Health Benefits of Resveratrol (SQ-74)

What is Resveratrol?

Resveratrol has been the focus of many animal and human studies; mostly because of its potential role in preventing premature ageing and associated chronic diseases.

Resveratrol is a polyphenol naturally produced by certain plant species in response to harsh environmental conditions. Plants produce resveratrol and other anti-oxidants as a part of their in-built defense mechanism to protect against injury, infection, disease, extreme climates and excess UV radiation. Grapes, berries, chocolate and peanuts are some of the most abundant sources of resveratrol in nature.  

It is believed that resveratrol has incredible health benefits to offer. Research shows that its antioxidant and anti-inflammatory properties are the mainstay of these health promoting effects, be it anti-aging potential or its role in suppressing inflammation and preventing (or delaying) the onset of many chronic conditions such as cardiovascular disease, Alzheimer’s, insulin resistance, type 2 diabetes and cancer. One other way resveratrol improves cellular function and performance is by activating Sirtuins. Let’s discuss all these health benefits in more detail.

1. Anti-aging benefits
   
   Both oxidative damage at cellular level and mitochondrial dysfunction are heavily implicated in how we age. As an antioxidant, resveratrol is efficient in rummaging and destroying free radicals. It also increases the concentration of some important antioxidant enzymes in the body. This limits the oxidative damage to cellular DNA and mitochondria, that can otherwise lead to premature aging. Now, this is one mechanism.
   
   Resveratrol also improves cellular longevity by activating sirtuins, SIRT1 in particular. Sirtuins, a class of enzyme, are extensively studied and proven for their role in improving health and lifespan in both animals and humans. Sirtuins regulate many biological pathways that are involved in ageing, such as metabolism, inflammatory processes, mitochondrial functions, DNA repair and how cells fight environmental stress. These pathways are poorly managed as we age, giving way to more oxidative stress, inflammation, errors in DNA repair and decreased resistance of cells to any kind of stress.
   
   Through sirtuins activation, resveratrol also maintains mitochondrial health. It increases the number and activity of mitochondria [1] – special structures within cells whose main job is to make energy for cells which they need to carry out all their functions (reproduction, growth, repair and survival).
   
   Recent research, though still in early stages, highlighted yet another mechanism in which resveratrol could help delay aging. It shows that resveratrol can rejuvenate old dysfunctional cells (senescent cells) that have lost their capacity to divide anymore. As we age, these old cells tend to build up and may cause many diseases generally rooted in old age. [2]
   
   
2. Protects brain from ageing and disease
   
   Resveratrol appears to be highly effective in promoting brain health and prevent, or at least delay, age-associated decline in cognitive functions. Studies suggest that it may reduce the risk of developing Alzheimer’s disease due to its antioxidant and anti-inflammatory effects.
   
   Resveratrol works through multiple mechanisms.
   
   
   • Improves blood flow to the brain by increasing Nitric Oxide (NO) availability.
   • Lowers inflammation in the brain, which is known to play a crucial role in the progression of Alzheimer’s and impaired brain functions.
   • Crosses the blood brain barrier and influences brain and nervous system health.
   • Clears amyloid beta (Aβ) peptides, an important step in slowing down the development of Alzheimer’s.
   • Reduces damage to nerve cells. 
   
   Studies show that resveratrol can enhance memory in healthy older adults as well as in individuals at high risk for dementia [3] [4]. Resveratrol supplementation has also been found to maintain cognitive performance in type 2 diabetes, by improving cerebrovascular function. [5]. Type 2 diabetics are at an increased risk of fast-paced dementia.
   
   A new study found that resveratrol restores the integrity of blood brain barrier in Alzheimer’s patients. This stops toxic immune molecules from the body to enter the brain tissues. These molecules can increase inflammation in the brain and kill neurons. The study also found that resveratrol led to the increase in molecules that help the immune system to remove and degrade proteins that are harmful to the brain. [6]
   
   
3. Reduces risk of heart disease
   
   Oxidative damage by free radicals causes inflammation in the arteries, lowers the bioavailability of nitric oxide in vessels and causes endothelium to function poorly. Endothelium is a thin, delicate layer of cells that line the inside of your arteries. A healthy endothelium is better at stopping LDL cholesterol from penetrating and being retained by the vessel wall. LDL oxidation in the blood vessels is believed to be one of the key step in the formation of plaques (atherosclerosis). All these factors increase the risk of cardiovascular disease.  
   
   Resveratrol, again as an antioxidant and anti-inflammatory, plays a huge role in promoting heart and overall vascular health.
   
   
   • Prevents oxidation of low density lipoproteins (LDL).
   • Improves endothelial functions and blood flow to the heart. Resveratrol stimulates NO production by a number of mechanisms and also prevents the inactivation of NO by free radicals [7].  NO is a critical molecule released by endothelium that preserves the functions and integrity of endothelium through various means. Most importantly, it helps blood vessels to dilate. By making NO more available, resveratrol improves endothelial function and increases blood flow to tissues including the heart and the brain. 
   • Increases the levels of important anti-oxidant enzymes in cells, such as glutathione peroxidase, heme oxygenase and superoxide dismutase. This lessens oxidative stress in cardiac and vascular cells.
   • Prevents clot formation by making platelets less sticky.
   
   Another very interesting animal study from China suggests another way resveratrol happens to be healthy for the heart. The researchers found that resveratrol modifies the microbial population in the gut to affect the production of bile acid. This reduces the levels of trimethylamine-N-oxide (TMAO), which is a known risk factor for the development of atherosclerosis. [8] Previous research has already established that gut microbiome plays a strong role in the build-up of plaque in the arteries.
   
   
4. Improved management of Type 2 diabetes and related complications
   
   Resveratrol has been found to be helpful in reversing insulin resistance as well as damage to blood vessels caused by diabetes. It also reduces the risk of obesity, which is an independent risk factor for Type 2 diabetes (T2DM), high blood pressure, cardiovascular diseases, and even some cancers.
   
   Studies have shown that regular consumption of resveratrol significantly reduces blood glucose levels, reverses insulin resistance and improves glucose uptake by cells in type 2 diabetes mellitus (T2DM) [9] [10] [11] [12]. However, these ant-diabetic benefits are not seen in healthy people.
   
   Other research in 2017 found that resveratrol reduces artery stiffness in people with type 2 diabetes. Stiff arteries are common in the elderly but in diabetic patient’s high glucose levels tend to damage arteries and cause premature stiffening. This increases the risk of heart attack, stroke and high blood pressure. However, in the study resveratrol doesn’t appear to relax blood vessels, suggesting that resveratrol may extend more benefits towards improving the structural damage in the aorta. This could mean that people without diabetes and with healthy arterial stiffness may not benefit as much from resveratrol supplementation. [13]
   
   Besides its direct antioxidant and anti-inflammation benefits, there are two major mechanisms by which resveratrol is believed to improve diabetic functions as well as reduce obesity risk.
   
   
   • Activates Sirtuin1, which helps to increase insulin sensitivity and also protect against metabolic damage caused by a fat rich diet. Activation of SIRT1 could also be a possible mechanism involved in decreasing stiffness in arteries, caused by aging, diabetes and also obesity.
   • Increases the activity of AMP-activated protein kinase (AMPK), an important enzyme responsible for regulating metabolism of fat and glucose in cells. AMPK is also called a master metabolic switch and it basically controls whether the available energy should be utilized to meet instant requirements or stored as fat to be used in the future. When activated, AMPK signals the body to use and not store the energy. 
   
   While there is a need for large-scale and better designed studies in the future, current data provides compelling evidence that resveratrol is very likely to work as an inexpensive and effective agent to manage diabetes as well as associated complications.

Is resveratrol safe?

Studies say that resveratrol is quite safe when taken in prescribed doses. However, resveratrol supplements may interact with certain health conditions and medications, and cause some unwanted effects.

Resveratrol has a chemical structure similar to the hormone estrogen. Therefore, it may interfere with its functions. Women with cancer in breast, ovary or uterus are advised not to take resveratrol supplements. It is also considered risky for women trying to become pregnant. Resveratrol is known to prevent the formation of blood clots. So, it can increase the risk of bleeding if you are taking blood-thinning drugs such as aspirin, ibuprofen and warfarin.  In addition, high doses may cause weight loss.

References:

1. K Peng at al. Resveratrol Regulates Mitochondrial Biogenesis and Fission/Fusion to Attenuate Rotenone-Induced Neurotoxicity. Oxid Med Cell Longev. 2016
2. E Latorre et al. Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence. BMC Cell Biology. 2017
3. Witte et al. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J Neurosci. 2014
4. Kobe et al. Impact of Resveratrol on Glucose Control, Hippocampal Structure and Connectivity, and Memory Performance in Patients with Mild Cognitive Impairment. Front Neurosci. 2017
5. Wong et al. Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus. Nutrition Metabolism & Cardiovascular Diseases. 2016.
6. Moussa et al. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. Journal of Neuroinflammation 2017
7. Xia et al. Resveratrol and endothelial nitric oxide. Molecules. 2014
8. Chen et al. Resveratrol attenuates trimethylamine-N-oxide (TMAO)-induced atherosclerosis by regulating TMAO synthesis and bile acid metabolism via remodeling of the gut microbiota. mBio. 2016.
9. Zhu et al. Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: systematic review and meta-analysis. Nutr Metab (Lond). 2017
10. Liu et al. Effect of resveratrol on glucose control and insulin sensitivity: a meta-analysis of 11 randomized controlled trials. Am J Clin Nutr. 2014
11. Goh et al. Effects of resveratrol in patients with type 2 diabetes mellitus on skeletal muscle SIRT1 expression and energy expenditure. Int J Sport Nutr Exerc Metab. 2014.
12. Oyenihi et al. Antidiabetic Effects of Resveratrol: The Way Forward in Its Clinical Utility. J Diabetes Res. 2016.
13. Can the antioxidant resveratrol reduce artery stiffness in diabetics? American Heart Association. 217.

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