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CN XANTHOHUMOL - THE MIRACLE MOLECULE
FROM ANTI-INFLAMMATORY TO ANTICANCER AND ANTI-NEURODEGRADATION PROPERTIES
See other articlesRESEARCH ON XANTHOHUMOL
Xanthohumol is a flavonoid found in hop cones (Humulus lupulus L.). Research on it began in the second half of the 20th century and has been developing rapidly since the 1990s. Hundreds of experiments have been conducted on xanthohumol, examining its antioxidant, anti-inflammatory, antifungal, neuroprotective, anticancer, immunomodulatory, and metabolic-supporting properties.
Research on xanthohumol is being conducted both in vitro (in laboratory conditions) and in vivo (in animals), and clinical trials in humans are also increasingly common. Many of these studies indicate that xanthohumol has enormous potential for maintaining good health. This may be the "silver bullet" the world has been searching for for years.
Inflammation is a natural process that helps our bodies fight infections and injuries, but when it persists for too long, it becomes a problem. Chronic inflammation is the root of many diseases, from heart disease to diabetes to depression.
Action of xanthohumol
The effects of xanthohumol are impressive, as it has the ability to effectively suppress inflammatory processes in the body. Laboratory and human studies have shown that even small doses of this substance can inhibit the activity of key inflammation regulators, such as the NF-κB pathway and the NLRP3 inflammasome [1], leading to a reduction in the production of proinflammatory cytokines and an enhancement of the cells' natural antioxidant mechanisms [2]. As a result, xanthohumol supports the body in reducing chronic inflammation, which underlies many diseases, including atherosclerosis and type 2 diabetes.
Reduces inflammation
One example is osteoarthritis, where xanthohumol inhibited cartilage degradation in laboratory studies. Besides inhibiting the production of inflammatory cytokines, xanthohumol also limits the activation and transfer of factor C/EBPβ to the cell nucleus, which is responsible for turning on genes associated with cartilage degradation. Furthermore, it increases the production of type II collagen and aggrecan, which are crucial for cartilage health, and their absence leads to its destruction [3].
ACTION OF XANTHOUMOL
True proof of xanthohumol's effect on inflammatory processes. A preliminary clinical study suggested that xanthohumol supplementation may be associated with improved inflammatory markers and a better course of coronavirus disease.
Administering xanthohumol during standard treatment significantly reduced mortality, shortened the duration of illness, and lowered levels of inflammatory markers in the body. This may hold the answer to future epidemiological challenges [4].
ANTIOXIDANT PROPERTIES AND DISEASE PREVENTION
Antioxidants are molecules that neutralize harmful free radicals in the body. Free radicals are unstable molecules that can cause oxidative damage to our cells, leading to chronic inflammation and the development of disease.
Antioxidants prevent or delay this damage by neutralizing free radicals before they can cause harm. Scientists have discovered that in this case, the effects of xanthohumol are equally impressive, as it has very powerful antioxidant properties and effectively neutralizes free radicals, which damage cells and accelerate the aging process [5].
GUARDIAN OF THE GLYCOCALIX – THE PROTECTIVE SHIELD OF CELLS
The glycocalyx is a thin, highly hydrated layer of glycoproteins and proteoglycans that covers the outer surface of almost all cells in our body. It acts as an invisible shield, protecting cells from mechanical and chemical damage by creating a barrier that protects the cell membrane from harmful external factors. In this way, it helps them function properly. Thanks to this layer, cells can recognize and communicate with each other.
The glycocalyx has another key function – it supports the immune system in recognizing different cells and enables proper intercellular communication, which is also crucial during the development of the entire organism. The composition and arrangement of specific sugars on the surface of each cell allows for mutual identification and interaction.
Furthermore, the glycocalyx plays an important role in cell signaling and helps protect intestinal cells from the effects of digestive enzymes, which is crucial for maintaining their integrity in the challenging environment of the gastrointestinal tract.
HOW DOES XANTHOUMOL HELPS PROTECT THE GLYCOCALIX?
The mechanism of glycocalyx degradation can be compared to the action of "molecular scissors" that cut through its sugar-protein chains. Important enzymes involved in this process include:
heparanase breaks down heparan sulfates, which are the main component of the glycocalyx
hyaluronidase destroys hyaluronic acid
matrix metalloproteinases break down proteins that hold the glycocalyx structure
Xanthohumol acts as a "molecular brake" on these enzymes. It reduces their activity and the production of their genes. Furthermore, xanthohumol indirectly stabilizes the structure of the glycocalyx by limiting the expression and action of degradative enzymes, which helps it maintain its shape and stability. As a result, xanthohumol not only stops its destruction but also supports its integrity [6], [7].
Xanthohumol not only inhibits glycocalyx breakdown but also supports its effective regeneration in the body. It stimulates various repair mechanisms, including enhancing the production of structural proteins such as syndecan and perlecan, which play a crucial role in glycocalyx stability. Preliminary data suggest that xanthohumol may support the expression of genes involved in the synthesis of glycosaminoglycans—the main components of this layer—and protect it from oxidative damage [8], [9].
GLYCOCALIX IN ENDOTHELIAL CELLS OF BLOOD VESSELS
The endothelial glycocalyx is relatively thicker and more complex than that of other cell types. It has important functions: regulating how easily blood flows through vessels, protecting vessels from damage, and transmitting signals between cells.
It helps prevent clots and regulates blood pressure.
This layer reduces friction between cells, preventing them from sticking together.
For example, on the surface of erythrocytes (red blood cells), the glycocalyx provides a smooth coating, allowing them to move freely through blood vessels without sticking to each other or the vessel walls.
CARDIOVASCULAR PROBLEMS
When this layer is damaged, for example, by disease, infection (e.g., sepsis, COVID-19), stress, or other factors, vessels become more permeable, leading to serious cardiovascular problems such as atherosclerosis or inflammatory clots.
Diseases such as diabetes, hypertension, trauma, and surgery can affect the degradation of the glycocalyx, especially when blood sugar or salt levels in the body are too high [10].
ANTIOXIDANT SHIELD
Xanthohumol breaks the vicious cycle of inflammation that worsens the glycocalyx. It reduces the adhesion of white blood cells to vessels, reduces the release of proinflammatory cytokines (TNF-α, IL-6), and strengthens the integrity of the junctions between endothelial cells [11], [12].
It also acts as an antioxidant shield – neutralizing free radicals and activating natural protective enzymes (HO-1, NQO1) via the NRF2-ARE pathway, protecting the glycocalyx from oxidative stress [13].
Improving endothelial function thanks to xanthohumol increases vascular elasticity and their ability to regulate blood pressure. Xanthohumol influences calcium signaling in endothelial cells, which has a beneficial effect on the entire vascular system [14].
TREATMENT OF COMPLICATIONS
Protecting the glycocalyx helps prevent atherosclerosis, reduces the risk of blood clots, and supports vascular repair after injury, making xanthohumol an important component of cardiovascular disease prevention [15].
In critical illnesses such as sepsis, xanthohumol can reduce vascular leakage, control excessive inflammation, and protect the blood-tissue barrier, which is important for treating complications [16], [17].
In chronic diseases (diabetes, hypertension, autoimmune diseases), xanthohumol slows glycocalyx degradation associated with chronic inflammation, supports vascular regeneration, and improves microcirculation, which may prevent vascular complications [18].
Due to its antioxidant and anti-inflammatory properties, xanthohumol also protects vessels from aging-related damage, making it a potential preventative measure for age-related vascular diseases.
In summary, the glycocalyx is a universal, multifunctional protective and communication layer for almost every cell. Therefore, its protection and regeneration, for example, through xanthohumol, harmonizes the functioning of most systems—from the immune to the nervous system—supporting homeostasis throughout the body at the cellular level.
XANTHOUMOL'S CANCER FIGHTING POTENTIAL
Cancer is a leading cause of death worldwide. Cancer development and progression is a complex process that involves various genetic and environmental factors. Studies have shown that xanthohumol exhibits a broad spectrum of anticancer effects through multi-target molecular mechanisms. These include:
Inducing cancer cell death (apoptosis) Xanthohumol helps "order" the death of diseased cancer cells. Normally, the diseased body clears itself through the process of programmed cell death, or apoptosis, but cancer cells often evade this mechanism. Xanthohumol can restore this process by activating proteins in cancer cells that cause the cells to turn off many of their own "defense mechanisms," leading to their death. [19]
Xanthohumol activates key apoptotic pathways by:
Mitochondrial pathway increases the expression of proapoptotic proteins (e.g., Bax, AIF) and decreases the amount of antiapoptotic proteins (e.g., Bcl-2, Bcl-XL), which causes loss of mitochondrial function and release of signals for cell death [20]
Activation of caspases stimulates caspase enzymes (3, 8, 9) to break down proteins and DNA [21]
Trail p53 increases the level of p53 protein, which stops cell division and triggers apoptosis [22]
Inhibiting the reproduction of cancer cells Xanthohumol halts the cancer cell life cycle by blocking the process of division and multiplication. It stops DNA duplication and blocks the PI3K/Akt/mTOR, ERK1/2, and NF-κB signaling pathways that control cell proliferation [23]
Blocking the formation of blood vessels around the tumor (angiogenesis) Xanthohumol inhibits the formation of new blood vessels that supply oxygen and nutrients to the tumor [24], [25]
Prevention of metastasis Xanthohumol strengthens the body's protective barriers and hinders the spread of cancer cells [26]
Anti-inflammatory effect Xanthohumol reduces the level of substances responsible for chronic inflammation that promote the development of cancer [27]
Disruption of energy metabolism in cancer cells Xanthohumol inhibits glycolysis (the process of energy production by cancer cells) by inhibiting hexokinase 2 and the EGFR-Akt-HK2 pathway, limiting glucose consumption and lactate production and promoting apoptosis [28], [29]
Moreover, xanthohumol acts selectively against cancer cells, showing greater toxicity towards them than towards healthy cells [30].
EXAMPLES OF CANCER CONDITIONS FOR WHICH XANTHOUMOL HAS BEEN USED:
Breast cancer [31]
Prostate cancer [32]
Lung cancer [33]
Nasopharyngeal carcinoma [34]
Cervical cancer [35]
Bile duct cancer [36]
Multiple myeloma [37]
Pancreatic cancer [38]
Glioblastoma multiforme [39]
Colon cancer [40]
Laryngeal cancer [41]
Leukemia [42]
Hepatocellular carcinoma [43]
Colon cancer [44]
Melanoma [45]
Lung glandular cancer (adenocarcinoma) [46]
Liver cancer [47]
Stomach cancer [48]
EFFECTIVENESS OF USE WITH CHEMOTHERAPY
According to laboratory experiments, xanthohumol can "boost" the effects of chemotherapy, facilitating the killing of cancer cells and weakening their resistance [49].
For this reason, combining xanthohumol with chemotherapy should only be done as part of a trial or with the explicit consent of the oncology team, as this is still a research direction, not a standard of care [50].
Mechanism of supporting chemotherapy at the molecular level
Xanthohumol may increase the sensitivity of colon cancer cells to standard drugs (e.g., 5-FU and oxaliplatin), which in practice means that cancer cells can be more easily "killed" by chemotherapy [51].
Administering xanthohumol before irinotecan (SN38) in cell models resulted in a synergistic effect, resulting in more dead cancer cells with the same or lower drug load [52].
Xanthohumol may reduce the activity of proteins responsible for drug resistance by actively effluxing drugs from cells (MDR1/ABCB1 and related proteins), making cells more susceptible to therapy [53].
It also acts as an "off switch" for important cancer cell survival signals (Wnt/β-catenin, NF-κB, Notch), further facilitating the effectiveness of chemotherapy [54].
What the models show
In 3D models of breast and lung cancer, xanthohumol reduced invasiveness and blocked the cell cycle, suggesting potential as an adjunct to combination therapy [55].
In pancreatic cancer, combining xanthohumol with plumbagin produced a more potent effect than either compound alone, illustrating the concept of combination synergy [56].
Studies on colon cancer stem cells have shown that xanthohumol combined with chemotherapy significantly increased treatment efficacy by reducing proliferation and inhibiting cell self-renewal (“stemness”) [57].
Sequential administration of xanthohumol and SN38 resulted in synergistic tumor cell death with reduced chemotherapeutic burden [58].
These studies highlight the ability of xanthohumol to enhance chemotherapy outcomes by sensitizing tumor cells and limiting their defense mechanisms.
SUPPORT IN MEDICATION THERAPIES
Xanthohumol may act synergistically or supportively with selected non-chemotherapeutic drugs, although research to date has focused primarily on specific substances and specific pharmacological effects. Xanthohumol has been shown to support the activity of some nonsteroidal and antitubercular drugs and improve the safety profile of the therapy through its anti-inflammatory and antioxidant properties, without causing significant adverse interactions with commonly used medications.
Combination with antibiotics for infections Xanthohumol can be combined with selected antibiotics, significantly increasing their antibacterial efficacy. Studies have shown that interaction with ciprofloxacin or polymyxin B enhances the therapeutic effect, helping to combat resistant strains of bacteria. Xanthohumol facilitates bacterial targeting by antibiotics [59].
Supporting the treatment of tuberculosis In animal models, the combination of xanthohumol with isoniazid reduced bacterial counts more effectively than the drug alone. Additionally, xanthohumol protected the liver from damage induced by long-term treatment, acting as a natural "bodyguard" for liver cells [60].
Support in the treatment of severe infections and sepsis In patients seriously ill with COVID-19, administering xanthohumol along with medications reduced mortality, shortened the duration of illness, and alleviated inflammation [61]. Studies are also underway to explore the use of xanthohumol in the treatment of sepsis, a serious, life-threatening infection [62].
Help with metabolic problems (e.g. diabetes, overweight) In people with metabolic problems, such as overweight or diabetes, the use of xanthohumol in modern forms, e.g. enclosed in micelles, resulted in improved glucose control and fat burning due to better absorption [63].
Protection of the heart and blood vessels As mentioned earlier, xanthohumol has protective effects on the circulatory system – it inhibits the formation of calcium deposits in vessels, preventing their hardening, and reduces the risk of blood clots [64]. It achieves the best results when combined with other substances that support vascular health, such as hyaluronic acid, fucoidan, glucosamine, and antioxidants that enhance protection against oxidative damage [65]. Comprehensive protection and regeneration of the glycocalyx, a key vascular structure, is enhanced by xanthohumol's synergy with heparan and heparin [66].
Pain relief and brain protection Animal studies have shown that xanthohumol reduced pain and inflammation in rheumatic diseases [67]. Another experiment showed that it protected brain cells during stroke, limiting damage and speeding recovery [68].
Support during viral infections, e.g. COVID-19 Xanthohumol can inhibit viral replication and mitigate cytokine storms—an overreaction of the immune system. Studies have shown that xanthohumol can be used as adjunctive therapy in severely ill patients with COVID-19—it demonstrates potent anti-inflammatory effects, improves clinical outcome, and reduces mortality. These results suggest that xanthohumol is a promising adjunct to COVID-19 treatment in intensive care settings [69], [70], [71].
In summary, xanthohumol is considered a safe aid in the treatment of many diseases, including infectious, cardiac, and metabolic. It helps improve the effectiveness of medications and protects the body from some of the side effects of therapy, which can help improve patients' quality of life during treatment.
SUPPORT IN THE TREATMENT OF EPILEPSY
Xanthohumol shows promising properties in the treatment of epilepsy, according to available animal and cell studies. In epilepsy models, it significantly reduced the severity of seizures, protected nerve cells, and reduced levels of glutamate – a substance that, in excess, can cause brain damage [72].
Its mechanism of action involves modulating GABA_A receptors, which are key in inhibiting excessive brain activity that triggers seizures. Xanthohumol increases the activity of these receptors, helping to control seizures while having fewer side effects than traditional benzodiazepine drugs [73].
Additionally, xanthohumol protects neurons from damage caused by excessive glutamate stimulation, neutralizes free radicals, and exhibits anti-inflammatory effects, which may contribute to long-term brain protection in people with epilepsy [74].
ANTIDEPRESSANT EFFECT
Depression isn't just a "bad mood"—it's a serious condition in which the brain literally "catches fire." Scientific research shows that chronic inflammation in the brain plays a key role in the development of depression. Xanthohumol may act as a natural antidepressant, although this has been confirmed primarily in animal studies.
A recent study from 2025 found that xanthohumol reduced levels of inflammation-causing substances often present in people with depression. It also strengthened the natural defense mechanisms of nerve cells and helped them regenerate faster under stress [77].
An older study from 2013 examined whether xanthohumol reduced anxiety. It found that it did not have a strong sedative effect, unlike benzodiazepines such as Relanium. However, scientists have not ruled out the possibility that xanthohumol may affect mood in a different way, acting on different mechanisms in the brain [78].
ADDITIONAL BENEFITS FOR YOUR BRAIN
Xanthohumol not only affects mood but also has other beneficial properties. Studies have shown that it protects the nervous system from premature aging [79], helps nerve cells defend themselves in conditions of hypoxia, such as during a stroke [80], and enhances the activity of compounds responsible for memory and proper connections between neurons [81].
Previous in vivo studies suggest that xanthohumol may support the fight against low mood and symptoms of depression. Its effects are multifaceted – it reduces inflammation in the brain, protects nerve cells, and helps the body cope with stress.
REBUILDING AND IMPROVING THE DIGESTIVE SYSTEM
Our intestines are not only the site of food digestion but also a veritable "second brain" that influences our health, mood, and mindset. The intestines are home to trillions of bacteria that make up the gut microbiota, which plays a crucial role in maintaining the health of the entire body. Xanthohumol acts as a good host for these beneficial microorganisms, demonstrating significant therapeutic potential in restoring and improving the digestive system, especially the intestines. Research indicates its multifaceted mechanisms of action [82], [83], [84].
EFFECT ON INTESTINAL MICROBIOTA
A key finding is that xanthohumol has a beneficial effect on glucose metabolism and gut function only when gut microbiota is present. In studies on germ-free mice, xanthohumol did not affect metabolic parameters, while in animals with a normal microbiota, a significant improvement in insulin sensitivity and glucose balance was observed [85].
Xanthohumol acts as a prebiotic and supports beneficial gut bacteria. Furthermore, its metabolites produced by gut bacteria can alter the composition of the gut microbiota and influence its function. In clinical studies in healthy adults, xanthohumol supplementation for 8 weeks induced specific effects, including a reduction in bile acid metabolism associated with Prevotella and Ruminococcus bacteria. An increase in the abundance of beneficial gut bacteria, including Akkermansia muciniphila, Parabacteroides goldsteinii, and Alistipes finegoldii, was also observed (86), [87].
CLINICAL TRIALS IN CROOHN'S DISEASE
Clinical trials are currently underway in which xanthohumol is administered to patients with active Crohn's disease. The XMaS study involves up to 32 patients receiving 24 mg of xanthohumol daily for 8 weeks. Safety biomarkers, inflammatory markers, platelet function, disease activity (CDAI), fecal microbiota composition, and xanthohumol metabolites are being monitored [88].
ACTION IN COLONITIS
In a mouse model of DSS-induced colitis, xanthohumol significantly ameliorated the disease. It protected the intestinal epithelium from damage, reduced the production of inflammatory cytokines and oxidative stress, and blocked the action of enzymes and factors involved in inflammation, such as cyclooxygenase-2 and the NF-κB pathway [89].
IMPACT ON BONE HEALTH IN BOWEL DISEASES
Recent reports indicate that xanthohumol may reduce the risk of osteoporosis in individuals with long-term inflammatory bowel disease. It works by limiting the amount of pro-inflammatory substances (e.g., IL-6, IL-17A, TNF-α), supporting bone metabolism, regulating bacterial tryptophan metabolism, and protecting the intestinal mucosa [90].
GASTROPROTECTIVE ACTION
Xanthohumol stimulates the healing process of the gastric mucosa. Hop leaf and cone extracts containing xanthohumol at doses of 100-150 mg/kg body weight effectively reduced gastric ulcers in rats [91].
A growing number of studies demonstrate xanthohumol's potential to improve and support digestive function by regulating gut bacteria, protecting the gut, reducing inflammation, and helping to treat inflammatory bowel disease. Clinical trials are currently underway to confirm its therapeutic efficacy in gastrointestinal conditions.
SAFETY OF USING XANTHOUMOL
One of the most comprehensive studies on the safety of xanthohumol was conducted in 2021 on a group of 30 healthy adults who were given 24 mg of the compound daily for eight weeks. The results showed that xanthohumol was well-tolerated and safe. No serious adverse events or significant changes in liver, kidney, or hematopoietic function parameters were observed [92], [93].
Previous studies in animal models have confirmed the lack of toxicity even at very high doses. Mice receiving approximately 1000 mg of xanthohumol per kilogram of body weight for three weeks showed no signs of organ damage or disturbances in homeostasis [94].
Hormonal contraindications Interactions with sex hormones are the most important group of contraindications. Xanthohumol acts as an estrogen antagonist by blocking estrogen receptors [95]. It may also inhibit the activity of the aromatase enzyme, which converts testosterone into estrogens.
Hormone therapy Xanthohumol may reduce the effectiveness of estrogen-based hormone preparations by competitively binding to estrogen receptors. Individuals taking hormone therapy should consult a physician before starting supplementation [96].
Oncological contraindications Advanced prostate cancer may be a relative contraindication to xanthohumol use. Although most studies indicate anticancer properties of this compound, there are reports suggesting that it may activate certain cellular pathways under certain conditions. In such cases, supplementation should be supervised by an oncologist [97].
Drug interactions
Xanthohumol may affect drug metabolism by inhibiting cytochrome P450 enzymes—specifically CYP1A1, CYP1A2, CYP1B1, and CYP3A4. This may lead to increased levels of certain medications in the body, including:
antipsychotics (e.g., clozapine, olanzapine),
antiarrhythmics (e.g., propranolol, mexiletine),
chemotherapeutic agents (e.g., paclitaxel, vinblastine),
calcium channel blockers [98]
People taking medications metabolized by these enzymes should consult a doctor before supplementing with xanthohumol.
RESEARCH IS STILL IN PROGRESS
Xanthohumol is an example of a natural substance with multifaceted health potential—from protecting cellular structures, through supporting the digestive and immune systems, to improving mood and increasing the effectiveness of therapy. This molecule is found in the highest commercially available content in Magavena's X8 product. It is a dietary supplement/Bioatractor made from hop cones from specially cultivated organic farms.
Thanks to a unique extraction method, X8 has a high concentration of the active molecule and high bioavailability, meaning it is easily absorbed and assimilated by the body.
While xanthohumol is not a panacea for all ailments, it can significantly support the body in everyday health challenges, accelerate regeneration, and enhance natural defenses. Although it is not yet a clinical standard, current research results are encouraging and open up opportunities for more effective health support. Xanthohumol is an example of how nature can provide effective solutions—it just takes the ability to discover and utilize them appropriately.
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