Trans-Pterostilbene
1. Identity
Chemical and Botanical Name
Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is a stilbenoid chemically related to resveratrol. The "trans" designation in its common supplement name refers to the geometry of its central ethylene double bond: some supplements are labeled "trans-pterostilbene" rather than simply "pterostilbene," and in chemistry, the word "trans" indicates that certain atoms or groups of atoms are on opposite sides of a molecule's physical structure, while "cis" indicates they are on the same side. Pterostilbene appears in both cis and trans isomeric structures, with the trans isomer being more dominant. The IUPAC name most commonly used in research literature is trans-3,5-dimethoxy-4′-hydroxystilbene, and the compound carries the CAS number 537-42-8. It is also known by the trade name pTeroPure® in several clinical studies.
Structural Relationship to Resveratrol
Pterostilbene is structurally different from resveratrol in that it possesses only one hydroxyl group; the remaining two hydroxyl groups present in resveratrol are replaced with methoxy groups, increasing the lipophilicity of pterostilbene. The enzyme trans-resveratrol di-O-methyltransferase adds two methyl groups to resveratrol, transferred from the cofactor S-adenosyl methionine (SAM); this enzyme was characterised from Vitis vinifera (grapevine).
Natural Sources
Natural sources include grapes, peanuts, and blueberries, as well as some plants widely used in traditional medicine, such as Pterocarpus marsupium, Pterocarpus santalinus, Vitis vinifera leaves, and the stem bark of Guibourtia tessmannii. Pterostilbene is a dimethyl ether analog of resveratrol.
Pterostilbene is found in almonds, various Vaccinium berries (including blueberries), and grape leaves and vines. It is also encountered in the xylem, particularly in the heartwood of Pterocarpus marsupium, as well as in other species of the Pterocarpus family, including Malay padauk, the Narra tree (Pterocarpus indicus), Muninga, and African padauk (Pterocarpus erinaceus), thus contributing to the high natural durability of these woods as a known phytoalexin.
The amount of daily pterostilbene consumption varies according to dietary fruit intake, and it has been estimated that pterostilbene content per blueberry varies from 99 ng to 520 ng/gram depending on the type of berry ingested. Other natural stilbenes derived from resveratrol, such as pterostilbene, display higher oral bioavailability and bioactivity than the parent compound but are far less abundant in natural sources.
Role in Plants
In plants, pterostilbene serves a defensive phytoalexin role. It is an antimicrobial phytoalexin produced in plants to protect against fungal infection and toxins. Functioning as a botanical antitoxin, it exhibits protective properties against diverse external factors such as ultraviolet radiation and pathogenic invasions.
Common Forms and Preparations
Pterostilbene is commercially available primarily as an oral dietary supplement. It primarily exists in supplement form (50 mg/pellet) and is found in small berries such as blueberries (151 ng/g), huckleberries (520 ng/g), and grapes (4.7 μg/g). Supplement forms include standalone capsules and tablets, as well as combination products. The best-known combination product is "Basis" (Elysium Health), a combination of nicotinamide riboside (NR), a NAD+ precursor vitamin found in milk, and pterostilbene (PT), a polyphenol found in blueberries. A picolinic acid cocrystal of pterostilbene has been identified in pharmaceutical research showing a 10-fold enhancement of oral bioavailability in rats, making it a candidate for new formulations with improved performance.
2. Traditional and Historical Use
Ayurvedic Medicine — Pterocarpus marsupium (Vijaysar / Bijasar)
Pterocarpus marsupium (Vijaysar) is a deciduous tree considered to have high insulinogenic properties. Since ancient times, Ayurveda practitioners believed that the heartwood of Vijaysar significantly reduced blood sugar levels in diabetes. In the Indian Ayurvedic system of medicine, the heartwood of Bijasar (Pterocarpus marsupium, family Leguminaceae) has been extensively used to treat diabetes mellitus.
In Ayurveda, it is called Vijaysar or Bijasar and is traditionally used for "madhumeha" (a syndrome consistent with diabetes), liver and digestive complaints, and inflammatory conditions. The heartwood of Pterocarpus marsupium is used as a depurative, hemostatic, and rejuvenating agent and is used to treat many life-threatening diseases such as diabetes, bronchitis, and leprosy.
It is believed that Vijaysar was first introduced by Susruta, the ancient surgeon from India, for diabetes. Since ancient times, Ayurvedic practitioners used blocks or pieces of Pterocarpus to control diabetes. A traditional folk practice involved drinking water stored overnight in vessels or cups carved from the wood of the tree, allowing the wood's active compounds — including pterostilbene — to leach into the water.
Pterostilbene was identified as the major phenolic compound in Drakshasava, a traditional Ayurvedic medicinal preparation used to treat cardiovascular and related problems, as well as in wood of Pterocarpus marsupium used in the treatment of diabetes. Both resveratrol and pterostilbene are found in Darakchasava, an Ayurvedic medicine that has been used for centuries in India. The main ingredient used to make Darakchasava is grapes (Vitis vinifera). This herbal remedy is given to people suffering from cancer and cardiovascular disorders because the phenolic compounds found in grapes are known to be antioxidants, cancer chemo-preventive agents, and protectors against coronary heart disease.
Traditional Chinese Medicine
Pterostilbene has been isolated in at least three plants used in Traditional Chinese Medicine (TCM). Two of these plants are Sphaerophysa salsula, a shrub called "ku ma du" used for the treatment of hypertension, and Rheum palmatum, referred to as Chinese rhubarb or "da huang," used to treat digestive disorders. Another source in traditional systems of medicine practiced throughout Asia is Pterocarpus santalinus, which goes by the common names red sanders, red sandalwood, and saunderswood. This is a red tree native to Southern India valued for its health-promoting bark, and its red wood yields a natural dye used as a food coloring and pharmaceutical preparation.
Other Traditional Cultures
Traditional diets rich in pterostilbene did not consciously identify the compound, but cultures used wild blueberries and grapes in multiple forms — fresh, fermented, or preserved. Native Americans valued blueberries for digestive support and seasonal detox. In Mediterranean cuisine, grape skins and red wine were prized, though Ayurvedic texts do not name pterostilbene; instead, grapes (Drakshā) appear under sweet, cooling foods to pacify Pitta.
Pterostilbene was first isolated in the 1970s from Pterocarpus marsupium tree bark (hence the name), but researchers noticed high levels in berries by the 1990s. Early studies focused on anti-cancer potential, though most work remains preclinical.
3. Key Constituents, Chemistry, and Mechanisms of Action
Chemical Classification
Pterostilbene is a prominent nonflavonoid polyphenolic compound naturally found in various plants. It belongs to the stilbenoid subclass of polyphenols. The stronger pharmacological properties of pterostilbene compared to resveratrol have been attributed to its two –OCH3 groups. As a result, pterostilbene is more lipophilic, which enhances its membrane permeability, bioavailability, and biological potency.
Bioavailability and Pharmacokinetics
Pterostilbene exhibits increased bioavailability due to the presence of two methoxy groups, which cause it to exhibit increased lipophilic and oral absorption. In animal studies, pterostilbene was shown to have 80% bioavailability compared to 20% for resveratrol, making it potentially advantageous as a therapeutic agent.
Pterostilbene exhibits greater bioavailability due to the presence of two methoxy groups that allow it to have increased lipophilic and oral absorption, as well as a longer half-life due to reduced oxidation. Pterostilbene is characterized by low molecular weight and good liposolubility, allowing it to easily cross the blood–brain barrier. Several studies have identified the robust pharmacodynamic features of pterostilbene, including better intestinal absorption and elevated hepatic stability than resveratrol. Due to its higher bioavailability paired with reduced toxicity compared to other stilbenes, pterostilbene has become an attractive compound.
The brain's unique metabolic response to pterostilbene highlights its potential in neurotherapeutic applications. This compound is selectively utilized by brain tissue, suggesting efficacy in treating neurological conditions. Its ability to cross the blood–brain barrier and engage in brain metabolism underscores its suitability for targeting brain-related disorders. This selective uptake suggests pterostilbene's promise in developing more focused and effective neurological treatments.
Established Molecular Targets and Mechanisms
Pterostilbene's mechanisms of action include activation of Nrf2, the transcription factor that regulates antioxidant defenses, and activation of the AMPK/SIRT1/PGC-1α axis important for energy and mitochondrial homeostasis.
Pterostilbene induces the antioxidative response through the activation and phosphorylation of nuclear factor-E2 p45-related factor 2 (Nrf2) signaling. It mediates its anti-inflammatory effect by inhibiting the transcription factors nuclear factor kappa B (NF-κB) and activating protein-1 (AP-1), which leads to the attenuation of downstream pro-inflammatory mediators, including inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α. Pterostilbene also exerts anti-Alzheimer's disease effects by regulating silent information regulator sirtuin 1 (SIRT1), monoamine oxidase B (MAO-B), peroxisome proliferator-activated receptor (PPAR)-α, and acetylcholinesterase (AChE) activities.
Pterostilbene demonstrates the highest induction of PPAR-α, with an 8- to 14-fold increase in activity relative to a control (ciprofibrate). This suggests that pterostilbene may be an effective PPAR-α agonist and thus a potent hypolipidemic agent.
Pterostilbene has demonstrated attenuation of angiotensin converting enzyme, activation of several antioxidant pathways, and upregulation of nitric oxide synthase in the vascular endothelium, all of which are potential mechanisms for blood pressure reduction.
Pterostilbene exerts its hypoglycemic activity by inhibiting the apoptosis of islet β cells. It increased the expression of anti-apoptotic protein Bcl-2 and downregulated the expression of pro-apoptotic Bax and caspase-3, thereby inhibiting the apoptosis of islet β cells in diabetic rats. A recent study suggested that the anti-diabetic mechanism of pterostilbene may be related to the activation of PPARγ and PI3K/AKT signaling pathways in adipose tissue.
In cancer cell research, numerous studies have demonstrated that pterostilbene possesses detoxification activities, mediating the anti-inflammation response, regulating the cell cycle, augmenting apoptosis, enhancing autophagy, and inhibiting tumor angiogenesis and invasion. Pterostilbene-induced G0/G1-phase arrest occurs when expressions of cyclin D3 and cyclin-dependent kinase (CDK)2/6 are inhibited. Pterostilbene-induced cell apoptosis occurs through activation of caspases-8-9/-3 and a mitochondrial membrane permeabilization (MMP)-dependent pathway. Moreover, treatment of cells with pterostilbene induces sustained activation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK)1/2.
4. Scientific Evidence by Area of Use
4.1 Cardiovascular Health — Blood Pressure
The highest-quality human evidence for pterostilbene concerns its effect on blood pressure. A randomized, double-blind, placebo-controlled study was conducted by University of Mississippi School of Pharmacy and School of Medicine researchers to determine whether pterostilbene improves cardiovascular health. Investigators evaluated the ingredient in 80 patients with high cholesterol. Twice daily for six to eight weeks, participants received either high (125 mg) doses of pterostilbene, low (50 mg) doses of pterostilbene, pterostilbene (50 mg) with grape extract (100 mg), or a placebo.
Both systolic (−7.8 mmHg; P < 0.01) and diastolic blood pressure (−7.3 mmHg; P < 0.001) were reduced with high-dose pterostilbene. The change in blood pressure appeared to be dose-dependent. A reduction in systolic blood pressure was also seen in the grape extract combination group (−6.72 mmHg; P = 0.016). Evidence level: One human RCT of moderate size (n = 80), with a short duration of 6–8 weeks. The blood pressure findings are clinically notable but require independent replication in larger and longer trials.
4.2 Cardiovascular Health — Lipids (LDL Cholesterol)
The same trial produced a finding of clinical concern. LDL increased with pterostilbene monotherapy (17.1 mg/dL; P = 0.001), which was not seen with the grape extract combination (P = 0.47). Presence of a baseline cholesterol medication appeared to attenuate LDL effects.
Other studies have reported dose-based elevations of low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C) within 4 to 8 weeks of daily dosing. The elevation of LDL-C may move previously normal ranges into borderline high or high reference range and has raised questions about the long-term cardiovascular risk of pterostilbene supplementation in humans.
In the double-blind randomized controlled trial that enrolled 80 people with high total or LDL cholesterol, pterostilbene treatment (50 mg or 125 mg twice daily) for 6–8 weeks significantly increased LDL cholesterol (17.1 mg/dL; p = 0.001), though when pterostilbene treatment (50 mg twice daily) was combined with grape extract (100 mg twice daily), this increase was attenuated.
This LDL elevation has also been observed in a study of the combination product NR + pterostilbene. The increase in cholesterol was more pronounced in people with higher BMI (overweight category, 25–32). Larger increases in total cholesterol and LDL cholesterol were observed in the double-dose NR + pterostilbene group (500 mg NR, 100 mg pterostilbene, daily). In a letter to the editor published in Clinical Nutrition critical of Elysium Health's study, scientists contended that pterostilbene has not been shown to bind to sirtuin 1, and that if the ingredient were activating sirtuin 1, it would be expected to improve lipid management; yet the research showed a significant increase in LDL cholesterol. Evidence level: Replicated finding across at least two independent human trials; the LDL increase is a verified clinical concern at supplement doses.
In preclinical models, a different pattern was observed. Hypercholesterolemic hamsters fed pterostilbene at 25 ppm of the diet showed 29% lower plasma LDL cholesterol, 7% higher plasma HDL cholesterol, and 14% lower plasma glucose compared to the control group. The LDL/HDL ratio was also statistically significantly lower for pterostilbene. Results from in vitro studies showed that pterostilbene acts as a PPARα agonist and may be a more effective PPARα agonist and hypolipidemic agent than resveratrol. The discrepancy between animal and human lipid findings highlights the limitation of extrapolating from preclinical models.
4.3 NAD+ Metabolism and Aging Biomarkers
The first-in-humans clinical trial designed to assess the safety and efficacy of a repeat dose of NRPT (nicotinamide riboside + pterostilbene, commercially known as Basis) was evaluated in a randomized, double-blind, and placebo-controlled study in a population of 120 healthy adults between the ages of 60 and 80 years. The study consisted of three treatment arms: placebo, recommended dose of NRPT (NRPT 1X), and double dose of NRPT (NRPT 2X). All subjects took their blinded supplement daily for eight weeks.
Analysis of NAD+ in whole blood demonstrated that NRPT significantly increases the concentration of NAD+ in a dose-dependent manner. NAD+ levels increased by approximately 40% in the NRPT 1X group and approximately 90% in the NRPT 2X group after 4 weeks as compared to placebo and baseline. However, the main limitation is that Elysium's human study measured a biomarker (NAD+ levels) rather than clinical endpoints like disease incidence, physical performance, cognitive function, or longevity. Furthermore, because the study tested a combination of NR and pterostilbene, the independent contribution of pterostilbene to the NAD+ increase cannot be determined from this trial. Evidence level: One industry-funded human RCT (n = 120); the NAD+ increase is attributed primarily to NR; pterostilbene's isolated role is unproven in this context.
4.4 Neurological Health and Cognitive Function
Pterostilbene has higher bioavailability than resveratrol. Studies in rodent models suggest cognitive benefits through antioxidative and anti-inflammatory effects. However, no clinical trials have confirmed these effects in humans. No studies have tested pterostilbene for the prevention of dementia or age-related cognitive decline in humans, and no studies have tested pterostilbene treatment in patients with dementia.
Analysis of laboratory literature reveals that pterostilbene may play a role in Alzheimer's disease treatment through various mechanisms, including anti-oxidative damage, anti-neuroinflammation, anti-apoptosis, cholinesterase activity inhibition, attenuation of β-amyloid deposition, and tau protein hyperphosphorylation.
Pterostilbene has demonstrated neuroprotective effects in preclinical models of Alzheimer's disease and Parkinson's disease, potentially due to its anti-inflammatory, antioxidant, and anti-apoptotic properties.
In animal work, in a rat model of memory decline induced by streptozotocin, pterostilbene treatment (10, 30, or 50 mg/kg, orally) for 13 days significantly improved memory, measured by Morris water maze and novel object recognition tests. Pterostilbene treatment upregulated sirtuin-1 (SIRT1, an NAD+-dependent enzyme), Nrf2 (the transcription factor that regulates antioxidant pathways), and SOD (an antioxidant enzyme), and inhibited mitochondria-dependent apoptosis. Evidence level: Preclinical (animal and cell culture) only. No human clinical trials have been conducted on cognitive endpoints.
4.5 Glycemic Control and Antidiabetic Activity
The two anti-diabetic principles pterostilbene and marsupsin were isolated by extensive chromatographic screening of the ethyl acetate extract of Pterocarpus marsupium. HPTLC studies revealed that levels of pterostilbene are several times more than that of marsupsin both in plant samples and in commercial formulations. Marsupsin, pterosupin, and pterostilbene are the three important phenolic constituents of the heartwood of Pterocarpus marsupium reported to significantly lower blood glucose levels.
Blood glucose and lipid homeostasis are two key factors that influence the progression of cardiovascular diseases. Currently, the positive effect of pterostilbene on hypoglycemia has been proved by several pre-clinical studies and clinical trials. In the Riche et al. human RCT described above, there were no adverse drug reactions on hepatic, renal, or glucose markers based on biochemical analysis, indicating no worsening of glycemic markers at the doses tested.
Pterostilbene exerts its hypoglycemic activity by inhibiting the apoptosis of islet β cells. It increased the expression of anti-apoptotic protein Bcl-2 and downregulated the expression of pro-apoptotic Bax and caspase-3, thereby inhibiting the apoptosis of islet β cells in diabetic rats. Evidence level: Animal models show consistent hypoglycemic effects; limited human data from a small subset of a single RCT; dedicated human trials on glycemic endpoints for isolated pterostilbene are lacking.
4.6 Anti-inflammatory Effects
The antioxidant activity of pterostilbene has been implicated in anticarcinogenesis, modulation of neurological disease, anti-inflammation, attenuation of vascular disease, and amelioration of diabetes. At the mechanistic level, NF-κB and AP-1 inhibition (described in Section 3 above) represent the primary documented anti-inflammatory pathways. Throughout research conducted to date, pterostilbene has demonstrated advantages across multiple areas, including neuroprotection, antioxidation, and anti-inflammatory and anticancer properties, positioning it as a promising subject for continued studies in health prevention. Evidence level: Mechanistic evidence from cell and animal studies is robust; dedicated human clinical trials evaluating inflammatory biomarkers as primary endpoints are not currently available.
4.7 Cancer Biology (Preclinical)
Pterostilbene is a naturally occurring small molecule stilbenoid that has garnered significant attention due to its potential therapeutic effects in tumor diseases. A comprehensive analysis has been conducted of its antitumor effects on various cancer types, including colon, breast, liver, lung, and pancreatic cancers.
Pterostilbene treatment effectively suppresses the growth of several tumor cells, such as urinary bladder, colon, lung, prostate, breast, gastric cancers, and leukemia, through autophagy and apoptosis induction. In pancreatic cancer cell lines specifically, pterostilbene induced S-phase cell cycle arrest, apoptosis, and autophagic cell death and inhibited multidrug resistance protein 1 (MDR1) expression by downregulating RAGE/PI3K/Akt signaling in both MIA PaCa-2 and gemcitabine-resistant cells.
Although applications of pterostilbene in cancer therapy are just beginning to be explored, it represents a potential adjuvant/sensitizing therapy which may improve the results of various oncotherapies. Evidence level: Entirely preclinical (in vitro and animal). No human cancer treatment or prevention trials have been conducted with isolated pterostilbene as of the available literature.
4.8 Obesity and Adipose Tissue
Pterostilbene inhibits the accumulation of white adipose tissue by enhancing energy metabolism and by partially inhibiting adipogenesis in obese animal models. Pterostilbene can also induce the browning of white adipose tissue. Analysis of inguinal white adipose tissue showed that the tendency of browning and the transcription of several marker genes (CIDA, EBF2, PGC1α, PPARγ, Sirt1, and Tbx1) increased significantly. In the Riche et al. human trial, patients not on cholesterol medication (n = 51) exhibited minor weight loss with pterostilbene (−0.62 kg/m2; P = 0.012). Evidence level: Animal models and one human secondary endpoint from a trial not designed for weight outcomes; dedicated human weight-loss trials do not exist.
5. Body Systems and Health Areas of Association
- Cardiovascular system: Pterostilbene exhibits pharmacological properties including antioxidant, cardioprotective, anti-atherosclerosis, and antihypertensive activities. Human evidence exists specifically for blood pressure reduction and LDL elevation at supplemental doses.
- Endocrine / metabolic system: Antidiabetic mechanisms documented in cell and animal models; PPAR-α and PPAR-γ activation; islet β-cell protection.
- Nervous system: Pterostilbene has been shown to be beneficial in treating various diseases affecting the central nervous system according to research; however, there is a lack of clinical data regarding its effectiveness. Blood–brain barrier penetration and selective brain uptake have been documented in preclinical models.
- Immune system / inflammation: NF-κB and AP-1 pathway inhibition; COX-2 and iNOS suppression documented in cell studies.
- Oncology: Preclinical antiproliferative activity across multiple cancer cell lines; apoptosis induction and autophagy enhancement.
- Cellular energy metabolism: AMPK/SIRT1/PGC-1α axis activation; relationship to NAD+ biology when co-administered with NR.
- Adipose tissue: White adipose tissue browning and anti-adipogenic effects in animal models.
6. Dosage Forms and Doses Reported in Studies
The following dosages come directly from the primary literature cited in this article and are reported as they appear in those sources. They are not recommendations.
- In the University of Mississippi double-blind, placebo-controlled human safety trial, four groups received: (1) pterostilbene 125 mg twice daily; (2) pterostilbene 50 mg twice daily; (3) pterostilbene 50 mg + grape extract (GE) 100 mg twice daily; and (4) matching placebo twice daily, for 6–8 weeks.
- In the Elysium Health/MIT Basis trial, two dosing arms were used: a regular dose of 250 mg NR + 50 mg pterostilbene daily, and a double dose of 500 mg NR + 100 mg pterostilbene daily, over 8 weeks.
- In a randomized controlled trial of 32 older people (aged 55–80) subjected to experimental muscle injury, treatment with NR and pterostilbene (500 mg NR and 100 mg pterostilbene, twice daily, orally) was initiated 14 days before injury and continued until 30 days after injury.
- In a rat model of memory decline induced by streptozotocin, pterostilbene was administered at 10, 30, or 50 mg/kg, orally, for 13 days.
- In a hereditary obesity model, two doses were studied: 15 and 30 mg/kg/day in obese rats.
- The Riche et al. safety trial concluded that pterostilbene is generally safe for use in humans up to 250 mg/day.
7. Safety Considerations and Drug Interactions
Human Safety Profile
The primary human safety trial was a prospective, randomized, double-blind, placebo-controlled intervention trial enrolling patients with hypercholesterolemia. Eighty subjects were divided equally into four groups, with the highest dose arm receiving pterostilbene 125 mg twice daily (250 mg/day) for 6–8 weeks. Safety markers included biochemical and subjective measures. There were no adverse drug reactions on hepatic, renal, or glucose markers based on biochemical analysis. There were no statistically significant self-reported or major adverse drug reactions.
LDL Cholesterol Elevation — A Replicated Safety Signal
Pterostilbene treatment may increase total and LDL-cholesterol. This has been observed in both the Riche et al. monotherapy arms and in the NR + pterostilbene combination trial. ChromaDex stopped taking new orders of pterostilbene effective July 31 because of research indicating the ingredient increases low-density lipoprotein (LDL) cholesterol. The LDL elevation in the Riche trial was partially attenuated when pterostilbene was combined with grape extract: LDL increased with pterostilbene monotherapy (17.1 mg/dL; P = 0.001), which was not seen with the grape extract combination (P = 0.47). Presence of a baseline cholesterol medication appeared to attenuate LDL effects.
Drug Interactions — UGT Enzyme Inhibition
Pterostilbene exhibited potent inhibition against HLM, UGT1A6, UGT1A9, UGT2B7, and UGT2B15, moderate inhibition against UGT1A1, UGT1A3, UGT1A8, and UGT2B4, and negligible inhibition against UGT1A4, UGT1A7, UGT1A10, and UGT2B17. Kinetic investigation demonstrated that pterostilbene exerted potent noncompetitive inhibition of UGT1A9, with IC50 and Ki values of 0.92 μM and 0.52 ± 0.04 μM, respectively.
Quantitative prediction suggested that coadministration of pterostilbene supplements at 100 mg/day or higher doses may result in at least a 50% increase in the AUC of drugs predominantly cleared by UGT1A9. Thus, coadministration of pterostilbene supplements and drugs primarily cleared by UGT1A9 may result in a potential drug interaction, and precautions should be taken.
Drugs cleared by UGT1A9 whose exposure may be increased include furosemide, mycophenolic acid, phenylbutazone, paracetamol (acetaminophen), propofol, sulfinpyrazone, baicalein, quercetin, kaempferol, apigenin, estrogens, and prostaglandins. The coadministration of pterostilbene with drugs primarily cleared by UGT1A9 might lead to potential drug interactions, and thus preventive measures should be considered.
Drug Interactions — CYP Enzyme Inhibition
Pterostilbene significantly inhibited CYP2C8 and UGT1A6 activities. The IC50 values for CYP2C8 and UGT1A6 inhibition were 3.0 ± 0.4 µM and 15.1 ± 2.8 µM, respectively; the volume per dose index (VDI) exceeded the predefined threshold of 5 L/dose for both CYP2C8 and UGT1A6, suggesting a potential for in vivo interaction. For CYP2C8, affected drugs include the antimalarial drug amodiaquine, cerivastatin, repaglinide, torasemide, and some chemotherapy drugs. For UGT1A6, affected drugs include acetaminophen and aspirin. Very few studies have investigated how pterostilbene interacts with medication.
Special Populations
There are currently no studies on the safety of pterostilbene for children or for pregnant or breastfeeding women. The trial exclusion criteria for the Riche et al. study included patients who had significant hepatic, renal, or GI tract disease or current overt cardiovascular disease; who were receiving thiazolidinediones or fibric acids; or who were women who were pregnant or of reproductive potential. No data exist on pterostilbene safety in these groups from human studies.
Evidence on SIRT1 Activation — Contested Mechanism
Researchers have contended that pterostilbene has not been shown to bind to sirtuin 1, and that if the ingredient were activating sirtuin 1, it would be expected to improve lipid management; yet the research showed a significant increase in LDL cholesterol. This remains an area of scientific controversy, as some in vitro and animal studies have reported SIRT1 upregulation while human data on the lipid outcome argue against physiologically meaningful SIRT1 activation at supplement doses.
References
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