By Dr. Mercola,
Resveratrol, a phytonutrient naturally found in grapes, wine, peanuts, cocoa and many berry species including blueberries, bilberries, cranberries1 and ligonberries,2 offers a remarkable array of benefits.
Studies show that resveratrol has anti-inflammatory, cardioprotective, antioxidant. antiaging and chemopreventive properties.3 Its therapeutic use has been explored in Alzheimer's disease,4including Alzheimer's plaque buildup,5 Parkinson's disease and stroke,6 vascular dementia,7depression8 and brain inflammation.9
Resveratrol has been studied for its use in improving learning, mood and memory.10 It has been found to have positive effects on environmental stresses11 including pathogenic attacks, fungal infections and UV irradiation, on injuries12 and to help improve high blood sugar in those with Type 2 diabetes mellitus.13
Now studies are revealing that resveratrol may boost your immunity as well.14 Resveratrol's immunomodulatory and immunoregulatory actions may be useful in treating chronic diseases like obesity, fatty liver disease, Crohn’s disease, rheumatoid arthritis and cancers, according to research in the journal Nutrients.15
Immune-Boosting Properties of Resveratrol
Resveratrol prevents chronic diseases or the progression of chronic disease through several immune functions, according to research in the journal Nutrients:16
" … resveratrol regulates immunity by interfering with immune cell regulation, proinflammatory cytokines’ synthesis, and gene expression … it targets sirtuin, adenosine monophosphate kinase, nuclear factor- κB, inflammatory cytokines, anti-oxidant enzymes along with … gluconeogenesis, lipid metabolism, mitochondrial biogenesis, angiogenesis, and apoptosis.
Resveratrol can suppress the toll-like receptor (TLR) and pro-inflammatory genes’ expression. The antioxidant activity of resveratrol and the ability to inhibit enzymes involved in the production of eicosanoids contribute to its anti-inflammation properties."
One of the most exciting outgrowths from research into resveratrol's effects on the immune system would be its possible effect on cancers. This is what the Nutrients researcher writes:17
"Resveratrol possesses therapeutic potential in boosting NKs [natural killer] activity against aggressive cell leukemia and lymphomas …
In lung cancer cells resveratrol treatment decreases the activity of STAT3 [an immune system factor] and inhibits lung cancer progression by suppressing the pro-tumor activation of TAMs. In addition, in a mouse lung cancer xenograft model, resveratrol significantly inhibits the tumor growth, decreasing cell proliferation and expression of p-STAT3 in tumor tissues …
Remarkably, isolated spleen NK cells of rats pre-treated with resveratrol displayed an enhanced killing efficacy … Low doses and non-cytotoxic doses of resveratrol prevents progression of B16 melanoma and of 4T1.2 breast cancer and abrogates lung metastasis."
Other Research Reveals Resveratrol Benefits
Research in Rejuvenation Research found resveratrol may exert positive improvements in older rats including in their longevity:18
"These observed changes in antibody responses in aged rats fed a resveratrol-supplemented diet are indicative of improvements in antigen-driven responses because total antigen nonspecific IgG levels were not affected. These results suggest that dietary resveratrol supplementation is able to modulate immune responses."
The journal Antioxidants also finds an important resveratrol role:19
"Resveratrol has antitumor activity in different human cancers such as hepatocellular carcinoma and ovarian carcinoma … Zhong and colleagues investigated the anti-tumoral effect of resveratrol in vivo in a rat orthotopic ovarian cancer model reporting that its intraperitoneal administration halted cancer cell proliferation without affecting normal tissues.
In greater detail, the blockade of glycolysis and inhibition of AMPK/mTOR signaling induced by resveratrol were responsible for its antitumor activity in ovarian cancer cells. Recently, Zhang and colleagues reported for the first time that resveratrol promoted not only apoptosis but also immunogenic cell death of human and murine ovarian carcinoma cells.
In addition, resveratrol has been extensively investigated for its ability to enhance cell killing by radiation and ionizing radiation mediated apoptosis in cancer cells."
Resveratrol Could Have a Role in Fighting Coronaviruses
After the severe acute respiratory syndrome (SARS) outbreak in 2003 and before the "new" coronavirus of 2019/2020, another serious coronavirus surfaced: Middle East respiratory syndrome, or MERS, which was described in Saudi Arabia in 2012.
According to the World Health Organization, of 2,442 people infected with MERS in May 2019, 842 died — giving the virus a case-fatality rate of approximately 35%.20 Like SARS and the 2020 coronavirus, MERS was thought to be zoonotic or caused by an animal disease jumping species — with bats the prime suspects.21
Yet research published in BMC Infectious Diseases in 2017 presents some positive news for addressing MERS:22
"Resveratrol significantly inhibited MERS-CoV infection and prolonged cellular survival after virus infection. We also found that the expression of nucleocapsid (N) protein essential for MERS-CoV replication was decreased after resveratrol treatment.
Furthermore, resveratrol down-regulated the apoptosis induced by MERS-CoV in vitro. By consecutive administration of resveratrol, we were able to reduce the concentration of resveratrol while achieving inhibitory effectiveness against MERS-CoV."
There existed some previous scientific evidence that might have suggested the effects that emerged in the study, write the researchers. Resveratrol had previously shown the ability to decrease the production of nitric oxide and inflammation in tissue and inhibit the Epstein-Barr virus, enterovirus, herpes simplex, influenza and respiratory syncytial virus in studies.
Resveratrol also constrained the bacteria Helicobacter pylori, Staphylococcus aureus and Toxoplasma gondii. Still the study findings on MERS, in cells placed in cultures with growth media, were impressive:23
"To determine whether resveratrol inhibits the entry or a post-entry step of MERS-Cov infection, we added resveratrol together with MERS-CoV immediately for 3 hours or after the infection has been initiated. We measured the cell proliferation and determined the viral titers in the supernatants …
The results demonstrated that even when resveratrol was given after MERS-CoV infection, it still reduced the viral titer. The same observations were made when cell proliferations and viral titers were measured, suggesting that resveratrol inhibits MERS-CoV infection after entry …
This data suggests that resveratrol treatment suppressed MERS-CoV RNA replication, although it requires relatively high concentrations of resveratrol to deliver persisted antiviral effects … Our results suggest that resveratrol reduced the MERS-CoV-mediated apoptosis."
The study of resveratrol could not come soon enough. Antimicrobial agents like ribavirin, lopinavir/ritonavir and type I interferon used against the SARS virus were ineffective and even caused renal dysfunction and other side effects, write the researchers.24
Resveratrol also proved effective against chikungunya, a mosquito-spread virus endemic to Africa, Asia, Europe and the Indian and Pacific Oceans.25 The researchers write:26
"Resveratrol not only inhibited MERS-CoV viral production but also reduced the production of chikungunya virus at concentrations of 250 and 125 μM. Altogether, our data suggests that resveratrol might be a lead candidate for further pre-clinical assessments of antiviral activity for MERS-CoV and additional emerging RNA viruses."
Immune-Boosting Actions of Resveratrol
Just as the human immune system is very complicated, so are the mechanisms resveratrol may exert to alter the immune system. Here is a summary of some of the mechanisms from research in the journal Nutrients.27
Inhibits inflammation — Resveratrol inhibits the production of inflammatory factors through the activation of a substance involved in metabolism, cancer and embryonic development called Sirt1.
Counteracts macrophage inflammation — Resveratrol causes anti-inflammatory actions in macrophages, which are white blood cells that can “eat” bacteria, viruses, fungi and other invaders.28
Reduced effects of mitochondrial damage — Resveratrol prevents the increase of acetylated α-tubulin caused by mitochondrial damage from stimulated macrophages making it a candidate for the treatment of NLRP3-related inflammatory diseases like Crohn's, ulcerative colitis and inflammatory bowel disease.29
Reduces production of GM-CSF — Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pro-inflammatory cytokine that is a marker for scar tissue and fatty deposits in artery walls, which pose a thrombosis risk.
Combats tumor-evoked regulatory B cells (tBregs) — Resveratrol can inhibit the generation and function of tBregs, which are elevated in cancers and can thwart protective anti-tumor immunity.30,31
Inhibits the actions of STAT3 — Resveratrol diminishes STAT3, signal transducers and activators of transcription 3 that increase tumor cell proliferation, invasion and survival and suppresses anti-tumor immunity.32
Diminishes abnormal T cell activation — Resveratrol can inhibit T cell activation associated with insulin-dependent diabetes, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis and possibly prevent their progression.
Boosts natural killer cells (NK) — Resveratrol can boost NK activity by inhibiting STAT3, an action seen in cases of cell leukemia and lymphomas.
Clearly, according to the research, resveratrol modulates immune behavior including modifying "cell morphology, gene expression, ligand-receptor interactions, signaling pathways, and foam-cell formation."33
A Resveratrol Drawback That Needs Exploring
The immune-enhancing properties and other benefits of resveratrol are very encouraging. But there is one obstacle to finding the correct dosages for health treatments based on resveratrol: bioavailability. Here is how research in the journal Antioxidants explains the bioavailability problem:34
"As reported by several in vivo studies conducted in animals and humans, resveratrol is characterized by a low oral bioavailability due to a very limited intestinal uptake of the molecule. This leads to minimum amounts in the bloodstream because of the extensive metabolism occurring in the gut and liver.
The short initial half-life of the primary molecule is essentially caused by its rapid metabolism. The bulk of an intravenous dose of resveratrol is processed in sulfate conjugates in just 30 minutes in humans …
The substitution of the hydroxyl groups with methoxyl groups meaningfully enhances resveratrol bioavailability by boosting its intestinal absorption and increasing hepatic stability. For this reason, different methoxylated analogues of resveratrol have been formulated with the purpose of obtaining novel agents for cancer chemoprevention."
Research in the journal Nutrients also considers the resveratrol bioavailability challenge and what can be done:35
" … the pharmacokinetic analysis reveals that resveratrol undergoes rapid metabolism in the body. Its bioavailability after oral administration is very low, despite absorption reaching 70%, this impacts the physiological significance of the high concentrations used in vitro studies …
some official systematic clinical trials using resveratrol treatment in humans had some disappointing outcomes and the difficulties of the clinical application of resveratrol are enormous, such as its poor water solubility, bioavailability, and dosage.
Therefore, various strategies are being implemented, which include the development of resveratrol analogues and formulations such as adjuvants, nanoparticles, liposomes, micelles, and phospholipid complexes, to improve its bioavailability.
In addition, several other approaches have been employed to enhance its bioavailability, which include altering the route of administering resveratrol and obstructing the metabolic pathways via co-treatment with other agents.
In fact, since resveratrol has multiple intracellular targets, additional data is needed to determine the consequences of the interaction or the synergistic effects between other polyphenols and vitamins, amino acids and other micronutrients or ordinarily used drugs."
Still, with the research about resveratrol's immune-enhancing properties, this phytonutrient shows promise for being very useful in the prevention and treatment of many autoimmune and inflammatory chronic diseases.