Name: Resveratrol, Grape antioxidants
Goes well with: Curcumin, Quercetin, Piperine, Green tea catechins
Number of scientific references: 51
Level of Evidence: Level I What is this?
Note: Resveratrol is a plant antioxidant that is predominantly acquired form grapes. Pre-clinical evidence suggests that it mediates an antidepressant action by influencing brain chemistry, lowers stress hormone levels, boosting antioxidant defences and promoting neuroplasticity.
It also improves metabolic health that can help reduce the risk of mood disorders. More research is required to confirm these benefits in humans. Dietary resveratrol can protect mood and brain health.
There is mounting evidence that resveratrol exerts a protective action in metabolic disorders and heart diseases.
Resveratrol is a small polyphenol found in grapes, berries, nuts and other plant sources. It exists in cis- and trans- form, trans-resveratrol is predominantly found in dietary sources.
Dietary polyphenols such as resveratrol are proven to improve metabolic health and thus can reduce depression risk.
Pre-clinical studies indicate that resveratrol deploys antidepressant action by regulating brain chemistry, improving antioxidant defences, reducing inflammation in the brain and promoting neuroplastic changes. It also improves various parameters of metabolic health to reduce the risk of depression and protects brain health.
But these findings are limited to animal studies and are still to be confirmed in humans.
6 Potential Benefits Of Resveratrol For Depression
Let’s go over the research studies that depict resveratrol’s antidepressant effect.
Table of Contents
- 1 6 Potential Benefits Of Resveratrol For Depression
- 2 Dosage of Resveratrol For Depression
- 3 Precautions with Resveratrol Use
- 4 Conclusion
1.Resveratrol is a natural antidepressant
Resveratrol is one such potential antidepressant polyphenol.
A recent study published in Molecular Neurobiology, 2017 reveals the various mechanisms behind resveratrol’s antidepressant action. 
These mechanisms (as evidenced by animal studies) include:
- Activating and increasing the level of proteins that support neuroplasticity such as Brain-Derived Neurotrophic Factor.  Neuroplasticity is the ability of the brain to adapt to changes and if influenced positively this can aid in depression recovery.
- Activating biochemical pathways that protect and support the survival of brain cells. 
- Reducing inflammation in the brain and supporting neurogenesis (formation of new brain cells) in the hippocampus 
- Regulating the activity of neurotransmitters or brain chemistry such as serotonin and noradrenaline that influence mood.  
Wang et al. have found that resveratrol’s antidepressant action is comparable to that of fluoxetine, a conventional antidepressant.  This is yet to be evaluated in humans.
Resveratrol has low bioavailability ( it is poorly absorbed in the body and does not reach the target tissue in desired concentrations) and this limits its use for therapeutic purposes.
Piperine the active constituent of black pepper is found to improve resveratrol’s bioavailability when administered with it. 
Studies in animal models suggest that piperine, apart from improving bioavailability, may also increase its antidepressant activity.   The duo regulates brain chemistry to reduce depression-like symptoms.
SIRT-1 or Silent Information Regulator-1 belong to the sirtuin group of proteins that are commonly referred to anti-ageing genes since they are involved in fat storage, DNA repair and inflammation.
As per pre-clinical studies, resveratrol is a potent activator of sirtuin and SIRT-1.
A study published in Frontiers in Molecular Neuroscience, 2015 explored the role of resveratrol, SIRT 1 and our sleep-wake cycle. 
The researchers highlighted that SIRT1 regulates our circadian rhythm or our body clock. Though light is the dominant cue for regulating our body clock and sleep cycle, researchers observed that resveratrol consumption also influences the signalling of our sleep hormone- melatonin.
And this possibly occurs as a result of the interaction of dietary nutrients such as resveratrol with SIRT1.
The researchers concluded that nutritional food elements should be employed as a part of a comprehensive treatment for brain and mental health disorders to improve therapeutic outcomes and quality of life.
SIRT-1 activity is found to be reduced in the hippocampus (part of the brain predominantly dealing with memory) and this is associated with increased depressive behaviour. (Biological Psychiatry, 2016) 
Contrastingly Kim and colleagues have found that SIRT1 levels are increased in nucleus accumbens (part of the brain that’s is involved in our reward circuitry and associated with motivation) in an animal model of chronic social defeat stress. 
As per this research study, this increase in SIRT1 plays an important role in mediating depressive behaviour. Since resveratrol is an activator of SIRT1, researchers decided to investigate whether resveratrol would worsen depression by increasing SIRT1 levels.
Systemic introduction of the grape antioxidant was not found to affect or worsen depressive behaviour. But its direct infusion in the nucleus accumbens increased depressive and anxiety-like symptoms.
The researchers highlighted that these findings are in contrast to earlier published studies and they suggest this could have occurred as result of the difference in dose of resveratrol used in the previous and current study, differences in duration of treatment and also due to differences in choice of an animal model used.
What would really help to understand and confirm the antidepressant action of resveratrol is studies in humans.
Dr Danilenko from Russian Academy of Medical Sciences has organized a clinical trial assessing the effect of resveratrol supplements in depression.  This study will be completed in February 2019 and possibly shed some light on the polyphenol’s antidepressant action.
Quick Gist: Pre-clinical studies show that resveratrol mediates antidepressant action by regulating brain chemistry, reducing inflammation in the brain, regulating our body clock, supporting neuroplasticity and by protecting brain cells from stress-induced damage.
Further research in the form of human studies is required to confirm it’s antidepressant action under clinical settings.
2. It prevents stress-induced changes
Chronic stress, sometimes, leads to depression. On a biochemical level, various disturbances occur during periods of chronic stress such as HPA axis dysfunction, high levels of stress hormone, elevated levels of inflammatory enzymes.
HPA axis or hypothalamic pituitary adrenal axis is a communication network between parts of the brain and the important hormone-secreting glands in the body. This communication regulates our stress response.
A study published in Neuropsychiatry disease and treatment, 2017 revealed that resveratrol ameliorates chronic stress-induced HPA axis hyperactivity and lowers cortisol (stress hormone) levels. 
Other studies in animal models have also confirmed that the polyphenol lowers stress hormone levels and supports neuroplasticity as a part of its antidepressant action in chronic stress like conditions.  
It may also counteract the deleterious effects of stress on other aspects of health such as disturbances, in metabolic health, insulin resistance, testicular dysfunction, neuroinflammation etc.    
Quick Gist: Animal studies indicate that that resveratrol lowers stress hormone levels and exerts an antidepressant action in chronic stress like conditions. It may also prevent stress-induced damage to the brain, metabolic health and reproductive health.
3.Resveratrol lowers oxidative stress and inflammation in the brain
One aspect that is not much discussed but is actively involved in the pathophysiology of depression, is immune system dysfunction.
This paves the way for oxidative/ nitrosative stress where reactive oxygen and nitrogen species cause cellular damage.  Oxidative damage further fuels inflammation giving rise to neuroinflammation or inflammation in the brain during the depression.
Microglia is cells that belong to the immune system of the central nervous system. These cells are activated during the depression and their dysfunction causes neuroinflammation. 
Resveratrol mediates anti-inflammatory action in the brain by preventing the activation of microglial cells. 
Another key pathological feature of various chronic diseases including depression is mitochondrial dysfunction.  Mitochondria are the energy-producing units of the cell that also help maintain cellular antioxidant defences.
Researchers are working on developing mitochondrial targeted antioxidant therapies for improving therapeutic outcomes in chronic illnesses.
Quick Gist: Resveratrol is a natural antioxidant that helps curb the oxidative stress and inflammation occurring in the brain during the depression. This action of the grape antioxidant, in turn, improves anxious and depressive behaviour and somatic symptoms occurring in depression.
4. It protects cognition
Mah and colleagues have stated that chronic stress and anxiety bring about degenerative changes in the structure and function of the brain which can manifest as cognitive impairment. 
Cognitive impairment in depression may simply mean brain fog, reduced ability to think, reason and calculate, reduced verbal fluency and minor memory lapses.
Resveratrol attenuates stress-induced cognitive impairments by increasing the levels of proteins that support neuroplasticity such as Brain-Derived Neurotrophic Factor and by activating cell survival pathways that protect brain cell.  
Along with piperine (250mg trans-resveratrol and 20mg piperine), it is found to improve blood flow in the brain of individuals performing cognitive tasks. 
A recent review study published in Nutrition Reviews, 2018 stated that resveratrol supplementation improved selective measures of cognition such as memory and mood but further research is required to confirm its benefits. 
Quick Gist: Animal studies indicate that resveratrol can attenuate depression and stress-induced cognitive deficits by promoting neuroplasticity. Studies in humans have found modest benefits of the grape antioxidant for cognition and memory and this could be attributed to its limited bioavailability.
5.It improves metabolic health and reduces the risk of depression
A study published Nutritional Neuroscience, 2018 demonstrated that consumption of a high-fat diet (a diet rich in unhealthy fats) induces a depressive behaviour and this anhedonia cannot be resolved by antidepressant treatment. 
Anhedonia is a loss of interest in activities that one used to enjoy earlier.
One link between poor metabolic health and diet and depressive symptoms is insulin resistance or lack of cellular response to actions of insulin.
In fact, somatic symptoms or physical symptoms of depression (such as lack of appetite, energy and sleep disturbances are strongly associated with insulin resistance. 
This improves cellular metabolism, lowers glucose levels, increases insulin sensitivity, lowers fat accumulation and thus improves various parameters associated with metabolic health.
Subclinical hypothyroidism is characterized by slightly elevated thyroid-stimulating hormone levels and normal T4 and T3 levels.
Subclinical hypothyroidism is associated with increased risk of developing depression.
Research carried out by Ge and colleagues show that resveratrol reduces the risk of developing depression and anxiety in subclinical hypothyroidism by lowering stress hormone levels and regulating the activity of hypothalamus-pituitary-thyroid axis. 
Quick Gist: Resveratrol is an excellent plant-derived bioactive for maintaining metabolic health. Apart from influencing brain chemistry, it can act on several parameters associated with metabolic health, especially insulin resistance, to help reduce the risk of developing depression.
6.Resveratrol offers neuroprotection
Resveratrol mediates a neuroprotective action or a brain protective action in many ways :
- Scavenging free radical species and reducing oxidative damage
- Lowering inflammation
- Reducing the risk of developing neurodegenerative diseases
- Maintaining cellular energy in brain cells
- Protecting brain cells from apoptosis or cell death
It enhances neural plasticity which can be a key factor for initiating recovery from depression and other mental health conditions. 
Epigenetic processes are those that can control a gene’s expression or turning genes on or off.  It is the possibility of changing genetic expressions without changing the DNA sequence.
Nutrition is a potential epigenetic regulator and this has several implications for brain health. 
Resveratrol is a natural epigenetic regulator.  By regulating epigenetic mechanisms, it helps improve resilience to stress by reducing inflammation in the brain and promoting neuroplasticity. 
Quick Gist: Dietary resveratrol can help protect brain health and reduce the risk of developing mental health conditions such as depression.
It protects neurons, promotes neuroplasticity and modifies epigenetic mechanisms to increase resilience to stress.
Dosage of Resveratrol For Depression
No studies in humans have investigated the antidepressant effect of resveratrol. Researchers are testing the effect of 500mg resveratrol supplementation in depression but the results of this study are yet to be published.
Its combination with piperine can help improve bioavailability.
It can be obtained from dietary sources: red and purple grapes, peanuts, pistachios, dark chocolate, blueberries.
Including fresh grape juice or a serving of fresh berries daily in diet can help. Snacking on berries and nuts is great. 20 g of dark chocolate daily (70% or more cocoa, no milk, no sugar) is great for heart and brain health.
Please consult a health practitioner before taking resveratrol supplements.
Precautions with Resveratrol Use
Resveratrol is found to be safe. At high doses (500mg or higher), side effects such as nausea, diarrhoea and other gastric symptoms have been noted.
It has antiplatelet activity; avoid if suffering from blood clotting related disorders or taking blood thinners.
Avoid taking resveratrol supplements at the same time as taking other medicines.
It is best to get resveratrol from the diet. Please consult a health practitioner before taking resveratrol supplements.
Resveratrol is a natural antioxidant with pleiotropic activity. Various scientific studies have proven the multiple therapeutic benefits associated with this grape polyphenol but it has not yet been translated into significant clinical use primarily because of its low bioavailability.
Similarly, in the field of natural alternatives for depression treatment, resveratrol is found to exert many therapeutic effects but these findings are limited to animal models.
It regulates brain chemistry, reduces inflammation in the brain, protects from oxidative damage and supports neuroplastic changes to reduce depression and anxiety.
It may also improve cognition by improving cerebral blood flow and improving antioxidant defences.
However, these findings are yet to be confirmed by robust studies in humans.
One great way of putting the currently available evidence of resveratrol and depression to use is consuming foods rich in this polyphenol.
Including resveratrol-rich foods in your diet can help lower depression risk and support recovery from depression.
Which food items in your diet are rich in resveratrol? Is it homemade berry juice or a small serving of nuts? Any thoughts on this, then please leave your comments below.