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Hops

  • Written by Shahrul
  • Updated on March 6, 2021


Plant Part Used

Strobiles

Active Constituents

Oleoresin, including alpha-bitter acids (humulone, cohumulone, adhumulone, valerianic acid) and beta-bitter acids (lupulone, colupulone, adlupulone) and their oxidative degradation products (2-methyl-3-buten-2-ol); flavonoids (kaempferol, astragalin, quercitin, rutin); tannins (gallocatechin); volatile oils, including beta-caryophyllene, farnescene, myrcene and humulene; prenylated flavonoids (including xanthohumol and 8-prenylnaringenin). (1) , (2) , (3), (24), (25)

[span class=alert] This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Hops have been used since the Roman times in brewing beer and other alcoholic beverages and as a traditional gastrointestinal, nerve, and sedative tonic. Hops are stated to possess sedative, hypnotic, antispasmodic, and topical bactericidal properties. (4) Traditional uses of hops include neuralgia, insomnia, excitability, topically for skin ulcerations, and primarily for restlessness associated with nervous tension. (5)

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

100-150mg (standardized extract), 1-3 times a day as needed.

Most Common Dosage

100mg (standardized extract), 1-3 times a day as needed.

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 5.2% bitter acids and/or 4% flavonoids per dose.

Uses

Frequently Reported Uses

  • Mild Hypnotic
  • Mild Sedative
  • Anti-Stress
  • Phytoestrogenic

Other Reported Uses

  • Antispasmodic
  • Antibacterial
  • Aromatic Bitter; Digestive Aid
  • Used In Combination With Other Herbs Such As Valerian Root And Passion Flower In Insomnia

 

Toxicities & Precautions

General

Hops has been reported safe in recommended doses.

Recommend caution while taking while driving an automobile or operating heavy machinery.

Health Conditions

Based on evidence that constituents contained in hops strobiles have estrogenic activity, use with caution in individuals susceptible to hormonally related cancers, such as breast, ovarian and prostate. (6)

Pregnancy/ Breast Feeding

If pregnant or nursing, consult a physician before use.

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.

Pharmacology

Antibacterial effect

Hops extracts have been reported to have antibacterial properties in laboratory animals, specifically against Gram-positive bacteria.(7) The constituents responsible for the antimicrobial activity appear to be humulone, lupulone and xanthohumol.(8),(9) The activity of the bitter acids toward Gram-positive bacteria is thought to involve primary membrane leakage. Resistance of Gram-negative bacteria to the bitter acids is attributed to phospholipid-containing outer membrane, as lupulone and humulone are inactivated by phospholipids.(10) Recent in vitro studies showed synergistic effects of hop constituents and several antibiotics in inhibiting Gram-positive bacteria and enhancing the inhibition of the antibiotics on Gram-negative bacteria.(27)

Antiviral effect

Xanthohumol, isoxanthohumol and iso-alpha acids were found to have low to moderate antiviral activity against several types of viruses.(28) Xanthohumol inhibited the HIV-1 reverse transcriptase,(29) the viral cytopathic effects and production of HIV-1 p24 antigen in C8166 lymphocytes. In addition to this, it was also shown to have inhibitory effect on the viral replication in peripheral blood mononuclear cells.(30)

Xanthohumol showed strong anti-BVDV (Bovine viral diarrhea virus, a surrogate for Hepatitis C virus) effect in a cell culture system. Apart from inhibition of the viral cytopathic effects, it inhibited BVDV E2 protein expression and reduced the viral RNA levels in a dose-dependent manner. When compared with drugs used for the treatment of chronic hepatitis C, xanthohumol’s antiviral effect was superior to ribavirin but weaker than alpha-interferon (IFN).(31) Interestingly, the combination of xanthohumol and IFN exhibited stronger antiviral activity.(32)

Sedative effect

Early research demonstrating the sedative action of hops in laboratory animals produced conflicting results.(11) However, it was later discovered that the contradictory results were mainly due to different method of extractions, dosages and routes of administration.(33) Sedative action of hops has been shown in many laboratory studies. Hops has been reported to increase narcotic-induced sleeping time.(12),(34) and improve sleep disturbances when given in combination with other sedative herbs.(13)

Human studies of the sedative action generally refer to hops being used in combinations with other sedative herbs. The efficacy of valerian-hops combination (Ze 91019) in treating insomnia was shown in several studies.(35),(36) The sedative effect of hops is still not fully understood. In vitro study reported that the hop component of Ze 91019 interact with serotonin and melatonin receptor subtypes which could explain its central action.(37)

Estrogenic effect

Hops has been reported to have a mild estrogenic activity, attributed to the presence of 8-prenylnaringenin (PN), isoxanthohumol, 6-PN and geranylated flavonoids. In in vitro study, 8-PN was reported to bind to both α- and β-estrogen receptors (ER),(38) with higher affinity for the ER-alpha receptors. 8-PN also has been regarded as an oestrogen agonist in female reproductive organs. It induced mitotic activity in the vaginal epithelium(39) and increased uterine weight of ovariectomised rats.(40) Human studies evaluating the benefit of hops in treating menopausal symptoms showed that 100 micrograms of 8-PN daily for 12-16 weeks able to improve menopausal discomforts.(41),(42)

Anti-cancer effect

Of recent interest are in vitro studies which reported that flavonoid constituents found in hops (including xanthohumol, dehydrocycloxanthohumol and isoxanthohumol) had antiproliferative activity (dose dependent) in certain human breast cancer, colon cancer, prostate cancer, thyroid cancer and ovarian cancer cells.(19),(20),(43),(44) This antiproliferative effect on various cancer cell lines may be due, in part, to inhibition of cytochrome P450 enzymes (including CYP1A1, CYP1B1 and CYP1A2) that activate carcinogens.(21) In studies on breast cancer cell lines, XN, IX and 8-PN were able to reduce oestrogen formation (by inhibiting aromatase), cell proliferation and induce apoptosis.(45),(46) In an in vivo study, XN prevented dimethyl-benz(a)antracene-induced preneoplastic mammary lesion formation.(47) In addition, XN has been shown in many in vitro studies to exert anticarcinogenic effects at different stages of carcinogenesis. It induced quinine reductase, an enzyme involved in detoxification of reactive metabolites,(48) protected DNA damage against procarcinogens, act as an antioxidant and anti-inflammatory agent and a free radical scavenger.(49),(50),(51),(52) XN also inhibited induced angiogenesis by suppressing endothelial cell invasion, migration and proliferation.(53),(54)

In another study on human colon cancer cell lines, hops proanthocyanidins were reported to exert cytotoxic effect by increasing the levels of intracellular reactive oxygen species, protein carbonyls and cytoskeletal disruption.(55)

Other effects

In vivo studies reported that isohumolones were able to reduce body weight and plasma triglycerol levels. It was shown that isohumolones modulated lipid metabolism via activation of peroxisome proliferator-activated receptors (PPARs).(56),(57),(58) The weight reduction effect of isohumolones was further tested in human and showed that 48 mg isohumolones per day for 12 weeks significantly decreased body weight of prediabetic patients.(59)

Isohumolones were also reported to have anti-hypertensive and anti-glycaemic effects in human studies.(60),(61)

The stimulating effects of hops on gastric secretion has been reported in laboratory animals.(22),(62) Hops reportedly exerts a strong spasmolytic action on smooth muscles when used as an extract.(23)

A recent in vivo study reported that 8-PN exerted a dose-dependent anaphrodisiac effect on naïve male rats.(63)

References

  1. View Abstract: Verschuere M, et al. Fractionation by SFE and Microcolumn Analysis of the Essential Oil and the Bitter Principles of Hops. J Chromatogr Sci. Oct1992;30(10):388-91.
  2. View Abstract: Yilmazer M, Stevens JF, Deinzer ML, et al. In Vitro Biotransformation of Xanthohumol, a Flavonoid from Hops (Humulus lupulus), by Rat Liver Microsomes. Drug Metab Dispos. Mar2001;29(3):223-231.
  3. View Abstract: Kumai A, et al. Extraction of the Hormonal Substance From Hop. Toxicol Lett. May1984;21(2):203-07.
  4. Newall CA, et al. Herbal Medicines: A Guide for Health Care Professionals. London: The Pharmaceutical Press; 1996:162-163.
  5. Bradley PR, ed. British Herbal Compendium. vol.1 Bournemouth: British Herbal Medicine Association; 1992:128-129.
  6. View Abstract: Milligan SR, Kalita JC, Pocock V, et al. The Endocrine Activities of 8-prenylnaringenin and Related Hop (Humulus lupulus L.) Flavonoids. J Clin Endocrinol Metab. Dec2000;85(12):4912-5.
  7. Teuber M, et al. Membrane Leakage in Bacillus subtilis 168 Induced by the Hop Constituents Lupulone, Humulone, Isohumulone and Humulinic Acid. Arch Mikrobiol. Dec1973;94(2):159-71.
  8. View Abstract: Langezaal CR, et al. Antimicrobial Screening of Essential Oils and Extracts of Some Humulus lupulus L. Cultivars. Pharm Weekbl Sci. Dec1992;14(6):353-56.
  9. View Abstract: Simpson WJ, et al. Factors Affecting Antibacterial Activity of Hop Compounds and Their Derivatives. J Appl Bacteriol. Apr1992;72(4):327-34.
  10. Teuber M, et al. Membrane Leakage in Bacillus subtilis 168 Induced by the Hop Constituents Lupulone, Humulone, Isohumulone and Humulinic Acid. Arch Mikrobiol. Dec1973;94(2):159-71.
  11. Bravo L, et al. Pharmacodynamic Study of the Lupulus’ (Humulus lupulus L.) Tranquilizing Action. Boll Chim Farm. May1974;13(5):310-15.
  12. Lee KM, et al. Effects of Humulus lupulus Extract on the Central Nervous System In Mice. Planta Medica. 1993;59(supp):A691.
  13. Bradley PR, ed. British Herbal Compendium. vol 1. Bournemouth: British Herbal Medicine Association; 1992:128-129.
  14. Wohlfart R, et al. Detection of Sedative-Hypnotic Active Ingredients in Hops. 5. Degradation of Bitter Acids to 2-methyl-3-buten-2-ol, a Hop Constituent With Sedative-Hypnotic Activity. Arch Pharm (Weinheim). 1983;316(2):132-37.
  15. View Abstract: Hansel R, et al. Sedative-Hypnotic Compounds in the Exhalation of Hops, II. Z Naturforsch. [C]. Dec1980;35(11-12):1096-97.
  16. Fenselau C, et al. Is Oestrogenic Activity Present in Hops? Food Cosmet Toxicol. Aug1973;11(4):597-603.
  17. View Abstract: Miranda CL, Stevens JF, Helmrich A, et al. Antiproliferative and Cytotoxic Effects of Prenylated Flavonoids from Hops (Humulus lupulus) in Human Cancer Cell Lines. Food Chem Toxicol. Apr1999;37(4):271-85.
  18. View Abstract: Milligan SR, et al. Identification of a Potent Phytoestrogen in Hops (Humulus lupulus L.) and Beer. J Clin Endocrinol Metab. Jun1999;84(6):2249-52.
  19. View Abstract: Miranda CL, Stevens JF, Helmrich A, et al. Antiproliferative and Cytotoxic Effects of Prenylated Flavonoids from Hops (Humulus lupulus) in Human Cancer Cell Lines. Food Chem Toxicol. Apr1999;37(4):271-85.
  20. View Abstract: Gerhauser C, Alt A, Heiss E, et al. Cancer chemopreventive activity of Xanthohumol, a natural product derived from hop. Mol Cancer Ther. Sep2002;1(11):959-69.
  21. View Abstract: Henderson MC, Miranda CL, Stevens JF, et al. In Vitro Inhibition of Human P450 Enzymes by Prenylated Flavonoids from Hops, Humulus lupulus. Xenobiotica. Mar2000;30(3):235-51.
  22. View Abstract: Krivenko VV, et al. Experience in Treating Digestive Organ Diseases with Medicinal Plants. Vrach Delo. Mar1989;(3):76-78.
  23. Caujolle F, et al. Spasmolytic Action of Hop. Agressologie. 1969;10(5):405-10.
  24. Verzele, M., Potter, M.D.E.. High-performance liquid chromatography of hop bitter substances. Journal of Chromatography. 1978;166:320–326.
  25. De Keukeleire J, Ooms G, Heyerick A, Roldan-Ruiz I, Van Bockstaele E, De Keukeleire D. Formation and accumulation of alpha-acids, beta-acids, desmethylxanthohumol, and xanthohumol during flowering of hops (Humulus lupulus L.) J Agric Food Chem. 16Jul2003;51(15):4436-4441.
  26. Zhang N, Liu Z, Han Q, Chen J, Lv Y. Xanthohumol enhances antiviral effect of interferon alpha-2b against bovine viral diarrhea virus, a surrogate of hepatitis C virus. Phytomedicine. Apr2010;17(5):310-316. Epub 2009 Sep 11.
  27. Natarajan P, Katta S, Andrei I, Babu Rao Ambati V, Leonida M, Haas GJ. Positive antibacterial co-action between hop (Humulus lupulus) constituents and selected antibiotics. Phytomedicine. Mar2008;15(3):194-201. Epub 2007 Dec 26.
  28. Buckwold VE, Wilson RJ, Nalca A, Beer BB, Voss TG, Turpin JA, Buckheit RW, Wei J, Wenzel-Mathers M, Walton EM, Smith RJ, Pallansch M, Ward P, Wells J, Chuvala L, Sloane S, Paulman R, Russell J, Hartman T, Ptak R. Antiviral activity of hop constituents against a series of DNA and RNA viruses. Antiviral Res. Jan2004;61(1):57-62.
  29. Matthée G, Wright AD, König GM. HIV reverse transcriptase inhibitors of natural origin. Planta Med. Aug1999;65(6):493-506.
  30. Wang Q, Ding ZH, Liu JK, Zheng YT. Xanthohumol, a novel anti-HIV-1 agent purified from Hops Humulus lupulus. Antiviral Res. Dec2004;64(3):189-194.
  31. Zhang N, Liu Z, Han Q, Chen J, Lou S, Qiu J, Zhang G. Inhibition of bovine viral diarrhea virus in vitro by xanthohumol: comparisons with ribavirin and interferon-alpha and implications for the development of anti-hepatitis C virus agents. Eur J Pharm Sci. 5Nov2009;38(4):332-340. Epub 2009 Aug 29.
  32. Zhang N, Liu Z, Han Q, Chen J, Lv Y. Xanthohumol enhances antiviral effect of interferon alpha-2b against bovine viral diarrhea virus, a surrogate of hepatitis C virus. Phytomedicine. Apr2010;17(5):310-316. Epub 2009 Sep 11.
  33. Zanoli P, Rivasi M, Zavatti M, Brusiani F, Baraldi M. New insight in the neuropharmacological activity of Humulus lupulus L. J Ethnopharmacol. 31Oct2005;102(1):102-106.
  34. Schiller H, Forster A, Vonhoff C, Hegger M, Biller A, Winterhoff H. Sedating effects of Humulus lupulus L. extracts. Phytomedicine. Sep2006;13(8):535-541. Epub 2006 Jul 24.
  35. Morin CM, Koetter U, Bastien C, Ware JC, Wooten V. Valerian-hops combination and diphenhydramine for treating insomnia: a randomized placebo-controlled clinical trial. Sleep. 1Nov2005;28(11):1465-1471.
  36. Koetter U, Schrader E, Käufeler R, Brattström A. A randomized, double blind, placebo-controlled, prospective clinical study to demonstrate clinical efficacy of a fixed valerian hops extract combination (Ze 91019) in patients suffering from non-organic sleep disorder. Phytother Res. Sep2007;21(9):847-851.
  37. Abourashed EA, Koetter U, Brattström A. In vitro binding experiments with a Valerian, hops and their fixed combination extract (Ze91019) to selected central nervous system receptors. Phytomedicine. Nov2004;11(7-8):633-638.
  38. Milligan SR, Kalita JC, Pocock V, Van De Kauter V, Stevens JF, Deinzer ML, Rong H, De Keukeleire D. The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids. J Clin Endocrinol Metab. Dec2000;85(12):4912-4915.
  39. Milligan S, Kalita J, Pocock V, Heyerick A, De Cooman L, Rong H, De Keukeleire D. Oestrogenic activity of the hop phyto-oestrogen, 8-prenylnaringenin. Reproduction. Feb2002;123(2):235-242.
  40. Overk CR, Guo J, Chadwick LR, Lantvit DD, Minassi A, Appendino G, Chen SN, Lankin DC, Farnsworth NR, Pauli GF, van Breemen RB, Bolton JL. In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin. Chem Biol Interact. 22Oct2008;176(1):30-39. Epub 2008 Jun 20.
  41. Heyerick A, Vervarcke S, Depypere H, Bracke M, De Keukeleire D. A first prospective, randomized, double-blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts. Maturitas. 20May2006;54(2):164-175.
  42. Erkkola R, Vervarcke S, Vansteelandt S, Rompotti P, De Keukeleire D, Heyerick A. A randomized, double-blind, placebo-controlled, cross-over pilot study on the use of a standardized hop extract to alleviate menopausal discomforts. Phytomedicine. May2010;17(6):389-396.
  43. Cook MR, Luo J, Ndiaye M, Chen H, Kunnimalaiyaan M. Xanthohumol inhibits the neuroendocrine transcription factor achaete-scute complex-like 1, suppresses proliferation, and induces phosphorylated ERK1/2 in medullary thyroid cancer. Am J Surg. Mar2010;199(3):315-318
  44. Delmulle L, Bellahcène A, Dhooge W, Comhaire F, Roelens F, Huvaere K, Heyerick A, Castronovo V, De Keukeleire D. Anti-proliferative properties of prenylated flavonoids from hops (Humulus lupulus L.) in human prostate cancer cell lines. Phytomedicine. 2006 Nov;13(9-10):732-734. Epub 2006 May 5.
  45. Monteiro R, Faria A, Azevedo I, Calhau C. Modulation of breast cancer cell survival by aromatase inhibiting hop (Humulus lupulus L.) flavonoids. J Steroid Biochem Mol Biol. Jun-Jul2007;105(1-5):124-130. Epub 2007 Jul 23.
  46. Brunelli E, Minassi A, Appendino G, Moro L. 8-Prenylnaringenin, inhibits estrogen receptor-alpha mediated cell growth and induces apoptosis in MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. Nov-Dec2007;107(3-5):140-148. Epub 2007 Jun 22.
  47. Gerhäuser C. Beer constituents as potential cancer chemopreventive agents. Eur J Cancer. Sep2005;41(13):1941-1954.
  48. Dietz BM, Kang YH, Liu G, Eggler AL, Yao P, Chadwick LR, Pauli GF, Farnsworth NR, Mesecar AD, van Breemen RB, Bolton JL. Xanthohumol isolated from Humulus lupulus Inhibits menadione-induced DNA damage through induction of quinone reductase. Chem Res Toxicol. Aug2005;18(8):1296-1305.
  49. Vogel S, Barbic M, Jürgenliemk G, Heilmann J. Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of chalcones and influence of A-ring modifications on the pharmacological effect. Eur J Med Chem. Jun2010;45(6):2206-2213. Epub 2010 Jan 29.
  50. Kac J, Plazar J, Mlinaric A, Zegura B, Lah TT, Filipic M. Antimutagenicity of hops (Humulus lupulus L.): bioassay-directed fractionation and isolation of xanthohumol. Phytomedicine. Mar2008;15(3):216-220. Epub 2007 Oct 23.
  51. Plazar J, Filipic M, Groothuis GM. Antigenotoxic effect of Xanthohumol in rat liver slices. Toxicol In Vitro. Mar2008;22(2):318-327. Epub 2007 Sep 25.
  52. Gerhäuser C. Beer constituents as potential cancer chemopreventive agents. Eur J Cancer. Sep2005;41(13):1941-1954.
  53. Albini A, Dell’Eva R, Vené R, Ferrari N, Buhler DR, Noonan DM, Fassina G. Mechanisms of the antiangiogenic activity by the hop flavonoid xanthohumol: NF-kappaB and Akt as targets. FASEB J. Mar2006;20(3):527-529. Epub 2005 Dec 30.
  54. Pepper MS, Hazel SJ, Hümpel M, Schleuning WD. 8-prenylnaringenin, a novel phytoestrogen, inhibits angiogenesis in vitro and in vivo. J Cell Physiol. Apr2004;199(1):98-107.
  55. Chung WG, Miranda CL, Stevens JF, Maier CS. Hop proanthocyanidins induce apoptosis, protein carbonylation, and cytoskeleton disorganization in human colorectal adenocarcinoma cells via reactive oxygen species. Food Chem Toxicol. Apr2009;47(4):827-836.
  56. Shimura M, Hasumi A, Minato T, Hosono M, Miura Y, Mizutani S, Kondo K, Oikawa S, Yoshida A. Isohumulones modulate blood lipid status through the activation of PPAR alpha. Biochim Biophys Acta. 5Sep2005;1736(1):51-60.
  57. Miura Y, Hosono M, Oyamada C, Odai H, Oikawa S, Kondo K. Dietary isohumulones, the bitter components of beer, raise plasma HDL-cholesterol levels and reduce liver cholesterol and triacylglycerol contents similar to PPARalpha activations in C57BL/6 mice. Br J Nutr. Apr2005;93(4):559-567.
  58. Yajima H, Noguchi T, Ikeshima E, Shiraki M, Kanaya T, Tsuboyama-Kasaoka N, Ezaki O, Oikawa S, Kondo K. Prevention of diet-induced obesity by dietary isomerized hop extract containing isohumulones, in rodents. Int J Obes (Lond). Aug2005;29(8):991-997.
  59. Obara K, Mizutani M, Hitomi Y, Yajima H, Kondo K. Isohumulones, the bitter component of beer, improve hyperglycemia and decrease body fat in Japanese subjects with prediabetes. Clin Nutr. Jun2009;28(3):278-284. Epub 2009 Apr 23.
  60. Yajima H, Ikeshima E, Shiraki M, Kanaya T, Fujiwara D, Odai H, Tsuboyama-Kasaoka N, Ezaki O, Oikawa S, Kondo K. Isohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor alpha and gamma and reduce insulin resistance. J Biol Chem. 6Aug2004;279(32):33456-33462. Epub 2004 Jun 3.
  61. Obara K, Mizutani M, Hitomi Y, Yajima H, Kondo K. Isohumulones, the bitter component of beer, improve hyperglycemia and decrease body fat in Japanese subjects with prediabetes. Clin Nutr. Jun2009;28(3):278-284. Epub 2009 Apr 23.
  62. Kurasawa T, Chikaraishi Y, Naito A, Toyoda Y, Notsu Y. Effect of Humulus lupulus on gastric secretion in a rat pylorus-ligated model. Biol Pharm Bull. Feb2005;28(2):353-357.
  63. Zanoli P, Zavatti M, Rivasi M, Benelli A, Avallone R, Baraldi M. Experimental evidence of the anaphrodisiac activity of Humulus lupulus L. in naïve male rats. J Ethnopharmacol. 17Aug2009;125(1):36-40. Epub 2009 Jun 26.

in this scope
Malaysian Herbal Monograph​
Medicinal Herbs & Plants Monographs​
Traditional Chinese Medicine Herbs (Professional Data)
Herbal Medicines Compendium (HMC) - U.S​

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