With Resveratrol, Our Cells Get a New Lease on Life

Resveratrol was dubbed the “Fountain of Youth” by Harvard Medical School researchers after studies showed that the antioxidant could increase cell survival and slow aging in live yeast, specifically Saccharomyces cerevisiae, and later in mice, by activating a “longevity” gene known as silent information regulator 1 (SIRT1). This groundbreaking research showed that activating the SIRT1 gene extended lifespan by 70 percent and increased DNA stability.² Sirtuins, such as SIRT1, regulate the aging process and are themselves regulated by diet and environmental stress. They also defend the body against free radicals, protecting cells against metabolic stresses.³

With Resveratrol, it’s Like Fasting… Without the Frustration

Fasting, calorie restriction, and exercise are all known to activate SIRT1. Research highlights resveratrol’s ability to mimic the benefits of fasting and calorie restriction—and thus, activation of SIRTI—without (the frustration of) actual fasting or calorie restriction.

A double-blind, crossover study of 11 obese men taking 150 mg of resveratrol daily for 30 days showed an increase in SIRT1, improved mitochondrial function, and an increase in AMP-activated protein kinase (AMPK), an enzyme known as the “master regulator of energy metabolism” which activates the uptake of glucose and fatty acids into cells for energy production. There was also a decrease in circulating blood glucose, triglyceride levels, and inflammation markers compared to the control group.⁴ Systolic blood pressure also dropped, while insulin resistance improved.⁵ The researchers concluded that just 30 days of resveratrol supplementation “induces metabolic changes in obese humans, mimicking the effects of calorie restriction.”⁶

Additional research in middle-aged, obese mice fed a high-calorie diet showed that the addition of resveratrol significantly improved their health, including increased insulin sensitivity, improved motor function, and increased AMPK.⁷ This study revealed that resveratrol “opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways.” It concluded that improving health in mammals using phytonutrients like resveratrol points to “new approaches for treating obesity-related disorders and diseases of aging.”⁸

I’d be remiss to say that this doesn’t give us the green light to become, or stay, overweight, ignoring exercise and eating right, but resveratrol does give us yet another powerful tool to combat the cellular effects and diseases associated with obesity and aging.

With Resveratrol, Blood Sugar, Type-2 Diabetes, and CHD Markers Improve

Resveratrol also has a direct effect on blood sugar in those with type-2 diabetes accompanied by coronary heart disease (CHD). In a randomized, double-blind, placebo-controlled trial of patients with type-2 diabetes and heart disease, those taking 500 mg of resveratrol a day for four weeks had reduced fasting glucose and insulin resistance and significantly increased insulin sensitivity compared with the placebo group. Those in the resveratrol group also saw a significant increase in HDL-cholesterol levels, a significant decrease in the total LDL/HDL-cholesterol ratio, and an increase in total antioxidant capacity, the body’s ability to scavenge free radicals. Furthermore, resveratrol upregulated SIRT1 in type-2 diabetes patients with coronary heart disease.⁹

In another randomized, controlled study of 62 type-2 diabetics, those taking 250 mg of resveratrol per day for three months had significantly improved long-term fasting blood sugar, systolic blood pressure, and total cholesterol compared to the control group.¹⁰

With Resveratrol, the Cardiovascular Benefits Abound

Taking a deeper dive into the cardiovascular effects of resveratrol, there are a lot of benefits to get excited about. For starters, it’s widely known that antioxidants are good for overall health, and resveratrol, found in foods like grapes and red wine, is one such antioxidant with “hearty” cardio-protective properties. It neutralizes free radicals, protects against hypertension, atherosclerosis, stroke, ischemic heart disease, arrhythmia, chemotherapy-induced cardiotoxicity, diabetic cardiomyopathy, and heart failure.¹¹ Once again, resveratrol supports the activation of the longevity gene SIRT1, AMPK, and endogenous antioxidant enzymes. In addition, the anti-inflammatory, insulin-sensitizing, endothelial-function improving (through the formation of nitric oxide), and lipid-lowering properties of resveratrol are also part of its unique cardiovascular benefits.^{12 13}

With Resveratrol, the Brain Benefits Are Bountiful

It may come as no surprise to learn that resveratrol is top-notch for brain health, so why not make it the top-of-mind nutrient the next time you’re searching for a brain-boosting supplement? Resveratrol is one of those unique antioxidants that crosses the blood-brain barrier, where it protects the brain and nerve cells.¹⁴ It has the ability to increase blood flow to the brain and positively benefit brain function. Results from one double-blind, placebo-controlled crossover study had 22 healthy adults aged 18 to 29 years take either a placebo, a single dose of 250 mg of trans-resveratrol (a more bioavailable form), or 500 mg of trans-resveratrol over three separate office visits. The results showed that both doses, but not the placebo, increased cerebral blood flow, which was sustained throughout task performance. The study concluded, “The results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables.”¹⁵

Resveratrol also impacts learning, mood, and memory in the elderly. In one study, resveratrol was shown to stimulate neurogenesis (the process of forming new neurons in the brain) and blood vessel formation in the hippocampus of healthy, aged rats. These structural changes were associated with “significant improvements in spatial learning, memory formation, and mood function.”¹⁶

With Resveratrol, Alzheimer’s Disease Biomarkers Improve

Alzheimer's disease (AD) is a devastating disorder that affects 1 in 10 Americans over the age of 65, and almost half of all Americans over 85 years old. Moreover, the odds of developing AD double every five years after the age of 65.¹⁷ There is emerging evidence that resveratrol combats Alzheimer’s disease in several ways—both as a preventative and treatment of the disease—by crossing the blood-brain barrier, preventing and reducing amyloid plaque formation, and directly acting on neuroinflammation.

One of the hallmark features of AD is the deposition and accumulation of amyloid-beta peptides (Aβ) into amyloid plaques in the hippocampus and cerebral cortex. Amyloid plaques are toxic to brain cells, resulting in neuronal dysfunction and death. In AD patients, abnormal levels of this naturally occurring protein bind together to form harmful plaques that collect between neurons and disrupt cell function.¹⁸

Evidence shows that resveratrol enhances and facilitates the clearance of amyloid-beta peptides, promotes cell survival in neurons, and reduces amyloid plaque formation and amyloid plaque counts in various brain regions.^{19 20} In one study, mice were fed resveratrol for 45 days, and results showed that resveratrol reduced amyloid plaque formation in the brain, with the largest reductions in amyloid plaques in the medial cortex, which plays a role in attention, inhibitory control, and long-term memory (-48%); the striatum, a critical part of motor function and reward (-89%); and the hypothalamus, a region of the brain that controls body temperature thirst, hunger, sleep, and emotions (-90%).^{21 22}

With Resveratrol, Pause the Effects of Menopause… Naturally

Menopause is a natural and normal part of the aging process of healthy women ages 40–55, when periods stop and the ovaries stop producing estrogen, but oftentimes, the symptoms of this natural change can be debilitating. With resveratrol, there’s hope.²³

Before menopause, normal estrogen levels can very between 30-400 picograms per milliliter (pg/mL), but after menopause, it falls below 30 pg/mL.²⁴ This drop in estrogen causes symptoms such as dry skin, tender breasts, weak or brittle bones, trouble concentrating, moodiness and irritability, vaginal dryness, hot flashes and night sweats, and irregular periods or no periods.²⁵ For many, hot flashes are one of the hallmark symptoms.

According to a randomized, controlled, double-blind crossover study of 50 patients, those taking resveratrol saw a 78.6 percent improvement in the intensity of hot flash symptoms and quality of life, compared to just 18 percent in the placebo group. Furthermore, the reduction in the number of hot flash episodes was 57 percent in the resveratrol group and just 9 percent in the placebo group. The study concluded, “Resveratrol is effective in reducing the number of episodes and intensity of hot flashes … and has the characteristics to be an alternative therapy in the treatment of hot flashes in menopause.”^{26 27}

With Resveratrol Women’s Health Goes Strong Beyond Menopause

The Resveratrol Supporting Healthy Aging in Women (RESHAW) study is the largest, longest-running study on resveratrol to date and focused on the effect of daily resveratrol supplementation in postmenopausal women. In separate published studies, the authors found that, compared to placebo, 75 mg of resveratrol two times a day for 12 months reduced overall pain scores, improved menopausal symptoms, and improved general wellbeing; it improved insulin sensitivity, cerebrovascular health, and overall cognitive performance; and it improved bone mineral density, leading to a significant improvement in T-scores, which is associated with a reduced risk of major fracture. How can one nutrient do so much? Resveratrol is a phytoestrogen with circulatory benefits making its effect wide reaching, especially for older women.^{28 29 30}

References

1. Intelligence, P&S. “Anti-Aging Market Revenue Worth $421.4 Billion by 2030: P&S Intelligence.” Anti-Aging Market Revenue Worth $421.4 Billion by 2030: P&S Intelligence, 15 Mar. 2021, https://www.prnewswire.com/news-releases/anti-aging-market-revenue-wort….
2. Howitz KT;Bitterman KJ;Cohen HY;Lamming DW;Lavu S;Wood JG;Zipkin RE;Chung P;Kisielewski A;Zhang LL;Scherer B;Sinclair DA; “Small Molecule Activators of Sirtuins Extend Saccharomyces Cerevisiae Lifespan.” Nature, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/12939617/.
3. L;, Chang HC;Guarente. “SIRT1 And Other Sirtuins in Metabolism.” Trends in Endocrinology and Metabolism: TEM, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/24388149/#:~:text=Sirtuins%20regulate%2….
4. Timmers S;Konings E;Bilet L;Houtkooper RH;van de Weijer T;Goossens GH;Hoeks J;van der Krieken S;Ryu D;Kersten S;Moonen-Kornips E;Hesselink MKC;Kunz I;Schrauwen-Hinderling VB;Blaak E;Auwerx J;Schrauwen P; “Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans.” Cell Metabolism, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/22055504/.
5. D;, Langin. “Adipose Tissue Lipolysis as a Metabolic Pathway to Define Pharmacological Strategies against Obesity and the Metabolic Syndrome.” Pharmacological Research, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/16644234/#:~:text=Adipose%20tissue%20li….
6. Timmers S;Konings E;Bilet L;Houtkooper RH;van de Weijer T;Goossens GH;Hoeks J;van der Krieken S;Ryu D;Kersten S;Moonen-Kornips E;Hesselink MKC;Kunz I;Schrauwen-Hinderling VB;Blaak E;Auwerx J;Schrauwen P; “Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans.” Cell Metabolism, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/22055504/.
7. Kim, Joungmok, et al. “AMPK Activators: Mechanisms of Action and Physiological Activities.” Nature News, Nature Publishing Group, 1 Apr. 2016, https://www.nature.com/articles/emm201616.
8. Baur JA;Pearson KJ;Price NL;Jamieson HA;Lerin C;Kalra A;Prabhu VV;Allard JS;Lopez-Lluch G;Lewis K;Pistell PJ;Poosala S;Becker KG;Boss O;Gwinn D;Wang M;Ramaswamy S;Fishbein KW;Spencer RG;Lakatta EG;Le Couteur D;Shaw RJ;Navas P;Puigserver P;Ingram DK;de Cab. “Resveratrol Improves Health and Survival of Mice on a High-Calorie Diet.” Nature, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/17086191/.
9. Hoseini, Asma, et al. “The Effects of Resveratrol on Metabolic Status in Patients with Type 2 Diabetes Mellitus and Coronary Heart Disease.” Food & Function, The Royal Society of Chemistry, 8 Aug. 2019, https://pubs.rsc.org/en/content/articlelanding/2019/FO/C9FO01075K.
10. MJ;, Bhatt JK;Thomas S;Nanjan. “Resveratrol Supplementation Improves Glycemic Control in Type 2 Diabetes Mellitus.” Nutrition Research (New York, N.Y.), U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/22901562/.
11. Raj, Pema, et al. “A Comprehensive Analysis of the Efficacy of Resveratrol in Atherosclerotic Cardiovascular Disease, Myocardial Infarction and Heart Failure.” Molecules (Basel, Switzerland), MDPI, 31 Oct. 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587649/.
12. JR;, Zordoky BN;Robertson IM;Dyck. “Preclinical and Clinical Evidence for the Role of Resveratrol in the Treatment of Cardiovascular Diseases.” Biochimica Et Biophysica Acta, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/25451966/.
13. Duffy SJ, Vita JA. Effects of phenolics on vascular endothelial function. Curr Opin Lipidol. 2003;14(1):21-27.
14. Snopek, Lukas, et al. “Contribution of Red Wine Consumption to Human Health Protection.” Molecules (Basel, Switzerland), MDPI, 11 July 2018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099584/#B4-molecules-23-0….
15. Kennedy DO;Wightman EL;Reay JL;Lietz G;Okello EJ;Wilde A;Haskell CF; “Effects of Resveratrol on Cerebral Blood Flow Variables and Cognitive Performance in Humans: A Double-Blind, Placebo-Controlled, Crossover Investigation.” The American Journal of Clinical Nutrition, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/20357044/.
16. Kodali M;Parihar VK;Hattiangady B;Mishra V;Shuai B;Shetty AK; “Resveratrol Prevents Age-Related Memory and Mood Dysfunction with Increased Hippocampal Neurogenesis and Microvasculature, and Reduced Glial Activation.” Scientific Reports, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/25627672/.
17. Pasinetti GM;Wang J;Ho L;Zhao W;Dubner L; “Roles of Resveratrol and Other Grape-Derived Polyphenols in Alzheimer's Disease Prevention and Treatment.” Biochimica Et Biophysica Acta, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/25315300/.
18. “Amyloid Beta Protein.” Amyloid Beta Protein - an Overview | ScienceDirect Topics, https://www.sciencedirect.com/topics/neuroscience/amyloid-beta-protein.
19. “Resveratrol.” Linus Pauling Institute, 3 Jan. 2022, https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/resverat….
20. X;, Jia Y;Wang N;Liu. “Resveratrol and Amyloid-Beta: Mechanistic Insights.” Nutrients, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/29036903/.
21. Karuppagounder SS;Pinto JT;Xu H;Chen HL;Beal MF;Gibson GE; “Dietary Supplementation with Resveratrol Reduces Plaque Pathology in a Transgenic Model of Alzheimer's Disease.” Neurochemistry International, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/19041676/.
22. X;, Jia Y;Wang N;Liu. “Resveratrol and Amyloid-Beta: Mechanistic Insights.” Nutrients, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/29036903/.
23. DM;, Henry LA;Witt. “Resveratrol: Phytoestrogen Effects on Reproductive Physiology and Behavior in Female Rats.” Hormones and Behavior, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/11855907/#:~:text=Resveratrol%20is%20a%…)%20subtypes%20ERalpha%20and%20ERbeta.
24. Tests to Determine Menopausal Status, https://www.breastcancer.org/treatment-side-effects/menopause/types/tes….
25. “Low Estrogen: Causes, Symptoms, Diagnosis & Treatment.” Cleveland Clinic, https://my.clevelandclinic.org/health/diseases/22354-low-estrogen.
26. Leo L;Surico D;Deambrogio F;Scatuzzi A;Marzullo P;Tinelli R;Molinari C;Surico N; “[Preliminary Data on the Effectiveness of Resveratrol in a New Formulation in Treatment of Hot Flushes].” Minerva Ginecologica, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/26491826/.
27. Henry Tianus. “Resveratrol Reduces the Risk of Cancer and Hot Flashes.” Henry Tianus, 25 June 2021, https://henrytianus.com/blogs/news/resveratrol-reduces-the-risk-of-canc….

28. Thaung Zaw, Jay Jay MBBS1; Howe, Peter R.C. PhD1,2,3; Wong, Rachel H.X. PhD1,2 Long term resveratrol supplementation improves pain perception, menopausal symptoms, and overall well-being in postmenopausal women: findings from a 24-month randomized, controlled, crossover trial, Menopause: January 2021 - Volume 28 - Issue 1 - p 40-49 doi: 10.1097/GME.0000000000001643

29. Thaung Zaw JJ, Howe PR, Wong RH. Long-term effects of resveratrol on cognition, cerebrovascular function and cardio-metabolic markers in postmenopausal women: A 24-month randomised, double-blind, placebo-controlled, crossover study. Clin Nutr. 2021;40(3):820-829. doi:10.1016/j.clnu.2020.08.025

30. Wong, R. H., Thaung Zaw, J. J., Xian, C. J., & Howe, P. R. (2020). Regular Supplementation With Resveratrol Improves Bone Mineral Density in Postmenopausal Women: A Randomized, Placebo-Controlled Trial. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 35(11), 2121–2131. https://doi.org/10.1002/jbmr.4115