Piceatannol

• Anti-inflammatory
• Antioxidant protection
• Metabolic health support
• Cardiovascular health

• Anti-cancer properties
• Neuroprotection
• Weight management
• Blood glucose regulation
• Immune system modulation
• Skin health

Piceatannol (3,3′,4,5′-tetrahydroxy-trans-stilbene) is a naturally occurring polyphenolic stilbene that functions through multiple molecular mechanisms to exert its biological effects. As a structural analog of resveratrol with an additional hydroxyl group, piceatannol demonstrates enhanced potency in several pathways. One of its primary mechanisms is potent antioxidant activity, directly scavenging reactive oxygen species (ROS) and free radicals through its hydroxyl groups, which can donate hydrogen atoms to neutralize these harmful molecules. This antioxidant capacity is further enhanced by piceatannol’s ability to upregulate endogenous antioxidant defense systems, including superoxide dismutase (SOD), catalase, and glutathione peroxidase.

Piceatannol exhibits significant anti-inflammatory properties by inhibiting key inflammatory signaling pathways. It potently suppresses nuclear factor-kappa B (NF-κB) activation, a master regulator of inflammatory responses, by preventing the phosphorylation and degradation of inhibitory kappa B (IκB). Additionally, piceatannol inhibits Janus kinase 1 (JAK1), a critical component of the JAK-STAT signaling pathway involved in cytokine signaling, with greater potency than resveratrol. This inhibition reduces the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β).

In metabolic regulation, piceatannol influences several pathways that impact glucose and lipid metabolism. It enhances insulin sensitivity by activating AMP-activated protein kinase (AMPK), a key energy sensor that regulates cellular metabolism. Piceatannol also inhibits adipogenesis (fat cell formation) by downregulating peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα), master regulators of adipocyte differentiation. Furthermore, it stimulates lipolysis while inhibiting lipogenesis in mature adipocytes, contributing to its potential anti-obesity effects.

Piceatannol demonstrates anticancer properties through multiple mechanisms. It induces cell cycle arrest by modulating cyclins and cyclin-dependent kinases, triggers apoptosis (programmed cell death) through both intrinsic (mitochondrial) and extrinsic (death receptor) pathways, and inhibits angiogenesis by downregulating vascular endothelial growth factor (VEGF). Importantly, piceatannol inhibits the Src family kinases, which are involved in various cancer signaling pathways, with greater specificity than resveratrol. In cardiovascular protection, piceatannol improves endothelial function by increasing nitric oxide (NO) production through activation of endothelial nitric oxide synthase (eNOS).

It also reduces platelet aggregation and adhesion, potentially decreasing thrombosis risk. Additionally, piceatannol’s ability to inhibit vascular smooth muscle cell proliferation and migration may contribute to its anti-atherosclerotic effects. Neurologically, piceatannol crosses the blood-brain barrier and exerts neuroprotective effects by reducing oxidative stress, inhibiting neuroinflammation, and modulating neurotransmitter systems. It may also influence sirtuins, particularly SIRT1, a longevity-associated protein that regulates various cellular processes including stress responses, metabolism, and aging.

This multi-target mechanism profile explains piceatannol’s diverse biological activities and potential therapeutic applications across various health conditions.

The optimal dosage of piceatannol has not been definitively established through comprehensive human clinical trials. Current research suggests effective doses range from 5-50 mg daily, with most studies using 10-20 mg daily for general health benefits. Due to limited human clinical data, dosage recommendations are primarily based on preclinical studies, small human trials, and extrapolation from research on related compounds like resveratrol.

Piceatannol demonstrates relatively low oral bioavailability, estimated at approximately 5-10% in humans, though this varies based on formulation and individual factors. As a polyphenolic compound, piceatannol undergoes extensive first-pass metabolism in the intestine and liver. Its absorption occurs primarily in the small intestine through passive diffusion and active transport mechanisms. Once absorbed, piceatannol is rapidly metabolized, primarily through glucuronidation and sulfation, resulting in various metabolites that may also possess biological activity.

Compared to resveratrol, piceatannol shows slightly better absorption due to its additional hydroxyl group, which increases its water solubility while maintaining sufficient lipophilicity for membrane permeation.

Consumption with dietary fats or a meal containing healthy fats to enhance 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, Co-administration with piperine (black pepper extract) to inhibit glucuronidation and extend half-life, Micronized formulations that increase surface area for absorption, Emulsified preparations that improve solubility and dispersion, Consumption with other polyphenols that may compete for metabolic enzymes, potentially extending half-life, Sustained-release formulations to prolong absorption time

Piceatannol is best absorbed when taken with a meal containing moderate amounts of fat, which can enhance its dissolution and absorption in the gastrointestinal tract. Morning or early afternoon administration may be preferable to align with natural circadian rhythms of metabolic activity, though no definitive evidence suggests a specific optimal time of day. For metabolic benefits, taking piceatannol approximately 30 minutes before meals may help optimize its effects on glucose metabolism. Due to its relatively short half-life (estimated at 1-4 hours), divided doses throughout the day may maintain more consistent blood levels compared to a single daily dose.

However, the biological effects of piceatannol may persist longer than its detectable presence in circulation due to its influence on gene expression and cellular signaling pathways. For individuals taking medications, it’s advisable to separate piceatannol supplementation by at least 2 hours to minimize potential interactions, though specific drug interactions are not well-documented.

• Mild gastrointestinal discomfort (occasional)
• Headache (rare)
• Dizziness (rare)
• Skin flushing (rare)
• Allergic reactions in sensitive individuals (very rare)

• Pregnancy and lactation due to insufficient safety data
• Children under 18 years due to lack of safety studies in pediatric populations
• Individuals with hormone-sensitive conditions (theoretical concern due to potential estrogenic activity)
• Patients scheduled for surgery (discontinue at least 2 weeks before due to potential antiplatelet effects)
• Individuals with known hypersensitivity to stilbenes or related compounds

• Anticoagulant and antiplatelet medications – Piceatannol may enhance their effects, potentially increasing bleeding risk
• Cytochrome P450 substrates – Piceatannol may inhibit certain CYP enzymes, potentially affecting the metabolism of drugs processed by these pathways
• Immunosuppressants – Theoretical interaction due to piceatannol’s immunomodulatory effects
• Antidiabetic medications – May enhance hypoglycemic effects, requiring monitoring of blood glucose levels
• Antihypertensive drugs – Potential additive effects on blood pressure reduction
• Hormone therapies – Possible interference due to piceatannol’s potential effects on estrogen signaling

No official upper limit has been established for piceatannol due to limited human clinical data. Preclinical toxicity studies suggest piceatannol 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 hundred milligrams in humans have been used without significant toxicity. However, as a precautionary approach, it is generally recommended to stay within the range of 5-50 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.

In the United States, piceatannol 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. Piceatannol does not have Generally Recognized as Safe (GRAS) status for food applications.

The FDA has not issued specific guidance or warnings regarding piceatannol supplementation, reflecting its relatively recent emergence in the supplement market and limited safety concerns to date.

Eu: In the European Union, piceatannol does not have Novel Food status, which would be required for its use in foods or food supplements if it was not consumed to a significant degree before May 15, 1997. However, passion fruit seed extract containing piceatannol may be marketed as a food supplement in some EU countries based on the traditional consumption of passion fruit. Regulatory status varies between member states, with some countries permitting its sale as a supplement ingredient while others may require additional safety documentation.

Japan: In Japan, piceatannol from passion fruit seed extract has been approved as a Food for Specified Health Uses (FOSHU) ingredient. Japan has conducted significant research on piceatannol, particularly from passion fruit sources, and recognizes certain health benefits in their regulatory framework.

Australia: The Therapeutic Goods Administration (TGA) in Australia regulates piceatannol 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.

Canada: Health Canada regulates piceatannol 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.

China: In China, piceatannol is regulated by the National Medical Products Administration (NMPA) and is not currently included in the list of approved new food ingredients. Its use in health food products requires specific approval based on safety and efficacy data.

Medium to high compared to more common supplements

For standardized piceatannol supplements (10-20 mg daily dose), the typical cost ranges from $1.00 to $3.00 per day, depending on brand, quality, and formulation. Passion fruit seed extracts standardized to contain piceatannol are generally less expensive than isolated piceatannol, with costs ranging from $0.50 to $1.50 per effective daily dose. Premium formulations with enhanced bioavailability (liposomal, nanoparticle, etc.) or combination products may cost $2.00-$4.00 per day.

Piceatannol represents a moderate value proposition in the supplement market, with several factors influencing its cost-efficiency assessment. First, as a relatively new supplement ingredient with limited commercial production, economies of scale have not yet fully developed, contributing to higher costs compared to more established supplements. Second, the extraction and purification processes for piceatannol are relatively complex and resource-intensive, particularly when derived from passion fruit seeds, which justifies some of the premium pricing. Third, the effective dose range (5-50 mg daily) is relatively small compared to many supplements, meaning a little goes a long way, which partially offsets the higher per-gram cost.

Fourth, piceatannol’s unique biological activities, particularly its enhanced potency compared to resveratrol for certain applications like Src kinase inhibition and anti-inflammatory effects, may justify the premium price for specific health concerns. For maximum cost efficiency, consumers should consider: standardized passion fruit seed extracts rather than isolated piceatannol, 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 resveratrol or quercetin for potentially synergistic effects. When comparing cost, the price per milligram of active piceatannol is a more relevant metric than the price per capsule, as potencies vary significantly between products. While piceatannol is generally more expensive than many common supplements, its unique biological properties and potential health benefits may make it a worthwhile investment for specific health concerns, particularly metabolic health, inflammation management, and antioxidant support.

Properly formulated and packaged piceatannol 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. Microencapsulated or stabilized formulations may have extended shelf life up to 3 years. Natural extracts containing piceatannol generally have shorter shelf life than isolated or synthetic piceatannol due to the presence of other compounds that may accelerate degradation.

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 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.

Exposure to ultraviolet light and direct sunlight – Piceatannol is highly photosensitive and can degrade rapidly when exposed to UV radiation, High temperatures – Heat accelerates oxidation processes that reduce potency, Oxygen exposure – Oxidation is the primary degradation pathway for piceatannol, Humidity – Can accelerate degradation, especially in powder formulations, pH extremes – Piceatannol is most stable at slightly acidic to neutral pH (pH 5-7), Presence of metal ions – Particularly iron and copper can catalyze oxidation, Enzymatic degradation – Certain enzymes can break down piceatannol, 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

Piceatannol 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 late 20th century. However, the natural sources of piceatannol have been used in various traditional medicine systems for centuries. Japanese knotweed (Polygonum cuspidatum), which contains both piceatannol and resveratrol, has been used in traditional Chinese and Japanese medicine for over 2,000 years to treat inflammation, infections, and cardiovascular conditions. This plant, known as ‘Hu Zhang’ in Chinese medicine, was traditionally used to treat arthritis, jaundice, amenorrhea, and various inflammatory conditions.

Similarly, rhubarb (Rheum species), another plant source of piceatannol, has a long history of medicinal use in Asian and European traditional medicine as a digestive aid and for treating various inflammatory conditions. Passion fruit, now recognized as one of the richest sources of piceatannol, has been consumed in South America for centuries, with indigenous populations using various parts of the plant for medicinal purposes, including sedative, anxiolytic, and anti-inflammatory applications. The scientific discovery and isolation of piceatannol occurred much later than its inadvertent traditional use. Piceatannol was first identified as a natural product in the 1980s, though its full chemical structure and relationship to resveratrol were not fully elucidated until later studies.

Initial scientific interest in piceatannol stemmed from its identification as a tyrosine kinase inhibitor, particularly its ability to inhibit Src kinase, which plays important roles in cellular signaling pathways. This discovery in the early 1990s sparked research into its potential anticancer properties. The connection between piceatannol and traditional medicine uses of its plant sources was not made until retrospective analysis in the late 1990s and early 2000s. The identification of piceatannol as a metabolite of resveratrol further increased scientific interest, as resveratrol had already gained attention for its potential health benefits, particularly following the ‘French Paradox’ observations regarding red wine consumption and cardiovascular health.

Commercial interest in piceatannol as a dietary supplement is even more recent, emerging primarily in the 2010s following studies identifying passion fruit seeds as a rich source and preliminary research suggesting benefits for metabolic health. The first standardized passion fruit seed extracts containing piceatannol became commercially available around 2015, marking the beginning of its intentional use as a dietary supplement. Unlike many traditional herbal medicines with centuries of documented use, piceatannol supplements represent a modern application of traditional plant materials, guided by scientific research rather than historical usage patterns.

No comprehensive meta-analyses specifically focused on piceatannol have been published to date, reflecting the relatively early stage of research on this compound compared to more extensively studied polyphenols like resveratrol.

Investigation of piceatannol-enriched passion fruit extract on glucose metabolism in prediabetic individuals, Evaluation of piceatannol supplementation on inflammatory biomarkers in individuals with metabolic syndrome, Effects of piceatannol on cognitive function and neuroinflammation in older adults, Topical application of piceatannol for photoaging and skin inflammation