century as being possessed of powerful sedative effects on the generative functions; the use of lupulin as an anaphrodisiac was first entertained by Debout and more recently elaborated upon by Zambaco. Zambaco administered the medicine in doses varying from 1 to 16 grammes and recorded the history of eight cases of painful erections following gonorrhea in which it was most successfully employed as a sedative. Besides being possessed of sedative and anti-blenorrhagic properties, which were attributed to its essential oil and resinous principle, lupulin contains a bitter element which was described as acting as an admirable tonic; Zambaco reported lupulin given as a tonic to strumous patients with improvement of appetite and strengthening of the digestive organs.
Humulus lupulus strobiles have a long traditional medicinal use in Europe, in the form of herbal tea, infusions, powdered herbal substance, or alcoholic extracts for the relief of insomnia, excitability, and specifically for restlessness associated with nervous tension, headache, and/or indigestion.
Hops pickers have reported sedation during harvest, and hops flowers have been added to pillows for relief of nervous conditions.
A recurring historical suggestion has been that hops (Humulus lupulus), used for centuries as a preservative and flavouring agent in beer, have powerful oestrogenic activity. When hops were picked by hand, menstrual disturbances amongst women pickers were reportedly common. Hop baths have been used for the treatment of gynaecological disorders, and hop extracts have been reported to reduce hot flushes in menopausal women.
The German Commission E Monographs advised use of the plant in the treatment of "discomforts during restlessness or anxiety and sleep disturbances." The German Commission E approved the use of hops for mood disturbances such as restlessness and anxiety as well as sleep disturbances. Hops are mostly used in combination with other sedative herbs such as valerian, passionflower, and lemon balm for the treatment of sleep disturbances.
The medicinal potential of hop (Humulus lupulus L.) is widely cited in ancient literature and is also allowed in several official pharmacopoeias for the treatment of a variety of ailments, mainly related to anxiety states. This is due to the plethora of phytoconstituents, including bitter acids, polyphenols, and prenyl flavonoids, present in the female inflorescences, endowed with anti-inflammatory, antioxidant, antimicrobial, and phytoestrogen activities.
Humulone (α-lupulic acid) is a bitter-tasting chemical compound found in the resin of mature hops (Humulus lupulus). Humulone is a prevalent member of the class of compounds known as alpha acids, which collectively give hopped beer its characteristic bitter flavor. In the plant the alpha-acids occur as humulone, cohumulone, and adhumulone. During the brewing process, these compounds are isomerized to the iso-alpha-acid series of compounds that possess the bitter taste.
The contents of alpha and beta bitter acids in hop cones represent 5 to 30% of the dry weight and are major chemical characteristics and economical traits of different cultivars during hop production.
The beta-acid fraction, also referred to as lupulones, includes compounds such as lupulone, colupulone, adlupulone, tetrahydroisohumulone, and hexahydrocolupulone. The presence of a prenyl group in the chemical structure of β-acids makes them less acidic than α-acids, and they do not undergo isomerization during wort boiling.
The hop (Humulus lupulus), a component of beer, is a sedative plant whose pharmacological activity is due principally to its bitter resins, especially the α-acid component 2-methyl-3-buten-2-ol. The mechanism of action of the resin of hop consists of increasing the activity of the neurotransmitter γ-aminobutyric acid (GABA), thereby inhibiting the central nervous system (CNS).
In 1980, Hänsel and his collaborators identified 2-methyl-3-buten-2-ol as the compound responsible for hops' sedative activity; it is a degradation product formed during the storage process of humulone and lupulone by auto-oxidation. The molecule, which is a volatile tertiary alcohol, is also found in hop essential oil. This molecule increases the activity of the neurotransmitter γ-aminobutyric acid (GABA), inhibiting the central nervous system.
The female inflorescences (cones) of H. lupulus contain essential oil (with constituents including β-myrcene, β-caryophyllene, α-humulene, β-farnesene, α-selinene, β-selinene, humulene epoxides, β-bisabolol, and 2-methyl-3-buten-2-ol), prenylated flavanones (isoxanthohumol, 6-prenylnaringenin, 8-prenylnaringenin), prenylated acylphloroglucinols (humulone and lupulones), chalcones (xanthohumol and desmethylxanthohumol), triterpenes, flavonols, and tannins.
Xanthohumol (XN) is the predominant prenylated chalcone. Xanthohumol is the major prenylflavonoid of hops, present at 0.1% to 1% on a dry weight basis. The structure of xanthohumol was first identified by Verzele et al. in 1957. However, the beneficial pharmacological properties of xanthohumol, including antioxidant, anti-inflammatory, antibacterial, antiviral, antifungal, and antiplasmodial activities, were not fully elucidated until the 1990s.
8-Prenylnaringenin (8-PN) is the most pharmacologically notable phytoestrogenic compound. 8-Prenylnaringenin (8-PN), structurally belonging to the group of prenylated flavonoids, has been shown to be a potent phytoestrogen and has become the topic of active research. The hop contains 8-prenylnaringenin (8-PN), the most potent phytoestrogen known to date.
Essential oil compositions show a high prevalence of monoterpene hydrocarbon myrcene and sesquiterpene hydrocarbons α-humulene and β-caryophyllene.
The chemical profile of hop cones includes a wide variety of phenolic compounds such as catechin, epicatechin, rutin, quercetin, and morin; various phenolic acids including ferulic, protocatechuic, 4-hydroxybenzoic, vanillic, gallic, p-coumaric, trans-cinnamic, gentisic, caffeic, and ellagic acids; and additional compounds such as syringic acid, coumarin, naringenin, and prenylflavonoids like xanthohumol.
Studies have aligned Humulus lupulus with the modulation of gamma-aminobutyric acid (GABAA) receptors, highlighting a potential pathway through which it contributes to sedation and restful repose. The primary compound identified as responsible is 2-methyl-3-buten-2-ol, a degradation product of humulone and lupulone. Both sedation and the hypothermic action of hops are possibly induced by distinguishable components in the hops extract, indicating that there are at least two active principles.
Xanthohumol (XH) is metabolized to isoxanthohumol, desmethylxanthohumol, 8-PN, and 6-PN. 8-PN has been reported to be one of the most potent estrogen receptor alpha (ERα) phytoestrogens known to date, which is likely responsible for menopausal symptom relief. 8-PN, in contrast to other phytoestrogens, is proven to have stronger activity and higher affinity for the α subtype of the estrogen receptor (ER).
Xanthohumol can act as an effective anti-inflammatory agent by inhibiting endogenous prostaglandin synthesis through inhibition of cyclooxygenases (constitutive COX-1 and inducible COX-2). Humulus lupulus extracts have in their composition different molecules, such as polyphenols, α-acids, β-acids, and hydrocarbons, which contribute to the plant's medicinal properties. These molecules are associated with antimicrobial, antioxidant, and anti-inflammatory activities.
Increasing evidence suggests the anticancer activity of xanthohumol against NSCLC, leukemia, hepatocellular carcinoma, breast cancer, prostate cancer, cholangiocarcinoma, glioblastoma, pancreatic cancer, colon cancer, cervical cancer, melanoma, thyroid cancer, laryngeal squamous cell carcinoma, and ovarian cancer. Multiple crucial signaling molecules and pathways are involved, such as Akt, NF-κB, ROS, and ERK1/2.
The antimicrobial activity of hop extracts correlates with a high concentration of xanthohumol rather than with the content of α-acids. Xanthohumol showed considerable activity against MRSA with a minimum inhibitory concentration (MIC) value of 3.9 µg/mL.
A search of the AMED and MEDLINE databases for literature published between 1950 and 2009, using keywords including valerian, Humulus lupulus, hops, sleep, and insomnia, identified sixteen studies meeting inclusion criteria. Twelve of these found that the use of valerian, on its own or in combination with hops, is associated with improvements in some sleep parameters such as sleep latency and quality of sleep. However, these results need to be interpreted cautiously as there were significant differences in design between the studies. Further randomised, double-blind, placebo-controlled trials are needed before such herbal treatments can be confidently recommended.
Clinical trials are available for a fixed hops-valerian extract combination. Administration in patients suffering from non-organic sleep disturbances showed reduction of sleep latency and wake after sleep onset, together with an enlargement of slow-wave sleep.
Time spent in sleep was significantly higher for the hops/valerian group compared with placebo. The time spent in deeper sleep between reference and medication nights was also statistically significant. Overall, a study showed that a single administration of the hops/valerian combination can have a significant impact on the duration and depth of sleep compared with placebo.
A notable study analyzed the sedative effect of hops on the sleep–wake rhythm in a work-stressed population. Test subjects included 17 healthy but work-stressed female nurses working rotating shifts, night shifts, or both. Overnight sleep and chronobiological parameters were assessed by actigraphy after moderate ingestion (333 mL) of a nonalcoholic beer containing hops with dinner for 14 nights. Results showed improvement of night sleep quality using parameters of sleep latency and total activity, with both showing a statistically significant reduction in the treatment versus the control group. The beverage also had reported anxiolytic effects within the treatment group.
Evidence strength: Moderate preclinical and animal evidence; available human clinical trials involve mostly combination products (hops + valerian) rather than lupulin/lupulinum alone. Effect sizes in human studies are generally modest, and most trials are small in size. Confounding by the valerian component is a recognized limitation.
In a randomized, double-blind trial in young individuals reporting mild depressive, anxiety, or stress symptoms, a significant decrease in depressive and anxiety symptoms (measured by the DASS) was observed after 4-week administration of a preparation containing H. lupulus extract; however, its effectiveness and safety needs more investigation.
Evidence strength: Preliminary. Based on a single small pilot study. No large-scale, adequately powered randomized controlled trials are available for hops alone as an anxiolytic in humans.
Due to its estrogenic effects, administration of 8-PN represents a novel therapeutic approach to the treatment of menopausal and postmenopausal symptoms that occur as a consequence of a progressive decline in hormone levels in women. Application of 8-PN in the treatment of menopause has been clinically examined with promising results.
The key human clinical trial in this area: A prospective, randomized, double-blind, placebo-controlled study over 12 weeks with 67 menopausal women administered a hop extract standardized on 8-PN (100 or 250 μg) assessed responses by means of a modified Kupperman index (KI) and a patients' questionnaire. All groups, including placebo, showed a significant reduction of the KI both after 6 weeks and after 12 weeks. The hop extract at 100 μg 8-PN was significantly superior to placebo after 6 weeks (P = 0.023) but not after 12 weeks (P = 0.086). Furthermore, a higher dose appeared less active, and no dose-response relationship could be established.
In a separate randomized clinical trial of 63 postmenopausal women, sexual function was evaluated using the Female Sexual Function Index (FSFI) questionnaire before and after intervention with a vaginal hop extract gel or vaginal estradiol. No statistically significant differences in FSFI scores were noticed after treatment between the two groups. Vaginal hop was found to be as effective as estradiol in improving sexual dysfunction among postmenopausal women, with no adverse events.
Studies in postmenopausal women have shown the particular effectiveness of 8-PN in reducing hot flashes. However, strong stimulation of the uterus by 8-PN may be associated with the occurrence of adverse effects such as bleeding and may increase the risk of carcinogenesis.
A clinical trial registered with ClinicalTrials.gov assessed bone health: the trial aimed to determine whether long-term consumption of Lifenol® (a polyphenolic extract standardized in 8-PN content) could reduce bone mineral density loss in postmenopausal women with osteopenia. One hundred postmenopausal women were enrolled to consume during 12 months either Lifenol® (at a dose of 100 µg of 8-PN per day) or a placebo.
Evidence strength: Moderate for relief of menopausal vasomotor symptoms, based on a small but properly designed RCT. The effect at 12 weeks did not achieve statistical significance versus placebo in the primary study, suggesting a modest and time-limited benefit. Data on bone health are still emerging. Long-term safety, particularly regarding uterine stimulation and carcinogenic risk, has not been fully characterized.
Xanthohumol is a prenylated flavonoid from hops with potent anticancer activity to inhibit carcinogenesis and metastasis in many types of cancer, with additional properties as a chemo- and radio-sensitizer. Numerous studies have demonstrated its anticancer activity, with a concentration of up to 0.96 mg/L found in beer.
Xanthohumol has been shown to inhibit the growth of a wide variety of human cancer cell lines including breast, colon, prostate, ovarian, and blood cancer by inhibiting proliferation and inducing apoptosis. In preclinical research testing the growth-inhibitory and apoptosis-inducing activity in hormone-sensitive and hormone-refractory human prostate cancer cell lines, prostate cancer cells were found to be highly sensitive to xanthohumol at a concentration range of 20–40 μM.
Multiple crucial signaling molecules and pathways are involved in the anticancer activity of xanthohumol, including Akt, NF-κB, ROS, and ERK1/2.
Evidence strength: Currently limited to in vitro and animal (in vivo) models only. The limitations of current studies and challenges for the clinical use of xanthohumol have been acknowledged by reviewers. No human clinical trials confirming anticancer efficacy of lupulin or xanthohumol alone have been published at the time of this writing. This area remains preclinical and requires substantial further investigation.
Administration of hop-derived extracts has been shown to reduce body weight, fat mass, and improve glucose homeostasis in both rodent and human studies. A laboratory has demonstrated that administration of a supercritical CO₂ hop extract can reduce subjective ratings of hunger during water-only fasting.
Several studies in murine models and human trials have shown the effectiveness of hop flavonoids in reducing menopausal symptoms while lowering the risk of cardiometabolic diseases through direct flavonoid interaction with endogenous antioxidant and anti-inflammatory pathways. Commercial hops-based dietary supplements contain a mixture of the flavonoids xanthohumol (XN), isoxanthohumol (IX), and 8-prenylnaringenin (8PN).
Evidence strength: Preliminary, with a small number of human trials of modest size. Most metabolic data are from rodent studies. Human evidence is insufficient to support clinical recommendations.
The antimicrobial activity of hop extracts has been investigated against eight human cocci pathogenic strains: Staphylococcus aureus MRSA (ATCC 43300), S. aureus MRSA (29213), S. aureus MSSA (ATCC 29213), S. epidermidis (ATCC 12228), Enterococcus faecalis (ATCC 29212), E. faecalis VRE (ATCC 51299), E. faecium (ATCC 19434), and Micrococcus luteus (ATCC 10240). Extracts were significantly more active than essential oils. The most susceptible strain was M. luteus, while the least susceptible was E. faecium. The antimicrobial activity correlated with a high concentration of xanthohumol rather than with the content of α-acids. Xanthohumol showed considerable activity against MRSA with an MIC value of 3.9 µg/mL.
Evidence strength: In vitro only. No human clinical trials have evaluated lupulin or lupulinum as an antimicrobial agent.
One study reveals that xanthohumol, besides its well-known anticancer properties, also possesses potent antiplatelet activity. Xanthohumol is the major prenylflavonoid of hops (0.1% to 1% on a dry weight basis). The daily intake of total prenylflavonoids through normal beer consumption is approximately 0.14 mg. Dietary intake of prenylflavonoids through normal beer consumption would not be sufficient to achieve plasma concentrations that could inhibit platelet activation.
Evidence strength: In vitro only. No human clinical trials have been conducted on antiplatelet effects of lupulin.
The following dosages are drawn directly from historical pharmacopeial sources and peer-reviewed clinical studies:
The appropriate dose of hops depends on several factors such as the user's age, health, and other conditions. At this time there is not enough scientific information to determine an appropriate range of doses for hops in general.
Both irritant and allergic effects have been described with Humulus lupulus. In hop harvesters, dermatitis has been attributed to mechanical abrasion by the rough hairs on the climbing stem. It has also been suggested that lupulin, the yellow powdery secretion of the glandular hairs on the scales of the strobiles, may be responsible for the irritation.
Skin contact with the plant causes dermatitis in susceptible people. Systemic and contact urticaria have been documented. Contact urticaria from dried hops occurred in a patient who had experienced urticaria and angioedema from peanut, chestnut, and banana. A patient who presented four times with systemic urticaria associated with arthralgia and fever has been reported, with investigation confirming allergy to hops.
Taking one tablet of a herbal sedative containing hop extract caused a relapse of dermatitis in a sensitized individual, demonstrating that the hop allergen responsible for contact allergy can also provoke reactions via the oral route.
Taking hops along with sedative medications may cause additive or excessive sleepiness. This interaction is rated as moderate. Medications that cause sleepiness are called sedatives. Some sedative medications include clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), and zolpidem (Ambien).
The use of phytoestrogens is frequently questioned regarding possible adverse effects associated with long-term consumption. The need for precise evidence and further investigations to define the safety risks related to the therapeutic use of 8-PN has been emphasized. While studies in postmenopausal women have shown the particular effectiveness of 8-PN in reducing hot flashes, strong stimulation of the uterus by 8-PN may be associated with the occurrence of adverse effects such as bleeding and may increase the risk of carcinogenesis.
Hop extract preparations are currently marketed as supplements, which makes control of the doses used difficult and increases the occurrence of uncontrolled self-treatment.
Owing to the presence of its essential oil, lupulin in quantities is liable to spontaneous combustion; a historic record of such combustion on board a vessel lying in Bremen harbor was documented in the American Journal of Pharmacy, 1893.
Unless carefully dried, lupulin soon loses its properties, which are impaired by keeping under all circumstances. It is always preferable to use it over the crude hop strobile for medicinal purposes.
The name "Lupulinum" also appears in homeopathic materia medica literature, where it is used in highly diluted preparations. Usage claims for homeopathic lupulinum products are based on homeopathic materia medica. There are no current federally recognized clinical or scientific studies in regard to the efficacy of homeopathic preparations, and the practice of homeopathic medicine is not accepted by all medical experts. The present article covers lupulinum as a phytopharmaceutical/herbal ingredient; claims made for highly diluted homeopathic preparations represent a categorically distinct tradition and are not supported by the scientific evidence discussed above.
Health conditions that Lupulinum may help support.
Body systems that Lupulinum may help support.