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Resveratrol ist eine natürlich vorkommende polyphenolische Verbindung (engl. polyphenolic compound), die in der wissenschaftlichen Gemeinschaft aufgrund ihrer potenziellen Rolle bei der Förderung der menschlichen Langlebigkeit und Gesundheitsspanne erhebliche Aufmerksamkeit erregt hat. Diese Verbindung findet sich in verschiedenen Pflanzen, wo sie als Schutzmechanismus gegen Stressfaktoren wie Infektionen oder ultraviolette Strahlung fungiert. Aus diesem Grund wird sie als eine xenohormetische Verbindung (engl. xenohormetic compound) angesehen.

Resveratrol ist eine Art natürliches Phenol und ein Phytoalexin, das von mehreren Pflanzen als Reaktion auf Verletzungen oder wenn die Pflanze von Pathogenen wie Bakterien oder Pilzen angegriffen wird, produziert wird. Seine molekulare Formel ist C₁₄H₁₂O₃, und es gehört zu einer Klasse von Verbindungen, die als Stilbene (engl. stilbenes) bekannt sind.

Das Potenzial von Resveratrol, die Langlebigkeit zu beeinflussen, ergibt sich aus seiner Fähigkeit, mehrere biologische Pfade zu modulieren, die im Alterungsprozess eine Rolle spielen. Es ist bekannt für seine antioxidativen (engl. antioxidant) und entzündungshemmenden Eigenschaften, die die schädlichen Effekte von oxidativem Stress (engl. oxidative stress) und Entzündungen, zwei Schlüsselfaktoren für Alterung und altersbedingte Krankheiten, mildern können. Zusätzlich ist bekannt, dass Resveratrol Sirtuine (engl. sirtuins), eine Familie von Proteinen, aktiviert, die eine entscheidende Rolle für die zelluläre Gesundheit und Langlebigkeit spielen.

Historischer Kontext

Resveratrol wurde erstmals 1939 von Michio Takaoka aus den Wurzeln des weißen Nieswurzes (Veratrum grandiflorum) identifiziert. Es erlangte jedoch in den 1990er Jahren erhebliche Aufmerksamkeit, als seine Präsenz in Rotwein entdeckt wurde, was eine mögliche Erklärung für das Französische Paradoxon darstellte – die Beobachtung, dass die französische Bevölkerung trotz einer Ernährung, die reich an gesättigten Fetten ist, eine relativ niedrige Inzidenz von Koronarherzkrankheiten aufweist.

Die frühen Studien konzentrierten sich hauptsächlich auf die antioxidativen (engl. antioxidant) Eigenschaften von Resveratrol. Forscher fanden heraus, dass es die Fähigkeit besitzt, freie Radikale zu neutralisieren und oxidativen Stress zu reduzieren, welche Schlüsselfaktoren für Alterung und altersbedingte Krankheiten sind. Diese anfänglichen Erkenntnisse weckten Interesse an Resveratrol als einem potenziellen Anti-Aging-Wirkstoff.

Im Laufe der Jahre hat sich die Forschung zu Resveratrol erweitert, um seinen Einfluss auf eine Vielzahl biologischer Prozesse im Zusammenhang mit dem Altern zu erforschen. Studien haben seine Rolle bei der Reduktion von Entzündungen, der Aktivierung von Sirtuinen und sein Potenzial untersucht, die Effekte der Kalorienrestriktion (engl. caloric restriction) zu imitieren – eine der wenigen wissenschaftlich unterstützten Interventionen, von denen bekannt ist, dass sie die Lebensdauer in verschiedenen Organismen verlängern. Das Forschungsgebiet hat sich erweitert und umfasst nun auch klinische Studien, die darauf abzielen, die Auswirkungen von Resveratrol auf die menschliche Gesundheit und Langlebigkeit zu verstehen.

Natürliche Vorkommen

Resveratrol findet sich hauptsächlich in der Haut von Trauben und in Rotwein, ist aber auch in anderen Früchten, Gemüsen und Pflanzen vorhanden. Hier sind einige der natürlichen Quellen von Resveratrol:

Trauben und Wein

Rote Trauben: Die Haut roter Trauben ist eine der reichsten Quellen für Resveratrol.
Rotwein: Hergestellt aus roten Trauben, ist Rotwein eine beliebte Quelle für Resveratrol, wobei die Gehalte je nach Weintyp und Anbaugebiet der Trauben variieren.

Beeren

Blaubeeren: Enthalten moderate Mengen an Resveratrol.
Cranberries: Eine weitere Beere, die eine Quelle von Resveratrol ist.
Maulbeeren: Diese Beeren sind ebenfalls bekannt dafür, Resveratrol zu enthalten.

Erdnüsse

Rohe Erdnüsse: Erdnüsse, insbesondere die Schalen, enthalten Resveratrol.
Erdnussbutter: Eine Quelle von Resveratrol, allerdings sind die Gehalte im Vergleich zu rohen Erdnüssen niedriger.

Biologische Mechanismen

Resveratrol ist bekannt für seine vielfältigen biologischen Mechanismen, die zu seinen potenziellen langlebigkeitsfördernden Eigenschaften beitragen können. Dieser Abschnitt erforscht die komplexen biologischen Pfade und Prozesse, die von Resveratrol beeinflusst werden.

Antioxidative Eigenschaften

Resveratrol zeigt starke antioxidative (engl. antioxidant) Eigenschaften, die eine entscheidende Rolle im Kampf gegen oxidativen Stress (engl. oxidative stress), einen Schlüsselfaktor für Alterung und altersbedingte Krankheiten, spielen. Es neutralisiert freie Radikale und reduziert oxidativen Schaden an Zellen, was potenziell die zelluläre Gesundheit und Vitalität verlängern kann.

Entzündungshemmende Effekte

Die entzündungshemmenden Effekte von Resveratrol sind im Kontext des Alterns bedeutend. Chronische Entzündungen spielen eine Rolle bei vielen altersbedingten Erkrankungen, und die Fähigkeit von Resveratrol, Entzündungsreaktionen zu mildern, könnte wesentlich sein, um die Folgen solcher Erkrankungen zu verringern.

Sirtuin-Aktivierung und -Regulation

Resveratrol ist dafür bekannt, Sirtuine (engl. sirtuins), eine Familie von Proteinen, die mit dem Altern und der Langlebigkeit assoziiert sind, zu aktivieren. Sirtuine regulieren verschiedene zelluläre Prozesse, einschließlich DNA-Reparatur, Stoffwechsel und Stressresistenz, und es wird angenommen, dass sie die Lebensspanne durch Förderung der zellulären Stabilität und Überlebensfähigkeit verlängern.

Auswirkungen auf Telomere

Telomere (engl. telomeres) sind die Schutzkappen am Ende der Chromosomen, die sich verkürzen, wenn sich Zellen teilen. Es wird angenommen, dass Resveratrol die Länge und Funktion von Telomeren beeinflusst, was potenziell die zelluläre Seneszenz (engl. cellular senescence) verzögern und die Lebensdauer von Zellen verlängern könnte.

Weitere Mechanismen

Zusätzlich zu den oben aufgeführten Mechanismen wurde gezeigt, dass Resveratrol auch:

Aktiviert AMPK, eine Proteinkinase, die eine zentrale Rolle bei der Regulierung des zellulären Stoffwechsels und der Energiehomöostase spielt. Die Aktivierung von AMPK wird mit einer Vielzahl von gesundheitlichen Vorteilen in Verbindung gebracht, einschließlich reduzierter Entzündungen, verbesserter Insulinsensitivität und erhöhter Stressresistenz.
Induziert Autophagie, einen zellulären Prozess, der beschädigte oder dysfunktionale Komponenten entfernt. Autophagie ist essenziell für die Aufrechterhaltung der zellulären Gesundheit und Funktion und wird als wichtig für die Prävention altersbedingter Krankheiten angesehen.
Modulieren die Expression einer Vielzahl von Genen, einschließlich Genen, die an Zellüberleben, Apoptose und Seneszenz beteiligt sind. Durch die Veränderung der Genexpression kann Resveratrol den Alterungsprozess auf fundamentaler Ebene beeinflussen.

Insgesamt befindet sich die Forschung zu den biologischen Mechanismen von Resveratrol noch in ihren Anfangsstadien, aber es ist klar, dass diese Verbindung eine breite Palette von Effekten auf zelluläre Prozesse hat, die für das Altern relevant sind. Weitere Forschungen sind notwendig, um vollständig zu verstehen, wie Resveratrol genutzt werden kann, um die Langlebigkeit zu fördern und die Gesundheitsspanne zu verbessern.

Resveratrol und Alterung

Resveratrol hat in der wissenschaftlichen Gemeinschaft erhebliche Aufmerksamkeit für seine potenzielle Rolle bei der Förderung von Gesundheit und Langlebigkeit erregt. Dieser Abschnitt geht auf die komplexe Beziehung zwischen Resveratrol und dem Altern ein und erforscht seine Auswirkungen auf die Lebensdauer und altersbedingte Krankheiten. ^[1]

Auswirkungen auf die Lebensdauer

Kaplan-Meier-Überlebenskurven von Mäusen, die mit einer Standarddiät, einer kalorienreichen Diät oder einer kalorienreichen Diät plus Resveratrol gefüttert wurden ^[2]

Es wird angenommen, dass Resveratrol die Lebensdauer durch seine Interaktion mit bestimmten Proteinen und Genen, die mit dem Altern in Verbindung stehen, verlängert. Studien an verschiedenen Organismen wie Hefe, Würmern, Fliegen und Mäusen haben vielversprechende Ergebnisse gezeigt, die auf eine Verlängerung der Lebensspanne durch die Einnahme von Resveratrol hinweisen.

In ^[2] wurden Mäuse mit einer Standarddiät, einer kalorienreichen Diät oder einer kalorienreichen Diät plus Resveratrol gefüttert. Die Studie fand heraus, dass Resveratrol Mäusen auf einer kalorienreichen Diät ähnliche gesundheitliche Vorteile bietet wie Mäusen auf einer regulären Diät. Dazu gehören eine bessere Lebensspanne, Beweglichkeit, Insulinreaktion, Organ-Gesundheit und verbesserte mitochondriale Funktion. Wichtig ist, dass diese Vorteile eintraten, ohne dass die Mäuse an Gewicht verloren.

Impact on Age-Related Diseases

Resveratrol’s potential in mitigating the risk of several age-related diseases is under extensive research. It has shown promise in the prevention and management of diseases such as:

Cardiovascular Diseases: Resveratrol helps in improving heart health by reducing inflammation and oxidative stress.
Neurodegenerative Diseases: It has potential neuroprotective effects, which can be beneficial in conditions like Alzheimer’s and Parkinson’s disease.
Cancer: Resveratrol may inhibit the growth of cancer cells and induce apoptosis, showing potential as an anti-cancer agent.

Cellular Senescence and Apoptosis

Resveratrol is studied for its role in reducing cellular senescence and promoting apoptosis, which are crucial processes related to aging and disease. It modulates various signaling pathways, influencing cell cycle, inflammation, and survival.

Caloric Restriction Mimetic

One of the mechanisms by which resveratrol is thought to impact aging is by mimicking the effects of caloric restriction, a well-known intervention for extending lifespan. It activates sirtuins (in particularly SIRT1), proteins associated with longevity, and influences metabolic processes related to aging.

A recent study ^[3] in a randomized trial involving adults aged 55 to 65 compared the effects of resveratrol supplementation to a caloric-restricted diet. Both interventions raised circulating SIRT1 levels and reduced plasma noradrenaline, suggesting cardiovascular benefits. However, the study found differences between the groups in vascular reactions. Specifically, improvements in nitrate-mediated vasodilation (NMD) were seen only with caloric restriction, not with resveratrol. Additionally, SIRT1 was linked to enhanced flow-mediated vasodilation (FMD) in men but not in women. This suggests that while resveratrol mirrors some benefits of caloric restriction, it doesn't capture all, especially regarding vascular effects.

Forms of Resveratrol

Chemical structures of cis- ((Z)-resveratrol, left) and trans-resveratrol ((E)-resveratrol, right)

Resveratrol exists in two geometric isomers: cis-resveratrol and trans-resveratrol.

Trans-resveratrol is the most abundant and biologically active form of resveratrol in plants. It is the form that has been most studied in scientific research and is thought to be responsible for the majority of the health benefits associated with resveratrol.
Cis-resveratrol is less abundant in nature and less biologically active than trans-resveratrol. However, it has still been shown to have some health benefits, such as antioxidant and anti-inflammatory effects.

In addition to cis- and trans-resveratrol, there are also a number of other forms of resveratrol, including:

Piceatannol: Piceatannol is a metabolite of resveratrol that is found in red grape skins and Japanese knotweed. It has been shown to have some similar health benefits to trans-resveratrol, such as antioxidant and anti-cancer effects.
Resveratrol glucosides: Resveratrol glucosides are conjugated forms of resveratrol that are linked to glucose molecules. These forms of resveratrol are less bioavailable than trans-resveratrol, but they may be more stable and easier to store.
Resveratrol dimers and oligomers: Resveratrol dimers and oligomers are formed when two or more molecules of resveratrol link together. These forms of resveratrol have been shown to have some unique biological activities, such as anti-cancer and anti-inflammatory effects.

The most common form of resveratrol available as a supplement is trans-resveratrol. Trans-resveratrol supplements are typically made from grape seed extract or Japanese knotweed extract.

Formulations and Bioavailability

Trans-Resveratrol

Trans-resveratrol unfortunately suffers from poor bioavailability and water solubility. Its solubility in water is less than 0.05 mg/ml. Studies have indicated varying plasma concentrations after repeated doses of resveratrol:

Reported resveratrol plasma concentration in humans after repeated doses of resveratrol (studies after 2010). ^[4] Expand
Number of Participants, Characteristics, Study Type	Dose (mg/day)	Days	Administration	Peak Plasma Concentration (ng/mL)
6, low BMI	2125	11	Tablet and drink	903.0
6, high BMI	2125	11	Tablet and drink	245.0
35, healthy males, cross-over study	800	5	Capsule	0.56
			Dairy drink	0.61
			Soy drink	0.58
			Protein-free drink	0.70
7, healthy	500	28	Capsule with Piperine	2967.25
40, healthy, repeated sequential dosing	500	29	Caplet	43.8
	1000			141
	2500			331
	5000			967
6, patients with hepatic metastases, randomized double-blind clinical trial	5000	14	Micronized resveratrol mixed in liquid	1942
8, healthy subjects	2000	7	Capsule	1274
19, overweight or obese, randomized, double-blind, placebo-controlled, crossover intervention	30	6	Capsule	181.31
	90			532.00
	270			1232.16

After consumption, 77-80% of resveratrol gets absorbed into the bloodstream through active transport via the intestinal epithelial cells. Once in the bloodstream, it associates with albumin and lipoproteins. Despite its efficient absorption, resveratrol possesses a short half-life of around 1.5 hours. This is attributed to its rapid absorption in the intestine and subsequent degradation in the liver. A significant amount of ingested resveratrol, approximately 49–61%, is eventually excreted through urine. ^[5]

Several factors lead to differences in how individuals respond to resveratrol intake: ^[4]

Gut Microbiota Composition: The unique blend of microorganisms in one's gut.
Genetic Differences: Variations in genes that affect metabolism enzymes (like UGTs and SULTs) and transporters.
Ethnicity & Geography: People from different ethnic backgrounds or geographical locations may metabolize resveratrol differently.
Lifestyle & Diet: Personal habits and food choices can influence resveratrol processing.
Natural Variation: Humans naturally vary, leading to different responses to resveratrol .

Resveratrol with Piperine

In 2021 Randomized Controlled Trial, participants receive a single dose of resveratrol 2500 mg, with piperine in 0 mg, 5 mg or 25 mg dose. Despite the observation of piperine coadministration significantly increasing bioavailability (C_max and AUC) of resveratrol in C57BL mice, no significant increase in resveratrol or decrease in resveratrol glucuronide could be observed in healthy adults taking 2500 gm of resveratrol with piperine (5 or 25 mg) as compared to resveratrol alone. ^[6]

Micronized Resveratrol

Micronized resveratrol is a form of resveratrol that has been ground into very small particles. This makes it easier for the body to absorb and use the resveratrol.

There is some evidence to suggest that micronized resveratrol may have higher bioavailability than other forms of resveratrol. For example, one study found that micronized resveratrol was absorbed twice as well as standard resveratrol powder.

However, more research is needed to confirm the bioavailability of micronized resveratrol and to determine whether it is more effective than other forms of resveratrol.

Liposomal Resveratrol

There are a number of liposomal resveratrol supplements on the market that claim to have higher bioavailability than other forms of resveratrol. However, there is no clinical trial evidence to support this claim.

Dosage and Administration

Recommended Dosage

The recommended dosage for adults is generally between 150 to 500 mg per day, although this can vary based on individual health conditions and specific product formulations. In a study ^[7], participants received resveratrol for 29 days at doses of up to 5.0g per day.

Dr. David Sinclair takes 500 mg resveratrol in the morning.

Forms of Administration

Oral (Capsule or Tablet): Resveratrol is most commonly available in capsule or tablet form, taken orally with water. Resveratrol is best taken with a meal.
Oral (Pulver): The molecule resveratrol is in fact a fat-soluble molecule. Therefore, it is recommended taking it together with a spoonful of vegetable oil (olive, flax or pumpkin seed oil - depending on your preference) or mixed in a yogurt.
Liquid Form: Some people prefer liquid resveratrol, which can be mixed with water or another beverage.

According to studies, the bioavailability of resveratrol is significantly better in the morning.

Resveratrol should not be taken with high-fat meals. In a study ^[8], a high-fat breakfast significantly decreased the bioavailability by 45% when compared with a standard breakfast.

Combined intake with quercetin or alcohol does not influence trans-resveratrol exposure. ^[8]

Safety

Resveratrol is generally considered safe when taken in recommended amounts, but excessive consumption can lead to side effects. In a study, it was found to be safe as no severe adverse reactions were observed based on clinical, biochemical, or hematological analyses.

Side Effects

Some people may experience gastrointestinal issues, headaches, or a feeling of jitteriness. In the mentioned study ^[7], the majority of adverse events in the higher doses (2.5g and 5.0g) were gastrointestinal symptoms, including nausea, flatulence, abdominal discomfort, and diarrhea. Symptoms typically began 2-4 days into the regimen and improved as the day progressed but would return after the next dose. They resolved within 2 days of completing the 29-day regimen.

ToDo

2013, Optimization of trans-Resveratrol bioavailability for human therapy ^[9]
2022, Micelle/Hydrogel Composite as a "Natural Self-Emulsifying Reversible Hybrid Hydrogel (N'SERH)" Enhances the Oral Bioavailability of Free (Unconjugated) Resveratrol ^[10]

References

↑ ^{Jump up to: 1.0} ^1.1 Zhou DD et al.: Effects and Mechanisms of Resveratrol on Aging and Age-Related Diseases. Oxid Med Cell Longev 2021. (PMID 34336123) [PubMed] [DOI] [Full text] Abstract
The aging of population has become an issue of great concern because of its rapid increase. Aging is an important risk factor of many chronic diseases. Resveratrol could be found in many foods, such as grapes, red wine, peanuts, and blueberries. Many studies reported that resveratrol possessed various bioactivities, such as antioxidant, anti-inflammatory, cardiovascular protection, anticancer, antidiabetes mellitus, antiobesity, neuroprotection, and antiaging effects. The antiaging mechanisms of resveratrol were mainly ameliorating oxidative stress, relieving inflammatory reaction, improving mitochondrial function, and regulating apoptosis. Resveratrol could be an effective and safe compound for the prevention and treatment of aging and age-related diseases. In this review, we summarize the effects of resveratrol on aging, life extension, and several age-related diseases, with special attention paid to the mechanisms of antiaging action.
↑ ^{Jump up to: 2.0} ^2.1 Baur JA et al.: Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006. (PMID 17086191) [PubMed] [DOI] [Full text] Abstract
Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.
↑ Gonçalinho GHF et al.: Sirtuin 1 and Vascular Function in Healthy Women and Men: A Randomized Clinical Trial Comparing the Effects of Energy Restriction and Resveratrol. Nutrients 2023. (PMID 37447275) [PubMed] [DOI] [Full text] Abstract
Background: Sirtuin 1 (SIRT1) has been associated with longevity and protection against cardiometabolic diseases, but little is known about how it influences human vascular function. Therefore, this study evaluated the effects of SIRT1 activation by resveratrol and energy restriction on vascular reactivity in adults. Methods: A randomized trial allocated 48 healthy adults (24 women and 24 men), aged 55 to 65 years, to resveratrol supplementation or energy restriction for 30 days. Blood lipids, glucose, insulin, C-reactive protein, noradrenaline, SIRT1 (circulating and gene expression), and flow-mediated vasodilation (FMD) and nitrate-mediated vasodilation (NMD) were measured. Results: Both interventions increased circulating SIRT1 (p < 0.001). Pre- and post-tests changes of plasma noradrenaline were significant for both groups (resveratrol: p = 0.037; energy restriction: p = 0.008). Baseline circulating SIRT1 was inversely correlated with noradrenaline (r = -0.508; p < 0.01), and post-treatment circulating SIRT1 was correlated with NMD (r = 0.433; p < 0.01). Circulating SIRT1 was a predictor of FMD in men (p = 0.045), but not in women. SIRT1 was an independent predictor of NMD (p = 0.026) only in the energy restriction group. Conclusions: Energy restriction and resveratrol increased circulating SIRT1 and reduced sympathetic activity similarly in healthy adults. SIRT1 was independently associated with NMD only in the energy restriction group.
↑ ^{Jump up to: 4.0} ^4.1 Springer M & Moco S: Resveratrol and Its Human Metabolites-Effects on Metabolic Health and Obesity. Nutrients 2019. (PMID 30641865) [PubMed] [DOI] [Full text] Abstract
Resveratrol is one of the most widely studied polyphenols and it has been assigned a plethora of metabolic effects with potential health benefits. Given its low bioavailability and extensive metabolism, clinical studies using resveratrol have not always replicated in vitro observations. In this review, we discuss human metabolism and biotransformation of resveratrol, and reported molecular mechanisms of action, within the context of metabolic health and obesity. Resveratrol has been described as mimicking caloric restriction, leading to improved exercise performance and insulin sensitivity (increasing energy expenditure), as well as having a body fat-lowering effect by inhibiting adipogenesis, and increasing lipid mobilization in adipose tissue. These multi-organ effects place resveratrol as an anti-obesity bioactive of potential therapeutic use.
↑ Galiniak S et al.: Health benefits of resveratrol administration. Acta Biochim Pol 2019. (PMID 30816367) [PubMed] [DOI] Abstract
Resveratrol is a polyphenol that is abundant in grape skin and seeds. Food sources of resveratrol include wine, berries, and peanuts. This compound has many properties, including activity against glycation, oxidative stress, inflammation, neurodegeneration, several types of cancer, and aging. Because resveratrol is generally welltolerated, it is believed to be a promising compound in preventing many diseases, such as diabetes and its complications. Unfortunately, this compound exhibits low bioavailability and solubility. The aim of this review is to summarize the latest information on the multiple effects of resveratrol on health and the benefits of its intake, based on in vitro and in vivo studies in animals and humans.
↑ Bailey HH et al.: A randomized, double-blind, dose-ranging, pilot trial of piperine with resveratrol on the effects on serum levels of resveratrol. Eur J Cancer Prev 2021. (PMID 32868637) [PubMed] [DOI] [Full text] Abstract
Resveratrol (3,4,5-trihydroxystilbene) is a naturally occurring phytoalexin with purported health-promoting effects, but with limited oral bioavailability. Our prior murine modeling research observed enhanced resveratrol bioavailability with piperine co-administration. In this study, single-dose pharmacokinetics of resveratrol with or without piperine and the associated toxicities were studied on a cohort of healthy volunteers. We performed a double-blind, randomized, three-arm pilot study. Participants were randomized to receive a single dose of resveratrol 2.5 g, with piperine in 0 mg, 5 mg, or 25 mg dose. An improved liquid chromatography/mass spectrometry assay was used to determine serum levels of resveratrol and resveratrol-glucuronide. Baseline through 24 h post-study drug serum analyses were performed and adverse events were followed for 30 days. Twenty-four participants were enroled. No significant relationship between dose and pharmacokinetic values were found. In the sex stratified analysis, Cmax for resveratrol in women showed a trend (P = 0.057) toward an increase with piperine. Pharmacokinetic values for resveratrol were: Cmax - 18.5 ± 16 ng/mL resveratrol alone, 29 ± 29 resveratrol + 5 mg piperine, 16 ± 13 resveratrol + 25 mg piperine; area under the concentration × time curve - 1270 ± 852 ng/h/mL resveratrol alone, 2083 ± 2284 resveratrol + 5 mg piperine, 1132 ± 222 resveratrol + 25 mg piperine. All subjects tolerated their protocol therapy with minimal to no toxicity and no evidence of differences between the three groups. The co-administration of resveratrol with piperine at 5 and 25 mg doses did not sufficiently alter the pharmacokinetics of resveratrol or resveratrol-glucuronide to demonstrate the significant enhancement observed in murine modeling.
↑ ^{Jump up to: 7.0} ^7.1 Brown VA et al.: Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res 2010. (PMID 20935227) [PubMed] [DOI] [Full text] Abstract
Resveratrol, a naturally occurring polyphenol, has cancer chemopreventive properties in preclinical models. It has been shown to downregulate the levels of insulin-like growth factor-1 (IGF-I) in rodents. The purpose of the study was to assess its safety, pharmacokinetics, and effects on circulating levels of IGF-I and IGF-binding protein-3 (IGFBP-3) after repeated dosing. Forty healthy volunteers ingested resveratrol at 0.5, 1.0, 2.5, or 5.0 g daily for 29 days. Levels of resveratrol and its metabolites were measured by high performance liquid chromatography-UV in plasma obtained before and up to 24 hours after a dose between days 21 and 28. IGF-I and IGFBP-3 were measured by ELISA in plasma taken predosing and on day 29. Resveratrol was safe, but the 2.5 and 5 g doses caused mild to moderate gastrointestinal symptoms. Resveratrol-3-O-sulfate, resveratrol-4'-O-glucuronide, and resveratrol-3-O-glucuronide were major plasma metabolites. Maximal plasma levels and areas under the concentration versus time curve for the metabolites dramatically exceeded those for resveratrol, in the case of areas under the concentration versus time curve, by up to 20.3-fold. Compared with predosing values, the ingestion of resveratrol caused a decrease in circulating IGF-I and IGFBP-3 (P<0.04 for both), respectively, in all volunteers. The decrease was most marked at the 2.5 g dose level. The results suggest that repeated administration of high doses of resveratrol generates micromolar concentrations of parent and much higher levels of glucuronide and sulfate conjugates in the plasma. The observed decrease in circulating IGF-I and IGFBP-3 might contribute to cancer chemopreventive activity.
↑ ^{Jump up to: 8.0} ^8.1 la Porte C et al.: Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects. Clin Pharmacokinet 2010. (PMID 20528005) [PubMed] [DOI] Abstract
BACKGROUND AND OBJECTIVE: Trans-resveratrol is a polyphenol, which is found in red wine and has cancer chemo-preventive properties and disease-preventive properties. The pharmacokinetics of trans-resveratrol have been investigated in single-dose studies and in studies with relatively low dosages. The present study aimed to investigate the steady-state pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol). METHODS: This was a two-period, open-label, single-arm, within-subject control study in eight healthy subjects. The steady-state 12-hour pharmacokinetics of trans-resveratrol 2000 mg twice daily were studied with a standard breakfast, a high-fat breakfast, quercetin 500 mg twice daily and 5% alcohol 100 mL. Trans-resveratrol plasma concentrations were determined using liquid chromatography with tandem mass spectrometry. RESULTS: The mean (SD) area under the plasma concentration-time curve from 0 to 12 hours (AUC(12)) and maximum plasma concentration (C(max)) of trans-resveratrol were 3558 (2195) ng * h/mL and 1274 (790) ng/mL, respectively, after the standard breakfast. The high-fat breakfast significantly decreased the AUC(12) and C(max) by 45% and 46%, respectively, when compared with the standard breakfast. Quercetin 500 mg twice daily or 5% alcohol 100 mL did not influence trans-resveratrol pharmacokinetics. Diarrhoea was reported in six of the eight subjects. Significant but not clinically relevant changes from baseline were observed in serum potassium and total bilirubin levels. CONCLUSION: Trans-resveratrol 2000 mg twice daily resulted in adequate exposure and was well tolerated by healthy subjects, although diarrhoea was frequently observed. In order to maximize trans-resveratrol exposure, it should be taken with a standard breakfast and not with a high-fat meal. Furthermore, combined intake with quercetin or alcohol did not influence trans-resveratrol exposure.
↑ Amiot MJ et al.: Optimization of trans-Resveratrol bioavailability for human therapy. Biochimie 2013. (PMID 23376875) [PubMed] [DOI] Abstract
We have developed an innovative soluble galenic form to overcome the low absorption of trans-Resveratrol (t-Res) as a dry powder. We present here data on pharmacokinetics, bioavailability, and toxicity of t-Res in human volunteers treated with this soluble form, plus additional data on biological effects in rodents. Fifteen healthy volunteers of both sexes received 40 mg of t-Res in two forms, the soluble formulation (caplets) and the original powder (capsules), in a crossover design. Blood samples were collected at 15 min, 30 min, and every hour for 5 h. Plasma concentrations of t-Res and its metabolites were analyzed by liquid chromatography and mass spectrometry. The single dose (40 mg) of the soluble t-Res was well absorbed and elicited biologically efficient blood levels (0.1-6 μM) for several hours, despite metabolization into glucuronide and sulfate conjugates coupled to renal elimination. In contrast, t-Res administered as a dry powder barely elicited efficient blood levels for a short duration. The new formulation led to 8.8-fold higher t-Res levels in plasma versus the powder. t-Res metabolism was not modified and neither intolerance nor toxicity were observed during the study and the following week. The soluble formulation elicited a robust anti-inflammatory effect in various tissues of mice fed a high-fat diet, while dry powder t-Res was almost inactive. Our data suggest that significant improvements in t-Res bioavailability and efficiency can be obtained by this soluble galenic form, also allowing lower doses. The use of t-Res in human therapy is thus greatly facilitated and the toxicity risk is reduced.
↑ Joseph A et al.: Micelle/Hydrogel Composite as a "Natural Self-Emulsifying Reversible Hybrid Hydrogel (N'SERH)" Enhances the Oral Bioavailability of Free (Unconjugated) Resveratrol. ACS Omega 2022. (PMID 35474815) [PubMed] [DOI] [Full text] Abstract
The poor oral bioavailability, rapid biotransformation to less active metabolites, and fast elimination from systemic circulation have been identified as the major limitations responsible for the clinical insignificance of many drug candidates and phytonutrients. Despite the technological advancements in the nanoformulations of synthetic drugs, there exist many challenges for nutritional therapy, due to the regulatory issues, use of high levels of synthetic emulsifiers and polymers, low stability, low loading levels, mainly liquid state, etc. Herein, we report the characterization and human pharmacokinetics of a natural self-emulsifying hybrid-hydrogel formulation of trans-resveratrol prepared by uniformly impregnating resveratrol micelles into the fenugreek galactomannan hydrogel scaffold to form a water-soluble micelle/hydrogel composite in powder form (RF-20). Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), particle size analysis by dynamic light scattering (DLS), and transmission electron microscopy (TEM) demonstrated the uniform impregnation of resveratrol micelles within the galactomannan hydrogel matrix to form a soluble (average particle size of 172.0 ± 10.4 nm and -21.0 ± 2.5 mV zeta potential) and amorphous powder form with smooth and translucent surface morphology for RF-20, with no chemical alterations. Upon pharmacokinetic studies on healthy human subjects (n = 16) following a randomized, double-blinded, placebo-controlled, 2-arm, 4-sequence crossover design and tandem mass spectrometry (UPLC-ESI-MS/MS), 80 mg of trans-resveratrol from RF-20 provided enhanced free resveratrol bioavailability and pharmacokinetic properties compared to the unformulated resveratrol with 98% purity. The enhancement in bioavailability was more when supplemented in sachet (12.98-fold) form than the capsule (10.48-fold) with improved absorption (C max = 50.97 ± 15.82 ng/mL), circulation half-life (t 1/2 = 7.01 ± 1.44 h), and sustained delivery (T max = 4.71 ± 0.73 h), as compared to the unformulated form (C max = 15.07 ± 5.10 ng/mL; t 1/2 = 1.58 ± 0.65 h; T max = 1.21 ± 0.42 h).

[pmid34336123-1] {Jump up to: 1.0} ^1.1 Zhou DD et al.: Effects and Mechanisms of Resveratrol on Aging and Age-Related Diseases. Oxid Med Cell Longev 2021. (PMID 34336123) [PubMed] [DOI] [Full text] Abstract
The aging of population has become an issue of great concern because of its rapid increase. Aging is an important risk factor of many chronic diseases. Resveratrol could be found in many foods, such as grapes, red wine, peanuts, and blueberries. Many studies reported that resveratrol possessed various bioactivities, such as antioxidant, anti-inflammatory, cardiovascular protection, anticancer, antidiabetes mellitus, antiobesity, neuroprotection, and antiaging effects. The antiaging mechanisms of resveratrol were mainly ameliorating oxidative stress, relieving inflammatory reaction, improving mitochondrial function, and regulating apoptosis. Resveratrol could be an effective and safe compound for the prevention and treatment of aging and age-related diseases. In this review, we summarize the effects of resveratrol on aging, life extension, and several age-related diseases, with special attention paid to the mechanisms of antiaging action.

[pmid17086191-2] {Jump up to: 2.0} ^2.1 Baur JA et al.: Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006. (PMID 17086191) [PubMed] [DOI] [Full text] Abstract
Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.

[pmid37447275-3] Gonçalinho GHF et al.: Sirtuin 1 and Vascular Function in Healthy Women and Men: A Randomized Clinical Trial Comparing the Effects of Energy Restriction and Resveratrol. Nutrients 2023. (PMID 37447275) [PubMed] [DOI] [Full text] Abstract
Background: Sirtuin 1 (SIRT1) has been associated with longevity and protection against cardiometabolic diseases, but little is known about how it influences human vascular function. Therefore, this study evaluated the effects of SIRT1 activation by resveratrol and energy restriction on vascular reactivity in adults. Methods: A randomized trial allocated 48 healthy adults (24 women and 24 men), aged 55 to 65 years, to resveratrol supplementation or energy restriction for 30 days. Blood lipids, glucose, insulin, C-reactive protein, noradrenaline, SIRT1 (circulating and gene expression), and flow-mediated vasodilation (FMD) and nitrate-mediated vasodilation (NMD) were measured. Results: Both interventions increased circulating SIRT1 (p < 0.001). Pre- and post-tests changes of plasma noradrenaline were significant for both groups (resveratrol: p = 0.037; energy restriction: p = 0.008). Baseline circulating SIRT1 was inversely correlated with noradrenaline (r = -0.508; p < 0.01), and post-treatment circulating SIRT1 was correlated with NMD (r = 0.433; p < 0.01). Circulating SIRT1 was a predictor of FMD in men (p = 0.045), but not in women. SIRT1 was an independent predictor of NMD (p = 0.026) only in the energy restriction group. Conclusions: Energy restriction and resveratrol increased circulating SIRT1 and reduced sympathetic activity similarly in healthy adults. SIRT1 was independently associated with NMD only in the energy restriction group.

[pmid30641865-4] {Jump up to: 4.0} ^4.1 Springer M & Moco S: Resveratrol and Its Human Metabolites-Effects on Metabolic Health and Obesity. Nutrients 2019. (PMID 30641865) [PubMed] [DOI] [Full text] Abstract
Resveratrol is one of the most widely studied polyphenols and it has been assigned a plethora of metabolic effects with potential health benefits. Given its low bioavailability and extensive metabolism, clinical studies using resveratrol have not always replicated in vitro observations. In this review, we discuss human metabolism and biotransformation of resveratrol, and reported molecular mechanisms of action, within the context of metabolic health and obesity. Resveratrol has been described as mimicking caloric restriction, leading to improved exercise performance and insulin sensitivity (increasing energy expenditure), as well as having a body fat-lowering effect by inhibiting adipogenesis, and increasing lipid mobilization in adipose tissue. These multi-organ effects place resveratrol as an anti-obesity bioactive of potential therapeutic use.

[pmid30816367-5] Galiniak S et al.: Health benefits of resveratrol administration. Acta Biochim Pol 2019. (PMID 30816367) [PubMed] [DOI] Abstract
Resveratrol is a polyphenol that is abundant in grape skin and seeds. Food sources of resveratrol include wine, berries, and peanuts. This compound has many properties, including activity against glycation, oxidative stress, inflammation, neurodegeneration, several types of cancer, and aging. Because resveratrol is generally welltolerated, it is believed to be a promising compound in preventing many diseases, such as diabetes and its complications. Unfortunately, this compound exhibits low bioavailability and solubility. The aim of this review is to summarize the latest information on the multiple effects of resveratrol on health and the benefits of its intake, based on in vitro and in vivo studies in animals and humans.

[pmid32868637-6] Bailey HH et al.: A randomized, double-blind, dose-ranging, pilot trial of piperine with resveratrol on the effects on serum levels of resveratrol. Eur J Cancer Prev 2021. (PMID 32868637) [PubMed] [DOI] [Full text] Abstract
Resveratrol (3,4,5-trihydroxystilbene) is a naturally occurring phytoalexin with purported health-promoting effects, but with limited oral bioavailability. Our prior murine modeling research observed enhanced resveratrol bioavailability with piperine co-administration. In this study, single-dose pharmacokinetics of resveratrol with or without piperine and the associated toxicities were studied on a cohort of healthy volunteers. We performed a double-blind, randomized, three-arm pilot study. Participants were randomized to receive a single dose of resveratrol 2.5 g, with piperine in 0 mg, 5 mg, or 25 mg dose. An improved liquid chromatography/mass spectrometry assay was used to determine serum levels of resveratrol and resveratrol-glucuronide. Baseline through 24 h post-study drug serum analyses were performed and adverse events were followed for 30 days. Twenty-four participants were enroled. No significant relationship between dose and pharmacokinetic values were found. In the sex stratified analysis, Cmax for resveratrol in women showed a trend (P = 0.057) toward an increase with piperine. Pharmacokinetic values for resveratrol were: Cmax - 18.5 ± 16 ng/mL resveratrol alone, 29 ± 29 resveratrol + 5 mg piperine, 16 ± 13 resveratrol + 25 mg piperine; area under the concentration × time curve - 1270 ± 852 ng/h/mL resveratrol alone, 2083 ± 2284 resveratrol + 5 mg piperine, 1132 ± 222 resveratrol + 25 mg piperine. All subjects tolerated their protocol therapy with minimal to no toxicity and no evidence of differences between the three groups. The co-administration of resveratrol with piperine at 5 and 25 mg doses did not sufficiently alter the pharmacokinetics of resveratrol or resveratrol-glucuronide to demonstrate the significant enhancement observed in murine modeling.

[pmid20935227-7] {Jump up to: 7.0} ^7.1 Brown VA et al.: Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res 2010. (PMID 20935227) [PubMed] [DOI] [Full text] Abstract
Resveratrol, a naturally occurring polyphenol, has cancer chemopreventive properties in preclinical models. It has been shown to downregulate the levels of insulin-like growth factor-1 (IGF-I) in rodents. The purpose of the study was to assess its safety, pharmacokinetics, and effects on circulating levels of IGF-I and IGF-binding protein-3 (IGFBP-3) after repeated dosing. Forty healthy volunteers ingested resveratrol at 0.5, 1.0, 2.5, or 5.0 g daily for 29 days. Levels of resveratrol and its metabolites were measured by high performance liquid chromatography-UV in plasma obtained before and up to 24 hours after a dose between days 21 and 28. IGF-I and IGFBP-3 were measured by ELISA in plasma taken predosing and on day 29. Resveratrol was safe, but the 2.5 and 5 g doses caused mild to moderate gastrointestinal symptoms. Resveratrol-3-O-sulfate, resveratrol-4'-O-glucuronide, and resveratrol-3-O-glucuronide were major plasma metabolites. Maximal plasma levels and areas under the concentration versus time curve for the metabolites dramatically exceeded those for resveratrol, in the case of areas under the concentration versus time curve, by up to 20.3-fold. Compared with predosing values, the ingestion of resveratrol caused a decrease in circulating IGF-I and IGFBP-3 (P<0.04 for both), respectively, in all volunteers. The decrease was most marked at the 2.5 g dose level. The results suggest that repeated administration of high doses of resveratrol generates micromolar concentrations of parent and much higher levels of glucuronide and sulfate conjugates in the plasma. The observed decrease in circulating IGF-I and IGFBP-3 might contribute to cancer chemopreventive activity.

[pmid20528005-8] {Jump up to: 8.0} ^8.1 la Porte C et al.: Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects. Clin Pharmacokinet 2010. (PMID 20528005) [PubMed] [DOI] Abstract
BACKGROUND AND OBJECTIVE: Trans-resveratrol is a polyphenol, which is found in red wine and has cancer chemo-preventive properties and disease-preventive properties. The pharmacokinetics of trans-resveratrol have been investigated in single-dose studies and in studies with relatively low dosages. The present study aimed to investigate the steady-state pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol). METHODS: This was a two-period, open-label, single-arm, within-subject control study in eight healthy subjects. The steady-state 12-hour pharmacokinetics of trans-resveratrol 2000 mg twice daily were studied with a standard breakfast, a high-fat breakfast, quercetin 500 mg twice daily and 5% alcohol 100 mL. Trans-resveratrol plasma concentrations were determined using liquid chromatography with tandem mass spectrometry. RESULTS: The mean (SD) area under the plasma concentration-time curve from 0 to 12 hours (AUC(12)) and maximum plasma concentration (C(max)) of trans-resveratrol were 3558 (2195) ng * h/mL and 1274 (790) ng/mL, respectively, after the standard breakfast. The high-fat breakfast significantly decreased the AUC(12) and C(max) by 45% and 46%, respectively, when compared with the standard breakfast. Quercetin 500 mg twice daily or 5% alcohol 100 mL did not influence trans-resveratrol pharmacokinetics. Diarrhoea was reported in six of the eight subjects. Significant but not clinically relevant changes from baseline were observed in serum potassium and total bilirubin levels. CONCLUSION: Trans-resveratrol 2000 mg twice daily resulted in adequate exposure and was well tolerated by healthy subjects, although diarrhoea was frequently observed. In order to maximize trans-resveratrol exposure, it should be taken with a standard breakfast and not with a high-fat meal. Furthermore, combined intake with quercetin or alcohol did not influence trans-resveratrol exposure.

[pmid23376875-9] Amiot MJ et al.: Optimization of trans-Resveratrol bioavailability for human therapy. Biochimie 2013. (PMID 23376875) [PubMed] [DOI] Abstract
We have developed an innovative soluble galenic form to overcome the low absorption of trans-Resveratrol (t-Res) as a dry powder. We present here data on pharmacokinetics, bioavailability, and toxicity of t-Res in human volunteers treated with this soluble form, plus additional data on biological effects in rodents. Fifteen healthy volunteers of both sexes received 40 mg of t-Res in two forms, the soluble formulation (caplets) and the original powder (capsules), in a crossover design. Blood samples were collected at 15 min, 30 min, and every hour for 5 h. Plasma concentrations of t-Res and its metabolites were analyzed by liquid chromatography and mass spectrometry. The single dose (40 mg) of the soluble t-Res was well absorbed and elicited biologically efficient blood levels (0.1-6 μM) for several hours, despite metabolization into glucuronide and sulfate conjugates coupled to renal elimination. In contrast, t-Res administered as a dry powder barely elicited efficient blood levels for a short duration. The new formulation led to 8.8-fold higher t-Res levels in plasma versus the powder. t-Res metabolism was not modified and neither intolerance nor toxicity were observed during the study and the following week. The soluble formulation elicited a robust anti-inflammatory effect in various tissues of mice fed a high-fat diet, while dry powder t-Res was almost inactive. Our data suggest that significant improvements in t-Res bioavailability and efficiency can be obtained by this soluble galenic form, also allowing lower doses. The use of t-Res in human therapy is thus greatly facilitated and the toxicity risk is reduced.

[pmid35474815-10] Joseph A et al.: Micelle/Hydrogel Composite as a "Natural Self-Emulsifying Reversible Hybrid Hydrogel (N'SERH)" Enhances the Oral Bioavailability of Free (Unconjugated) Resveratrol. ACS Omega 2022. (PMID 35474815) [PubMed] [DOI] [Full text] Abstract
The poor oral bioavailability, rapid biotransformation to less active metabolites, and fast elimination from systemic circulation have been identified as the major limitations responsible for the clinical insignificance of many drug candidates and phytonutrients. Despite the technological advancements in the nanoformulations of synthetic drugs, there exist many challenges for nutritional therapy, due to the regulatory issues, use of high levels of synthetic emulsifiers and polymers, low stability, low loading levels, mainly liquid state, etc. Herein, we report the characterization and human pharmacokinetics of a natural self-emulsifying hybrid-hydrogel formulation of trans-resveratrol prepared by uniformly impregnating resveratrol micelles into the fenugreek galactomannan hydrogel scaffold to form a water-soluble micelle/hydrogel composite in powder form (RF-20). Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), particle size analysis by dynamic light scattering (DLS), and transmission electron microscopy (TEM) demonstrated the uniform impregnation of resveratrol micelles within the galactomannan hydrogel matrix to form a soluble (average particle size of 172.0 ± 10.4 nm and -21.0 ± 2.5 mV zeta potential) and amorphous powder form with smooth and translucent surface morphology for RF-20, with no chemical alterations. Upon pharmacokinetic studies on healthy human subjects (n = 16) following a randomized, double-blinded, placebo-controlled, 2-arm, 4-sequence crossover design and tandem mass spectrometry (UPLC-ESI-MS/MS), 80 mg of trans-resveratrol from RF-20 provided enhanced free resveratrol bioavailability and pharmacokinetic properties compared to the unformulated resveratrol with 98% purity. The enhancement in bioavailability was more when supplemented in sachet (12.98-fold) form than the capsule (10.48-fold) with improved absorption (C max = 50.97 ± 15.82 ng/mL), circulation half-life (t 1/2 = 7.01 ± 1.44 h), and sustained delivery (T max = 4.71 ± 0.73 h), as compared to the unformulated form (C max = 15.07 ± 5.10 ng/mL; t 1/2 = 1.58 ± 0.65 h; T max = 1.21 ± 0.42 h).

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@@ Line 1: / Line 1: @@
 <languages />
-<div class="mw-translate-fuzzy">
 [[File:Resveratrol molecule spacefill from xtal.png|right|frameless|alt=Space-filling model of the resveratrol molecule]]
 [[File:Resveratrol.svg|right|frameless|alt=Skeletal formula of trans-resveratrol]]
 '''Resveratrol''' ist eine natürlich vorkommende polyphenolische Verbindung {{engl|polyphenolic compound}}, die in der wissenschaftlichen Gemeinschaft aufgrund ihrer potenziellen Rolle bei der Förderung der menschlichen Langlebigkeit und Gesundheitsspanne erhebliche Aufmerksamkeit erregt hat. Diese Verbindung findet sich in verschiedenen Pflanzen, wo sie als Schutzmechanismus gegen Stressfaktoren wie Infektionen oder [[UV Radiation|ultraviolette Strahlung]] fungiert. Aus diesem Grund wird sie als eine [[Xenohormesis|xenohormetische Verbindung {{engl|xenohormetic compound}}]] angesehen.
-</div>
 Resveratrol ist eine Art natürliches Phenol und ein Phytoalexin, das von mehreren Pflanzen als Reaktion auf Verletzungen oder wenn die Pflanze von Pathogenen wie Bakterien oder Pilzen angegriffen wird, produziert wird. Seine molekulare Formel ist C₁₄H₁₂O₃, und es gehört zu einer Klasse von Verbindungen, die als Stilbene {{engl|stilbenes}} bekannt sind.
-<div class="mw-translate-fuzzy">
 Das Potenzial von Resveratrol, die Langlebigkeit zu beeinflussen, ergibt sich aus seiner Fähigkeit, mehrere biologische Pfade zu modulieren, die im Alterungsprozess eine Rolle spielen. Es ist bekannt für seine [[Antioxidant|antioxidativen {{engl|antioxidant}}]] und entzündungshemmenden Eigenschaften, die die schädlichen Effekte von [[Oxidative Stress|oxidativem Stress {{engl|oxidative stress}}]] und Entzündungen, zwei Schlüsselfaktoren für Alterung und altersbedingte Krankheiten, mildern können. Zusätzlich ist bekannt, dass Resveratrol [[Sirtuins|Sirtuine {{engl|sirtuins}}]], eine Familie von Proteinen, aktiviert, die eine entscheidende Rolle für die zelluläre Gesundheit und Langlebigkeit spielen.
-</div>
 == Historischer Kontext ==
@@ Line 19: / Line 15: @@
 Im Laufe der Jahre hat sich die Forschung zu Resveratrol erweitert, um seinen Einfluss auf eine Vielzahl biologischer Prozesse im Zusammenhang mit dem Altern zu erforschen. Studien haben seine Rolle bei der Reduktion von Entzündungen, der Aktivierung von Sirtuinen und sein Potenzial untersucht, die Effekte der [[Caloric Restriction|Kalorienrestriktion {{engl|caloric restriction}}]] zu imitieren – eine der wenigen wissenschaftlich unterstützten Interventionen, von denen bekannt ist, dass sie die Lebensdauer in verschiedenen Organismen verlängern. Das Forschungsgebiet hat sich erweitert und umfasst nun auch klinische Studien, die darauf abzielen, die Auswirkungen von Resveratrol auf die menschliche Gesundheit und Langlebigkeit zu verstehen.
-<div class="mw-translate-fuzzy">
+== Natürliche Vorkommen ==
-== Natürliche Quellen ==
-</div>
 Resveratrol findet sich hauptsächlich in der Haut von Trauben und in Rotwein, ist aber auch in anderen Früchten, Gemüsen und Pflanzen vorhanden. Hier sind einige der natürlichen Quellen von Resveratrol:
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 * '''Maulbeeren:''' Diese Beeren sind ebenfalls bekannt dafür, Resveratrol zu enthalten.
-<div class="mw-translate-fuzzy">
 ==== Erdnüsse ====
 * '''Rohe Erdnüsse:''' Erdnüsse, insbesondere die Schalen, enthalten Resveratrol.
 * '''Erdnussbutter:''' Eine Quelle von Resveratrol, allerdings sind die Gehalte im Vergleich zu rohen Erdnüssen niedriger.
-</div>
 == Biologische Mechanismen ==
@@ Line 48: / Line 40: @@
 Resveratrol zeigt starke [[Antioxidant|antioxidative {{engl|antioxidant}}]] Eigenschaften, die eine entscheidende Rolle im Kampf gegen [[Oxidative Stress|oxidativen Stress {{engl|oxidative stress}}]], einen Schlüsselfaktor für Alterung und altersbedingte Krankheiten, spielen. Es neutralisiert freie Radikale und reduziert oxidativen Schaden an Zellen, was potenziell die zelluläre Gesundheit und Vitalität verlängern kann.
-<div class="mw-translate-fuzzy">
 === Entzündungshemmende Effekte ===
-</div>
+Die entzündungshemmenden Effekte von Resveratrol sind im Kontext des Alterns bedeutend. Chronische Entzündungen spielen eine Rolle bei vielen altersbedingten Erkrankungen, und die Fähigkeit von Resveratrol, Entzündungsreaktionen zu mildern, könnte wesentlich sein, um die Folgen solcher Erkrankungen zu verringern.
-<div class="mw-translate-fuzzy">
 === Sirtuin-Aktivierung und -Regulation ===
-</div>
+Resveratrol ist dafür bekannt, [[Sirtuins|Sirtuine {{engl|sirtuins}}]], eine Familie von Proteinen, die mit dem Altern und der Langlebigkeit assoziiert sind, zu aktivieren. Sirtuine regulieren verschiedene zelluläre Prozesse, einschließlich DNA-Reparatur, Stoffwechsel und Stressresistenz, und es wird angenommen, dass sie die Lebensspanne durch Förderung der zellulären Stabilität und Überlebensfähigkeit verlängern.
-<div class="mw-translate-fuzzy">
 === Auswirkungen auf Telomere ===
-</div>
+[[Telomeres|Telomere {{engl|telomeres}}]] sind die Schutzkappen am Ende der Chromosomen, die sich verkürzen, wenn sich Zellen teilen. Es wird angenommen, dass Resveratrol die Länge und Funktion von Telomeren beeinflusst, was potenziell die [[Cellular Senescence|zelluläre Seneszenz {{engl|cellular senescence}}]] verzögern und die Lebensdauer von Zellen verlängern könnte.
-<div lang="en" dir="ltr" class="mw-content-ltr">
+=== Weitere Mechanismen ===
-=== Additional Mechanisms ===
+Zusätzlich zu den oben aufgeführten Mechanismen wurde gezeigt, dass Resveratrol auch:
-In addition to the mechanisms listed above, resveratrol has also been shown to:
-</div>
-<div lang="en" dir="ltr" class="mw-content-ltr">
+* Aktiviert AMPK, eine Proteinkinase, die eine zentrale Rolle bei der Regulierung des zellulären Stoffwechsels und der Energiehomöostase spielt. Die Aktivierung von AMPK wird mit einer Vielzahl von gesundheitlichen Vorteilen in Verbindung gebracht, einschließlich reduzierter Entzündungen, verbesserter Insulinsensitivität und erhöhter Stressresistenz.
-* Activate AMPK, a protein kinase that plays a central role in regulating cellular metabolism and energy homeostasis. AMPK activation is associated with a variety of health benefits, including reduced inflammation, improved insulin sensitivity, and increased stress resistance.
+* Induziert Autophagie, einen zellulären Prozess, der beschädigte oder dysfunktionale Komponenten entfernt. Autophagie ist essenziell für die Aufrechterhaltung der zellulären Gesundheit und Funktion und wird als wichtig für die Prävention altersbedingter Krankheiten angesehen.
-* Induce autophagy, a cellular process that removes damaged or dysfunctional components. Autophagy is essential for maintaining cellular health and function, and it is thought to play a role in preventing age-related diseases.
+* Modulieren die Expression einer Vielzahl von Genen, einschließlich Genen, die an Zellüberleben, Apoptose und Seneszenz beteiligt sind. Durch die Veränderung der Genexpression kann Resveratrol den Alterungsprozess auf fundamentaler Ebene beeinflussen.
-* Modulate the expression of a variety of genes, including genes involved in cell survival, apoptosis, and senescence. By altering gene expression, resveratrol can influence the aging process at a fundamental level.
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+Insgesamt befindet sich die Forschung zu den biologischen Mechanismen von Resveratrol noch in ihren Anfangsstadien, aber es ist klar, dass diese Verbindung eine breite Palette von Effekten auf zelluläre Prozesse hat, die für das Altern relevant sind. Weitere Forschungen sind notwendig, um vollständig zu verstehen, wie Resveratrol genutzt werden kann, um die Langlebigkeit zu fördern und die Gesundheitsspanne zu verbessern.
-Overall, the research on the biological mechanisms of resveratrol is still in its early stages, but it is clear that this compound has a wide range of effects on cellular processes that are relevant to aging. Further research is needed to fully understand how resveratrol can be leveraged to promote longevity and improve healthspan.
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+== Resveratrol und Alterung ==
-== Resveratrol and Aging ==
+Resveratrol hat in der wissenschaftlichen Gemeinschaft erhebliche Aufmerksamkeit für seine potenzielle Rolle bei der Förderung von Gesundheit und Langlebigkeit erregt. Dieser Abschnitt geht auf die komplexe Beziehung zwischen Resveratrol und dem Altern ein und erforscht seine Auswirkungen auf die Lebensdauer und altersbedingte Krankheiten. {{#pmid:34336123|pmid34336123}}
-Resveratrol has garnered significant attention in the scientific community for its potential role in promoting health and longevity. This section delves into the intricate relationship between resveratrol and aging, exploring its effects on lifespan and age-related diseases. {{#pmid:34336123|pmid34336123}}
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+=== Auswirkungen auf die Lebensdauer ===
-=== Effects on Lifespan ===
+[[File:Resveratrol Improves Health and Survival of Mice on a High-calorie Diet.png|thumb|[[Kaplan–Meier Survival Curve|Kaplan-Meier-Überlebenskurven]] von Mäusen, die mit einer Standarddiät, einer kalorienreichen Diät oder einer kalorienreichen Diät plus Resveratrol gefüttert wurden {{#pmid:17086191|pmid17086191}}|alt=Kaplan-Meier-Überlebenskurven von Mäusen, die mit einer Standarddiät, einer kalorienreichen Diät oder einer kalorienreichen Diät plus Resveratrol gefüttert wurden.]]
-[[File:Resveratrol Improves Health and Survival of Mice on a High-calorie Diet.png|thumb|[[Kaplan–Meier Survival Curve|Kaplan–Meier survival curves]] of mice fed a standard diet, high-calorie diet or high-calorie diet plus resveratrol {{#pmid:17086191|pmid17086191}}|alt=Kaplan–Meier survival curves of mice fed a standard diet, high-calorie diet or high-calorie diet plus resveratrol.]]
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+Es wird angenommen, dass Resveratrol die Lebensdauer durch seine Interaktion mit bestimmten Proteinen und Genen, die mit dem Altern in Verbindung stehen, verlängert. Studien an verschiedenen Organismen wie Hefe, Würmern, Fliegen und Mäusen haben vielversprechende Ergebnisse gezeigt, die auf eine Verlängerung der Lebensspanne durch die Einnahme von Resveratrol hinweisen.
-Resveratrol is believed to extend lifespan through its interaction with certain proteins and genes associated with aging. Studies in various organisms, including yeast, worms, flies, and mice, have shown promising results, indicating an increase in lifespan with resveratrol supplementation.
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+In {{#pmid:17086191|pmid17086191}} wurden Mäuse mit einer Standarddiät, einer kalorienreichen Diät oder einer kalorienreichen Diät plus Resveratrol gefüttert. Die Studie fand heraus, dass Resveratrol Mäusen auf einer kalorienreichen Diät ähnliche gesundheitliche Vorteile bietet wie Mäusen auf einer regulären Diät. Dazu gehören eine bessere Lebensspanne, Beweglichkeit, Insulinreaktion, Organ-Gesundheit und verbesserte mitochondriale Funktion. Wichtig ist, dass diese Vorteile eintraten, ohne dass die Mäuse an Gewicht verloren.
-In {{#pmid:17086191|pmid17086191}} mice fed a standard diet, high-calorie diet or high-calorie diet plus resveratrol. The study found that resveratrol helps mice on a high-calorie diet have similar health benefits to mice on a regular diet. This includes better lifespan, movement, insulin response, organ health, and improved mitochondrial function. Importantly, these benefits happened without the mice losing weight.
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