Summary of Pterostilbene
Primary Information, Benefits, Effects, and Important Facts
Pterostilbene is a methylated stilbene molecule with structural similarity to resveratrol, the only difference being two methoxy groups on the pterostilbene molecule that replace hydroxy groups on the resveratrol molecule. While most of the actions of the two are comparable, pterostilbene appears to be much more well absorbed following oral ingestion and may be a more potent antioxidant and anticancer molecule.
Only one study has evaluated pterostilbene in humans. It found an increase in LDL-cholesterol and a trend towards lower HDL levels in people with high cholesterol levels who took 100 or 250 mg per day. It was unclear if the lower dose led to a reduction in blood pressure, but the reduction in the group who took the higher dose was potent.
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Things To Know & Note
Also Known As
trans-3, 5-dimethoxy-4-hydroxystilbene, 3, 5-dimethoxy-4-hydroxystilbene
Do Not Confuse With
Resveratrol (different molecule also from grapes)
Goes Well With
Grape seed extract (mitigates adverse effects on cholesterol profiles)
Caution NoticeExamine.com Medical Disclaimer
How to Take Pterostilbene
Recommended dosage, active amounts, other details
Supplementation of pterostilbene for the purpose of aiding glucose and lipid metabolism tends to be around 20- 40mg/kg oral ingestion in rats, which is an estimated human dosage range of:
215-430mg for a 150lb person
290-580mg for a 200lb person
365-730mg for a 250lb person
Possible anxiolytic properties of pterostilbene are seen at 1-2mg/kg in mice, which is an estimated human dose of:
5.5-11mg for a 150lb person
7.3-14.5mg for a 200lb person
9-18mg for a 250lb person
Which is notable as 5-10mg/kg in these mice (slightly over double the dose) has failed to have the same anxiolytic effects, suggesting a bell-curve that may favor lower dosages such as is found in food consumption rather than higher dosages from supplementation.
Limited human studies have used either 50mg twice a day or 125mg twice a day, and the addition of Grape seed extract (100mg at both dosing times) with the low dose may mitigate some adverse effects on cholesterol seen with pterostilbene in isolation.
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Human Effect Matrix
The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects pterostilbene has on your body, and how strong these effects are.
|Grade||Level of Evidence [show legend]|
|Robust research conducted with repeated double-blind clinical trials|
|Multiple studies where at least two are double-blind and placebo controlled|
|Single double-blind study or multiple cohort studies|
|Uncontrolled or observational studies only|
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
|Minor||- See study|
|Minor||- See study|
|Minor||- See study|
|Minor||- See study|
|Minor||- See study|
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Studies Excluded from Consideration
Confounded with the inclusion of other nutrients
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Research Breakdown on Pterostilbene
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Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is a stilbene compound that is structurally similar to other popular stilbenes such as resveratrol or piceatannol; it is named after its first discovered source (the pterocarpus genus) but is also a component of blueberries and grape products. It is a phytoalexin (compound produced by plants as a defense against parasites and insects) similar to resveratrol albeit more potent.
Pterostilbene is a phytoalexin (plant chemical defense) similar to resveratrol, belonging to the stilbene class of molecules; it is named after the pterocarpus genus of plants
Its sources include:
The Dracaena genus
Rheum rhaponticum (root)
Peanuts (Arachis hypogaea)
Pterostilbene is contained in low quantities in a few plants, most notably blueberries and grapes. Despite being in low concentrations, it is likely bioactive following oral ingestion of these fruits and their products (such as wine)
The structure of pterostilbene is very similar to resveratrol, although the 3,5-dihydroxy part of resveratrol (the two hydroxyl groups on the benzene ring to the left) are replaced with methoxy groups.
The antioxidant capacities of resveratrol requires that there is a hydroxylation at the 4' position (right side of the molecule) and that the overall molecule is in a trans configuration rather than cis. The above stilbenes all abide by these requirements while others such as pinosylvin do not. The methoxy groups on perostilbene appear to allow a greater antioxidative capacity relative to resveratrol.
Pterostilbene is a methoxylated resveratrol, essentially. It has a larger difference in structure from resveratrol than piceatannol (another common stilbene compound, which is more similar to resveratrol). These three structures form the common dietary stilbenes
Pterostilbene, due to the two methoxy groups, exhibits increased hydrophobicity and oral absorption relative to resveratrol. Relative to the approximate 20% bioavailability of resveratrol following oral ingestion, pterostilbene's is near 80% at oral doses of 56-168mg/kg and a bit lower (59.2+/-19.6% when paired with 2-hydroxypropyl-β-cyclodextrin, a delivery system that complexes pterostilbene) at 15mg/kg. The general idea of methylated flavonoids or polyphenols having greater absorption is well known.
Taking pterostilbene by itself has been noted to have a lower bioavailability (15.9+/-7.8%) than when taken as part of a delivery system, and bioavailability is further significantly reduced when taken in a fasted state (less than 5.5%). Increasing the dosage to 60mg/kg under these same conditions increases the bioavailability two-fold.
Sublingual absorption of pterostilbene has a bioavailability of 25.8+/-13.1%.
Pterostilbene appears to be well absorbed, and better absorbed than resveratrol. While its absorption is somewhat respectable (for a polyphenolic) at lower oral doses, higher oral doses appear to actually be better absorbed than lower doses. Pterostilbene can be absorbed sublingually
A single dose of 56-168mg/kg pterostilbene has noted a Cmax of 2,820ng/mL (56mg/kg) and 7,780ng/mL (168mg/kg) at a Tmax of 2 or 4 hours and half-lives of 90 and 114 minutes, respectively.
56-168mg/kg pterostilbene daily for two weeks has noted a Cmax of 2,550ng/mL (56mg/kg) or 5,560ng/mL (168mg/kg) at a Tmax of 2 and 8 hours with half-lives of 96 and 114 minutes, respectively. Repeated dosing appears to be associated with a higher overall AUC for 56mg/kg (15,000ng/h/mL versus 13,700ng/h/mL) but not 168mg/kg (49,600ng/h/mL versus 57,700ng/h/mL).
Chronic dosing of pterostilbene appears to reduce the peak serum values while prolonging the time to reach peak levels. When looking at overall bodily exposure to pterostilbene, there isn't a predictable difference
While resveratrol appears to mostly be metabolized into a glucuronide conjugate, pterostilbene is mostly metabolized into pterostilbene sulfate.
Pterostilbene appears to exert anxiolytic effects in the 1-2mg/kg oral dosing range in mice subjected to an elevated maze test, although it appears ineffective at 5-10mg/kg; this is thought to be related to ERK phosphorylation in the hippocampus which is known to be related to anxiety and mood.
Supplementation of pterostilbene at 125mg twice daily appeared to reduce blood pressure (diastolic and systolic) in hypercholesteromic adults, an effect not observed with 50mg taken twice daily but partially replicated (systolic only) when 50mg was paired with 100mg grape seed extract (GSE) also taken twice daily.
Pterostilbene has been noted to increase the signalling of PPARα receptors at 100µM (8-fold) and 300µM (14-fold) concentrations, with 100µM of pterostilbene being 74.2% more effective than 100µM ciprofibrate as assessed by relative luciferase units. At concentrations of 1-10µM pterostilbene, the receptors were mostly inactive. Since pterostilbene is known to bind to PPARα it appeared to be an agonist of this receptor.
Pterostilbene may be a PPARα ligand
Oral ingestion of pterostilbene at 25mcg/kg of the diet of hamsters with high cholesterol is able to subsequently reduce LDL-C (29%) and increase HDL-C (7%), and reductions in LDL-C (57%) and improvements in HDL-C (73.1%) have been noted in diabetic rats given 40mg/kg pterostilbene.
Animal studies show an improvement in cholesterol metabolism with low dose supplementation of pterostilbene
When supplemented to subjects with high cholesterol (200mg/dL) and high LDL-C, pterostilbene at both doses (50mg or 125mg, both taken twice daily) appeared to increase total cholesterol and LDL cholesterol relative to placebo, with the group given the low dose pterostilbene with grape seed extract (GSE; 100mg twice daily) not seeing this increase; the benefits to blood pressure seen with high dose pterostilbene were replicated with GSE.
HDL cholesterol was noted to be unchanged overall, but in people not on cholesterol medication taking the higher dose of pterostilbene there was a decrease relative to control.
High doses of pterostilbene supplementation (50-125mg twice daily) appear to increase, rather than decrease, cholesterol and LDL levels in subjects who already have high LDL concentrations; those not on cholesterol lowering medications also noted a decrease in HDL cholesterol
Serum triglycerides were reduced by 30% following six weeks of supplementation with 40mg/kg pterostilbene in diabetic rats, the potency exceeding that of 500mg/kg metformin but not fully normalizing relative to nondiabetic control.
In humans (hypercholesterolemic but with normal triglycerides) given 50mg or 125mg pterostilbene twice daily over the course of 52 days, there were no observable changes in serum triglyceride concentrations relative to control; the addition of 100mg grape seed extract to the low dose group also did not confer any beenfits.
25mcg/kg of pterostilbene to the diets of hypercholesterolemic hamsters is able to reduce blood glucose by 14% and in diabetic rats 40mg/kg pterostilbene for six weeks a reduction in glucose with a concomitant increase in insulin was noted; this extended to otherwise healthy rats to a lesser degree (6.3% reduction) and in hyperglycemic rats the potency of pterostilbene (40mg/kg) is comparable to metformin (500mg/kg).
Pterostilbene has been noted to inhibit LPS-induced PGE2 production from white blood cells with an IC50 value of 1.0+/-0.6µM (compared to the IC50 of resveratrol at 3.2+/-1.4µM) and can inhibit iNOS activity in macrophages with an IC50 of 9.9µg/mL (comparable to resveratrol and weaker than parthenolide from feverfew at 0.42µg/mL).
Pterostilbene may exert antiinflammatory effects at low concentrations with a potency greater than resveratrol; these effects may be relevant to oral supplementation of higher doses of pterostilbene
Neutrophils are known to produce oxidation when activated via the NADPH oxidase enzyme which may lead to injury in excessive levels (despite being protective against bacterial invaders at lower activity); resveratrol has previously been implicated as an NADPH oxidase inhibitor, and this activity appears to extend to pterostilbene as it can reduce chemiluminescence of neutrophils (an indication of antioxidant activity). And while pterostilbene doesn't inherently affect superoxide levels in neutrophils, 100µM is able to reduce superoxide production and subsequent myeloperoxidase (MPO) production to around 60% of control with lower concentrations ineffective.
When comparing potencies, pterostilbene appears to be less effective than resveratrol (assessed by IC50 values of reducing extracellular chemiluminescence) with pterostilbene also being less potent than piceatannol, and the potency of curcumin lying between resveratrol and piceatannol. When looking at intracellular chemiluminescence, curcumin seems most potent (IC50 3.57µM to pterostilbene's 21.58µM) and resveratrol is intermediate to the two.
Reduced chemiluminescence has been noted in rats following ingestion of 30mg/kg pterostilbene (partial reduction), suggesting that the above is biologically relevant in higher doses to a small degree.
Pterostilbene appears to reduce oxidation in neutrophils (the main mechanism of action of spirulina), although the effect seems to occur only at very high concentrations. It appears to be active following oral ingestion, but not to a large degree
30mg/kg pterostilbene in a rat model of arthritis has shown weak anti-inflammatory effects, having no significant effect on hind paw volume (a marker of edema) or MPO while minorly reducing chemiluminescence (a marker of neutrophil oxidation).
Current preliminary evidence suggests no significant benefit of pterostilbene on inflammation, just a minor antioxidative effect
Resveratrol has previously been noted to increase apoptosis via the Notch signalling pathway (which induces Cyclin D1 and survivin as it is prosurvival) which appears to extend to pterostilbene in lung cancer cells (A549) with an IC50 value on cell growth of 3.476µM. Pterostilbene appears to reduce the Notch1-dependent survial while induces production of reactive oxygen species, leading to apoptosis.
Pterostilbene appears to reduce viability of lung cancer cells in vitro, and does so at a concentration that is probably relevant to oral supplementation
Pterostilbene (70μM) has been noted to upregulate a variety of mitochondrial genes in a yeast assay (148 up and 13 downregulated) involved in respiration, electron transport, mitochondrial protein targeting, and mitochondrial protein synthesis.
The oxidative stress seen during the aging process in neurons appears to be attenuated with low dietary levels of pterostilbene (0.004-0.016% of the diet), with a potency greater than resveratrol.
In mice, doses of pterostilbene up to 3,000mg/kg daily (500-fold the estimated human intake) have failed to exert any significant clinical or biochemical toxicity.
Pterostilbene up to 250mg daily (125mg twice daily) in humans over the course of 6-8 weeks has failed to cause any biochemical or clinical signs of toxicity, with side effects not significantly different than placebo aside from one dropout due to worsening cholesterol which may be related to an increase in LDL-C seen with this dose when tested elsewhere in hypercholesterolemic adults.
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