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If you're a doctor, one of your duties is figuring out which drug or drugs to prescribe to a sick patient. Unfortunately, most of the drugs in a doctor's arsenal are what's called "mono-targeted" in that they attack disease through just one biochemical pathway.
For example, the drug gefitinib is used to treat lung cancer by targeting something called epidermal growth factor receptor, but only 10% of patients respond to the drug and even that 10% of people eventually grow resistant to the drug, in addition to sometimes suffering severe side effects.
There are lots of such examples of the failure of mono-targeted drugs. The problem is that most chronic diseases can be attributed to a failure or dysregulation of multiple genes instead of just one. Pinning your hopes on one drug is like putting all your money on a horse named "Sassy Tumor Monkey" when the odds against it are 20 to 1.
What's needed is a paradigm shift from targeted therapies. What's needed is the identification and use of "pleiotropic" substances, which are substances that produce more than one effect; substances that can address the dysregulation of the multiple genes involved in most chronic diseases.
All of that, at least, is the thinking of a group of Indian researchers (Singh, et al. 2019) who published a meta-study on a substance that seems to have the pleiotropic effects they're looking for. That substance is resveratrol.
It's been consumed for centuries and, as such, passes the safety test. It's been administered to both healthy and unhealthy individuals for both prevention and therapy.
And, as alluded to, it's known to "modulate multiple cell signaling pathways," qualifying it as a drug that, rather than trying to cure diseases with one roundhouse punch, attacks them with a flurry of relentless, devastating blows from multiple angles.
Cytokines, caspases, matrix metalloproteinases (MMPS), Wnt, nuclear factor kappa B, Notch pathway, 5'-AMP-activated protein kinase (AMPK), intercellular adhesion molecule (CAM), vascular cell adhesion molecule (VCAM), sirtuin type 1 (SIRT 1), tumor necrosis factor alpha (TNF-alpha), peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1 alpha), insulin-like growth factor 1 (IGF-1), insulin-like growth factor activating protein 3 (IGFBP-3), Ras association domain family 1-alpha, pAkt, vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2), nuclear factor erythroid 2 like 2 (Nrf2), and Kelch-like ECH-associated protein.
That's one impressive alphabet soup, but before I describe exactly what diseases or conditions resveratrol affects, it's relevant to describe where the powerful polyphenol came from and why it first drew the scientific world's interest.
Resveratrol was first isolated in 1939 from the roots of a plant called white hellebore, but it's since been found in multiple plant sources such as grapes, berries, peanuts, and plums, among others.
No one paid much attention to it, as Singh and associates point out, until the 1990's when people started talking about the "French Paradox." For those of you who weren't around then or don't remember, the French Paradox had to do with the typical French diet.
Despite eating a ton of foods that, according to beliefs held at that time, should have caused a lot of French men to clutch their chest, shout "Mon Dieu, it was the frommage!" and die, they didn't. The French had and continue to have a comparatively low rate of cardiovascular disease.
This paradox was then attributed to the resveratrol found in the red wine (courtesy of the grape) that the French are reputedly so fond of. Resveratrol still gets some of the credit today for saving generations of Frenchmen from an early death, but it now has to share some of that credit with some of the other polyphenols found in the typical French diet, courtesy of foods like olive oil, vegetables, fruits, and grains.
Regardless, that association between resveratrol and low cardiovascular disease ushered in a couple of decades of intensive resveratrol research. Singh and colleagues found an incredible 244 completed resveratrol trials as of April, 2018, and noted an additional 27 that were then ongoing.
Their paper, appearing in a recent edition of Medical Research Review ("Health benefits of resveratrol: Evidence from clinical studies"), discusses all of that clinical data and describes the supplement's use in the prevention, management, and treatment of various diseases and disorders, many of which are summarized in the next section.
The compound even reduced the incidence of foot ulcers, which plague at least 25% of diabetic patients.
Low doses of resveratrol (150 mg. a day) were also shown to reduce the size of adipocytes in obese men, whereas higher doses (1500 mg. a day) led to reductions in weight, body mass index, waist circumference, and total insulin secretion in patients afflicted with metabolic syndrome.
Several types of cancer, in fact, have been shown to respond to resveratrol, among them colon cancer, breast cancer, and multiple myeoloma.
Resveratrol, however, has been shown to quench inflammation in a number disease states, including cardiovascular inflammation and ulcerative colitis.
It's also thought to aid in anxiety and depression by enhancing "cerebrovascular responsiveness."
While only a few clinical studies involving resveratrol and cardiovascular disease (CVD) have been undertaken, the compound "appears to have significant therapeutic potential against CVDs."
Additionally, resveratrol was involved in ongoing trials in the following conditions or diseases at the time Singh et al. published their paper: Prediabetes, infertility, macular degeneration, knee osteoarthritis, post menopausal insulin resistance, a type of pancreatitis, aging in general, Huntington's Disease, Gulf War illness, and erectile dysfunction.
Lest you think resveratrol's use is limited to those that are afflicted with some sort of medical condition, or who want to prevent sickness in general, you're selling her short. It's in fact fair to call resveratrol a performance-enhancing supplement, as has been demonstrated in a number of studies that didn't fit into Singh et al.'s discussion of resveratrol's use in the disease state.
For example, resveratrol supplementation, at least in animals, increased testosterone by 51.6%. It's also been shown to be a powerful aromatase inhibitor, and by decreasing the amount of testosterone that's converted to estrogen, you ipso facto boost testosterone further.
The polyphenol has also been shown to make muscle fibers grow longer and stronger. Montesanto et al. (2013) found that resveratrol induces young muscle cells (myoblasts) to differentiate, along with controlling regulatory factors and the synthesis of muscle-specific proteins. Resveratrol signals IGF-1 through a couple of regulating enzymes, which activates proteins and induces hypertrophic morphological changes.
Montesanto et al. concluded the following:
"Our data demonstrate that resveratrol could control proliferation, start the myogenesis process and induce hypertrophy. Our in vitro studies may constitute novel proof of principle to potential applications of the compound to prevent or reverse muscle impairment by stimulating myogenesis, and emphasize a new possible use of resveratrol to enhance muscle performance."
People on blood thinners, however, should consult their doctor before taking resveratrol, as the compound has anti-platelet effects similar to anti-coagulant drugs, NSAIDS, or fish oil.
Singh et al. encapsulated the possibility of resveratrol's potential side effects this way:
"It would seem that the side effects of resveratrol are mild and sporadic compared to its overwhelming health benefits."
It's like a car blasting through your intestinal neighborhood at 60 MPH when the speed limit's 25, causing all the other nutrients to shake their fists at it in anger.
In fact, normal resveratrol, while having a healthy absorption rate of about 70%, only has about 1% bioavailability. Despite that measly bioavailability, clinicians still documented all the beneficial effects listed in this article. However, you can certainly attribute any inter-individual or inter-study variations to low bioavailability in general.
Still, imagine what's possible with a resveratrol product that's had its bioavailability enhanced several-fold. However, it appears that 200 mg. a day (assuming a high bioavailability) would work for general health purposes, while doses of up to 600 mg. a day might be necessary to raise testosterone, lower estrogen, increase muscle fiber size, or have any effect on the diseases/conditions listed in Singh et al.'s research paper.
For example, the drug gefitinib is used to treat lung cancer by targeting something called epidermal growth factor receptor, but only 10% of patients respond to the drug and even that 10% of people eventually grow resistant to the drug, in addition to sometimes suffering severe side effects.
There are lots of such examples of the failure of mono-targeted drugs. The problem is that most chronic diseases can be attributed to a failure or dysregulation of multiple genes instead of just one. Pinning your hopes on one drug is like putting all your money on a horse named "Sassy Tumor Monkey" when the odds against it are 20 to 1.
What's needed is a paradigm shift from targeted therapies. What's needed is the identification and use of "pleiotropic" substances, which are substances that produce more than one effect; substances that can address the dysregulation of the multiple genes involved in most chronic diseases.
All of that, at least, is the thinking of a group of Indian researchers (Singh, et al. 2019) who published a meta-study on a substance that seems to have the pleiotropic effects they're looking for. That substance is resveratrol.
It's been consumed for centuries and, as such, passes the safety test. It's been administered to both healthy and unhealthy individuals for both prevention and therapy.
And, as alluded to, it's known to "modulate multiple cell signaling pathways," qualifying it as a drug that, rather than trying to cure diseases with one roundhouse punch, attacks them with a flurry of relentless, devastating blows from multiple angles.
Lots of Superpowers
Listed below are some of the known molecules modulated by resveratrol, proving it's anything but a mono-targeting substance. (They might not mean a lot to you unless you're a scientist, doctor, or biologist of some sort, but that's okay – I just wanted to illustrate the sheer enormity of resveratrol's powers.)Cytokines, caspases, matrix metalloproteinases (MMPS), Wnt, nuclear factor kappa B, Notch pathway, 5'-AMP-activated protein kinase (AMPK), intercellular adhesion molecule (CAM), vascular cell adhesion molecule (VCAM), sirtuin type 1 (SIRT 1), tumor necrosis factor alpha (TNF-alpha), peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1 alpha), insulin-like growth factor 1 (IGF-1), insulin-like growth factor activating protein 3 (IGFBP-3), Ras association domain family 1-alpha, pAkt, vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2), nuclear factor erythroid 2 like 2 (Nrf2), and Kelch-like ECH-associated protein.
That's one impressive alphabet soup, but before I describe exactly what diseases or conditions resveratrol affects, it's relevant to describe where the powerful polyphenol came from and why it first drew the scientific world's interest.
Saved From Frommage
Resveratrol was first isolated in 1939 from the roots of a plant called white hellebore, but it's since been found in multiple plant sources such as grapes, berries, peanuts, and plums, among others.
No one paid much attention to it, as Singh and associates point out, until the 1990's when people started talking about the "French Paradox." For those of you who weren't around then or don't remember, the French Paradox had to do with the typical French diet.
Despite eating a ton of foods that, according to beliefs held at that time, should have caused a lot of French men to clutch their chest, shout "Mon Dieu, it was the frommage!" and die, they didn't. The French had and continue to have a comparatively low rate of cardiovascular disease.
This paradox was then attributed to the resveratrol found in the red wine (courtesy of the grape) that the French are reputedly so fond of. Resveratrol still gets some of the credit today for saving generations of Frenchmen from an early death, but it now has to share some of that credit with some of the other polyphenols found in the typical French diet, courtesy of foods like olive oil, vegetables, fruits, and grains.
Regardless, that association between resveratrol and low cardiovascular disease ushered in a couple of decades of intensive resveratrol research. Singh and colleagues found an incredible 244 completed resveratrol trials as of April, 2018, and noted an additional 27 that were then ongoing.
Their paper, appearing in a recent edition of Medical Research Review ("Health benefits of resveratrol: Evidence from clinical studies"), discusses all of that clinical data and describes the supplement's use in the prevention, management, and treatment of various diseases and disorders, many of which are summarized in the next section.
Name a Disease Resveratrol Doesn't Affect. Go Ahead, I Dare Ya'
Resveratrol has shown to be effective in addressing the following diseases or categories of diseases, which is an impressive testament to its ability to modulate multiple molecules and chemical pathways:DIABETES, OBESITY, AND METABOLIC SYNDROME
A number of studies have found that resveratrol has the potential to control/treat diabetes, obesity, and metabolic syndrome. It does this by decreasing blood glucose levels and hemoglobin A1c (a test that evaluates the amount of glucose in the blood over the preceding 2 or 3 months), in addition to improving insulin sensitivity.The compound even reduced the incidence of foot ulcers, which plague at least 25% of diabetic patients.
Low doses of resveratrol (150 mg. a day) were also shown to reduce the size of adipocytes in obese men, whereas higher doses (1500 mg. a day) led to reductions in weight, body mass index, waist circumference, and total insulin secretion in patients afflicted with metabolic syndrome.
CANCER
As pointed out above, cancer is a disease caused by dysregulation of multiple genes, but most drug therapies are designed to attack a single pathway. This is why researchers are hopeful that resveratrol, with its multi-targeting properties, might prove effective in combating cancer.Several types of cancer, in fact, have been shown to respond to resveratrol, among them colon cancer, breast cancer, and multiple myeoloma.
INFLAMMATORY DISEASES
Inflammation is the scourge of mankind, playing a pivotal role in almost any disease or condition. While acute inflammation is an integral part of healing, chronic inflammation can lead to chronic diseases or exacerbate existing ones.Resveratrol, however, has been shown to quench inflammation in a number disease states, including cardiovascular inflammation and ulcerative colitis.
NON-ALCOHOLIC FATTY LIVER DISEASE
A recent clinical trial found that resveratrol (600 mg. a day for 3 months) reduced glucose, insulin resistance, cholesterol, and the liver enzymes ALT and aspartate aminotransferase in patients with non-alcoholic fatty liver disease.NEUROLOGICAL DISEASES
A number of genes and pathways, including those that affect oxidative stress and mitochondrial damage, are implicated in Alzheimer's and cognitive impairment in general, and resveratrol has shown potential in treating both.It's also thought to aid in anxiety and depression by enhancing "cerebrovascular responsiveness."
CARDIOVASCULAR DISEASE
Lots of things can cause your heart to malfunction, including hypertension, hyperlipidemia, and diabetes, and resveratrol's cardio-protective and multi-targeting properties make it a promising ally in the treatment of these diseases.While only a few clinical studies involving resveratrol and cardiovascular disease (CVD) have been undertaken, the compound "appears to have significant therapeutic potential against CVDs."
KIDNEY DISEASES
Animal studies using resveratrol have found it to have "well-proven utility" in treating diabetic nephropathy, drug-induced injury, ischemia-reperfusion, and sepsis-induced kidney injury.MISCELLANEOUS DISEASES
In addition to all the preceding categories, resveratrol has been found to have varying degrees of effectiveness in treating various specific conditions, including polycystic ovary syndrome, cataracts, high blood pressure, rhinopharyngitis in children, acne vulgaris (through the use of a resveratrol cream), anxiety, schizophrenia, Parkinson's disease, endometriosis, sports concussions, knee discomfort, cellulite, and spastic paraplegia.Additionally, resveratrol was involved in ongoing trials in the following conditions or diseases at the time Singh et al. published their paper: Prediabetes, infertility, macular degeneration, knee osteoarthritis, post menopausal insulin resistance, a type of pancreatitis, aging in general, Huntington's Disease, Gulf War illness, and erectile dysfunction.
Effects of Resveratrol in Athletes and Lifters
Lest you think resveratrol's use is limited to those that are afflicted with some sort of medical condition, or who want to prevent sickness in general, you're selling her short. It's in fact fair to call resveratrol a performance-enhancing supplement, as has been demonstrated in a number of studies that didn't fit into Singh et al.'s discussion of resveratrol's use in the disease state.
For example, resveratrol supplementation, at least in animals, increased testosterone by 51.6%. It's also been shown to be a powerful aromatase inhibitor, and by decreasing the amount of testosterone that's converted to estrogen, you ipso facto boost testosterone further.
The polyphenol has also been shown to make muscle fibers grow longer and stronger. Montesanto et al. (2013) found that resveratrol induces young muscle cells (myoblasts) to differentiate, along with controlling regulatory factors and the synthesis of muscle-specific proteins. Resveratrol signals IGF-1 through a couple of regulating enzymes, which activates proteins and induces hypertrophic morphological changes.
Montesanto et al. concluded the following:
"Our data demonstrate that resveratrol could control proliferation, start the myogenesis process and induce hypertrophy. Our in vitro studies may constitute novel proof of principle to potential applications of the compound to prevent or reverse muscle impairment by stimulating myogenesis, and emphasize a new possible use of resveratrol to enhance muscle performance."
Any Side Effects?
Another great thing about resveratrol is its lack of significant or serious side effects, even at doses of 600 mg. a day or much higher. Doses of 2.5 to 5.0 grams a day did result in a few reports of nausea and abdominal discomfort, but that's a higher dose than any human would probably ever need.People on blood thinners, however, should consult their doctor before taking resveratrol, as the compound has anti-platelet effects similar to anti-coagulant drugs, NSAIDS, or fish oil.
Singh et al. encapsulated the possibility of resveratrol's potential side effects this way:
"It would seem that the side effects of resveratrol are mild and sporadic compared to its overwhelming health benefits."
Sounds Great, But There's One Possible Problem...
The body absorbs resveratrol really, really well, but that doesn't mean its bioavailability is high. It's absorbed fast, all right, but it's usually metabolized and excreted just as quickly.It's like a car blasting through your intestinal neighborhood at 60 MPH when the speed limit's 25, causing all the other nutrients to shake their fists at it in anger.
In fact, normal resveratrol, while having a healthy absorption rate of about 70%, only has about 1% bioavailability. Despite that measly bioavailability, clinicians still documented all the beneficial effects listed in this article. However, you can certainly attribute any inter-individual or inter-study variations to low bioavailability in general.
Still, imagine what's possible with a resveratrol product that's had its bioavailability enhanced several-fold. However, it appears that 200 mg. a day (assuming a high bioavailability) would work for general health purposes, while doses of up to 600 mg. a day might be necessary to raise testosterone, lower estrogen, increase muscle fiber size, or have any effect on the diseases/conditions listed in Singh et al.'s research paper.
