Apigenin

• Anti-inflammatory
• Antioxidant
• Neuroprotection
• Sleep enhancement

• Anxiety reduction
• Cancer prevention
• Cardiovascular support
• Immune modulation
• Metabolic health
• Skin protection

Apigenin exerts its diverse biological effects through multiple mechanisms at the molecular level. One of its most well-established actions is as a positive allosteric modulator of GABA-A receptors, binding to the benzodiazepine site but with milder effects than pharmaceutical benzodiazepines. This GABA-ergic activity explains apigenin’s anxiolytic and sleep-enhancing properties, as it increases the inhibitory effects of GABA in the central nervous system without causing strong sedation or dependence. As an antioxidant, apigenin directly scavenges reactive oxygen species (ROS) and free radicals through its hydroxyl groups, which can donate hydrogen atoms to stabilize these harmful molecules.

Beyond direct antioxidant activity, apigenin upregulates endogenous antioxidant defense systems by activating nuclear factor erythroid 2-related factor 2 (Nrf2), which increases the expression of antioxidant enzymes like glutathione peroxidase, catalase, and superoxide dismutase. Apigenin exhibits potent anti-inflammatory effects by inhibiting nuclear factor-kappa B (NF-κB) activation and reducing the production of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). It also inhibits cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), further reducing inflammatory mediator production. In cancer prevention and potential treatment, apigenin modulates multiple pathways involved in cell proliferation, differentiation, and survival.

It induces cell cycle arrest at G2/M phase by regulating cyclin B and cyclin-dependent kinase 1 (CDK1). Apigenin promotes apoptosis in cancer cells through both intrinsic (mitochondrial) and extrinsic (death receptor) pathways, while generally sparing normal cells. It inhibits angiogenesis by downregulating vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Additionally, apigenin inhibits several protein kinases involved in cancer progression, including PI3K/Akt, MAPK, and JAK/STAT pathways.

For cardiovascular protection, apigenin enhances nitric oxide production by activating endothelial nitric oxide synthase (eNOS), promoting vasodilation and improving blood flow. It inhibits platelet aggregation, potentially reducing thrombosis risk, and improves lipid profiles by affecting cholesterol metabolism genes. In metabolic health, apigenin activates AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis that promotes glucose uptake and fatty acid oxidation. It enhances insulin sensitivity by improving insulin receptor signaling and GLUT4 translocation to cell membranes.

Apigenin also inhibits adipogenesis and promotes browning of white adipose tissue, potentially supporting weight management. In the brain, apigenin crosses the blood-brain barrier and exhibits neuroprotective effects by reducing oxidative stress, modulating neurotransmitter systems, and inhibiting microglial activation. It may protect against neurodegenerative conditions by reducing amyloid-β aggregation and tau hyperphosphorylation. At the epigenetic level, apigenin inhibits DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), potentially reversing aberrant epigenetic modifications associated with various diseases.

It also modulates microRNA expression, affecting gene regulation at the post-transcriptional level.

No Recommended Dietary Allowance (RDA) or Adequate Intake (AI) has been established for apigenin, as it is not considered an essential nutrient. Clinical research on isolated apigenin supplementation in humans is limited, making precise dosage recommendations challenging. Based on the available research and traditional usage patterns, effective doses typically range from 25-100 mg of pure apigenin per day. For chamomile extracts standardized to apigenin content (typically 1-5%), doses providing 5-50 mg of apigenin are common.

Dietary intake from food sources is much lower, estimated at 0.3-4.5 mg per day in typical Western diets, with Mediterranean diets potentially providing up to 10-20 mg daily.

Apigenin has relatively poor oral bioavailability, with estimates ranging from 5-12% of an ingested dose reaching systemic circulation in humans. Several factors contribute to this limited bioavailability: Apigenin has low water solubility, limiting dissolution in the gastrointestinal tract; it undergoes extensive first-pass metabolism in the intestinal mucosa and liver, where it is conjugated through glucuronidation and sulfation; it is subject to efflux back into the intestinal lumen via P-glycoprotein and breast cancer resistance protein (BCRP); and it has limited intestinal permeability due to its chemical structure. Additionally, apigenin can bind to proteins in the digestive tract, further reducing absorption. Once absorbed, apigenin has a relatively short plasma half-life of approximately 3-7 hours, with peak plasma concentrations typically occurring 2-3 hours after ingestion.

Apigenin can cross the blood-brain barrier, though in limited amounts, which is significant for its neurological effects. The bioavailability of apigenin may be higher when consumed as part of whole plant extracts (like chamomile) compared to isolated apigenin, possibly due to the presence of other compounds that enhance absorption or inhibit metabolism.

Taking with dietary fats or oils can enhance absorption due to apigenin’s lipophilic nature, Piperine (black pepper extract) may inhibit intestinal and hepatic glucuronidation of apigenin, potentially increasing bioavailability, Liposomal and phytosomal formulations can increase bioavailability 2-4 fold by improving solubility and enhancing cellular uptake, Consuming with quercetin may inhibit the metabolism of apigenin, potentially extending its half-life, Nanoparticle formulations significantly improve dissolution rate and absorption, Micronization (reducing particle size) increases surface area and improves dissolution, Consuming as part of whole plant extracts (particularly chamomile) may provide better absorption due to the presence of other beneficial compounds, Cyclodextrin complexation improves water solubility while protecting from degradation, Taking multiple smaller doses throughout the day rather than a single large dose may result in higher overall absorption and more consistent blood levels

For general health benefits, apigenin can be taken with meals containing some fat to enhance absorption. For sleep enhancement, taking apigenin 30-60 minutes before bedtime is typically recommended, ideally with a small amount of healthy fat to improve absorption. When using apigenin for its anxiolytic effects, morning or early afternoon dosing may be preferable for daytime anxiety, while evening dosing may be more appropriate for those whose anxiety affects sleep. For cognitive benefits, some research suggests morning or early afternoon dosing may be preferable to avoid any potential mild sedative effects interfering with cognitive performance, though these effects are typically subtle.

When using multiple daily doses for anti-inflammatory or antioxidant purposes, spacing them at least 4-6 hours apart may help maintain more consistent blood levels throughout the day. To minimize potential interactions with medications, apigenin supplements should generally be taken at least 2 hours before or after other medications, particularly those with narrow therapeutic windows. For digestive comfort, taking apigenin or chamomile preparations 15-30 minutes before meals may provide the most direct benefits for the digestive tract. Consistency in daily supplementation is generally more important than specific timing for many of apigenin’s benefits, as some effects may develop through regular, long-term use.

• Generally well-tolerated with minimal reported side effects at recommended doses
• Mild sedation or drowsiness (particularly at higher doses)
• Gastrointestinal discomfort (mild nausea, stomach pain) – uncommon
• Potential for allergic reactions in individuals sensitive to plants in the Asteraceae family (includes chamomile)
• Mild headache (rare)
• Dizziness (rare)
• Contact dermatitis (with topical application in sensitive individuals)
• Potential for mild hypotension at higher doses (theoretical)
• Potential for mild hormone modulation at very high doses (theoretical, based on weak estrogenic activity in some studies)

• Known allergy to chamomile, ragweed, chrysanthemums, marigolds, or other plants in the Asteraceae family
• Scheduled surgery (discontinue 2 weeks before due to potential mild anticoagulant effects)
• Pregnancy and breastfeeding (isolated supplements; chamomile tea in moderation is generally considered safe)
• Caution advised in patients with hormone-sensitive conditions (theoretical concern at very high doses)
• Caution in patients taking sedative medications or CNS depressants (potential additive effects)
• Caution in patients with bleeding disorders (due to potential mild antiplatelet effects)
• Caution in patients with low blood pressure (theoretical concern at higher doses)

• Sedative medications and CNS depressants (potential additive effects)
• Anticoagulant/antiplatelet medications (potential mild additive effect increasing bleeding risk)
• Cytochrome P450 substrates (apigenin may inhibit certain CYP enzymes, potentially affecting drug metabolism)
• Hormone therapies (theoretical interaction due to potential weak estrogenic effects at high doses)
• Benzodiazepines (potential for enhanced effects due to shared GABA-A receptor activity)
• Alcohol (potential additive sedative effects)
• Drugs transported by P-glycoprotein (potential interaction)
• Tamoxifen and other selective estrogen receptor modulators (theoretical interaction at high doses)

No official Tolerable Upper Intake Level (UL) has been established for apigenin. Based on available research and traditional usage patterns, doses up to 100 mg per day appear to be well-tolerated by most healthy adults for extended use. Higher doses have been used in some research settings without significant adverse effects, but long-term safety data for doses above 100 mg daily is limited. Chamomile tea, a natural source of apigenin, has been consumed safely for centuries, with consumption of 3-4 cups daily generally recognized as safe for most individuals.

As with any supplement, it’s prudent to use the lowest effective dose for the intended purpose, particularly for long-term use. Those with pre-existing health conditions, on medications, or with specific sensitivities should consult healthcare providers before using higher doses of apigenin.

Apigenin is not specifically approved as a food additive by the FDA, but it is naturally present in many common foods and herbs. As a dietary supplement ingredient, apigenin falls under the regulations of the Dietary Supplement Health and Education Act (DSHEA) of 1994. The FDA has not approved specific health claims for apigenin supplements. Chamomile, a primary source of apigenin, is Generally Recognized as Safe (GRAS) for use as a spice, seasoning, or flavoring agent.

It is also included in the FDA’s list of herbs and botanicals that can be used in dietary supplements. The FDA has acknowledged chamomile’s traditional use as a sleep aid and digestive support, though without formally approving these as structure/function claims.

Eu: The European Food Safety Authority (EFSA) has not approved specific health claims for apigenin. Chamomile is recognized in the European Pharmacopoeia and is approved for traditional use for mild digestive complaints and as a sleep aid. The European Medicines Agency (EMA) has published a monograph on chamomile flower, recognizing its traditional medicinal uses. In Germany, chamomile is approved by Commission E (the German regulatory authority for herbs) for internal use for digestive complaints and external use for skin and mucous membrane inflammation.

Canada: Health Canada has approved chamomile as a Natural Health Product (NHP) ingredient with authorized claims related to its traditional use as a sleep aid, digestive support, and anti-inflammatory. Isolated apigenin is permitted as an NHP ingredient but with more limited approved claims compared to whole chamomile extracts.

Australia: The Therapeutic Goods Administration (TGA) regulates chamomile extracts as listed complementary medicines with approved uses for mild anxiety, insomnia, and digestive complaints. Isolated apigenin is permitted in listed medicines but with more restricted indications than whole plant extracts.

Japan: Chamomile is recognized as a food ingredient and is also used in Kampo (traditional Japanese herbal medicine). Isolated apigenin is not specifically regulated as a separate entity but is permitted as a component of natural extracts.

China: Chamomile is included in the Chinese Pharmacopoeia and is recognized for its traditional medicinal properties. In Traditional Chinese Medicine, chamomile is used for digestive issues, inflammation, and calming effects.

Moderate to high for isolated apigenin; low for natural sources

$0.50-$2.00 per day for pure apigenin supplements (25-100 mg); $0.20-$0.75 per day for standardized chamomile extracts; $0.05-$0.15 per day for chamomile tea (2-3 cups)

The value proposition for apigenin varies significantly based on form and intended use. Pure apigenin supplements command premium prices due to the extraction and isolation processes required, but provide precise dosing and higher potency than plant extracts. For sleep enhancement and anxiety reduction, the primary evidence-based applications of apigenin, standardized chamomile extracts often provide the best balance of cost and effectiveness. These extracts deliver apigenin alongside other beneficial compounds in chamomile that may work synergistically.

For general health maintenance and mild benefits, chamomile tea represents exceptional value, providing meaningful amounts of apigenin at minimal cost. High-quality loose-leaf German chamomile typically offers better value than tea bags due to higher apigenin content and the ability to control steeping time and temperature. Enhanced bioavailability formulations of apigenin (liposomal, phytosomal, etc.) cost more but may offer superior value for certain applications by improving absorption and requiring lower doses. When comparing products, calculate the cost per milligram of apigenin rather than per capsule, as potency varies widely between brands.

For specific therapeutic applications, the value should also consider potential cost savings from reduced need for other interventions. For example, effective sleep support from apigenin might reduce reliance on other sleep aids, providing additional value. For those who consume a diet rich in apigenin-containing foods (parsley, celery, chamomile tea), supplementation may provide less incremental value unless targeting specific therapeutic effects requiring higher doses. Combination products that pair apigenin with synergistic compounds like GABA, melatonin, or magnesium for sleep support may offer good value by addressing multiple aspects of sleep quality simultaneously.

Properly formulated and packaged apigenin supplements typically have a shelf life of 2-3 years. Pure apigenin powder is relatively stable in dry form when protected from light, heat, and moisture. Plant extracts standardized for apigenin content may have slightly shorter shelf lives due to the presence of other compounds that could affect stability. Enhanced bioavailability formulations may have different stability profiles depending on the specific technology used.

Manufacturers often add antioxidants like vitamin E or rosemary extract to extend shelf life by preventing oxidation.

Store in a cool, dry place away from direct light and heat (below 25°C/77°F). Apigenin is sensitive to light degradation, so opaque containers are preferable. Keep containers tightly closed to prevent moisture exposure, as apigenin can degrade in moist conditions. Refrigeration is not necessary for dry products but may extend shelf life, particularly after opening.

For liquid formulations, refrigeration after opening is typically recommended. Avoid freezing liquid formulations unless specifically recommended by the manufacturer. For chamomile tea, store dried flowers in an airtight container away from light and moisture to preserve apigenin content.

Light exposure (particularly UV light, causes significant degradation), Heat (accelerates oxidation and degradation; significant degradation occurs above 40°C/104°F), Oxygen exposure (leads to oxidation), Alkaline conditions (apigenin is more stable in slightly acidic to neutral pH), Moisture (promotes hydrolysis and degradation), Transition metals (iron, copper can catalyze oxidation), Enzymes in raw plant materials (polyphenol oxidases can degrade apigenin), Microbial contamination (more relevant for liquid formulations or improperly stored plant materials)

Synthesis Methods

Natural Sources

Quality Considerations

While apigenin itself was not isolated and identified until the 20th century, its primary plant sources, particularly chamomile, have been used medicinally for thousands of years. Chamomile is one of the oldest documented medicinal plants, with records of its use dating back to ancient Egypt, where it was dedicated to the sun god Ra for its healing properties and used in embalming processes. Ancient Egyptians valued chamomile for treating fever (referred to as the ‘plant doctor’ or ‘ague plant’), and it appears in the Ebers Papyrus (1550 BCE), one of the oldest preserved medical documents. In ancient Greece, Hippocrates, Dioscorides, and Galen all documented chamomile’s medicinal properties for digestive issues, women’s health, and inflammation.

The Greek name ‘chamaimēlon’ means ‘earth apple,’ referring to the apple-like scent of the flowers. Romans used chamomile for beverages, incense, and medicinal purposes, spreading its cultivation throughout their empire. In the Middle Ages, chamomile was one of the nine sacred herbs in Anglo-Saxon medicine, used for ceremonies and healing rituals. European monasteries cultivated chamomile in their medicinal gardens, with Benedictine monks particularly known for their herbal knowledge.

Traditional European folk medicine employed chamomile for digestive complaints, inflammation, anxiety, insomnia, and as a gentle remedy for children. In traditional German medicine, chamomile was so widely used that it became known as ‘alles zutraut’ (capable of anything). Parsley, another rich source of apigenin, has its own extensive history in Mediterranean and Middle Eastern traditional medicine, used for digestive support, urinary health, and as an anti-inflammatory. Celery, also containing significant apigenin, was used medicinally in ancient China, India, and Rome, primarily for arthritis, nervous disorders, and as a diuretic.

The modern scientific study of apigenin began in the early 20th century, with initial isolation and basic characterization of the compound from plant sources. The term ‘apigenin’ derives from Apium genus plants (which includes celery), with the name first appearing in scientific literature in the 1900s. Significant research into apigenin’s pharmacological properties began in the 1980s, with studies on its anti-inflammatory and antioxidant effects. The breakthrough discovery of apigenin’s interaction with benzodiazepine receptors came in 1995, when researchers identified it as the primary compound responsible for chamomile’s anxiolytic effects.

This finding provided a scientific explanation for chamomile’s traditional use as a calming agent. In the early 2000s, research expanded to explore apigenin’s potential in cancer prevention, with studies demonstrating its ability to induce apoptosis in various cancer cell lines. Recent decades have seen growing interest in apigenin’s neuroprotective properties, sleep-enhancing effects, and potential applications in metabolic health. The first isolated apigenin supplements became commercially available in the early 2010s, marketed primarily for sleep support and anxiety reduction.

Today, apigenin is recognized as one of the key bioactive compounds in many traditional medicinal plants, with research continuing to elucidate its diverse biological activities and potential therapeutic applications.

Apigenin for sleep quality improvement in older adults, Chamomile extract (standardized for apigenin) for generalized anxiety disorder, Apigenin as adjunctive therapy for mild cognitive impairment, Topical apigenin formulations for skin photoprotection and aging, Apigenin’s effects on inflammatory biomarkers in metabolic syndrome, Chamomile extract for irritable bowel syndrome symptom management, Apigenin for exercise-induced oxidative stress reduction, Combination of apigenin with other flavonoids for synergistic effects