Ellagic Acid

• Potent antioxidant protection
• Anti-inflammatory effects
• Cardiovascular health support
• Metabolic health regulation

• Cancer prevention potential
• Liver protection
• Blood glucose regulation
• Skin health and photoprotection
• Neuroprotective effects
• Antimicrobial properties
• Gut health support

Ellagic acid (EA) exerts its diverse biological effects through multiple molecular mechanisms. As a polyphenolic compound with four hydroxyl groups and two lactone groups, EA’s primary mechanism is its potent antioxidant activity. It directly scavenges reactive oxygen species (ROS) and free radicals, including superoxide anions, hydroxyl radicals, and peroxyl radicals, through hydrogen atom donation from its hydroxyl groups. Beyond direct scavenging, EA enhances endogenous antioxidant defense systems by upregulating antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST), while increasing cellular glutathione levels.

This dual antioxidant action provides comprehensive protection against oxidative stress. EA’s anti-inflammatory effects are mediated through inhibition of key inflammatory signaling pathways. It suppresses nuclear factor-kappa B (NF-κB) activation by preventing IκB kinase phosphorylation and subsequent degradation of inhibitory kappa B (IκB). This inhibition reduces the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), chemokines, and inflammatory enzymes (COX-2, iNOS).

Additionally, EA inhibits mitogen-activated protein kinases (MAPKs), including p38, JNK, and ERK, further dampening inflammatory responses. EA also modulates the NLRP3 inflammasome, a critical regulator of inflammation, reducing IL-1β and IL-18 production. In cancer prevention and treatment, EA operates through multiple mechanisms. It induces cell cycle arrest by modulating cyclins and cyclin-dependent kinases (CDKs), particularly at the G0/G1 and G2/M phases.

EA triggers apoptosis (programmed cell death) via both intrinsic (mitochondrial) and extrinsic (death receptor) pathways by increasing pro-apoptotic proteins (Bax, Bad) while decreasing anti-apoptotic proteins (Bcl-2, Bcl-xL). It also inhibits angiogenesis by downregulating vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Furthermore, EA inhibits DNA topoisomerases and directly binds to DNA, potentially preventing carcinogen-induced DNA damage. EA’s metabolic effects include enhanced insulin sensitivity through activation of insulin receptor substrate-1 (IRS-1) and downstream signaling pathways, including phosphatidylinositol 3-kinase (PI3K)/Akt.

It also activates AMP-activated protein kinase (AMPK), a key energy sensor that regulates glucose and lipid metabolism. EA inhibits α-amylase and α-glucosidase, enzymes involved in carbohydrate digestion, potentially reducing postprandial glucose spikes. In lipid metabolism, EA reduces lipogenesis by downregulating sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) while enhancing fatty acid oxidation. For cardiovascular protection, EA improves endothelial function by increasing nitric oxide (NO) production through endothelial nitric oxide synthase (eNOS) activation.

It inhibits platelet aggregation and adhesion, potentially reducing thrombosis risk. EA also inhibits angiotensin-converting enzyme (ACE), contributing to blood pressure regulation. In the liver, EA activates nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidant responses, inducing detoxification enzymes and protecting against hepatotoxicity. It also inhibits hepatic stellate cell activation, reducing liver fibrosis.

EA’s neuroprotective effects involve reducing oxidative stress and neuroinflammation in the brain, while modulating neurotransmitter systems and potentially enhancing brain-derived neurotrophic factor (BDNF) expression. A unique aspect of EA’s bioactivity involves its conversion by gut microbiota into urolithins (especially urolithin A), which may mediate many of EA’s health benefits through improved bioavailability and distinct biological activities, including mitophagy enhancement and anti-inflammatory effects.

The optimal dosage of ellagic acid has not been definitively established through comprehensive human clinical trials. Current research suggests effective doses range from 30-500 mg daily, with most studies using 100-300 mg daily for general health benefits. Due to limited human clinical data, dosage recommendations are primarily based on preliminary human studies, animal research, and traditional usage patterns of ellagic acid-rich foods and extracts.

Ellagic acid demonstrates relatively poor oral bioavailability, estimated at approximately 0.2-6% in humans, primarily due to its low water solubility, limited intestinal permeability, and extensive first-pass metabolism. When consumed, ellagic acid undergoes complex absorption and metabolic processes. In the stomach, some free ellagic acid may be released from ellagitannins due to acidic hydrolysis. In the small intestine, a small portion of free ellagic acid is absorbed through passive diffusion, while the majority passes to the colon.

There, gut microbiota metabolize ellagic acid to produce urolithins (especially urolithin A, B, C, and D), which are more readily absorbed and may be responsible for many of the health benefits attributed to ellagic acid. These urolithins undergo enterohepatic circulation and can be detected in plasma for up to 48-72 hours after consumption. Individual variations in gut microbiota composition significantly influence the metabolism of ellagic acid to urolithins, creating substantial differences in bioavailability between individuals.

Consumption with dietary fats or a meal containing healthy fats to enhance solubility and absorption, Liposomal formulations that protect the molecule and improve cellular uptake, Nanoparticle delivery systems that increase stability and targeted delivery, Phospholipid complexation to improve membrane transport, Micronized formulations that increase surface area for absorption, Co-administration with piperine (black pepper extract) to inhibit glucuronidation and extend half-life, Consumption of whole food sources (pomegranate, berries) that contain natural co-factors enhancing bioavailability, Sustained-release formulations to prolong absorption time, Consumption of probiotics or prebiotics that support beneficial gut bacteria capable of converting ellagic acid to urolithins, Emulsified preparations that improve solubility and dispersion

Ellagic acid is best absorbed when taken with a meal containing moderate amounts of fat, which can enhance its dissolution and absorption in the gastrointestinal tract. For general health benefits, consistent daily intake is more important than specific timing, as the metabolites (urolithins) have relatively long half-lives in circulation. For blood glucose management, taking ellagic acid approximately 30 minutes before meals may help optimize its effects on carbohydrate digestion and glucose metabolism. Due to its relatively poor direct absorption but extended metabolite presence through urolithins, once-daily dosing is typically sufficient to maintain beneficial effects.

For individuals taking medications, it’s advisable to separate ellagic acid supplementation by at least 2 hours to minimize potential interactions, though specific drug interactions are not well-documented. Consistent daily consumption over extended periods (weeks to months) may be necessary to establish optimal gut microbiota capable of efficiently converting ellagic acid to bioactive urolithins, as this conversion capacity can develop and improve over time with regular exposure.

• Mild gastrointestinal discomfort (occasional)
• Nausea (rare)
• Diarrhea (rare)
• Allergic reactions in sensitive individuals (very rare)
• Temporary changes in stool color (with high doses from pomegranate or berry sources)

• Pregnancy and lactation due to insufficient safety data
• Children under 18 years due to lack of safety studies in pediatric populations
• Individuals with known hypersensitivity to ellagic acid or ellagitannin-containing foods
• Patients scheduled for surgery (discontinue at least 2 weeks before due to potential antiplatelet effects)
• Individuals with severe kidney disease (theoretical concern due to limited excretion pathways)

• Anticoagulant and antiplatelet medications – Ellagic acid may enhance their effects, potentially increasing bleeding risk
• Antihypertensive drugs – Potential additive effects on blood pressure reduction
• Antidiabetic medications – May enhance hypoglycemic effects, requiring monitoring of blood glucose levels
• Cytochrome P450 substrates – Ellagic acid may inhibit certain CYP enzymes, potentially affecting the metabolism of drugs processed by these pathways
• Drugs with narrow therapeutic indices – Caution advised due to potential alterations in drug metabolism
• Immunosuppressants – Theoretical interaction due to ellagic acid’s immunomodulatory effects

No official upper limit has been established for ellagic acid due to limited human clinical data. Preclinical toxicity studies suggest ellagic acid has a favorable safety profile with no observed adverse effects at doses significantly higher than those typically used in supplementation. In animal studies, doses equivalent to several grams in humans have been used without significant toxicity. However, as a precautionary approach, it is generally recommended to stay within the range of 30-500 mg daily for adults until more comprehensive safety data becomes available.

Higher doses should be approached with caution and preferably under healthcare provider supervision. Long-term safety data beyond several months of continuous use is currently lacking. Most safety data comes from studies using ellagic acid-rich foods and extracts rather than isolated ellagic acid, which may have different safety profiles.

In the United States, ellagic acid is regulated as a dietary supplement ingredient under the Dietary Supplement Health and Education Act (DSHEA) of 1994. It has not been approved as a drug for the prevention or treatment of any disease. As a dietary supplement ingredient, manufacturers and distributors must ensure product safety and cannot make disease treatment claims. The FDA has not issued specific guidance or warnings regarding ellagic acid supplementation, reflecting its relatively low safety concern profile.

Ellagic acid is also permitted as a component of foods in its natural forms (berries, pomegranates, nuts, etc.). Pomegranate extract, a common source of ellagic acid in supplements, has been granted Generally Recognized as Safe (GRAS) status for certain food applications, though this designation does not specifically address isolated ellagic acid.

Eu: In the European Union, ellagic acid is not specifically regulated as a novel food ingredient, as it has been consumed as part of traditional foods (berries, pomegranates, nuts) prior to May 15, 1997. It is permitted in food supplements, though health claims related to ellagic acid must be authorized by the European Food Safety Authority (EFSA). To date, EFSA has not approved specific health claims for ellagic acid. Plant extracts containing ellagic acid (such as pomegranate extract) are regulated under the traditional herbal medicinal products directive in some EU countries when marketed with medicinal claims.

Canada: Health Canada regulates ellagic acid under the Natural Health Products Regulations. It is permitted as a medicinal ingredient in natural health products with appropriate evidence for safety and efficacy. Product license applications must include quality, safety, and efficacy information. Health Canada has not issued specific monographs for ellagic acid, but products containing it may be licensed based on general evidence for antioxidants or specific evidence submitted by manufacturers.

Australia: The Therapeutic Goods Administration (TGA) in Australia regulates ellagic acid as a complementary medicine ingredient. It is listed in the Australian Register of Therapeutic Goods (ARTG) when used in appropriate formulations and dosages. Claims must be supported by adequate evidence as per TGA guidelines. Ellagic acid is generally permitted in listed medicines (lower risk category) rather than registered medicines.

Japan: In Japan, ellagic acid is permitted as a food ingredient and in ‘Foods with Function Claims’ (FFC) when appropriate scientific evidence supports the claimed benefits. It is not specifically listed as a designated food additive but is accepted as a natural component of foods. Pomegranate extract containing ellagic acid has been used in various functional food products in the Japanese market.

China: In China, ellagic acid is regulated by the National Medical Products Administration (NMPA) and is included in the inventory of ingredients permitted for use in health food products. Health food products containing ellagic acid require specific approval based on safety and efficacy data. Traditional Chinese Medicine formulations containing ellagic acid-rich plants are regulated under separate provisions for traditional medicines.

Medium compared to common supplements, with significant variation based on source and formulation

For standardized ellagic acid supplements (100-300 mg daily dose), the typical cost ranges from $0.50 to $2.00 per day, depending on brand, quality, and formulation. Pomegranate extract standardized for ellagic acid content is generally less expensive than isolated ellagic acid, with costs ranging from $0.30 to $1.00 per effective daily dose. Berry extracts (raspberry, strawberry) containing ellagic acid typically cost $0.40-$1.20 per day. Premium formulations with enhanced bioavailability (liposomal, nanoparticle, etc.) may cost $1.50-$3.00 per day.

Ellagic acid represents a moderate value proposition in the supplement market, with several factors influencing its cost-efficiency assessment. First, the source of ellagic acid significantly impacts both cost and potential efficacy. Whole food extracts (pomegranate, berries, walnuts) generally provide better value than isolated ellagic acid, as they contain beneficial co-factors that may enhance bioavailability and provide synergistic effects. These natural extracts are typically less expensive per effective dose than highly purified ellagic acid.

Second, the conversion of ellagic acid to bioactive urolithins by gut microbiota is crucial for many health benefits, yet this conversion varies significantly between individuals. This variability means that the same ellagic acid supplement may provide excellent value for some users (good converters) but poor value for others (poor converters), making personalized approaches potentially more cost-effective. Third, the effective dose range (100-300 mg daily for most applications) is moderate compared to many supplements, meaning a little goes a long way, which partially offsets the higher per-gram cost of quality products. Fourth, ellagic acid’s multiple mechanisms of action (antioxidant, anti-inflammatory, metabolic, cardiovascular) may provide comprehensive health benefits that would otherwise require multiple separate supplements, potentially increasing its overall value proposition.

For maximum cost efficiency, consumers should consider: standardized pomegranate or berry extracts rather than isolated ellagic acid, as these provide the active compound along with potentially beneficial co-factors at a lower price point; products with verified potency through third-party testing to ensure you’re getting what you pay for; formulations that enhance bioavailability, potentially allowing for lower effective doses; and combination products that include complementary compounds like quercetin or resveratrol for potentially synergistic effects. When comparing cost, the price per milligram of active ellagic acid is a more relevant metric than the price per capsule, as potencies vary significantly between products. Whole food sources like pomegranates, berries, and walnuts may provide the most cost-effective source of ellagic acid for general health maintenance, though supplements offer more precise dosing for specific health concerns.

Properly formulated and packaged ellagic acid supplements typically have a shelf life of 1-2 years from the date of manufacture. However, this can vary significantly based on formulation, packaging, and storage conditions. Pure ellagic acid is relatively stable in dry form but more susceptible to degradation in solution. Natural extracts containing ellagic acid (pomegranate, berry extracts) generally have shorter shelf life than isolated ellagic acid due to the presence of other compounds that may accelerate degradation.

Microencapsulated or stabilized formulations may have extended shelf life up to 3 years.

Store in a cool, dry place away from direct sunlight and heat sources. Optimal temperature range is 59-77°F (15-25°C). Refrigeration is not necessary for dry products but may extend potency in hot climates. Keep container tightly closed to protect from moisture and oxygen exposure.

For liquid formulations, refrigeration after opening is recommended to maintain freshness. Avoid storing in bathrooms or other humid environments. If available in dark or opaque containers, maintain in original packaging to protect from light exposure. For bulk powder, consider transferring smaller amounts to a separate container for regular use while keeping the main supply sealed.

Stability is best maintained in slightly acidic conditions (pH 4-6); avoid exposure to alkaline substances.

Exposure to ultraviolet light and direct sunlight – Ellagic acid is photosensitive and can degrade when exposed to UV radiation, High temperatures – Heat accelerates oxidation processes that reduce potency, Oxygen exposure – Oxidation is a primary degradation pathway for ellagic acid, Humidity – Can accelerate degradation, especially in powder formulations, Alkaline conditions – Ellagic acid is unstable at high pH (above 7.5) and undergoes rapid degradation, Presence of metal ions – Particularly iron and copper can catalyze oxidation reactions, Enzymatic degradation – Certain enzymes can break down ellagic acid, Microbial contamination – Can lead to degradation in liquid formulations, Improper packaging – Permeable packaging materials can allow oxygen and moisture penetration, Freeze-thaw cycles – Can affect stability, particularly in liquid formulations

Synthesis Methods

Natural Sources

Quality Considerations

Ellagic acid as a specific isolated compound has a relatively short history in terms of intentional human consumption, with scientific identification and characterization occurring primarily in the 19th and 20th centuries. However, the natural sources of ellagic acid have been used in various traditional medicine systems for thousands of years. Pomegranate (Punica granatum), one of the richest sources of ellagic acid, has been cultivated since ancient times and holds significant cultural and medicinal importance in many civilizations. Ancient Egyptian, Greek, Persian, and Chinese texts mention pomegranate for treating various ailments, including intestinal parasites, inflammation, and digestive disorders.

In Ayurvedic medicine, dating back over 3,000 years, several ellagic acid-rich plants are prominent, including amla (Phyllanthus emblica), which forms part of the famous Triphala formulation, and is used for rejuvenation, digestion, and longevity. Similarly, Terminalia chebula and Terminalia bellirica, both containing significant amounts of ellagic acid, are valued in Ayurvedic traditions for their astringent and healing properties. Native American tribes traditionally used various berries rich in ellagic acid, particularly blackberries and raspberries, for treating coughs, digestive issues, and as blood purifiers. The astringent properties of these fruits were recognized and utilized for their medicinal benefits long before the active compounds were identified.

Oak bark and acorns, which contain ellagitannins that hydrolyze to ellagic acid, were used in European folk medicine for treating diarrhea, inflammation, and wounds due to their astringent properties. The tannin-rich nature of these plants was valued for leather tanning and medicinal applications. The scientific discovery and isolation of ellagic acid occurred in 1831 when chemist Henri Braconnot first isolated it from oak gall infusions. The name ‘ellagic’ was derived from the French word for oak gall (‘galle’ spelled backward with an additional ‘i’).

However, its chemical structure wasn’t fully elucidated until the early 20th century. Modern scientific interest in ellagic acid began to accelerate in the 1960s and 1970s with research into its potential anticarcinogenic properties. Studies in the 1980s and 1990s further explored its antioxidant capacity and potential health benefits. The discovery of urolithins as gut microbiota metabolites of ellagic acid in the early 2000s marked a significant advancement in understanding its bioactivity, as these metabolites are now recognized as mediating many of ellagic acid’s health effects.

Commercial interest in ellagic acid as a dietary supplement is relatively recent, emerging primarily in the late 1990s and early 2000s following research highlighting its potential health benefits. Initially marketed primarily as an antioxidant and cancer-preventive agent, its applications have expanded to include cardiovascular health, metabolic support, and anti-aging properties. Unlike many traditional herbal medicines with centuries of documented use, ellagic acid supplements represent a modern application of traditional plant materials, guided by scientific research rather than historical usage patterns.

Ríos JL, Giner RM, Marín M, Recio MC. A pharmacological update of ellagic acid. Planta Med. 2018;84(15):1068-1093. doi:10.1055/a-0633-9492, Ceci C, Lacal PM, Tentori L, De Martino MG, Miano R, Graziani G. Experimental evidence of the antitumor, antimetastatic and antiangiogenic activity of ellagic acid. Nutrients. 2018;10(11):1756. doi:10.3390/nu10111756, Kang I, Buckner T, Shay NF, Gu L, Chung S. Improvements in metabolic health with consumption of ellagic acid and subsequent conversion into urolithins: evidence and mechanisms. Adv Nutr. 2016;7(5):961-972. doi:10.3945/an.116.012575

Investigation of ellagic acid-rich pomegranate extract on endothelial function in individuals with metabolic syndrome, Evaluation of ellagic acid supplementation on inflammatory biomarkers in patients with type 2 diabetes, Effects of ellagic acid on cognitive function and neuroinflammation in older adults, Topical application of ellagic acid for photoaging and skin inflammation