Trans-resveratrol – “the molecule of longevity”

Trans-resveratrol is involved in fundamental cellular mechanisms related to defense, energy efficiency and adaptation to stress. Science associates all of these processes with healthy aging, namely:

• Activates sirtuins (SIRT1) – enzymes associated with cellular defense and healthy aging processes.
• Helps protect cells from oxidative stress, one of the main factors in cellular aging.
• Maintains the energy efficiency of cells by participating in processes related to mitochondrial function.
• Helps cells adapt to stress, including metabolic and oxidative stress.
• It relates to the mechanisms of caloric restriction that science associates with healthy life extension.
• Among the most widely studied polyphenols associated with longevity and aging-slowing processes.

It is no coincidence that Trans-Resveratrol is one of the most studied polyphenols in the world. It has been the subject of thousands of scientific publications in the context of aging, cellular defense and metabolism. It is this extensive scientific interest that contributes to its popular name.

It is found mainly in:

Japanese knotweed (Polygonum cuspidatum) is one of the richest natural sources of resveratrol. This is the reason why it occupies a central place in modern research and production of dietary supplements. The plant contains high concentrations of trans-resveratrol, allowing the production of standardized extracts of high purity. It is this stability and predictable content that makes it the most commonly used source of resveratrol in the dietary supplement industry. In a scientific context, Polygonum cuspidatum extracts are being investigated for their antioxidant potential and role in cellular protection. Due to these characteristics, Japanese knotweed is emerging as a key plant source in the development of high-quality resveratrol formulations aimed at supporting healthy aging.

The Zip of Red Grapes and Red Wine – Resveratrol has gained widespread popularity thanks to the so-called “French paradox” – the observation that France reports a lower incidence of cardiovascular problems despite a diet rich in fat. This phenomenon has drawn scientists’ attention to regular, moderate consumption of red wine as a possible contributing factor. The focus of scientific interest is trans-resveratrol, a natural polyphenol found mainly in the skin of red grapes. It has been studied for its antioxidant potential and its role in protecting cells from oxidative stress. It is these properties that place trans-resveratrol among the key compounds considered in the context of cardiovascular health and longevity.

Peanuts – Resveratrol also occurs naturally in peanuts, making them an interesting subject of scientific interest, outside the context of grapes and red wine. Research has shown that peanuts are one of the few nuts that contain significant amounts of resveratrol in a natural form. For this reason, they are part of a balanced diet related to protecting cells from oxidative stress. The presence of resveratrol contributes to the antioxidant profile of peanuts and to the interest in them as promoting cardiovascular health. It is this combination of plant bioactive compounds that places peanuts among the foods associated with current research on healthy aging.

The “trans” form of resveratrol is the most biologically active and the most thoroughly studied, which puts it at the forefront of modern cellular health and longevity science. In contrast to the “cis” form, trans-resveratrol features higher stability and bioactivity, which determine its application in high-quality dietary supplements. This is why choosing a product with pure trans-resveratrol is key for those seeking an informed and quality approach to health care.

Resveratrol and metabolic health – clinical data:

Resveratrol is a phytonutrient that has been intensively studied for its role in maintaining metabolic homeostasis, especially in conditions associated with metabolic stress such as type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome. Its effect is seen not as a direct “cure” but as a modulation of key metabolic and inflammatory pathways that help restore balance in the body.

Effects on glucose metabolism and insulin sensitivity:

Clinical studies in patients with type 2 diabetes have shown that intake of resveratrol (in doses of 10 mg to 1 g daily^)1,2,3 can lead to:

• decrease in fasting blood glucose.

• HbA1c reduction.

• improved insulin sensitivity and reduced insulin resistance index.

• increase in HDL-cholesterol.

The improvement in insulin sensitivity is associated with a reduction in oxidative stress and activation of key signalling molecules in the insulin pathway (e.g. protein kinase B/Akt). Meta-analyses have shown that these effects are mainly observed in diabetic patients but not in healthy individuals, suggesting that resveratrol acts mostly in the presence of metabolic imbalance.

Metabolic efficiency and “calorie-restriction-like” effects:

Resveratrol is seen as a mimic of caloric restriction, as at moderate ^doses6:

• reduces basal metabolic cost.

• improves metabolic efficiency.

• lowers inflammatory and metabolic markers (ALT, triglycerides, glucose).

However, these effects are not consistently observed at high doses (1500g/day⁾⁷.

Dose-dependent effect:

Data from clinical trials indicate a U-shaped dose-effect^{relationship1}:

• low to moderate doses often show better metabolic results,

• High doses (≥1-1.5 g/day) do not always result in additional benefit and in some cases have no measurable effect.

Differences between studies are likely due to individual factors such as age, sex, body weight and stage of disease.

Type 2 diabetes is often accompanied by other conditions (periodontitis, hard-to-heal wounds, etc.). In such conditions, resveratrol improves insulin sensitivity, promotes wound healing, and is associated with improved vascular function. ⁴

The mechanisms are associated with AMPK activation, improved vascularization and better control of inflammatory processes.

Inflammation and immune regulation:

Chronic low-grade inflammation is a key factor in the development of insulin resistance and metabolic disorders. Clinical ^evidence5 suggests that resveratrol and resveratrol-rich extracts:

• lower pro-inflammatory cytokines such as IL-6, TNF-α and IL-1β.

• modulate inflammatory gene expression and associated microRNAs.

• these effects are particularly relevant in pre-diabetic conditions and in the elderly.

However, not all clinical studies confirm a significant anti-inflammatory effect, highlighting the need for further research.

Resveratrol and inflammation – clinical observations:

Inflammation is a fundamental mechanism of the innate immune response. While acute inflammation is protective and necessary, chronic inflammation is associated with the development of multiple chronic diseases. Major factors that maintain it are oxidative, nitrosative and metabolic stress. In this context, resveratrol has been the subject of clinical research for its potential to modulate the inflammatory response.

Clinical evidence of anti-inflammatory effect

Clinical studies have shown that resveratrol can lower markers of inflammation in a variety of conditions:

• In patients with Takayasu arteritis, a significant decrease in the activity of vascular inflammation was observed. Decreases in CRP, TNF-α , and erythrocyte sedimentation rate were found, with the effect mainly associated with TNF-α reduction. ⁸

• In a study with intake of Polygonum cuspidatum extract containing 40 mg of resveratrol taken for 6 weeks by healthy subjects, a significant decrease in TNF-α, IL-6 and CRP was observed. In parallel, suppression of key pro-inflammatory signaling pathways including NF-κB, JNK1 and IKKβ, as well as a reduction in markers associated with oxidative stress was reported. ⁹
• In patients with ulcerative colitis, administration of 500 mg of resveratrol daily for 6 weeks resulted in a significant decrease in TNF-α, hsCRP, and NF-κB, as well as an improvement in the clinical disease activity index. ¹⁰

*Food supplements are not medicine!
* Supplements are not a substitute for a varied diet!
*Consult a doctor before use!

References:

1. Singh AP, Singh R, Verma SS, et al. Health benefits of resveratrol: Evidence from

clinical studies. Med Res Rev. 2019;1-41. https://doi.org/10.1002/med.21565

2. Movahed A, Nabipour I, Lieben Louis X, et al. Antihyperglycemic effects of short term resveratrol supplementation in type 2 diabetic patients. Evid Based Complement Alternat Med. 2013;2013:851267.
3. Brasnyó P, Molnár GA, Mohás M, 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):383-389.11
4. Bashmakov YK, Assaad-Khalil SH, Abou Seif M, et al. Resveratrol promotes foot ulcer size reduction in type 2 diabetes patients. Int Sch Res Notices Endocrinol. 2014;2014:816307.

5.Tomé-Carneiro J, Larrosa M, Yáñez-Gascón MJ, et al. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetic and hypertensive patients with coronary artery disease. Pharmacol Res. 2013;72:69-82.

6.Timmers S, Konings E, Bilet L, et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011;14(5):612-622.

7. Poulsen MM, Vestergaard PF, Clasen BF, et al. High-dose resveratrol supplementation in obese men: an investigatorinitiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. Diabetes. 2013;62(4):1186-1195.
8. Shi G, Hua M, Xu Q, Ren T. Resveratrol improves treatment outcome and laboratory parameters in patients with Takayasu arteritis: a randomized double-blind and placebo-controlled trial. Immunobiology. 2017;222(2):164-168.
9. Ghanim H, Sia CL, Abuaysheh S, et al. Antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. J Clin Endocrinol Metab. 2010;95(9):E1-E8.
10. Samsami-kor M, Daryani NE, Asl PR, Hekmatdoost A. Anti-inflammatory effects of resveratrol in patients with ulcerative colitis: a randomized, double-blind, placebo-controlled pilot study. Arch Med Res. 2015;46(4):280-285.