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    What is Apigenin? Benefits, Dosage, and Risks

    What is Apigenin? Benefits, Dosage, and Risks
    October 24, 2022 Vitality Pro

    Apigenin:

    Benefits, Dosage, and Risks

    Have you ever felt the calming effects of chamomile tea, or experienced contentedness after drinking a tall glass of cold pressed green juice? If so, you might have apigenin to thank. This dynamic flavonoid has been part of human culture and medicine for centuries, dating back as early as Ancient Egypt. Today, thousands of apigenin studies illustrate the important role this compound plays in promoting vitality, balanced mood, and cellular longevity.

    What is Apigenin?

    Apigenin is a flavone, a specific subclass of flavonoids known to promote various health and longevity benefits. Chamomile tea, tabbouleh (Lebanese-style parsley salad), and celery juice are just a few examples of popular foods and beverages that are rich in this phytochemical. Like other flavonoids and flavones, apigenin functions as an anti-inflammatory and anti-cancer agent. What makes this compound unique, however, is its ability to reduce the incidence of age-related disease by promoting cellular apoptosis.

    Most of what is known about apigenin has been gathered from cell and animal-based studies. Although apigenin-rich plants and teas have played a vital role in human culture for centuries, clinical trials are needed to better understand the efficacy, potential side effects, and ideal dosage of apigenin supplements.

    However, apigenin consumption is widespread. Chamomile– a potent source of apigenin– is officially acknowledged as a medicinal drug in at least 26 countries, including Germany, Belgium, France, and the United Kingdom. Moreover, use of chamomile is listed in the World Health Organization monograph on medicinal plants for treatment of indigestion, bloating, mild insomnia, nervousness, inflammation, and oral infections.

    Overview of Potential Benefits and Risks

    Disclaimer: Always consult your health care professional prior to making changes in your diet or exercise regimen, including whether to use supplements like quercetin. Pregnant women, women who are nursing, and children especially must always consult a physician prior to taking supplements or medications.

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    Overview of potential apigenin health benefits:

    • Reduced Inflammation
    • Reduced Risk of Cancer
    • Enhanced NAD Levels
    • Reduced Feelings of Anxiety
    • Reduced Feelings of Depression
    • Lower Cholesterol and Obesity Prevention
    • Protection from Oxidative Stress
    • Relief from Rheumatoid Arthritis
    • Treatment of Autoimmune Disease
    • Prevention of Neurodegenerative Disease
    • Treatment of Migraines
    • Improved Sleep

    Overview of potential risks and side effects:

    • Human Trials Are Lacking
    • Known Adverse Reactions with Alcohol, Medicines, and Prescription Drugs

    How Does Apigenin Work?

    Humans have enjoyed the medicinal value of plant compounds like apigenin for centuries. Modern research indicates these flavonoids have several mechanisms of action, exhibiting powerful antioxidant, anti-inflammatory, and anti-cancer effects. More specifically, apigenin research illustrates this compound’s unique therapeutic ability to promote apoptosis, prevent cancer, and reduce inflammation.

    Promoting apoptosis (programmed cell death)

    Apoptosis is the process by which healthy cells experience a phenomenon biologists call programmed cell death. This type of cell death is normal. In fact, failure of a cell to undergo apoptosis is believed to be a leading cause of premature aging, neurodegenerative disease, and cancer.

    According to a 2017 article published in the journal Cell and Bioscience, apigenin may promote apoptosis and pave the way for vital longevity processes, including:

    • Cell autophagy– the process by which healthy cells clean out damaged cells and organelles, thereby preventing disease
    • Suppression of cell migration and invasion, which may prevent tumor proliferation

    Authors of the study further explain that these mechanisms are driven by apigenin’s impact on the following signaling pathways:

    • Intracellular pathways PI3K/AKT, AK/STAT, and MAPK/ERK, which help to regulate immunity, cell division, and apoptosis
    • NF-κB pathway, which modulates cellular response to environmental stressors

    Preventing cancer

    In the aforementioned study published by Cell and Bioscience, authors also call apigenin a “promising reagent for cancer therapy” due to its unique ability to modulate vital cellular pathways. For example, authors noted that apigenin may prevent abnormal PI3K/AKT signaling. That’s important, because abnormal signaling along this pathway is known to induce and spread cancer.

    Apigenin has also demonstrated anti-cancer effects in animal studies. In 2015, researchers found the plant compound to reduce the development of skin tumors in mice by blocking the enzyme COX-2. Enzymes are like chemical messengers that create action, usually telling something to start or stop. When it comes to cancer, the enzyme COX-2 tells cancer to “go” by creating cancer stem cells, promoting apoptotic resistance, causing inflammation, and driving the metastasis of cancerous cells.

    Although human trials are lacking, researchers have made some encouraging observations with regard to flavonoids and cancer prevention. For example, epidemiological studies show a decreased risk of cancer in populations where plant and flavonoid-rich diets are common.

    Reducing inflammation

    Inflammation is believed to be a primary driver of both aging and age-related disease. According to research published by The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, two key biological systems that drive inflammation include the NF-κB signaling pathway and immune system cytokines. Apigenin appears to reduce inflammation by acting on each of these systems.

    First, apigenin appears to modulate the NF-κB signaling pathway. In doing so, the compound may prevent inflammation and protect cells from the deleterious effects of chronic stress.

    Cytokines are another means through which organisms mediate inflammation. These unique proteins can be pro-inflammatory, meaning they induce inflammation. Apigenin appears to reduce the expression of such pro-inflammatory cytokines, including IL-1β, IL-2, IL-6, IL-8, and TNF-α.

    Moreover, consider that non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen achieve their effects by suppressing COX-2. Apigenin demonstrates the very same mechanism of action and effect in animal models, making it a natural anti-inflammatory.

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    Boosting NAD levels for healthier aging

    Nicotinamide adenine dinucleotide (NAD) is an essential chemical for health and longevity. As a co-factor, NAD can be thought of as a “helper molecule” that triggers certain enzymatic reactions within cells. Leading longevity research now tells us at least four important things about NAD and aging:

    1. NAD is required for cellular metabolism and DNA repair
    2. As humans age, NAD levels naturally decrease
    3. As NAD decreases, incidence of age-related disease increases dramatically
    4. Increasing NAD levels may prevent disease and extend lifespan

    Time is not NAD’s only enemy, however. The human immune system also plays a role in NAD degradation. Under certain conditions, white blood cells called macrophages have been shown to produce an enzyme called CD38 that cannibalizes NAD molecules. When left unchecked, CD38 depletes NAD over time and may cause inflammation, oxidative stress, and neurodegeneration.

    Apigenin may help, as studies show it effectively inhibits CD38 production. This preserves natural NAD levels, enabling the helper molecule to do what it does best—promote healthy metabolism, repair DNA, and reduce the incidence of age-related disease.

    What Foods Naturally Contain Apigenin?

    Apigenin naturally occurs in a diverse range of herbs, vegetables, and drinks. Most common food sources include:

    • Herbs like parsley, cilantro, basil, oregano, saw thistle leaves, chives, corn poppy, crown daisy, fennel, hartwort, horseradish, peppermint, perilla, Queen Anne’s lace, rosemary, and thyme
    • Vegetables like celery, carrots, artichokes, beets, Brussels sprouts, cabbage, cauliflower, kohlrabi, kale, Lettuce, green peas, hot and sweet peppers, rutabagas, spinach, and water spinach
    • Drinks like chamomile tea, red wine, and certain beers

    The best, most potent food sources of apigenin include:

    • Dried parsley (45,035 μg/g)
    • Dried chamomile flower (3,000 to 5,000 μg/g)
    • Celery seeds (786.5 μg/g)
    • Vine spinach (622 μg/g)
    • Chinese celery (240.2 μg/g)

    Apigenin Dosages and Supplements

    Disclaimer: Always consult your health care professional prior to making changes in your diet or exercise regimen, including whether to use supplements like apigenin.

    Little data is available on safe dosage and duration for apigenin supplementation. However, a half dozen studies indicate that Americans, Europeans, and Chinese ingest about 1.35mg, 3mg, and 4.23mg per day, respectively. These numbers are based on dietary intake. Be aware that supplements are often 10-12x more concentrated than natural food sources.

    Dosage

    Typical dosage ranges from 50mg to 400mg per day. Individual apigenin supplements vary.

    Frequency

    Long term usage data on apigenin supplements is not available.

    At the time of this writing, apigenin is not labeled “Generally Recognized as Safe” (GRAS) by the U.S. Food and Drug Administration. However, it is abundant in low concentrations throughout nature and modern food supplies.

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    Apigenin Potential Health Benefits

    Reduced Inflammation

    A variety of cell-based and animal studies demonstrate the ability of apigenin to suppress inflammation. These studies explore various applications, ranging from use as an immune system suppressant to protection against heart inflammation.

    In March 2016, a rodent study demonstrated apigenin’s ability to suppress inflammation by down-regulating the NF-κB pathway in the lungs. Apigenin not only protected mice from an otherwise lethal injection of Lipopolysaccharide (LPS), but also helped to preserve lung architecture and health. Researchers note this was likely due to apigenin’s ability to suppress inflammation response while also preventing the spread and accumulation of inflammatory cells.

    In April 2016, a paper published in the Journal of Nutritional Biochemistry identified apigenin as a potential supplement for treating colitis, a condition characterized by extreme inflammation and discomfort in the GI tract and colon. In the study, mice that were fed a diet of 0.1% apigenin exhibited significant reductions in colitis symptoms and damage after just 56 days. When analyzing the results, researchers point to apigenin’s ability to down-regulate the NF-κB pathway while also inhibiting pro-inflammatory cytokines IL-1β and IL-18.

    By June of the same year, a third noteworthy animal study was published by the journal Immunopharmacology and Immunotoxicology. This time, scientists devised a study to test apigenin’s ability to attenuate the effects of inflammation and oxidative stress among 64 laboratory mice. Following a controlled infection, mice pre-treated with apigenin experienced less inflammation and oxidative stress. Notably, this study provided further evidence of apigenin’s ability to increase production of the anti-inflammatory cytokine IL-10.

    More recently, a 2018 animal-based study showed apigenin’s anti-inflammatory ability extends to cardiac tissue as well. Specifically, apigenin was found to prevent inflammation in cardiac tissue exposed to the oral bacteria Streptococcus sanguinis. Moreover, researchers noted apigenin had no cytotoxic effects, making it a promising tool in the fight against this common type of cardiac infection.

    Reduced Risk of Cancer

    A key characteristic of effective cancer treatments is the ability to selectively target and kill cancerous cells, without causing damage to healthy tissues. This is a difficult task, however. An estimated 65% of cancer patients lose their hair during chemotherapy, a stunning fact that demonstrates just how challenging it can be to selectively target cancerous cells with radiation therapy.

    That’s why researchers are excited by the anti-cancer effects of phytochemicals like apigenin. Writing for the peer-reviewed journal Cell and Bioscience, researchers note that “apigenin shows significant cell cytotoxicity selectively against various types of cancer cells” while showing very little toxicity toward healthy ones. The keyword: Selectivity. Apigenin seems to naturally identify and shut-down cancerous cells while remaining minimally toxic toward surrounding tissues.

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    Interestingly, apigenin’s anti-inflammatory properties may help to explain its ability to function as an anti-cancer agent. Cancers often develop in areas plagued by irritation, which has led scientists to name chronic inflammation a “critical driver” of tumour progression. In this way, the anti-inflammatory properties of flavonoids like apigenin have the potential to prevent cancerous cell development and proliferation.

    In one clinical trial, researchers studied the progression of colon cancer in 87 patients over the course of 3 to 4 years. Patients were divided into two groups. One took a daily flavonoid mixture consisting of 20mg apigenin and 20mg epigallocatechin-gallat (EGCG), an antioxidant catechin found in several varieties of tea. The other served as a control group, taking a placebo. Over 4 years, the group taking the flavonoid mixture experienced 0% cancer recurrence, while recurrence for the control group was an alarming 20%.

    Enhanced NAD Levels

    Apigenin has been shown in cell and animal studies to enhance NAD levels. This may promote several downstream activities that help to protect DNA, fight cancer, reduce inflammation, and may even extend lifespan.

    In a 2021 cell-based study, apigenin was shown to inhibit the enzyme CD38, increase NAD levels, and reduce the impact of senescence in lung disease cells. Senescent cells are known to increase inflammation and dysfunction, which has been shown to “increase the malignant potency of cancer cells“. More studies are needed, but these results indicate the NAD-boosting ability of apigenin may play a crucial role in future cancer treatments and preventions.

    Apigenin’s role as a CD38 inhibitor may also help to prevent damage and inflammation associated with diabetes. In a 2020 study, researchers discovered that apigenin significantly reduced cell damage and pro-inflammatory gene expression in diabetic mice. In their analysis, researchers credited the outcome to apigenin’s ability to restore NAD levels, specifically through CD38 inhibition.

    Some studies indicate that even better outcomes can be attained through supplementing with both apigenin and nicotinamide riboside (NR), a potent precursor to natural NAD production. In a study published by the Journal of Neurochemistry, a combination of apigenin and NR was found to suppress neuroinflammation in cell cultures. Commenting on the study, researchers suggest this combination could potentially help prevent neurodegenerative diseases like multiple sclerosis and Alzheimer’s.

    Reduced Feelings of Anxiety

    Apigenin has been studied in both animal and human models. In both scenarios, the compound has been shown to decrease the symptoms of anxiety. However, it is important to note the experience of “anxiety” exists on a broad spectrum. On one end, symptoms are extremely mild and resemble that of excitement. On the other, symptoms are so extreme they cause shortness of breath, panic attacks, and even loss of consciousness. More research is needed to determine if apigenin can someday replace prescription medications for severe anxiety disorders.

    In 2014, researchers demonstrated the anti-anxiety effects of apigenin in mice. The compound was extracted from Stachys tibetica Vatke, a tea native to the Himalayan mountains. This revered tea had been used by tribal healers for centuries to treat fever, cough, and even certain phobias. In the study, researchers found the apigenin extract to exhibit anti-anxiety effects, noting it could be an important molecule for future anxiety treatments.

    Results have also been observed in human studies. In one double-blind, placebo-controlled trial, the compound was found to have a modest anti-anxiety effect on patients with mild to moderate Generalized Anxiety Disorder. For this study, participants received chamomile extract containing 1.2% apigenin.

    Results were also seen in a long-term study of patients with Generalized Anxiety Disorder. Over 38 weeks, participants received either 1500mg of chamomile extract or a placebo. Results indicate long term chamomile use to be safe and significantly reduce symptoms of moderate to severe Generalized Anxiety Disorder.

    It is important to note this study did not specify the exact concentration of apigenin in the chamomile extract. However, apigenin is known to be the primary compound behind the calming effects of chamomile. As researchers note, additional studies are needed to further understand the therapeutic potential of this tea.

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    Reduced Feelings of Depression

    Plant compounds have been used to treat depression for thousands of years. As noted in the journal Current Pharmaceutical Biotechnology, the ability for these plant compounds to modulate cellular activity, reduce oxidative stress, and curb inflammation makes them a likely ally in the prevention of depression. Current medical literature paints a hopeful future for the treatment of depression with polyphenols and flavonoids, although human studies are needed.

    In a 2013 article published by Expert Opinion on Investigational Drugs, apigenin is among several polyphenols researchers note as being an exciting therapeutic prospect in the treatment of major depression. Others include curcumin, quercetin, and resveratrol.

    By 2016, multiple animal-based studies demonstrated apigenin’s ability to reduce the symptoms of depression. One notable example was published in the European Journal of Pharmacology, a study the authors believe “intensively confirmed the antidepressant-like effects of apigenin” in rodent models. Interestingly, researchers were able to correlate apigenin’s effects with an up-regulation in brain-derived neurotrophic factor (BDNF) in the hippocampus.

    Lower Cholesterol and Obesity Prevention

    Apigenin appears to lower LDL cholesterol while also down-regulating certain genes associated with obesity. This was shown in a rodent study where mice were fed a high fat diet to induce weight gain. Mice were divided in two groups, one fed a high fat diet and the other fed the same diet along with apigenin 0.005%. In the group that supplemented with apigenin, researchers saw corresponding decreases in blood lipids, total cholesterol, and inhibition of lipolytic and lipogenic genes.

    Although human trials are needed, apigenin’s inhibition of lipolytic genes is a good sign. In clinical trials, researchers have established a link between these genes and obesity. Specifically, lipolytic gene inhibition appears to reduce the risk of obesity by improving glucose metabolism insulin sensitivity.

    Apigenin may also prevent weight gain, obesity, and related health issues indirectly. There is a well-established link between depression and weight gain. Given its ability to potentially alleviate depression, apigenin may also prevent weight gain by stabilizing mood and reducing depressive episodes. However, human studies are needed to establish such a claim.

    Protection from Oxidative Stress

    Many studies illustrate apigenin’s role in promoting cellular health and longevity through antioxidant properties. One such study was published in the June 2016 issue of Immunopharmacology and Immunotoxicology. In this study, rodents exhibiting signs of sepsis experienced a decrease in inflammation and “normalization” of oxidative stress parameters when pre-treated with apigenin. Additionally, researchers note that rodents treated with apigenin also experienced an increase in the anti-inflammatory cytokine IL-10.

    Apigenin appears to exhibit the same antioxidant potential in humans. In a 2016 clinical trial, the compound effectively protected skin cells from UVA-radiation. Authors attribute this to the antioxidant potential of apigenin, which helped preserve skin density, elasticity, and reduce the length of fine wrinkles.

    Relief from Rheumatoid Arthritis

    Apigenin appears to reduce symptoms of arthritis, though scientists admit the mechanism of action is unclear. This was the case in 2019, when researchers investigated the impact of apigenin on rheumatoid arthritis in laboratory mice. In the study, apigenin alleviated symptoms by inhibiting synovial hyperplasia, angiogenesis, and osteoclastogenesis— 3 hallmarks of rheumatoid arthritis. Apigenin’s ability to down-regulate growth factors VEGF and VEGFR played a critical role in the experiment’s outcome. More studies are needed to determine if apigenin might achieve similar results in humans.

    Treatment of Autoimmune Disease

    Autoimmune diseases are characterized by the immune system attacking itself, typically as a result of being triggered by a foreign substance. It is estimated that more than 23 million Americans suffer with such conditions, which include things like rheumatoid arthritis and Celiac disease.

    Modern medical research has increasingly looked toward polyphenols and flavonoids to help treat such disease, given the relatively low toxicity and tolerability of such compounds. In a systematic review of apigenin and four other popular flavonoids, researchers conclude such compounds exhibit “considerable potential” due to their antioxidant and anti-inflammatory properties.

    This potential was put on display in 2014, when apigenin appeared to protect mice from the development of autoimmune myocarditis. Mice received apigenin treatments for just 21 days. Commenting on the study, researchers note apigenin significantly reduced cardiac hypertrophy and dysfunction in the mice, thereby alleviating the autoimmune response. Moreover, apigenin was found to calm the immune response by decreasing pro-inflammatory cytokines.

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    Prevention of Neurodegenerative Disease

    Remarkably, certain flavonoids are known to promote cell development, proliferation, and network connectivity– often referred to as neural plasticity. There are likely many mechanisms of action, including the ability of flavonoids like apigenin to modulate the production of estrogen. Estrogen promotes neurogenesis (the creation of neurons) while also acting as a neuro-protectant. Increasingly, scientists are studying the efficacy of apigenin for promoting nervous system health and longevity.

    Parkinson’s disease.To date, there is no cure for Parkinson’s. It is estimated this neurodegenerative disease affects more than 10 million people globally. Parkinson’s is the 14th leading cause of death in the United States, although the disease itself is not fatal. Increasingly, scientists are investigating flavonoids like apigenin to treat neurodegenerative conditions.

    In a cell-based study, researchers in Brazil found apigenin to promote neuronal genesis and connectivity after binding to estrogen receptors in human stem cells. As a result, researchers believe apigenin may be able to promote neuron development, proliferation, and brain plasticity. Estrogens are also known to have neuro-protective effects. As such, researchers believe apigenin may also help to prevent the onset of neurodegenerative diseases.

    Alzheimer’s disease. Dementia is the most common neurodegenerative disease, affecting a staggering 55 million people worldwide. Roughly 50-75% of patient cases are classified as Alzheimer’s disease, a specific kind of dementia characterized by loss of memory, speech, and decision making abilities. Like Parkinson’s, researchers hope to find unique flavonoids that can help to preserve nervous system function and delay the onset of such a devastating disease.

    In a 2020 review of such research, scientists identify apigenin as a potential tool for delaying the onset of Alzheimer’s disease by acting as an antioxidant and cognition-enhancing compound. Scientists note apigenin appears to have “anti-amyloidogenic” properties, meaning it can prevent the formation of the amyloid plaque known to cause Alzheimer’s.

    In a clinical review published one year prior, researchers came to a similar conclusion. After summarizing both animal and human trials, apigenin was identified as a potential therapeutic that may delay the onset of Alzheimer’s.

    Treatment of Migraines

    In a double-blind clinical trial, researchers tested the effects of a topical chamomile extraction containing 0.233mg per gram apigenin against a placebo. Interestingly, this study was conducted as a “crossover” trial.

    In one group, 38 participants took the chamomile extraction first, followed by the placebo. In the second group, 34 patients took the placebo first, and then the chamomile extraction. Throughout the experiment, migraine symptoms like pain, nausea, vomiting, photophobia (eye discomfort caused by bright light), and phonophobia (fear of sound) were measured. Results demonstrated a significant reduction of each symptom following administration of chamomile extract.

    Improved Sleep

    Apigenin is perhaps most known for its sleep-enhancing properties, commonly as chamomile tea. Despite the wide-ranging anecdotal evidence suggesting that apigenin-rich teas like chamomile can induce sleep, there is a lack of human trials to support such claims.

    However, apigenin has shown promise in animal studies. In a 2012 study published by Archives of Pharmacal Research, researchers found the plant compound to increase both rate of sleep and sleep duration in mice.

    Recently, a human trial also correlates polyphenols like apigenin with sleep quality. Published by the journal Nutrients, this study indicates people who eat a diet rich in polyphenols– and flavonoids like apigenin, in particular– may be associated with better quality of sleep.

    Potential Health Risks and Side Effects

    More studies are needed to better understand the health risks and side effects of apigenin. This is especially true if taking a supplement, as such products are likely to contain much higher concentrations apigenin per serving compared to natural food and tea sources.

    Moreover, the long-term effects of apigenin supplementation is largely unexplored. Therefore, it is wise to exercise caution when taking a high potency apigenin supplement for long periods of time.

    Chamomile tea is known to cause the following adverse reactions with alcohol, medicines, and prescription drugs*:

    • Blood-thinning medications (anticoagulants and anti-platelets): May increase risk of bleeding
    • Blood pressure medications: May cause abrupt drops in blood pressure
    • Diabetes medications: May increase risk of low blood sugar or hypoglycemia
    • Hormonal therapies: Because it binds to estrogen receptors, apigenin might interfere with certain hormonal therapies like nolvadex
    • Other drugs that are processed by the liver: May cause interactions with fexofenadine, statins, birth control pills, and certain antifungal drugs
    • Sedatives like alcohol and antidepressants (see below)

    Apigenin promotes feelings of calm, so individuals who take sedatives should exercise caution. Specifically, apigenin may increase the effects of the following**:

    • Anti-seizure medications like Dilantin and Depakote
    • Benzodiazepines like Xanax and Valium
    • Insomnia drugs like Ambien, Sonata, Lunesta, and Rozerem
    • Tricyclic antidepressants, like Elavil
    • Alcoholic beverages like beer, wine, and liquor

    *Aforementioned side effects and adverse reactions have been observed in chamomile tea. Chamomile represents a logical proxy, as it is high in apigenin and commonly used. However, additional human trials are needed to determine the exact side effects and interactions of concentrated apigenin supplements.

    **Not a comprehensive list. Always consult your physician prior to making changes to your medicine or supplement regimen.

    Conclusion: This Ancient Plant Compound Will Likely Become a Powerful Nutraceutical

    As with most flavonoids, apigenin research is at a crossroads. On one hand, it has been used as a medicinal tea for thousands of years, dating back as early as the Ancient Egyptians. On the other hand, the modern quest to distill this natural plant compound into a concentrated nutraceutical leaves questions about efficacy and human safety unanswered. The future looks bright, and it is exciting to think what future clinical trials will tell us about this dynamic plant compound.

    Following some recent EU regulation changes, some products have been removed until we have clarification on their effect on the UK market.

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