Resveratrol can Improve Symptoms of Anxiety and Depression

 

What is Resveratrol

Resveratrol is a non-flavonoid phenolic substance, which belongs to the plant antitoxin and antioxidant of stilbene compounds. Resveratrol is a substance produced by plants to defend against invasion by bacteria or fungi.[1][2]

Resveratrol was first discovered in the 1940s. It was originally isolated from an Asian plant called Veratrum grandiflorum, hence its name. Resveratrol is used in traditional Chinese medicine, of which resveratrol is one of the active ingredients. Later, researchers discovered that resveratrol is also found in many other plants, especially in grape skins and red wine.

The molecular structure of resveratrol [3] is a natural polyphenol compound with the chemical formula C14H12O3. The molecule of resveratrol contains two benzene rings and a 2-phenylethylene structure. This special structure gives resveratrol its antioxidant and biological activities.

Sources of resveratrol in food

Sources: Resveratrol is found in a variety of foods and plants, especially from the following sources:

• Red wine: Red wine is rich in resveratrol and is one of its best-known sources.

• Grape skins: Grape skins contain higher levels of resveratrol, so both red grapes and red wine contain relatively more resveratrol.

• Blueberries: Blueberries also contain some amount of resveratrol.

• Peanuts: Peanuts contain some resveratrol, especially if they are not overly processed.

Resveratrol benefits for brain and nerves

Resveratrol exerts specific effects on brain and nervous system function. While research is still ongoing, preliminary findings suggest that it may have a favorable influence on neuroprotection and neurological well-being. Here are a few potential impacts of resveratrol on the brain and nervous system:

1. Antioxidant: Resveratrol is a powerful antioxidant [4][5]that can help neutralize free radicals and reduce oxidative stress. This helps reduce oxidative damage to nerve cells, thereby helping to maintain a healthy nervous system.

2. Anti-inflammatory effects: Resveratrol has anti-inflammatory properties[6][7] that reduce inflammatory responses in the nervous system. Inflammation is linked to the development and progression of anxiety, depression, neurodegenerative diseases such as Alzheimer's and Parkinson's disease, and other neurological disorders.[8][9]

3. Neuroprotection: Research shows that resveratrol may help protect nerve cells from damage and toxic effects.[10][11][12] This neuroprotective effect helps reduce the risk of neurodegenerative diseases.

4. Effects on neurotransmitters: Some laboratory studies suggest that resveratrol may have some effects on neurotransmitters in the brain, such as dopamine and glutamate, that are involved in mood regulation. [13][14]

5. Cognitive function: Some research suggests that resveratrol may have a positive impact on cognitive function. It may help improve learning and memory, especially in older adults.[15]

6. Anti-aging: Laboratory studies have found that resveratrol may help slow down the aging process of cells, including nerve cells. This may help keep the nervous system youthful.[16]

Can Resveratrol Improve Symptoms of Anxiety and Depression?
Dosage

In a 2018 clinical study, which was a double-blind randomized controlled trial [23], 70 patients diagnosed with hepatic encephalopathy were divided into two groups. One group received a daily regimen of resveratrol (19.8g) + NAC (600mg) for 90 days, along with Lactoferrin (23.6g), while the other group received a placebo consisting of NAC and Lactoferrin. The results indicated a significant reduction in depressive symptoms among the group that received resveratrol. This led the researchers to suggest that resveratrol may be a promising option for individuals dealing with depression.

In 2019, Iranian researchers carried out an animal study [17] comparing the impact of resveratrol and curcumin on depression. They discovered that both compounds had notable effects in reducing depressive symptoms in mice, with resveratrol showing a more pronounced effect.

In 2017, researchers from Anhui Medical University conducted an animal experiment [18] that provided additional evidence of resveratrol's effectiveness in alleviating depressive symptoms in mice. A more in-depth examination of the study revealed that resveratrol was able to curtail the overactivity of the HPA axis in mice, leading to a decrease in the secretion of inflammatory cytokines such as IL-6, TNF-A, and C-reactive protein. Additionally, it increased the levels of the beneficial BDNF in the hippocampus of the brain and reduced inflammatory processes in the brain.

In 2017, a research paper from the Shanghai Institute of Sport [20] provided further confirmation that resveratrol is effective in reducing depressive symptoms in mice. This study induced depression in normal mice by using LPS and then investigated how resveratrol mitigated these symptoms. The research revealed that when brain hippocampal cells suffered from LPS-induced inflammation, the mitochondria within these cells experienced oxidative stress, resulting in reduced ATP production, which is essential for cellular energy. Notably, resveratrol was able to reverse this oxidative stress in the mitochondria, reducing cell death and enhancing ATP production in the hippocampus.

Animal experiments published by Xinxiang Medical College in 2019 also reached similar conclusions [19]. Resveratrol can reduce depressive symptoms in mice while increasing BDNF and serotonin in the brain.

Animal experiments in 2016 found [21] that resveratrol can reverse stress-induced depression, and its antidepressant effect is equivalent to that of SSRI drugs (fluoxetine).

It's important to highlight that these studies were primarily carried out in laboratory settings, and there is a relative scarcity of clinical trials and research in this domain. However, it's worth noting that resveratrol is perhaps the most widely used bioflavonoid nutrient by the general population. It has a strong safety profile, and research on various chronic conditions has demonstrated its positive effects. Consequently, resveratrol emerges as a viable bioflavonoid option for addressing depression.

The recommended dosage of resveratrol can vary based on individual differences and purposes. Typically, resveratrol can be obtained through food or dietary supplements. Here are some general dosage recommendations:

• By food: Resveratrol is found in some foods, such as red grapes, blueberries, peanuts, and red wine. Resveratrol can be consumed by consuming these foods, but the intake is usually low.

• Dietary supplements: If you are considering getting a higher dose of resveratrol from a dietary supplement, it is recommended to follow the dosage guidance on the product label. Webmd recommends an oral dosage of 250-1000 mg per day for up to 3 months. Before considering the use of any dietary supplement, it is best to consult a doctor or professional healthcare provider for advice on the best dosage for your situation.

Safety of use: Resveratrol is generally considered safe, especially in its natural form in food. However, with high-dose dietary supplements, the following safety issues should be considered:

• Side Effects: In some studies, high doses of resveratrol may cause some gastrointestinal discomfort, such as diarrhea or abdominal pain. Please consult your doctor before using supplements.

• Pregnancy and Breastfeeding: Pregnant and breastfeeding women should be especially cautious when using any supplement, including resveratrol. In these cases, it is best to seek medical advice.

• Individual Differences: Resveratrol tolerance varies from person to person. Some people may be more sensitive to higher doses of supplements and should be used with caution in reduced doses.

In general, resveratrol is deemed safe when taken in moderate quantities, but if you're contemplating high-dose supplements, particularly in the presence of any underlying health conditions or concurrent medication use, it's advisable to consult with your healthcare provider. Opting for natural sources of resveratrol, like through your diet, is typically a safer choice. To ensure the right dosage, follow the recommendations provided on the product label.

REF:

[1]Higdon J, Drake VJ, Steward WP. Resveratrol. Micronutrient Information Center. Linus Pauling Institute, Oregon State University, Corvallis, OR. 2016 [2014-03-17].

[2]Fremont, Lucie. Biological Effects of Resveratrol. Life Sciences. January 2000, 66 (8): 663–673 [6 June 2014]. PMID 10680575. doi:10.1016/S0024-3205(99)00410-5.

[3]”Resveratrol”. Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR. 11 June 2015. Retrieved 26 August 2019. https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/resveratrol last viewed: December 13, 2023

[4]Duarte A., Martinho A., Luís Â., Figueiras A., Oleastro M., Domingues F.C., Silva F. Resveratrol encapsulation with methyl-β-cyclodextrin for antibacterial and antioxidant delivery applications. Food Sci. Technol. 2015;63:1254–1260. doi: 10.1016/j.lwt.2015.04.004. 

[5]Malhotra A., Bath S., Elbarbry F. An organ system approach to explore the antioxidative, anti-inflammatory, and cytoprotective actions of resveratrol. Oxid. Med. Cell. Longev. 2015;2015:803971. doi: 10.1155/2015/803971. 

[6]Zhou Z.X., Mou S.F., Chen X.Q., Gong L.L., Ge W.S. Anti-inflammatory activity of resveratrol prevents inflammation by inhibiting NF-kB in animal models of acute pharyngitis. Mol. Med. Rep. 2018;17:1269–1274. https://doi.org/10.3892/mmr.2017.7933

[7]Wang G., Hu Z., Song X., Cui Q., Fu Q., Jia R., Zou Y., Li L., Yin Z. Analgesic and anti-inflammatory activities of resveratrol through classic models in mice and rats. Evid. Based Complement. Alternat. Med. 2017;2017:9. doi: 10.1155/2017/5197567.

[8]Zhang F., Liu J., Shi J.S. Anti-inflammatory activities of resveratrol in the brain: Role of resveratrol in microglial activation. Eur. J. Pharmacol. 2010;636:1–7. doi: 10.1016/j.ejphar.2010.03.043.

[9]Nunes S., Danesi F., Del Rio D., Silva P. Resveratrol and inflammatory bowel disease: The evidence so far. Nutr. Res. Rev. 2018;31:85–97. doi: 10.1017/S095442241700021X.

[10]Sun A.Y., Wang Q., Simonyi A., Sun G.Y. Resveratrol as a therapeutic agent for neurodegenerative diseases. Mol. Neurobiol. 2010;41:375–383. doi: 10.1007/s12035-010-8111-y.

[11]Tellone E., Galtieri A., Russo A., Giardina B., Ficarra S. Resveratrol: A focus on several neurodegenerative diseases. Oxid. Med. Cell. Longev. 2015;2015:14. doi: 10.1155/2015/392169. 

[12]Bastianetto S., Ménard C., Quirion R. Neuroprotective action of resveratrol. Biochim. Biophys. Acta. 2015;1852:1195–1201. doi: 10.1016/j.bbadis.2014.09.011.

[13]Gu Z, Chu L, Han Y. (2019) Therapeutic effect of resveratrol on mice with depression. Exp Ther Med. 17(4):3061–4. https://doi.org/10.3892/etm.2019.7311

[14]Marx,W.; Kelly, J.T.; Marshall, S.; Cutajar, J.; Annois, B.; Pipingas, A.; Tierney, A.; Itsiopoulos, C. (2018) Effect of resveratrol supplementation on cognitive performance and mood in adults: A systematic literature review and meta-analysis of randomized controlled trials. Nutr. Rev. 76, 432–443. https://doi.org/10.1093/nutrit/nuy010

[15]Anton SD, Ebner N, Dzierzewski JM, Zlatar ZZ, Gurka MJ, Dotson VM, Kirton J, Mankowski RT, Marsiske M, Manini TM. Effects of 90 Days of Resveratrol Supplementation on Cognitive Function in Elders: A Pilot Study. J Altern Complement Med. 2018 Jul;24(7):725-732. doi: 10.1089/acm.2017.0398. Epub 2018 Mar 27. PMID: 29583015; PMCID: PMC6065512

[16]Wahab A., Gao K., Jia C., Zhang F., Tian G., Murtaza G., Chen J. Significance of resveratrol in clinical management of chronic diseases. Molecules. 2017;22:1329. doi: 10.3390/molecules22081329.

[23] Malaguarnera, G., Pennisi, M., Bertino, G., Motta, M., Borzì, A. M., Vicari, E., Bella, R., Drago, F., & Malaguarnera, M. (2018). Resveratrol in Patients with Minimal Hepatic Encephalopathy. Nutrients, 10(3), 329. https://doi.org/10.3390/nu10030329

[17] sanaee, alireza & Ataie, Amin. (2019). comparison between effects of curcumin and resveratrol with nortriptiline in reducing of depression signs. https://www.researchgate.net/publication/334098839_comparison_between_effects_of_curcumin

_and_resveratrol_with_nortriptiline_in_reducing_of_depression_signs

[18] Yang, X. H., Song, S. Q., & Xu, Y. (2017). Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/β-catenin pathway in rats. Neuropsychiatric disease and treatment, 13, 2727–2736. https://doi.org/10.2147/NDT.S15

[20] Chen, W. J., Du, J. K., Hu, X., Yu, Q., Li, D. X., Wang, C. N., Zhu, X. Y., & Liu, Y. J. (2017). Protective effects of resveratrol on mitochondrial function in the hippocampus improves inflammation-induced depressive-like behavior. Physiology & behavior, 182, 54–61. https://doi.org/10.1016/j.physb

[19] Gu, Z., Chu, L., & Han, Y. (2019). Therapeutic effect of resveratrol on mice with depression. Experimental and therapeutic medicine, 17(4), 3061–3064. https://doi.org/10.3892/etm.201

[21] Wang, Xueer & Xie, Yunkai & Zhang, Tiantian & Bo, Shishi & Bai, Xuemei & Liu, Hansen & Li, Tong & Liu, Song & Zhou, Yaru & Cong, Xiang & Wang, Zhen & Liu, Dexiang. (2016). Resveratrol reverses chronic restraint stress-induced depression-like behaviour: Involvement of BDNF level, ERK phosphorylation and expression of Bcl-2 and Bax in rats. Brain Research Bulletin. 125. 10.1016/j.brainresbull.2016.06.014. https://doi.org/10.1016/j.brainresbull.2016.06.014