Pterostilbene
Overview
Pterostilbene is a naturally occurring stilbenoid chemically similar to resveratrol but with enhanced bioavailability. It's found in blueberries, grapes, and certain tree bark at much lower concentrations than resveratrol in its food sources.
The key advantage over resveratrol is structural: pterostilbene has two methoxy groups where resveratrol has two hydroxy groups. This methylation makes pterostilbene more lipophilic and resistant to metabolism, dramatically improving bioavailability (estimated 80-95% for pterostilbene versus less than 1% for resveratrol).
Primary applications mirror resveratrol: longevity and anti-aging, cardiovascular health, cognitive support, glucose metabolism, and antioxidant effects. The better bioavailability theoretically makes pterostilbene more effective at achieving these benefits.
However, human research is more limited than resveratrol's already-limited evidence base. Most pterostilbene research is preclinical, creating uncertainty about clinical translation.
Safety appears good at typical supplemental doses based on limited human trials and use.
What it means
Pterostilbene is similar to resveratrol (both stilbenoids from foods like blueberries, grapes) but way better absorbed. Structural difference: pterostilbene has methoxy groups where resveratrol has hydroxy groups - makes it more fat-sol uble and resistant to metabolism. Bioavailability: 80-95% for pterostilbene vs less than 1% for resveratrol - huge difference. Used for same things as resveratrol: longevity/anti-aging, heart health, cognition, blood sugar, antioxidant. Better absorption theoretically makes it more effective. But human research is even more limited than resveratrol's - mostly preclinical. Safe at normal doses based on limited data.
Mechanisms of Action
SIRT1 activation and related sirtuin modulation likely occur similarly to resveratrol, though whether pterostilbene directly activates SIRT1 at physiological concentrations shares the same controversies as resveratrol.
The better bioavailability means pterostilbene achieves higher systemic concentrations, making SIRT1 activation more plausible than with resveratrol if the mechanism is real.
Antioxidant activity is well-demonstrated with pterostilbene scavenging free radicals and upregulating endogenous antioxidant enzymes.
Anti-inflammatory effects occur through NF-κB inhibition, COX enzyme modulation, and reduction of inflammatory cytokines - mechanisms shared with resveratrol.
PPARα activation (peroxisome proliferator-activated receptor alpha) affects lipid and glucose metabolism. Pterostilbene shows particularly strong PPARα agonist activity, potentially explaining glucose and cholesterol effects.
Neuroprotection mechanisms include antioxidant effects, modulation of dopamine-related pathways (potentially relevant for Parkinson's disease in animal models), and anti-inflammatory actions in neural tissue.
Cardiovascular effects include improved endothelial function, reduced platelet aggregation, favorable lipid modulation, and modest blood pressure effects.
Unlike resveratrol, the bioavailability advantage means these mechanisms occur at concentrations actually achievable through oral supplementation, making mechanistic research more relevant to human use.
What it means
Pterostilbene supposedly activates SIRT1 (longevity enzyme) like resveratrol - same controversies about whether this really happens. But better bioavailability means higher blood levels, making it more plausible than resveratrol. Strong antioxidant (scavenges free radicals, boosts your own antioxidant enzymes). Anti-inflammatory (blocks NF-κB, COX enzymes, reduces inflammatory cytokines). Strong PPARα activator (affects fat and sugar metabolism) - potentially explains glucose/cholesterol benefits. Protects brain through antioxidant, dopamine modulation (Parkinson's relevance in animals), and anti-inflammatory effects. Heart benefits: better blood vessels, reduces clotting, improves cholesterol, lowers BP modestly. Unlike resveratrol, pterostilbene's bioavailability means these mechanisms happen at achievable concentrations - makes research more relevant.
Effects and Benefits
Cardiovascular Health and Cholesterol
A human study by Riche et al. (2013) found 250 mg pterostilbene daily (with or without grape extract) reduced LDL cholesterol and improved lipid ratios in hypercholesterolemic adults.
However, some subjects experienced LDL increases rather than decreases, suggesting variable individual response.
Blood pressure reductions are modest and inconsistent across studies, similar to resveratrol but with better bioavailability potentially improving effects.
Glucose Metabolism and Diabetes
Animal research shows improved insulin sensitivity and glucose control. Human evidence is extremely limited but preliminary data suggests possible benefits for glucose metabolism at doses of 125-250 mg daily.
The PPARα activation mechanism provides plausible biological basis for metabolic effects.
Cognitive Function
Animal models, particularly using aged rodents, show cognitive improvements and neuroprotection. Human cognitive research is essentially absent.
One small study suggested possible cognitive benefits in older adults, but sample size and methodological quality limit conclusions.
Longevity and Anti-Aging
Like resveratrol, pterostilbene shows lifespan extension in some animal models (particularly simple organisms). Translation to human longevity is speculative and unstudied.
The better bioavailability theoretically makes pterostilbene a more promising longevity intervention than resveratrol if the mechanisms are valid, but human evidence doesn't exist.
Cancer Prevention
Preclinical research suggests anti-cancer properties through multiple mechanisms. Human application is completely unstudied and speculative.
What it means
For heart/cholesterol, one human study (250 mg daily) reduced LDL and improved lipid ratios in high-cholesterol people. But some people's LDL increased instead - variable response. BP drops modest and inconsistent. For blood sugar/diabetes, animal research positive. Human evidence extremely limited but preliminary data suggests possible benefits at 125-250 mg daily. PPARα activation makes metabolic effects plausible. For cognition, animal studies (especially aged rodents) show improvements. Human cognitive research essentially absent - one tiny study maybe positive but too small/poor quality to conclude. For longevity, like resveratrol shows lifespan extension in simple animals. Human longevity totally speculative and unstudied. Better bioavailability theoretically makes it more promising than resveratrol but still no human proof. Cancer prevention looks good in labs - completely unstudied in humans, speculative.
Dosing and Timing
Typical supplemental doses range from 50 to 250 mg daily. Research uses 125 to 250 mg daily most commonly.
For cardiovascular and metabolic applications, 125 to 250 mg daily is used in most human studies.
For general antioxidant and anti-aging purposes, 50 to 150 mg daily is common though optimal dosing lacks robust evidence.
Taking with fats enhances absorption given pterostilbene's lipophilic nature. While bioavailability is already good, taking with fatty meals might further optimize absorption.
Timing throughout the day doesn't appear critical. Single daily dosing or split dosing both appear acceptable.
Effects develop gradually with chronic use. Pterostilbene is not an acute intervention but rather a long-term supplementation strategy.
What it means
Use 50-250 mg daily - research commonly uses 125-250 mg. For heart/metabolism, 125-250 mg daily in studies. For general antioxidant/anti-aging, 50-150 mg daily (optimal dose unclear). Take with fats for even better absorption (already good bioavailability but fats might help more). Timing doesn't matter - single or split doses both fine. Works gradually with chronic use, not acutely - long-term strategy.
Safety and Interactions
General Safety
Pterostilbene appears safe at doses up to 250 mg daily based on limited human trials lasting weeks to months.
Mild increases in LDL cholesterol occurred in some subjects in the Riche et al. study, raising questions about cardiovascular safety despite theoretical benefits. Individual monitoring might be warranted for those using pterostilbene for cardiovascular purposes.
GI upset is rare at typical doses. High doses (above 250 mg) haven't been systematically studied for safety.
Long-term safety data (years) is absent given pterostilbene's recent emergence as a supplement.
Medication Interactions
Anticoagulants and antiplatelets: Like resveratrol, pterostilbene has antiplatelet effects and might increase bleeding risk when combined with warfarin, aspirin, clopidogrel, or similar medications.
Diabetes medications: Given potential effects on glucose metabolism, combining with diabetes medications might create additive glucose-lowering requiring dose adjustments. Monitor blood glucose carefully.
Cholesterol medications: Effects on lipids create potential interactions with statins or other lipid-lowering drugs, though clinical significance is uncertain.
Cytochrome P450 substrates: Pterostilbene affects CYP enzymes. Theoretical interactions with numerous medications exist though clinical documentation is limited.
Surgery
Discontinue pterostilbene at least 2 weeks before surgery due to antiplatelet effects and potential bleeding risk.
Population Considerations
Pregnancy and breastfeeding: Safety data is absent. While pterostilbene is in foods at trace levels, supplemental doses during pregnancy or lactation lack study.
Children: Safety and efficacy unstudied. Dietary sources safe; supplement doses should involve medical guidance.
What it means
Pterostilbene looks safe at up to 250 mg daily in limited (weeks-months) human trials. BUT some people got LDL increases in one study - questions cardiovascular safety despite theoretical benefits. Might need monitoring if using for heart health. Rare GI upset at normal doses. High doses (above 250 mg) not studied. Long-term safety (years) unknown - too new. May increase bleeding risk with blood thinners (warfarin, aspirin, etc.) - stop 2 weeks before surgery. Might lower blood sugar with diabetes meds - monitor glucose, may need dose adjustment. Might interact with cholesterol meds (statins) - uncertain significance. Affects drug-metabolizing enzymes - theoretical interactions. No pregnancy/breastfeeding data. Not studied in children.
Stacking and Combinations
With Resveratrol
Combining pterostilbene with resveratrol might provide synergistic benefits through slightly different mechanisms and bioavailability profiles, though this is theoretical rather than validated.
Given pterostilbene's superior bioavailability, using it alone might be more efficient than combining.
With Quercetin
Both are polyphenols with antioxidant and anti-inflammatory properties. Combining addresses health through complementary plant compounds, common in longevity formulations.
With NAD+ Precursors (NMN, NR)
For comprehensive longevity approaches, combining pterostilbene (potential sirtuin activator) with NAD+ precursors (sirtuin fuel) addresses both activation and substrate availability. This is popular in longevity-focused stacks though human evidence is very limited.
With Berberine or Metformin
For glucose metabolism and longevity, combining pterostilbene with berberine or metformin targets overlapping pathways (AMPK activation, metabolic modulation). Medical supervision recommended given potential additive glucose-lowering.
What it means
Pairing pterostilbene with resveratrol might be synergistic (different mechanisms, different bioavailability) but theoretical. Pterostilbene alone might be more efficient given way better absorption. Combine with quercetin for complementary polyphenol benefits - common in longevity formulas. Stack with NAD+ precursors (NMN, NR) for comprehensive longevity approach - popular but human evidence very limited. Pair with berberine or metformin for glucose/longevity - targets overlapping pathways but needs medical supervision (additive glucose-lowering).
Research Strength and Limitations
Pterostilbene research is less extensive than resveratrol's (which is already limited). Most studies are preclinical with impressive animal results but minimal human translation.
The few human trials are small, short-duration, and often industry-funded. Independent replication is rare.
Bioavailability advantage over resveratrol is well-established and makes pterostilbene theoretically more promising for achieving purported polyphenol benefits.
Individual variability in response (exemplified by some subjects experiencing LDL increases) suggests genetic or physiological factors affect outcomes, but these aren't characterized.
Long-term human safety and efficacy are completely unstudied. All research is short-term.
The mechanisms (PPARα activation, antioxidant effects, anti-inflammatory actions) are biologically plausible and better-supported than resveratrol's more controversial SIRT1 story, but human clinical validation is minimal.
What it means
Pterostilbene research is even less than resveratrol's (already limited) - mostly impressive animal studies, minimal human proof. Few human trials: small, short, often industry-funded, rare replication. Bioavailability advantage is proven - makes it theoretically more promising than resveratrol. Individual response varies (some people's LDL increases) - suggests genetic/physiological factors but these aren't characterized. Long-term (years) unstudied - all research short-term. Mechanisms (PPARα, antioxidant, anti-inflammatory) more plausible than resveratrol's controversial SIRT1 claims but still lack human validation.
Practical Considerations
Pterostilbene makes more sense than resveratrol given dramatically better bioavailability. If you're choosing between the two for polyphenol supplementation, pterostilbene is the more rational choice.
Realistic applications: modest cardiovascular support (with monitoring for paradoxical LDL effects), glucose metabolism support, general antioxidant/anti-inflammatory supplementation, and speculative anti-aging hedge betting.
Don't expect dramatic longevity effects or transformative health improvements - set realistic expectations similar to resveratrol but with potentially better efficacy given bioavailability.
Cost is higher than resveratrol, though justify through superior bioavailability. You're paying more but getting better absorption and likely better effects per milligram.
Product quality varies. Third-party testing (USP, ConsumerLab, Informed Sport) provides assurance of purity and accurate dosing.
Dietary sources (blueberries) contain pterostilbene but at extremely low concentrations. Matching supplemental doses (50-250 mg) through food is impractical.
For glucose or cholesterol management, consider medical monitoring given variable individual responses and potential for paradoxical effects.
Pterostilbene is a more rational polyphenol choice than resveratrol but still represents speculative supplementation rather than evidence-based medicine. Better alternatives exist for most specific health goals.
What it means
Pterostilbene makes WAY more sense than resveratrol given dramatically better bioavailability. If choosing between them, pterostilbene is more rational. Realistic uses: modest heart support (monitor LDL for paradoxical effects), glucose support, general antioxidant/anti-inflammatory, speculative anti-aging hedge. Don't expect longevity miracles or transformative improvements - similar realistic expectations as resveratrol but potentially better efficacy. Costs more than resveratrol but justified by superior absorption - paying more, getting better results per mg. Check product quality - third-party testing (USP, ConsumerLab). Food (blueberries) has pterostilbene but extremely low - can't match supplement doses. For glucose/cholesterol, consider monitoring given variable response and possible paradoxical effects. More rational than resveratrol but still speculative, not evidence-based medicine. Better alternatives exist for specific goals.
References
Kapetanovic IM, Muzzio M, Huang Z, Thompson TN, McCormick DL. Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats. Cancer Chemother Pharmacol. 2011;68(3):593-601.
Riche DM, McEwen CL, Riche KD, et al. Analysis of safety from a human clinical trial with pterostilbene. J Toxicol. 2013;2013:463595.
Riche DM, Riche KD, Blackshear CT, et al. Pterostilbene on metabolic parameters: a randomized, double-blind, and placebo-controlled trial. Evid Based Complement Alternat Med. 2014;2014:459165.