In a randomized, controlled trial published in Nutrients, researchers tested supplementation with resveratrol, vitamin C, and a combination of both. They learned that all of the treatments had a similar positive impact on oxidative stress in postmenopausal women [1].
Menopausal transition
Around the world, a significant proportion of women have reached the post-menopausal stage. In Mexico, where the study was conducted, 15% of women have reaced this threshold. As life expectancy increases, this fraction will also increase in the coming years.
Menopause is followed by decreased antioxidant capacity, resulting in an imbalance between oxidant molecule generation and antioxidant capacity. Such imbalance creates oxidative stress (OS). During oxidative stress, oxidizing agents can attack and break down molecules that are essential to cells and tissues, such as lipids and proteins.
This group of researchers previously reported “that postmenopausal women present higher concentrations of OS markers than women of reproductive age” [2]. Therefore, using antioxidants seems like a reasonable strategy to reduce the detrimental effect of oxidative damage on lipids and proteins.
Those researchers chose resveratrol and vitamin C because previous research had described them as having “cardioprotective, anti-sclerotic, anti-inflammatory, and antioxidant properties“ [3].
Resveratrol is a natural phytoestrogen and a polyphenolic flavonoid that is well tolerated and not toxic. Resveratrol was previously described to have a role in increasing both the expression and activity of antioxidant enzymes while reducing oxidative load [4, 5].
Clinical trial of postmenopausal females
The researchers conducted a pilot randomized, double-blind clinical trial. They recruited women between 50 and 60 years old who were in the early postmenopause stage and had insulin resistance.
Among the exclusion criteria were the use of hormone replacement therapy or drugs such as anticoagulants, metformin, bezafibrate, statins, or any antioxidant in the three months before the beginning of the study. Active smokers and women with some health conditions were also excluded.
The study participants were divided into one of three groups: 13 participants in the resveratrol group plus a vitamin C placebo (group A), 15 participants in the resveratrol and vitamin C (group B), and 14 participants in the vitamin C plus a resveratrol placebo (group C). Depending on the group assignment, the participants received 500 mg resveratrol capsules, vitamin C/ascorbic acid tablets, or placebo tablets for three months.
Reduced oxidative stress
First, the researchers analyzed baseline clinical and biochemical blood test results. In the intra-group analysis, baseline measurements were compared to after-treatment measurements, and no significant differences were found in measurements such as weight, BMI, glucose, insulin, lipid profile, and uric acid.
When groups were compared with each other after a three-month intervention, the researchers observed significantly lower total cholesterol levels and significantly higher triglyceride levels in the vitamin C group compared to the resveratrol group. The researchers also observed significantly lower triglyceride concentrations in the combined group compared to the vitamin C-only group.
Comparing the baseline and after-treatment levels of lipohydroperoxides (LPH), a measure of oxidative deterioration of lipids, showed a significant decrease of 33% in the combined group. The resveratrol group and the vitamin C group had 25% and 15% decreases in LPH levels, respectively. However, those differences were not statistically significant. The researchers hypothesize that it was due to the sample size being too small, and future research with a bigger sample size might lead to significant results in those groups as well.
The researchers also analyzed the levels of MDA, the end product of lipoperoxidation. All three groups showed statistically significant differences between initial measurement before the treatment and following the 3-month treatmnet. MDA levels were reduced by 26% in the resveratrol group, 32% in the combined group, and 38% in the vitamin C group.
Previous experiments conducted on rats that received resveratrol achieved similar results [6]. Similarly, a study of people under 18 taking vitamin C also showed MDA reduction [7].
After measuring lipid damage, the researchers analyzed protein oxidative damage. A statistically significant reduction was also observed in all groups. The differences between before and after treatment measurements show 39% reduction in the combined group and 29% in both the resveratrol and vitamin C groups.
There were also differences in antioxidant capacity. However, this time, there was an increase of 30% for the combined group and 28% for the vitamin C group following the treatment compared to baseline.
No improvements in insulin resistance
Despite previous research linking oxidative state and insulin resistance, none of this study’s groups demonstrated statistically significant differences in insulin resistance.
The researchers discuss previous studies on humans that, except for one, all reported that resveratrol does not affect insulin resistance. Those studies looked at different populations of participants with different health conditions and variable durations and doses of treatment.
Similarity of all groups
The authors caution when interpreting the results, as the research has some limitations. For example, the generalizability of the results from a homogenous group of participants, including only females from the Valley of Mexico metropolitan area, was limited.
Additionally, the researchers did not include a control, untreated group. However, as the authors explain, their question addressed how the combined treatments compare with a single treatment and whether there is possible synergy between them. Their experimental setup allowed for those comparisons and comparisons of the changes that the women experienced compared to baseline.
The researchers conclude that despite the differences in the effects of different measurements of oxidative stress, “none of the three interventions were superior to the others.”
Literature
[1] Montoya-Estrada, A., García-Cortés, A. Y., Romo-Yañez, J., Ortiz-Luna, G. F., Arellano-Eguiluz, A., Belmont-Gómez, A., Lopéz-Ugalde, V., León-Reyes, G., Flores-Pliego, A., Espejel-Nuñez, A., Solis-Paredes, J. M., & Reyes-Muñoz, E. (2024). The Administration of Resveratrol and Vitamin C Reduces Oxidative Stress in Postmenopausal Women-A Pilot Randomized Clinical Trial. Nutrients, 16(21), 3775.
[2] Montoya-Estrada, A., Velázquez-Yescas, K. G., Veruete-Bedolla, D. B., Ruiz-Herrera, J. D., Villarreal-Barranca, A., Romo-Yañez, J., Ortiz-Luna, G. F., Arellano-Eguiluz, A., Solis-Paredes, M., Flores-Pliego, A., Espejel-Nuñez, A., Estrada-Gutierrez, G., & Reyes-Muñoz, E. (2020). Parameters of Oxidative Stress in Reproductive and Postmenopausal Mexican Women. International journal of environmental research and public health, 17(5), 1492.
[3] Breuss, J. M., Atanasov, A. G., & Uhrin, P. (2019). Resveratrol and Its Effects on the Vascular System. International journal of molecular sciences, 20(7), 1523.
[4] Xia, N., Daiber, A., Förstermann, U., & Li, H. (2017). Antioxidant effects of resveratrol in the cardiovascular system. British journal of pharmacology, 174(12), 1633–1646.
[5] Livraghi, V., Mazza, L., Chiappori, F., Cardano, M., Cazzalini, O., Puglisi, R., Capoferri, R., Pozzi, A., Stivala, L. A., Zannini, L., & Savio, M. (2024). A proteasome-dependent inhibition of SIRT-1 by the resveratrol analogue 4,4′-dihydroxy-trans-stilbene. Journal of traditional and complementary medicine, 14(5), 534–543.
[6] Kong, D., Yan, Y., He, X. Y., Yang, H., Liang, B., Wang, J., He, Y., Ding, Y., & Yu, H. (2019). Effects of Resveratrol on the Mechanisms of Antioxidants and Estrogen in Alzheimer’s Disease. BioMed research international, 2019, 8983752.
[7] Ismy, J., Soebadi, A., Mangunatmadja, I., Monica, M., Sari, T. T., & Yuliarti, K. (2024). Role of antioxidants in reducing oxidative stress and seizure frequency in drug-resistant epileptic patients. Narra J, 4(2), e790.
