Best known for their role in beer brewing, the female flowers of the hop are being increasingly used in supplements for insomnia, anxiety, and menopausal symptoms. Read more to learn about their active components, how they work, and what cell research can tell us.
What Are Hops?
Hops are the female flowers of hop (Humulus lupulus L.), a climbing plant belonging to the same family as hemp (Cannabaceae). Hop most likely originated in China, Southern Caucasus and Siberia, or Mesopotamia, from where it spread to Japan, America, and Central Europe [1, 2].
Due to its role in beer brewing, which accounts for 98% of its use, hop is nowadays cultivated in all warmer regions. The different compounds in hops add a bitter flavor to beer, prevent the growth of unwanted microorganisms during the brewing process, and stabilize foam [1].
Hops in Traditional Medicine
Hops have long been used in traditional medicine, especially for [1, 2]:
- Insomnia
- Nervousness
- Restlessness
- Lack of appetite
- Digestive issues
- Painful teeth, ears, and nerves
- Headache
- Rheumatism
- Tuberculosis
- Silicosis
- Asbestosis
- Leprosy
- Pneumonia
- Kidney stones and urinary inflammation
- Water retention
- Spasms
- Skin ulcers and injuries
- Foot odor
- Constipation
- Blood ‘purification’
However, many of these uses remain scientifically unproven.
In 2003, the European Scientific Cooperative on Phytotherapy approved the use of hops as a remedy for mood disorders such as [1, 2]:
- Excitability
- Anxiety
- Restlessness
- Sleep disturbances
Due to this, research has recently focused on identifying the main biologically active compounds present in hops [2].
Although they are not approved by the FDA, supplements containing hops extract are marketed for improving mood disorders and menopausal symptoms. Some commercial brand names are [3, 4]:
- Melcalin HOPs
- MenoHop
Components
The main active components of the hop plant are found in the female flowers. Volatile oils, bitter acids, and prenylflavonoids are produced by hair-shaped glands, while the rest of flavonoid types are most abundant in seeds and specialized leaves [1, 2].
The volatile oils of hops (0.3-1% of hops weight) are very rich in terpenoids, especially [1, 5]:
- Myrcene
- β-Caryophyllene
- Humulene
- Farnesene
Hops terpenoids are partly responsible for their purported anti-inflammatory, anticancer, antioxidant, and antimicrobial activities [5].
Bitter acids (5-20% of hops weight) are essential to the beer brewing process and can be classified as [1, 6]:
- α-Acids: The main ones are humulone (35-70% of total α-acids), cohumulone (20-65%), and adhumulone (10-15%).
- β-Acids: Such as lupulone (30-55% of total β-acids), colupulone (40-58%), and adlupulone (6-30%).
Other, less abundant bitter acids include pre- and post- lupulone and humulone. Hops α-acids undergo some chemical reactions that convert them to iso-α-acids [1].
Hops also contain six different classes of flavonoids [2]:
- Flavan-3-ols: Catechin, gallocatechin
- Proanthocyanidins: Procyanidins B1, B3, and B4, proanthocyanidin C2
- Flavonols: Quercetin, kaempferol, myricetin
- Flavanones: Naringenin
- Flavonol glycosides: Quercetin and kaempferol glycosides
- Prenylflavonoids: Xanthohumol, 8-prenylnaringenin
Among flavonoids, xanthohumol (1% of hops’ dry weight) is the most abundant and important component. It has numerous properties and can be converted to isoxanthohumol in the stomach [7, 1].
Gut bacteria can transform isoxanthohumol to 8-prenylnaringenin, which has strong female sex hormone activity [8, 1].
Although to a lower extent than in hops, active compounds can also be found in other parts of the hop plant such as male flowers (xanthohumol and bitter acids) and leaves (xanthohumol, volatile compounds, and bitter acids) [9, 1].
Mechanisms of Action
Several studies have investigated the mechanisms of the main active components of hops extract. Importantly, these studies were done in animals and cells. The effects of these compounds may not be the same in humans.
1) Female Sex Hormone Mechanisms
Some plant substances are called phytoestrogens because they can interact with female sex hormone (estrogen) receptors and trigger some of their responses. The main phytoestrogen found in hops is 8-prenylnaringenin [10, 11].
Female sex hormones are recognized by two kinds of cell receptors [12]:
- ERα: Mostly present in the inner layer of the uterus (endometrium), ovaries, bones, and breast glands
- ERβ: Most common in fatty tissue, the inner lining of blood vessels (endothelium), brain, kidneys, and prostate
Although most phytoestrogens preferentially bind to ERβ, 8-prenylnaringenin binds to ERα. In the tissues where this receptor is found, 8-prenylnaringenin caused the following effects in animal studies [10, 8]:
- Reduced bone mass loss [13]
- Reduced production of the hormones LH and FSH [14]
- Increased production of the hormones prolactin and IGF-1 [14]
- Increased breast secretion [15]
- Increased tissue growth in the vagina and uterus [16, 15]
However, 8-prenylnaringenin can also have anti-female sex hormone effects by blocking aromatase, a key enzyme in estrogen production [17].
2) Sedative and Anti-Stress Mechanisms
GABA is the main sleep-promoting neurotransmitter. Low GABA levels are also associated with disorders such as anxiety, depression, and hyperactivity [18].
In cell studies, hops extract increased GABA activity but blocked GAD, the enzyme that produces this neurotransmitter [19, 20].
In mice, both α- and β-bitter acids had antidepressant activity and increased the sedative effect of ketamine but they differed in their effect on sleepiness induced by pentobarbital. While α-acids enhanced its effect, β-acids reduced it. Only β-acids reduced the activity of GABA [21, 22, 23].
Although xanthohumol stimulates the binding of GABA to its receptors, it failed to reduce anxiety in a study in rats [24, 25].
A fixed valerian-hops combination promoted sleepiness in mice and rats by binding to four different types of receptors:
3) Potential Anticancer Mechanisms
Based on mechanistic studies, Hops extract and one of its main compounds, xanthohumol, may reduce cancer risk by preventing cancer-causing substances from damaging DNA [29, 30, 31].
Xanthohumol also killed cancer cells by blocking proteins that promote cell survival, such as:
- Bcl-2 [32], Survivin [33]
- mTOR [33], Akt [33]
- NF-κB [34]
- Topoisomerase [35]
- Aromatase [36]
- STAT3 [37]
Other mechanisms by which xanthohumol may cause cancer cell death include:
- Increased superoxide production [38]
- Activation of unfolded protein response [39]
- Reduced nitric oxide production [40]
- Reduced production of cytokines (MCP-1 and TNFα ) [41]
- Activation of programmed cell death [42, 43, 44] and cancer cell autophagy [45]
- Increased production of proteins that block cell growth and division (p21 and p53) [46]
Xanthohumol may also prevent the formation of new blood vessels in tumors by blocking growth pathways (NF-κB and Akt) [47].
Xanthohumol may reduce the production of proteins that promote resistance to radiation and chemotherapy (EGFR, STAT3, and MDR1) [48, 49].
Finally, xanthohumol reduces the ability of cancer cells to invade other tissues by:
- Blocking prostaglandin production [50]
- Reducing the production of a protein that allows cancer cells to migrate outside the tumor (MMP-9) [32]
- Stimulating an anti-invasive protein complex (E-cadherin/catenin) [51]
- Reducing the production of chemokine receptors (CXCR4) [52] and cell attachment proteins (ICAM-1) [53]
These anticancer effects have been studied in cells and animals at high dosages, but often this doesn’t translate to benefits in humans, especially at normal dosages.
4) Antioxidant Mechanisms
Reactive oxygen species are formed through chemical reactions in the body and cause oxidative damage to DNA, proteins, and fatty molecules. Plant flavonoids prevent the oxidative damage of reactive oxygen species by [54, 55]:
- Breaking them down
- Blocking the enzymes that produce them
- Retaining the minerals required for their production
Xanthohumol and other hops flavonoids activated the following antioxidant proteins:
Hops compounds, especially xanthohumol, have proven antioxidant effects in the liver, brain, heart, kidneys, lungs, and blood vessels [60, 61, 62, 63].
Other hops flavonoids, especially myricetin, had antioxidant effects in white blood cells (lymphocytes) [64].
5) Anti-Inflammatory Mechanisms
Both hops extract and xanthohumol have several proven anti-inflammatory effects, including:
- Reducing T cell growth and killer T cell development [65]
- Blocking proinflammatory proteins (TLR4, NF-κB, CREB, COX1, and COX2) [66, 67, 68, 69]
- Decreasing cytokine (IL-2, IL-6, IL-12, IFN-γ, MCP-1, and TNF-α) and antibody (IgE) production [65, 41, 66, 70, 71]
- Reducing histamine release [72]
- Blocking nitric oxide production [40]
6) Fat/Cholesterol-Lowering Mechanisms
Xanthohumol blocks a key enzyme in triglyceride production (diacylglycerol acyltransferase) and the protein that binds newly formed triglycerides to lipoproteins (MTP). This results in a decreased release of the lipoprotein that transports triglycerides through blood (apolipoprotein B) [73, 74, 75, 76].
Xanthohumol also reduces cholesterol buildup inside the arteries by preventing damage to LDL and blocking the protein that transports this fatty molecule from HDL to LDL (cholesteryl ester transfer protein) [77, 78, 79].
Xanthohumol reduces the development and stimulates the death of fatty cells by reducing PPAR-gamma levels, which lowers total body fat accumulation. In turn, isohumulones reduce blood triglyceride levels by activating PPARα. In the liver, xanthohumol prevents triglyceride buildup by binding to the farnesoid X receptor (FXR), which decreases the levels of an enzyme that promotes fat production and fatty cell development (SRBEP1c) [80, 81, 82, 83].
7) Sugar-Lowering Mechanisms
The simultaneous activation of PPAR-alpha and PPAR-gamma by isohumulones lowers blood sugar levels by reducing insulin resistance. Hops bitter acids also activate the bitter taste receptors and stimulate the production of GLP-1, a protein that triggers insulin production in response to sugar [81, 84].
Xanthohumol lowers blood sugar levels by:
- Binding to the farnesoid X receptor [82, 85]
- Blocking sugar uptake [86]
- Blocking an enzyme that produces sugar from complex carbohydrates (α-glycosidase) [87]
While some hops flavonoids (e.g., quercetin) also reduce sugar uptake, others (e.g., catechin) increase it. The hops flavonoids catechin, epicatechin, quercetin, and rutin also lower blood sugar levels by stimulating the growth of the cells that produce insulin (β-cells) [86, 88].
Side Effects & Precautions
Keep in mind that the safety profile of hops and their active compounds is relatively unknown given the scarcity of clinical studies. The list of side effects below is, therefore, not a definite one. You should consult your doctor about other potential side effects based on your health condition and possible drug or supplement interactions.
Although no side effects derived from its use as a medicinal supplement have been reported, hops can trigger allergic reactions in sensitive people, especially in those exposed to high amounts [1].
In workers harvesting and processing hops, inhaling hops dust caused [89, 90, 91, 92]:
- Asthma
- Allergic rhinitis
- Chronic obstructive pulmonary disease
- Bronchial irritation and inflammation
- Dry cough
- Breathing difficulties
- Reduced lung function
Additionally, exposure to hops may cause other allergic symptoms such as [93+, 94+, 95]:
- Eczema
- Skin redness
- Fluid buildup in the eyelids
- Conjunctivitis
Due to the lack of studies investigating its effects, hops extract should not be used by children younger than 3 years old or women who are pregnant or breastfeeding.
Although some preliminary evidence suggests that 8-prenylnaringenin has anticancer activity, it may stimulate the growth of tumors with female sex hormone receptors (estrogen-positive) and interfere with some breast cancer therapies due to its capacity to bind to estrogen receptors. People with a history of estrogen-positive cancer or receiving breast cancer therapy should contact their doctors before taking hops extract [96, 97, 17, 98].
Hops 8-prenylnaringenin alters the production and effects of female sex hormones, which can lead to fertility problems in premenopausal women. Therefore, young women may want to avoid high dosages of phytoestrogen supplements over extended periods [99].
Drug Interactions
The hops compounds xanthohumol and lupulone increased the antibacterial power of the following antibiotics [100]:
- Polymyxin
- Ciprofloxacin
- Tobramycin
In a study in rats, xanthohumol increased the effect of midazolam in reducing anxiety [25].
In a study in mice, the extracts of two hop varieties (Aroma and Magnum) reduced the hypnotic effect of pentobarbital and diazepam. In both cases, Magnum was the variety with the strongest effect [101].
In another study, the excitatory effect of cocaine (measured as increased spontaneous movement) was totally blocked by Magnum and partially blocked by wild plant extract. Aroma, Magnum, and wild plant extracts stimulated the pain-relief effect of Tylenol, with Aroma showing a stronger activity than the other two. Hops extract enhanced the effects of Tylenol by slowing down its breakdown in the liver [102, 103].
Due to its sedative effect, hops extract should not be mixed with alcohol or with other medications causing sleepiness, such as [104, 105]:
- Clonazepam
- Lorazepam
- Phenobarbital
- Zolpidem
- Propofol
Hops may increase the effect of several drugs in the body by blocking the following cytochrome P450 enzymes that break them down [106, 107]:
Genetics/Genetic Predispositions
In the liver and bowel, the enzyme CYP1A2 produces 8-prenylnaringenin from xanthohumol and isoxanthohumol, while CYP2C8 and CYP2C19 convert 8-prenylnaringenin and isoxanthohumol to other compounds with lower female sex hormone activity. Variants of these proteins may increase or reduce the female sex hormone effects of hops [108].
Variants of Akt, Bcl-2, mTOR, aromatase, and STAT3 that change their capacity to bind to xanthohumol may increase or reduce the anticancer effect of this hops component [33, 109, 36, 37].
Similarly, variants of NF-κB, COX1, and COX2 may be more or less susceptible to blocking by hops components and thus alter their anti-inflammatory effects [67, 68, 69].
The antioxidant effect of hops extract can be altered in people with versions of Nrf2 and NQO1 that change the capacity of these proteins to bind to hops flavonoids [56, 59].
Variants of PPAR-alpha and PPAR-gamma may have increased or reduced capacity to bind to lupulones. Similarly, farnesoid X receptor versions may have altered capacity to bind to xanthohumol. In both cases, this may alter their effects on blood sugar and fatty molecule levels [81, 82].
Dosage and Toxicity
Because hops extract is approved by the FDA as a food additive but not as a remedy for any conditions, there is no official dose. Supplement manufacturers and users have established unofficial guidelines based on trial and error.
The optimal dose of 8-prenylnaringenin for menopausal discomfort in one study was 100-250 μg 1x/day [4, 110, 111].
The recommended dose for mood disorders such as anxiety, restlessness, and depression is 200 mg hops extract 2x/day [3].
Based on their long-term use in brewing and traditional medicine, hops are generally recognized as safe [112].
A standardized hops extract (21 mg xanthohumol, 1.3 mg 6-prenylnaringenin, 0.8 mg isoxanthohumol, 0.25 mg 8-prenylnaringenin) taken up to 4x/day for one week had no toxicity signs in a study on 5 postmenopausal women [113].
In rats, a study found no adverse effects derived from up to 4000 mg hops extract/ kg body weight per day. However, high xanthohumol doses (0.5% of diet or 1000 mg/kg body weight) reduced liver weight and breast gland development in another study. Males taking xanthohumol before mating had a higher proportion of male offspring [114, 115].
Dogs that took boiled hops residues experienced a strong malignant reaction characterized by [116]:
- Increased body temperature
- Restlessness
- Panting
- Vomiting
- Stomach pain
- Seizures
- Death (in 4 out of 5 cases)
User Experiences
The opinions expressed in this section are solely those of users who may or may not have medical or scientific training. Their reviews do not represent the opinions of SelfHacked. SelfHacked does not endorse any specific product, service, or treatment.
Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice from your doctor or other qualified healthcare providers because of something you have read on SelfHacked. We understand that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
Most people took hops supplements for insomnia and anxiety. Users were generally happy with the results and reported being able to sleep longer and feeling more relaxed without experiencing side effects such as drowsiness.
Dissatisfied users complained that the supplement had little or no effect. Only one male user reported mild unwanted female sex hormone effects, which he didn’t describe in detail.
Similarly, women taking hops supplements for menopausal symptoms were mostly happy and reported experiencing fewer hot flashes. In some cases, the users complained not feeling any results.
A few users took hops supplements to reduce inflammation and pain. They all reported satisfactory outcomes.
Despite the lack of scientific evidence to back this claim [117, 118], a few users reported satisfactory results when using hops extract for breast enlargement.
Takeaway
Hops are the female flowers of hop (Humulus lupulus L.), a climbing plant belonging to the same family as hemp (Cannabaceae). 98% of the modern use of hops is in beer brewing, but research is ongoing into its potential health benefits.
Hops contain many active compounds, including flavonoids and phytoestrogens. These phytoestrogens can bind to estrogen receptors in human cells, while the flavonoids have demonstrated many interactions with cellular components. Hops may promote the release of GABA, turn on the cell’s antioxidant mechanisms, suppress inflammation, and prevent the release of sugars.
Hops are considered safe to consume, but there is no currently accepted dose for health purposes, and its safety profile in pregnant women and children is incomplete.
