Pterostilbene

• Antioxidant protection
• Cellular signaling modulation
• Metabolic health
• Cognitive function

• Cardiovascular support
• Blood glucose regulation
• Neuroprotection
• Anti-inflammatory
• Cellular stress resistance
• DNA repair support

Pterostilbene exerts its diverse biological effects through multiple mechanisms at the molecular level. As a structural analog of resveratrol with two methoxy groups replacing two hydroxyl groups, pterostilbene exhibits enhanced lipophilicity, metabolic stability, and cellular uptake compared to resveratrol, contributing to its superior bioavailability and potentially greater biological activity. One of pterostilbene’s primary mechanisms is activation of sirtuins, particularly SIRT1, a class of NAD+-dependent deacetylases that regulate numerous cellular processes including energy metabolism, stress resistance, and longevity. By activating SIRT1, pterostilbene influences mitochondrial biogenesis, fatty acid oxidation, and glucose metabolism.

This sirtuin activation also leads to deacetylation of transcription factors like PGC-1α, FOXO proteins, and p53, affecting their activity and downstream targets related to cellular stress resistance and longevity. Pterostilbene is a potent activator of AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis. AMPK activation promotes glucose uptake, fatty acid oxidation, and mitochondrial biogenesis while inhibiting lipogenesis and gluconeogenesis. This mechanism contributes significantly to pterostilbene’s metabolic benefits, including improved insulin sensitivity and lipid profiles.

As an antioxidant, pterostilbene directly scavenges reactive oxygen species (ROS) and free radicals through its hydroxyl group, which can donate hydrogen atoms to stabilize these harmful molecules. Beyond direct antioxidant activity, pterostilbene 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, superoxide dismutase, and heme oxygenase-1. Pterostilbene 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 the brain, pterostilbene crosses the blood-brain barrier more efficiently than resveratrol due to its greater lipophilicity. It exhibits neuroprotective effects by reducing oxidative stress, inhibiting microglial activation, and modulating neurotransmitter systems. Pterostilbene enhances brain-derived neurotrophic factor (BDNF) levels, supporting neuronal health and plasticity. It may protect against neurodegenerative conditions by reducing amyloid-β aggregation and tau hyperphosphorylation.

For cardiovascular protection, pterostilbene 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 and enhancing reverse cholesterol transport. Pterostilbene modulates numerous cell signaling pathways involved in cell proliferation, differentiation, and survival, including PI3K/Akt, MAPK, and JAK/STAT pathways. It induces cell cycle arrest and apoptosis in cancer cells while generally sparing normal cells, contributing to its potential cancer-preventive effects.

At the epigenetic level, pterostilbene influences DNA methylation patterns and histone modifications, potentially reversing aberrant epigenetic changes associated with aging and disease. It also modulates microRNA expression, affecting gene regulation at the post-transcriptional level. Additionally, pterostilbene enhances autophagy, the cellular process for removing damaged organelles and proteins, which is crucial for cellular maintenance and longevity.

No Recommended Dietary Allowance (RDA) or Adequate Intake (AI) has been established for pterostilbene, as

it is not considered an essential nutrient. Based on clinical studies, effective doses typically range from 50-250 mg per day for general health benefits. Lower doses (50-100 mg) may be sufficient for antioxidant support and general health maintenance,

while higher doses (150-250 mg) have been used in studies targeting specific conditions like cognitive function or metabolic health. Dietary intake from food sources is very low, estimated at less than 1 mg per day even in diets rich in berries, making supplementation necessary to achieve the doses used in clinical research.

Pterostilbene exhibits significantly better bioavailability compared to its structural analog resveratrol, with approximately 80% oral bioavailability in humans versus about 20% for resveratrol. This superior bioavailability is primarily due to pterostilbene’s two methoxy groups (compared to resveratrol’s hydroxyl groups), which increase its lipophilicity, membrane permeability, and metabolic stability. The methoxy groups make pterostilbene more resistant to glucuronidation and sulfation, the primary metabolic pathways that limit resveratrol’s bioavailability. After oral administration, pterostilbene is absorbed in the small intestine, with peak plasma concentrations typically occurring 2-3 hours after ingestion.

It undergoes some first-pass metabolism in the liver but to a lesser extent than resveratrol. Pterostilbene has a longer plasma half-life of approximately 105 minutes compared to resveratrol’s 14 minutes, allowing for more sustained biological effects. It also demonstrates better tissue distribution, particularly to the brain, due to its enhanced ability to cross the blood-brain barrier. This improved pharmacokinetic profile may explain why pterostilbene often shows greater biological activity than resveratrol in various experimental models despite their structural similarity.

Taking with dietary fats or oils can enhance absorption due to pterostilbene’s lipophilic nature, Liposomal and phytosomal formulations can further increase bioavailability by improving solubility and enhancing cellular uptake, Piperine (black pepper extract) may inhibit glucuronidation enzymes, potentially extending pterostilbene’s half-life, Nanoparticle formulations significantly improve dissolution rate and absorption, Micronization (reducing particle size) increases surface area and improves dissolution, Combining with quercetin may inhibit the metabolism of pterostilbene, potentially extending its half-life, Emulsified formulations improve dispersion in the digestive tract, Taking multiple smaller doses throughout the day rather than a single large dose may result in more consistent blood levels

For general health benefits, pterostilbene can be taken once daily with a meal containing some fat to enhance absorption. The long half-life of pterostilbene compared to resveratrol means that once-daily dosing is typically sufficient to maintain effective blood levels. For cognitive benefits, morning dosing may be preferable to align with daily cognitive demands, though there is no strong evidence that timing significantly affects cognitive outcomes. When using pterostilbene for its metabolic benefits, taking it before meals may theoretically help modulate postprandial glucose and lipid metabolism, though research specifically examining timing effects is limited.

For those taking multiple supplements, pterostilbene can be taken alongside other fat-soluble compounds to simplify supplementation regimens and potentially enhance absorption of all compounds. To minimize potential interactions with medications, pterostilbene supplements should generally be taken at least 2 hours before or after other medications, particularly those with narrow therapeutic windows. For sleep quality, some users report benefits from evening dosing, though the mechanism for sleep effects is not well-established and may be indirect through general health improvements. Consistency in daily supplementation is generally more important than specific timing for many of pterostilbene’s benefits, as some effects may develop through regular, long-term use and cumulative action on cellular signaling pathways.

• Generally well-tolerated with minimal reported side effects at recommended doses
• Mild gastrointestinal discomfort (nausea, stomach pain) – uncommon
• Potential for mild elevation in LDL cholesterol at higher doses (observed in some human studies)
• Mild headache (rare)
• Dizziness (rare)
• Potential for mild blood pressure changes (both increases and decreases have been reported)
• Mild sleep disturbances in sensitive individuals (uncommon)
• Potential for mild hormone modulation at very high doses (theoretical, based on limited evidence)

• Known hypersensitivity to pterostilbene or related compounds
• Pregnancy and breastfeeding (due to limited safety data)
• Scheduled surgery (discontinue 2 weeks before due to theoretical anticoagulant effects)
• Caution advised in patients with hormone-sensitive conditions (theoretical concern at very high doses)
• Caution in patients taking medications for high cholesterol (due to potential LDL effects)
• Caution in patients with bleeding disorders (due to potential mild antiplatelet effects)
• Caution in patients with low blood pressure (theoretical concern)
• Caution in children and adolescents (limited safety data)

• Anticoagulant/antiplatelet medications (potential mild additive effect increasing bleeding risk)
• Cytochrome P450 substrates (pterostilbene may inhibit certain CYP enzymes, potentially affecting drug metabolism)
• Cholesterol-lowering medications (potential interaction due to pterostilbene’s effects on lipid profiles)
• Antidiabetic medications (potential additive effect on blood glucose, requiring monitoring)
• Antihypertensive medications (potential interaction with blood pressure regulation)
• Hormone therapies (theoretical interaction due to potential weak estrogenic effects at high doses)
• Drugs transported by P-glycoprotein (potential interaction)
• Medications with narrow therapeutic windows (caution due to potential metabolic interactions)

No official Tolerable Upper Intake Level (UL) has been established for pterostilbene. Based on available research, doses up to 250 mg per day appear to be well-tolerated by most healthy adults for extended use. A human clinical trial using doses up to 250 mg twice daily (500 mg total) reported no serious adverse events, though some participants experienced elevated LDL cholesterol at this dose. This potential effect on LDL cholesterol suggests caution with long-term use of doses above 250 mg daily, particularly in individuals with existing cholesterol concerns.

Animal studies have used much higher doses (equivalent to several grams in humans) without acute toxicity, but long-term safety at such doses is not established. 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 pterostilbene.

Pterostilbene is not specifically approved as a food additive by the FDA. As a dietary supplement ingredient, pterostilbene falls under the regulations of the Dietary Supplement Health and Education Act (DSHEA) of 1994. Under DSHEA, manufacturers are responsible for determining that their products are safe before marketing, but do not need FDA approval. The FDA has not approved specific health claims for pterostilbene supplements.

In 2011, ChromaDex, a major supplier of pterostilbene (under the brand name pTeroPure®), received Generally Recognized as Safe (GRAS) status for their pterostilbene ingredient, allowing its use in food and beverage products at specified levels. This GRAS determination was based on a self-affirmation process rather than FDA notification. The FDA has not taken any specific regulatory actions against pterostilbene supplements, suggesting tacit acceptance of its status as a dietary supplement ingredient.

Eu: In the European Union, pterostilbene is not specifically approved as a food additive. It falls under the Novel Food Regulation, which requires safety assessment and authorization for foods and ingredients not significantly consumed in the EU before May 1997. As of 2023, pterostilbene does not appear to have received Novel Food authorization, limiting its legal use in food products. However, it may be available as a food supplement in some EU countries under national regulations.

Canada: Health Canada has not issued specific regulations for pterostilbene. It may be sold as a Natural Health Product (NHP) if manufacturers can provide evidence of safety and efficacy to obtain a product license. Some pterostilbene products are available on the Canadian market, suggesting at least some have received approval under the NHP regulations.

Australia: The Therapeutic Goods Administration (TGA) has not issued specific regulations for pterostilbene. It may be included in listed complementary medicines if manufacturers can provide evidence of safety. As with many newer supplement ingredients, regulatory status may be evolving.

Japan: Pterostilbene is not specifically recognized under Japan’s Foods for Specified Health Uses (FOSHU) system. Its regulatory status for use in supplements in Japan is not well-documented in publicly available English-language sources.

China: Information on pterostilbene’s regulatory status in China is limited in publicly available English-language sources. As a relatively new supplement ingredient, it may not yet have specific regulatory recognition.

Moderate to high

$0.50-$2.00 per day for standard pterostilbene (50-150 mg); $1.00-$3.00 per day for enhanced bioavailability formulations; $1.50-$4.00 per day for combination products with resveratrol or other synergistic compounds

Pterostilbene commands a premium price compared to many other polyphenol supplements, including its structural analog resveratrol. However, its superior bioavailability (approximately 80% compared to resveratrol’s 20%) may justify the higher cost, as lower doses can potentially provide comparable or superior biological effects. When comparing pterostilbene to resveratrol on a bioavailability-adjusted basis, the value proposition becomes more favorable – 50 mg of pterostilbene may provide similar bioactive exposure as 200 mg of resveratrol, potentially making the effective cost comparable despite the higher price per milligram. For specific health concerns like cognitive function and metabolic health, pterostilbene’s ability to cross the blood-brain barrier more effectively than resveratrol and its potentially stronger effects on certain metabolic pathways may provide better targeted value despite the higher cost.

The most cost-effective approach for many users may be moderate doses (50-100 mg daily) of pure pterostilbene rather than higher doses or complex formulations, as this range appears effective for many of pterostilbene’s benefits while minimizing cost and potential side effects like LDL elevation observed at higher doses. Combination products that pair pterostilbene with synergistic compounds like resveratrol, quercetin, or nicotinamide riboside typically cost more but may offer superior value by targeting multiple aspects of cellular health simultaneously. When comparing products, calculate the cost per milligram of active pterostilbene rather than per capsule, as potency varies widely between brands. Some manufacturers provide purity testing results, which can be an important value consideration given the relatively high cost of this supplement.

For those primarily interested in general antioxidant benefits rather than pterostilbene’s specific mechanisms, other polyphenols like quercetin may offer better value at significantly lower cost. However, for those specifically seeking pterostilbene’s unique benefits for cognitive function, metabolic health, or its superior bioavailability compared to resveratrol, the premium price may be justified by the targeted effects and reduced need for other supplements.

Properly formulated and packaged pterostilbene supplements typically have a shelf life of 2-3 years. Pure pterostilbene is more stable than its structural analog resveratrol, primarily due to the two methoxy groups that replace hydroxyl groups, making it less susceptible to oxidation. In powder form, pterostilbene is relatively stable when protected from light, heat, and moisture. Enhanced bioavailability formulations may have different stability profiles depending on the specific technology used.

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

Store in a cool, dry place away from direct light and heat (below 25°C/77°F). While pterostilbene is more stable than resveratrol, it is still sensitive to light degradation, so opaque containers are preferable. Keep containers tightly closed to prevent moisture exposure, as pterostilbene 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. Some manufacturers recommend storing pterostilbene supplements with desiccant packets to minimize moisture exposure.

Light exposure (particularly UV light, causes gradual degradation), Heat (accelerates oxidation and degradation; significant degradation occurs above 40°C/104°F), Oxygen exposure (leads to oxidation, though slower than with resveratrol), Alkaline conditions (pterostilbene is more stable in slightly acidic to neutral pH), Moisture (promotes hydrolysis and degradation), Transition metals (iron, copper can catalyze oxidation), Repeated freeze-thaw cycles (for liquid formulations)

Synthesis Methods

Natural Sources

Quality Considerations

Unlike many traditional herbal compounds, pterostilbene has a relatively short history of human use as an isolated compound, having been identified and characterized only in recent decades. However, its natural sources have longer historical usage in traditional medicine systems. Pterocarpus marsupium (Indian Kino Tree), one of the richest natural sources of pterostilbene, has been used in Ayurvedic medicine for over 2,000 years, primarily for treating diabetes and skin conditions. In traditional Ayurvedic practice, the heartwood of Pterocarpus marsupium was used to make medicinal drinking vessels, and water stored in these vessels was believed to have anti-diabetic properties.

Modern research has confirmed the presence of pterostilbene and other bioactive compounds in this wood that may indeed help regulate blood glucose levels. Blueberries, another natural source of pterostilbene (albeit in very small amounts), have been consumed by humans for thousands of years and were used medicinally by Native American tribes for various conditions, including as a cough remedy and to treat morning sickness during pregnancy. However, these traditional uses were not specifically linked to pterostilbene content, which is present in concentrations too low to exert significant pharmacological effects through normal consumption. The scientific discovery and characterization of pterostilbene has a much more recent history.

Pterostilbene was first isolated from Pterocarpus santalinus (red sandalwood) and identified as a chemical compound in 1941 by M.V. Nair and colleagues, though its structure was not fully elucidated until later. The compound remained relatively obscure in scientific literature until the 1990s, when interest in resveratrol and related stilbenes began to grow following the discovery of resveratrol in red wine and its potential connection to the ‘French Paradox’ (the observation that French people had lower rates of heart disease despite diets high in saturated fats). Significant research into pterostilbene’s biological activities began in the early 2000s, with studies demonstrating its superior bioavailability compared to resveratrol and its potential benefits for various health conditions.

A key milestone was the 2004 publication by Agnes Rimando and colleagues at the USDA, which identified pterostilbene in blueberries and demonstrated its potential anti-diabetic properties. The first commercial pterostilbene supplements became available around 2010-2011, marketed primarily as a more bioavailable alternative to resveratrol for anti-aging and metabolic health. The first human clinical trials with pterostilbene were published in the 2010s, including studies on its effects on lipid profiles, blood pressure, and cognitive function. Unlike many traditional herbal supplements with centuries of human use, pterostilbene’s history as a supplement is still unfolding, with ongoing research continuing to elucidate its mechanisms of action and potential health benefits.

This relatively short history of human use means that long-term effects of supplementation are still being established, though safety data from clinical trials has generally been reassuring for short to medium-term use.

Pterostilbene for cognitive function in older adults with mild cognitive impairment, Effects of pterostilbene on insulin sensitivity and glucose metabolism, Pterostilbene as adjunctive therapy for metabolic syndrome, Combination of pterostilbene with resveratrol for synergistic effects, Pterostilbene’s effects on inflammatory biomarkers in cardiovascular disease, Pterostilbene for exercise performance and recovery, Pterostilbene’s impact on gut microbiome composition and function, Long-term safety and efficacy of pterostilbene supplementation