Nitro500 Micronized Resveratrol: A Dual-Formula Approach to the Bioavailability Challenge
What you need to know: Resveratrol (Wikidata Q407445) showed remarkable promise in laboratory studies for sirtuin activation and longevity, but translating those results to humans has been challenging due to poor bioavailability. Research shows that while resveratrol is well-absorbed (70%+), rapid metabolism means very little unchanged compound reaches circulation. Nitro500 addresses this by combining two approaches: micronized particles for faster dissolution and M98 Polydatin for active transport pathways.
📊 Research Background
Key findings from published studies: Walle et al. (Drug Metab Dispos 2004) found resveratrol absorption exceeds 70%, but plasma levels of unchanged resveratrol were less than 5 ng/mL due to rapid conjugation. A Phase I study of micronized resveratrol (SRT501) by Howells et al. (Cancer Prev Res 2011) demonstrated 3.6-fold higher peak plasma levels compared to non-micronized resveratrol. Studies on Polydatin show it uses active transport via SGLT1 in addition to passive diffusion (Henry et al., J Agric Food Chem 2005).
All cited studies are peer-reviewed and available on PubMed
Understanding the Resveratrol Bioavailability Challenge
Resveratrol captured scientific attention in 2003 when Howitz et al. published their landmark study in Nature showing it activated sirtuins and extended yeast lifespan. Subsequent research by Baur et al. (Nature 2006) demonstrated that resveratrol improved health and survival in mice on high-calorie diets. These findings launched enormous interest in resveratrol supplementation.
However, translating laboratory results to human benefits has proven difficult. The core problem is bioavailability. A 2004 study by Walle et al. using radiolabeled resveratrol in human volunteers found that while absorption of a 25mg oral dose exceeded 70%, only trace amounts of unchanged resveratrol (less than 5 ng/mL) appeared in plasma. Most of the absorbed compound was rapidly converted to glucuronide and sulfate metabolites.
This rapid metabolism creates a significant gap between what researchers use in laboratory studies and what actually reaches tissues in people taking supplements. Laboratory studies often expose cells to resveratrol concentrations far higher than what standard supplements can achieve in human plasma.
Key Point: Resveratrol is well-absorbed but poorly bioavailable. Absorption exceeds 70%, but rapid metabolism in the intestine and liver means very little unchanged resveratrol reaches circulation. This has driven research into formulation approaches that can increase plasma levels of the parent compound.
Two Approaches to Improving Bioavailability
Research has identified several strategies to address resveratrol's bioavailability limitations. Nitro500 combines two of the most promising approaches in a single formula:
Micronized Trans-Resveratrol
Reducing particle size increases surface area available for dissolution. Smaller particles dissolve faster in the digestive tract, potentially improving the rate and extent of absorption. The micronized formulation SRT501 achieved 3.6-fold higher plasma levels in clinical studies (Howells et al., 2011).
M98 Polydatin
Trans-Resveratrol-3-O-glucoside (Polydatin) has an attached glucose molecule that enables transport via SGLT1 glucose transporters. Studies show this glycoside form achieves higher serum concentrations than free resveratrol at equivalent doses (Henry et al., 2005; Wang et al., 2015).
What Does the Research Show?
Several clinical studies have examined approaches to improving resveratrol bioavailability. Understanding this research helps set realistic expectations for what enhanced formulations can achieve.
Micronized Resveratrol Research
The most relevant clinical data comes from the Phase I study of SRT501, a micronized resveratrol formulation developed by Sirtris (later acquired by GSK). Howells et al. published results in Cancer Prevention Research in 2011 showing:
- Mean peak plasma resveratrol of 1942 ng/mL with SRT501 vs. 538 ng/mL with standard resveratrol (3.6-fold improvement)
- Time to peak concentration increased from 1.5 hours to 2.8 hours
- Area under the curve (AUC) increased from 1319 to 6327 ng*h/mL at the 5g dose
- Measurable resveratrol detected in liver metastases tissue
This study demonstrated that particle size reduction through micronization can meaningfully improve plasma resveratrol levels in humans.
Polydatin (Glycoside) Research
Studies on Trans-Resveratrol-3-O-glucoside (Polydatin) show it uses different absorption pathways than free resveratrol. Henry et al. (J Agric Food Chem 2005) found that while trans-resveratrol uses passive transport, trans-piceid (polydatin) likely uses active transport via SGLT1. This dual-pathway absorption may contribute to improved bioavailability.
A comprehensive review by Du et al. (Pharm Biol 2013) documented polydatin's pharmacology and pharmacokinetics, noting its better metabolic stability compared to free resveratrol.
| Approach | Mechanism | Research Support |
|---|---|---|
| Micronization | Increased surface area for dissolution | 3.6x higher plasma levels (Howells 2011) |
| Polydatin (Glycoside) | Active transport via SGLT1 | 3-4x higher serum concentrations (Wang 2015) |
| Standard Resveratrol | Passive diffusion only | <5 ng/mL unchanged in plasma (Walle 2004) |
Key Point: Clinical research supports that both micronization and glycoside forms can improve resveratrol plasma levels compared to standard supplements. Nitro500 combines both approaches in a single formula.
Resveratrol and Sirtuin Activation: What We Know
Sirtuins (Wikidata Q898830) are a family of proteins that regulate cellular health, metabolism, and stress responses. Interest in resveratrol largely stems from its identification as a sirtuin activator in the 2003 study by Howitz et al. published in Nature.
That study showed resveratrol activated yeast Sir2 and extended lifespan by up to 70%. Subsequent research by Baur et al. (Nature 2006) found resveratrol improved health markers and survival in mice fed high-calorie diets. Baur and Sinclair's comprehensive review (Nat Rev Drug Discov 2006) outlined the therapeutic potential suggested by preclinical research.
Important Context
While early research was promising, human clinical trials have shown mixed results. A 2024 meta-analysis in the Journal of the Academy of Nutrition and Dietetics examined 11 randomized controlled trials and found that resveratrol supplementation did not significantly influence SIRT1 levels overall, though subgroup analyses suggested effects may depend on duration and dose.
The bioavailability challenge likely contributes to these mixed results. Laboratory studies typically expose cells to resveratrol concentrations that may be difficult to achieve in human plasma with standard supplements. This underscores the importance of formulation approaches that can improve bioavailability.
Key Point: Resveratrol's sirtuin-activating potential was demonstrated in laboratory and animal studies. Human clinical trials have shown mixed results, possibly due to bioavailability limitations. Enhanced formulations aim to achieve plasma levels that may better replicate the conditions used in successful preclinical research.
Nitro500 Product Specifications
Nitro500 delivers 500mg of a dual-formula resveratrol blend per vegetarian capsule. The formula combines micronized trans-resveratrol with M98 Polydatin to address bioavailability through multiple mechanisms.
Serving Size: 1 Capsule
Servings Per Container: Varies by bottle size
| Dual-Formula Resveratrol Blend | 500mg |
| Micronized Trans-Resveratrol (99%) | |
| M98 Polydatin (Trans-Resveratrol-3-O-glucoside) |
Other Ingredients: Vegetarian capsule (HPMC)
Quality and Manufacturing
| Purity | 99% for both resveratrol components |
| Capsule Type | Vegetarian (HPMC) |
| Manufacturing | Made in USA, GMP-certified facility |
| Testing | Third-party verified for purity and potency |
| Additives | No artificial colors, flavors, or preservatives |
| Guarantee | 30-day satisfaction guarantee (U.S. customers) |
Suggested Use
Take 1-2 capsules daily with food or liquid. Taking with food may support absorption. Consult your healthcare provider before starting any supplement, especially if you take medications or have health conditions. Resveratrol may interact with anticoagulants and some other medications.
Choosing the Right Resveratrol Supplement
RevGenetics offers multiple resveratrol products designed for different preferences and goals. Understanding the differences helps you choose the right option.
| Product | Formula | Format | Best For |
|---|---|---|---|
| Nitro500 | Micronized + M98 Polydatin | Capsules | Convenience, dual-approach formula |
| M98 Complete | Pure Polydatin only | Powder | Flexible dosing, glycoside-only approach |
Nitro500 is ideal if you prefer the convenience of capsules and want a dual-approach formula combining both micronized resveratrol and the glycoside form. It includes a 30-day satisfaction guarantee.
M98 Resveratrol Complete is better if you prefer powder format for flexible dosing and want to focus on the polydatin glycoside form alone. Note that M98 does not include a refund policy due to its specialized powder format.
Combining Nitro500 with Other Supplements
Many users incorporate resveratrol into broader longevity-focused supplement regimens. Some commonly combined supplements include:
With NMN Supplements: NMN supports NAD+ levels, while resveratrol targets sirtuin pathways. Since sirtuins require NAD+ as a cofactor, some researchers suggest combining them may be complementary.
With EGCG 800: EGCG from green tea targets different pathways including AMPK and autophagy. Combining polyphenols provides diverse plant-based compounds.
With MetaCurcumin: Curcumin offers anti-inflammatory support through different mechanisms than resveratrol, potentially providing complementary benefits.
Important: Consult your healthcare provider before combining multiple supplements, especially if you take medications. Resveratrol may interact with anticoagulants, antiplatelet drugs, and some other medications.
Frequently Asked Questions
What makes Nitro500 different from standard resveratrol supplements?
Nitro500 uses a dual-formula combining two forms: micronized trans-resveratrol with reduced particle size for faster dissolution, and M98 Polydatin which uses active transport pathways. Research shows both approaches can improve plasma resveratrol levels compared to standard supplements. The combination addresses bioavailability through multiple mechanisms.
What does the research show about micronized resveratrol?
A Phase I clinical study of the micronized formulation SRT501 (Howells et al., Cancer Prev Res 2011) found it achieved 3.6-fold higher peak plasma levels compared to non-micronized resveratrol (1942 ng/mL vs 538 ng/mL). Micronization increases surface area for dissolution, which can improve the rate and extent of absorption.
Why is resveratrol bioavailability such a challenge?
Research by Walle et al. (Drug Metab Dispos 2004) found that while resveratrol absorption exceeds 70%, only trace amounts (less than 5 ng/mL) of unchanged resveratrol appeared in plasma. Rapid metabolism in the intestine and liver converts most resveratrol to glucuronide and sulfate conjugates before it reaches systemic circulation.
Is Nitro500 vegetarian?
Yes, Nitro500 uses vegetarian HPMC capsules and contains no animal-derived ingredients. The formula is 99% pure with no artificial colors, flavors, or preservatives.
How should I take Nitro500?
Take 1-2 capsules daily with food or liquid. Taking with food may support absorption. Consult your healthcare provider before starting any supplement regimen, especially if you take medications or have health conditions.
What is the return policy?
Nitro500 comes with a 30-day satisfaction guarantee for U.S. customers. If you are not satisfied with your purchase, you can return it within 30 days for a refund.
Can resveratrol interact with medications?
Yes, resveratrol may interact with certain medications including anticoagulants (blood thinners), antiplatelet drugs, and medications metabolized by cytochrome P450 enzymes. Consult your healthcare provider before taking resveratrol if you use any medications.
How does Nitro500 compare to M98 Resveratrol Complete?
Nitro500 offers a dual-formula approach (micronized + polydatin) in convenient capsules with a 30-day guarantee. M98 Resveratrol Complete is pure polydatin in powder format for flexible dosing but does not include a refund policy. Choose based on your preferred format and whether you want the dual-formula approach or glycoside-only.
Scientific References
- Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK. (2004). "High absorption but very low bioavailability of oral resveratrol in humans." Drug Metab Dispos, 32(12):1377-82. PubMed: 15333514
- Howells LM, Berry DP, Elliott PJ, et al. (2011). "Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases: safety, pharmacokinetics, and pharmacodynamics." Cancer Prev Res (Phila), 4(9):1419-25. PubMed: 21680702
- Howitz KT, Bitterman KJ, Cohen HY, et al. (2003). "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan." Nature, 425(6954):191-6. PubMed: 12939617
- Baur JA, Pearson KJ, Price NL, et al. (2006). "Resveratrol improves health and survival of mice on a high-calorie diet." Nature, 444(7117):337-42. PubMed: 17086191
- Baur JA, Sinclair DA. (2006). "Therapeutic potential of resveratrol: the in vivo evidence." Nat Rev Drug Discov, 5(6):493-506. PubMed: 16732220
- Henry C, Vitrac X, Decendit A, et al. (2005). "Cellular uptake and efflux of trans-piceid and its aglycone trans-resveratrol on the apical membrane of human intestinal Caco-2 cells." J Agric Food Chem, 53(3):798-803. PubMed: 15686436
- Du QH, Peng C, Zhang H. (2013). "Polydatin: A review of pharmacology and pharmacokinetics." Pharm Biol, 51(11):1347-54. PubMed: 23862567
- Smoliga JM, Blanchard O. (2014). "Enhancing the delivery of resveratrol in humans: if low bioavailability is the problem, what is the solution?" Molecules, 19(11):17154-72. PubMed: 25347459
- Wang HL, Gao JP, Han YL, et al. (2015). "Comparative studies of polydatin and resveratrol on mutual transformation and antioxidative effect in vivo." Phytomedicine, 22(5):553-9. PubMed: 25981921
Note: All references are peer-reviewed studies available on PubMed. Research in resveratrol pharmacology continues to evolve.