Resveratrol: Promoting longevity through a myriad of properties

Compound description

Resveratrol is a non-flavonoid polyphenol found in many fruits and vegetables, like peanuts, berries, and grapes (1, 2). This bioactive compound has drawn attention due to its numerous biological effects, like anticancer, antimicrobial, cardioprotective, antidiabetic, and antiaging properties (2, 3). In addition, resveratrol has been found to have anti-inflammatory and antioxidant characteristics (4, 5).

 Properties

For decades, resveratrol has been investigated by many researchers for its various properties. It produces many of its effects by modulating several pathways (2). For example, the literature indicates that the bioactive compound is an activator of SIRT1 (a member of the sirtuin family of proteins) (5). SIRT1 is involved in cell survival, senescence, metabolism, inflammation and stress resistance(2). This, in opinion of some researchers, makes resveratrol a potential game changer in aging and longevity interventions (2, 3, 6).

The literature indicates that in addition to SIRT1, resveratrol plays a role in the nuclear factor κB (NF-κB) signaling pathway (2). The latter pathway plays a role in inflammation and aging. The bioactive molecule has been found to promote NF-κB, therefore decreasing inflammatory mediators, like interleukin-1 and tumor necrosis factor-α (7). The outcome is the inhibition of inflammation, which can be used to treat many age-related diseases and promote healthy aging.

In its capacity as an anti-inflammatory agent, resveratrol has also been found to inhibit cyclooxygenases (2). The latter are enzymes that convert arachidonic acid into prostaglandin (lipid-based molecules that play a role in inflammation signaling and initiation). Suppression of the said pathway has been suggested to reduce inflammation (2). This highlights the resveratrol value in controlling a process that accelerates aging.

The antioxidant capacity of resveratrol has also been highlighted in the literature. In this context, research has shown that the bioactive molecule modulates the activity of nuclear factor erythroid-2 related factor 2 (Nrf2) (5, 7). NrF2 activation with resveratrol promotes antioxidant enzymes, like superoxide dismutase and catalase. The outcome of this process is reactive oxygen species (ROS) suppression, reducing oxidative stress (7). Excess ROS accelerates the aging process and the development of age-related disorders.

Based on the above, resveratrol acts on multiple processes and pathways within the body to promote healthy aging and longevity (3). Through these pathways, it produces many of its antiaging, cardioprotective, neuroprotective, and anti-inflammatory properties (2, 3, 5).

Use as a supplement

The value of resveratrol has been explored in both preclinical and clinical settings. In this context, researchers have highlighted the value of this bioactive compound in combating age-related pathologies, like cardiovascular disorders, neurodegenerative diseases, diabetes, and others (2, 7).

The cardioprotective properties of resveratrol have been highlighted in the literature, but some results are inconclusive. For example, clinical studies have shown that resveratrol supplementation improved ventricular function and reduced low-density lipoprotein (bad cholesterol) (2, 8). Also, the bioactive compound has been found to improve endothelial function, preventing atherosclerosis and coronary artery diseases. Further investigations revealed that resveratrol reduces inflammatory mediators and mechanisms that mediate atherosclerosis (2, 9). Other cardiovascular effects of the compound were reduced blood pressure and oxidative stress. These outcomes were attributed to resveratrol's antioxidant and anti-inflammatory properties, which are critical in fighting age-related diseases and promoting healthy longevity (2, 7). It is important to note that further research is needed to verify the effectiveness of this compound.

Through its ability to modulate SIRT1, 5' adenosine monophosphate-activated protein kinase, and its antioxidant and anti-inflammatory properties, resveratrol has been hypothesized to be helpful in neurological disorders like Alzheimer’s disease and ischemic stroke (2, 10, 11). These studies have highlighted the capacity of the bioactive compound to fortify the brain by reducing inflammatory mediators’ permeability.

The value of resveratrol in glycemic control has also been explored in clinical studies. In this context, resveratrol use was found to improve glycated hemoglobin (a marker of glycemic control over three months) (2, 12). Also, the bioactive compound has been suggested to reduce insulin resistance and blood glucose and delay glucose peak after meals (2, 13). Also, the antioxidant properties of the molecule help fight oxidative stress, a contributor to insulin resistance and subsequent type 2 diabetes (2). It is important to note that some of these results do not help derive a definitive conclusion. 

The doses used in clinical studies ranged from 150mg to 3000mg. In our Marketplace under the vendor DoNotAge, you can find resveratrol as capsules (Pure Resveratrol). Pure Resveratrol provides the body with 1000mg of the bioactive molecule per serving (serving is two capsules). Also, DoNotAge provides resveratrol in micronized powder dosage form (Pure Resveratrol Powder).

Side effects

In small doses, resveratrol appears to be safe (14). Higher doses or more extended periods of use were not associated with serious adverse events. Examples include diarrhea, heartburn, increased or decreased appetite, vivid dreams, hot flashes, insomnia, flatulence, and other mild gastrointestinal (GIT) symptoms. In certain instances, like high doses, mild-to-moderate adverse events appeared, including the abovementioned GIT symptoms, chest pain, pruritis, itchy eyes, and dry mouth, among others (14). The literature indicates that the use of ≥500mg for prolonged periods produces reversible adverse events. Resveratrol is an inhibitor of cytochrome P450; therefore, it could interact with many medications. It is recommended to use this supplement only after consulting a licensed healthcare professional, like a physician or pharmacist.

References

1.            Ahmadi Z, Mohammadinejad R, Ashrafizadeh M. Drug delivery systems for resveratrol, a non-flavonoid polyphenol: Emerging evidence in last decades. Journal of Drug Delivery Science and Technology. 2019;51:591-604.

2.            Berman AY, Motechin RA, Wiesenfeld MY, Holz MK. The therapeutic potential of resveratrol: a review of clinical trials. npj Precision Oncology. 2017;1(1):35.

3.            Zhang L-X, Li C-X, Kakar MU, Khan MS, Wu P-F, Amir RM, et al. Resveratrol (RV): A pharmacological review and call for further research. Biomedicine & Pharmacotherapy. 2021;143:112164.

4.            Madeo F, Carmona-Gutierrez D, Hofer SJ, Kroemer G. Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential. Cell Metabolism. 2019;29(3):592-610.

5.            Smoliga JM, Baur JA, Hausenblas HA. Resveratrol and health – A comprehensive review of human clinical trials. Molecular Nutrition & Food Research. 2011;55(8):1129-41.

6.            Patel KR, Scott E, Brown VA, Gescher AJ, Steward WP, Brown K. Clinical trials of resveratrol. Annals of the New York Academy of Sciences. 2011;1215(1):161-9.

7.            Zhou D-D, Luo M, Huang S-Y, Saimaiti A, Shang A, Gan R-Y, et al. Effects and Mechanisms of Resveratrol on Aging and Age-Related Diseases. Oxidative medicine and cellular longevity. 2021;2021:9932218-.

8.            Magyar K, Halmosi R, Palfi A, Feher G, Czopf L, Fulop A, et al. Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease. Clin Hemorheol Microcirc. 2012;50(3):179-87.

9.            Tomé-Carneiro J, Gonzálvez M, Larrosa M, García-Almagro FJ, Avilés-Plaza F, Parra S, et al. Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: a triple-blind, 6-month follow-up, placebo-controlled, randomized trial. Mol Nutr Food Res. 2012;56(5):810-21.

10.          Moussa C, Hebron M, Huang X, Ahn J, Rissman RA, Aisen PS, et al. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer's disease. J Neuroinflammation. 2017;14(1):1.

11.          Chen J, Bai Q, Zhao Z, Sui H, Xie X. Resveratrol improves delayed r-tPA treatment outcome by reducing MMPs. Acta Neurol Scand. 2016;134(1):54-60.

12.          Bhatt JK, Thomas S, Nanjan MJ. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr Res. 2012;32(7):537-41.

13.          Brasnyó P, Molnár GA, Mohás M, Markó L, Laczy B, Cseh J, et al. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr. 2011;106(3):383-9.

14.          Cottart C-H, Nivet-Antoine V, Beaudeux J-L. Review of recent data on the metabolism, biological effects, and toxicity of resveratrol in humans. Molecular Nutrition & Food Research. 2014;58(1):7-21.

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