© by Elizabeth Lee Vliet MD and Kathy Kresnik
It is a sad commentary on our fragmented, Big Pharma-driven medical system today that millions of women struggle with intractable sleep disruption, debilitating hot flashes and unpredictable mood swings for years without relief–or they are given multiple prescription medicines with negative side effects to serve as band-aids for sleep, anxiety, depression, fatigue, and other symptoms in the menopausal syndrome. Rarely are they offered either physiologically natural 17-beta estradiol therapy to replace what is lost at menopause, OR natural medicines that help to ameliorate these disruptive symptoms that rob women of quality years of life.
The good news is that help IS available, with low-cost options that have few unwanted side effects and have many years of clinical studies to confirm the benefits. In fact, I have spent the last 40 years in medical practice helping women with individualized integrative strategies—both prescription hormone options, non-hormonal natural options, complementary modalities and lifestyle changes—to help with these perimenopausal, menopausal, post-hysterectomy and even post-partum “change of life” impacts to your health that cause so many debilitating problems as women age.
Today’s health tip is not just about red wine per se, even though a glass of a nice full-bodied red wine adds a pleasant ambience at dinner. Today’s post is about resveratrol, a specific nutrient found in red wine and other dark berries that is available in purified, concentrated form in high-quality supplements that has specific and important health benefits to add to your menopause “tool kit.”
Resveratrol is a polyphenol found in plant-based foods such as red grapes, dark berries, plums, nuts, apples, black olives, capers, red wine and cocoa, foods common in the Mediterranean Diet. Resveratrol is actually a stilbenol derived from stilbene, a plant compound that has cell-protecting properties. In the 1990s, its claim to fame was as a potential answer to the “French Paradox,” the puzzling finding that French people eat so many high fat dairy and meat foods, yet have lower risk of heart disease than do people in the US. Later, resveratrol was characterized as a potential chemoprotective molecule. Fast forward to the present day and resveratrol continues to be one of the most studied polyphenols in our basket of natural medicine options.
Red wine contains about 1-2 mg of resveratrol per liter, which is not much. You would have to drink far too many bottles of wine to come anywhere near the amount of resveratrol used in clinical studies that have shown benefit on chronic pain, bone density, heart disease and vascular function. Daily alcohol intake equivalent to just 2 glasses of wine a day leads to as much as a 12% increase in the risk of breast cancer, according to studies from Italy more than 25 years ago. So that’s a major reason—along with other negative effects of too much alcohol on a daily basis—that red wine alone can’t do what you need to provide the benefits of resveratrol.
Difficulty getting enough resveratrol from red wine and other food sources is also why I selected TruResveratrol™ Complex for our Truth for Health Store because it is unique in providing a complete bioflavonoid complex with resveratrol, quercetin, and pterostilbene. These three antioxidants work together synergistically. Pterostilbene is methylated resveratrol, a bio-optimized form that complements resveratrol and quercetin. This methylation results in dramatically higher metabolic stability in the liver, improves intestinal absorption and facilitates membrane transport compared to unmethylated resveratrol and quercetin. All of these properties aid in the absorption of resveratrol.
Quick Review: Resveratrol is well known for its anti-inflammatory, antioxidant, antibacterial and antiviral properties, and current emerging research highlights many more exciting health benefits in the fields of oncology (cancer treatment), cardiology, neurology and mitochondrial function, obesity and diabetes, and many changes associated with improving longevity:
- Increased insulin sensitivity,
- Increased mitochondrial number and improved motor function
- Reduced insulin growth factor-1 (IGF-1)
- Increased AMP-activated protein kinase a key player in obesity, type 2 diabetes, and metabolic syndrome
- Relieved the effects of the high calorie diets
- Activates sirtuins (SIR2 and SIRT1) important in cellular longevity and protection of nerve cells
- Modulation of liver apolipoprotein and lipid synthesis and
- inhibition of platelet aggregation and protection against atherosclerosis
- Numerous anti-inflammatory properties include inhibiting synthesis and release of pro-inflammatory mediators, modifying eicosanoid synthesis (which are often associated with disease, including inflammatory disease and cancer), and inhibiting activated immune cells.
Bone Loss, Heart Disease, and Pain: Resveratrol Benefits For Menopausal Women
There were exciting findings from a recent systematic review and meta-analysis Effects of Resveratrol on Postmenopausal Women, the first meta-analysis to comprehensively evaluate resveratrol’s effects across multiple health domains in postmenopausal women specifically. It pooled 10 RCTs with 928 participants, with treatment durations ranging from 14 weeks to 12 months. Five studies used resveratrol and five used trans-resveratrol, with dosages including 150 mg/d and 250 mg/d among those reported.
This pooled analysis shows that pain reduction and inhibition of bone loss have the strongest evidence for resveratrol benefit in peri-and postmenopausal women, likely mediated through anti-inflammatory, antioxidant, and SERM-like mechanisms. The strong anti-inflammatory and antioxidative effects also play a role in reducing cardiometabolic risk and improving vascular function, both components of Metabolic Syndrome, which is much more common in menopause due to loss of estradiol. Before menopause, optimal estradiol production improves insulin sensitivity, lipids, blood pressure and metabolism.
Some symptoms of menopause—memory, mood, metabolism, and sleep—did not show relief with resveratrol (more on this later in my article). We cannot look at resveratrol as a “menopause magic pill” but we can use it as an additional strategy to help specific adverse vascular changes, pain reduction and help prevent bone loss. So, let’s take this one by one.
Pain Reduction
Resveratrol was found to significantly improve chronic musculoskeletal pain associated with age-related osteoarthritis. The proposed analgesic mechanisms involve modulation of pain signaling pathways (TNFR1/NF-κB, PI3K/Akt/mTOR, Nrf2, Sirt1, MAPK) and increased nitric oxide bioavailability for better vasodilation and tissue blood flow. Resveratrol was found, in vitro, to also reduce inflammation in joint cartilage cells (chondrocytes) by reducing a pro-inflammatory cytokine (IL-1β) that is one of the primary drivers of cartilage degradation in osteoarthritis.
This is especially important because chondrocytes are the cells that produce and maintain the cartilage matrix in human joints. In menopausal women, these cells are under increased oxidative and inflammatory stress due to loss of estradiol and testosterone from the ovaries. Adrenal androgens (DHEA, DHEA-S, androstenedione) still help to some extent, but without functioning ovaries, these adrenal androgens cannot be converted into estradiol.
Bone Metabolism — KEY POINT: Bone is Living Tissue in Constant Turnover
Most people think of bones as static, like the frame of a house. In reality, bone is living tissue that is constantly being broken down and rebuilt throughout your entire life to avoid buildup of old, brittle bone that would be prone to many fractures. This ongoing process is called bone metabolism or bone remodeling.
Two types of cells drive this process:
- Osteoclasts — the “demolition crew.” They dissolve and remove old or damaged bone in the process called bone resorption (commonly referred to as bone breakdown). Bone resorption involves releasing enzymes that break down hardened bone matrix, creating space for new, healthier tissue to be formed by osteoblasts. Bone breakdown accelerates when estradiol blood levels drop below about 60 pg/ml.
- Osteoblasts — the “construction crew.” They lay down fresh, new bone to replace what was removed, thereby building healthy, strong bone to replace the old, brittle bone cleared out by the resorption process.
In a healthy younger adult, these two crews work at roughly equal pace — bone is broken down and rebuilt in balance, maintaining normal, healthy bone density. After menopause, the sharp drop in estradiol, and loss of ovarian testosterone, causes the demolition crew (osteoclasts) to speed up, while the construction crew (osteoblasts) can’t keep up. The result is a net loss of bone over time.
CTX (C-terminal telopeptide of type 1 collagen) is a fragment — essentially a small piece of debris — released into the bloodstream when osteoclasts break down bone. Think of it like sawdust at a demolition site. We can measure these fragments in blood or urine tests to determine whether bone breakdown is excessive or not.
- Higher CTX levels in the blood or urine mean more bone is being broken down — the demolition crew is very active.
- Lower CTX levels in the blood or urine (as in pre-menopausal women, or menopausal women taking estradiol prescription hormone therapy) mean less bone is being torn down — the demolition has slowed.
Bone density is simply how much mineral (mostly calcium and phosphorus) is packed into a given volume of bone. It is what a dual-energy X-ray Absorptiometry (DEXA) scan measures in a test of hip and spine bone density. I order this test for my patients beginning at age 45-50, or earlier if they have increased risk factors for bone loss.
Now, in peri and post menopausal women, remember the demolition crew, when the demolition crew outpaces the construction crew over months and years:
- CTX levels rise (more breakdown happening)
- Bone density gradually decreases
- Bones become more porous and fragile
- Eventually this reaches the threshold we call osteoporosis — literally “porous bones” — where fracture risk is significantly elevated.
So how do we connect CTX, bone density and osteoporosis? CTX is a useful, low-cost blood or urine test to measure how fast someone is losing bone in real time. We can measure changes in CTX taking place as soon as 3 months after risk factors increase, rather than having to wait at least a year to see bone loss changes enough to show on a repeat DEXA scan to determine bone loss.
In this meta-analysis, resveratrol significantly reduced CTX levels marker of bone breakdown in menopausal women. In practical terms, that means it slowed down the demolition crew down (osteoclasts), reducing the rate of bone breakdown. If less bone is being torn down while the construction crew (osteoblasts0 continues working, the net effect is to preserve healthy bone density. The meta-analysis showed resveratrol had a protective effect against menopausal bone loss.
This does not mean, however, that resveratrol reverses osteoporosis — it just slowed down the resorption (loss) of bone. This is the fundamental principle behind prescription medications like bisphosphonates (Fosamax, Boniva) and denosumab (Prolia). Resveratrol’s effect is more modest than the prescription medicines, but it has minimal to none of the serious side effects of these prescription drugs.
Resveratrol for Heart and Vascular Health After Menopause
Estrogen and Endothelial Lining
The years following menopause bring a rapid increase in risk of heart disease in women, unlike the lower risk of CVD seen in pre-menopausal women. Increase in heart disease risk in menopausal women has been confirmed for more than 50 years as primarily due to the loss of ovarian 17-beta estradiol. A woman who spent decades with relatively low rates of heart disease suddenly faces odds that rival — and can exceed — those of men her age. This shift is not coincidental. Higher pre-menopausal levels of 17-beta estradiol actively protects the lining of blood vessels, keeps arteries supple, helps govern blood flow throughout the body, reduces inflammation, increases nitric oxide release, maintains healthy cholesterol, HDL, LDL and TG levels, and improves insulin sensitivity. When blood levels of estradiol drop below about 60 pg/ml, these major protective effects are lost.
Resveratrol interacts with the same cellular receptors that estrogen targets. Despite lacking a steroid backbone, resveratrol binds to estrogen receptors (ERα and ERβ) and modulates estrogen-responsive genes, exerting selective estrogen receptor modulator (SERM)-like activity. For menopausal women not taking hormone therapy or estrogen alone, that overlap makes resveratrol an interesting option to help improve health of the endothelium (vascular lining), even though it does not replace the full scope of estradiol benefits.
Estrogen acts on receptors called ERα and ERβ (alpha and beta estrogen receptors) embedded in the cells that line blood vessels — the endothelium. When estrogen binds those receptors, it triggers the production of nitric oxide, a signaling molecule that causes blood vessels to relax and widen. This process, called nitric oxide-mediated vasodilation, helps maintain healthy blood pressure, supports blood flow to organs and tissues, and keeps the arterial wall from stiffening.
After menopause, circulating estrogen drops sharply, in particular the critical 17-beta estradiol pre-menopausal estrogen that is loss when the ovaries stop producing hormones. Without that crucial 17-beta estradiol signal, the endothelium becomes less responsive, nitric oxide production falls, and blood vessels gradually stiffen and lose flexibility. Lipids increase, insulin resistance increase, and blood pressure increases from the vascular stiffness and loss of elasticity.
Researchers call the resulting vascular stiffness “accelerated arterial aging.” Microcirculation — the fine network of tiny vessels that deliver oxygen and nutrients deep into tissue — deteriorates. Delivery of oxygen and critical nutrients to organs declines, oxidative stress and inflammation increase. The heart and brain, two organs with very high metabolic demands, decline quickly due to those crucial losses.
Oxidative stress (a state in which damaging free-radical molecules accumulate faster than the body can neutralize them) also increases significantly after menopause, and researchers have linked this elevated oxidative burden specifically to cerebrovascular changes — meaning the small vessels feeding the brain are particularly vulnerable to accelerated damage. This partly explains why postmenopausal women have increased rates of cognitive decline, dementia and stroke than do premenopausal women. This difference in risk is present even when we compare surgically menopausal and pre-menopausal women of the same age, and younger than the typical age of natural menopause at 51.
Resveratrol Supportive Role in Vascular Health
Resveratrol does not contain a steroid backbone, which means structurally it is different from a woman’s various estrogens. Yet resveratrol still binds to both ERα and ERβ receptors and can help modulate estrogen-responsive genes. Pharmacologists call this SERM-like activity — SERM stands for Selective Estrogen Receptor Modulator. This means resveratrol can mimic some estrogen functions in tissues where those receptors are active, which includes the endothelium. There are many plant-derived phytoestrogens as well as prescription drugs that are in this same SERM group, and as a group, SERMs have many different effects in the body—some beneficial, some are unwanted effects.
Beyond receptor activity, resveratrol also acts as an antioxidant, suppressing certain inflammatory signaling pathways. In animal studies, resveratrol increases the activity of eNOS (endothelial nitric oxide synthase), the enzyme that generates nitric oxide in blood vessel walls. On paper, these mechanisms address the same deficits and health risks that menopausal loss of estradiol creates: reduced nitric oxide production, increased oxidative stress, and vascular inflammation.
The question is whether those mechanisms translate into meaningful effects in actual human trials — and here, the picture becomes considerably more complex. As a result, there is no simple answer!
Endothelial Function
The most consistent finding across recent meta-analyses is that resveratrol can improve flow-mediated dilation (FMD)— a non-invasive test that measures how well an artery widens in response to increased blood flow. FMD serves as a proxy for the health of the endothelial lining of blood vessels. A 2022 meta-analysis of randomized controlled trials found that resveratrol significantly improved flow-mediated dilation, particularly in people who already had cardiovascular disease.
A 2024 crossover randomized controlled trial in older adults with stage 3 chronic kidney disease and type 2 diabetes pushed those findings further: participants taking 400 mg per day of resveratrol for six weeks showed a 43% relative improvement in flow-mediated dilation compared to placebo, but without meaningful changes in blood pressure, blood sugar control (HbA1c), or nitro-mediated dilation.
That last detail — improvement in flow-mediated dilation, but not in nitro-mediated dilation — suggests resveratrol may specifically support endothelial function rather than acting more broadly on smooth muscle or other vascular mechanisms. For postmenopausal women, whose endothelial function declines precisely because of lost estrogen signaling, an intervention that targets the endothelium directly may be quite helpful, especially in women not on Rx estradiol therapy.
Inflammation
A 2024 systematic review focused on coronary artery disease found that in primary prevention studies of strategies to avoid a first cardiovascular event like MI or stroke, low-dose resveratrol at approximately 15 mg per day significantly reduced TNF-α (tumor necrosis factor-alpha, a key driver of vascular inflammation).
What Resveratrol Doesn’t Do for Menopausal Women
In the 2025 meta-analysis by Wu and colleagues, resveratrol significantly reduced pain, slowed bone resorption and improved vascular function in postmenopausal women. This analysis, however, found no significant improvement in metabolic parameters, blood pressure, memory/cognitive function, mood, or hot flashes. That last point is a big one.
Hot flashes, sleep disruption, memory and blood pressure ALL are regulated specifically by 17-beta estradiol (E2) acting directly at brain E2 receptors, especially in the limbic system centers regulating these key functions. Resveratrol does not appear to trigger these limbic system receptor pathways in the same way that women’s own estradiol does before menopause, even though resveratrol has some limited estrogen-receptor activity. So resveratrol supplements do not replace the benefits of estradiol therapy, but the two together have additive benefits to reduce bone loss, improve pain, and improve vascular function.
Dosing Based on Evidence from Studies
Studies that showed endothelial or flow-mediated dilation benefits in groups of women with increased CVD risk generally used doses between 100 and 400 mg per day, taken for six to twelve weeks. Very low doses around 15 mg per day showed some anti-inflammatory signal in primary prevention. That range — low to moderate — represents the current evidence-supported zone. As you can see, at 1-2 mg per liter of red wine, it would take a minimum of SEVEN bottles of wine a day to provide even 15 mg resveratrol a day! Obviously that’s not possible. That’s why resveratrol supplements are important options to consider in your regimen.
For women who have optimized standard cardiovascular care (blood pressure, lipids, glucose, and lifestyle) and still carry documented endothelial dysfunction or elevated inflammatory burden, a trial of 100 to 200 mg per day of trans-resveratrol taken with food for eight to twelve weeks is a reasonable, evidence-based step to discuss with their physicians. Avoid doses above 500 mg per day on an ongoing basis, particularly if you take multiple medications or supplements. If you use resveratrol beyond three to six months, it is important to ask your doctor to check liver function tests since we don’t have a great deal of long-term safety data.
High doses for extended periods of time (1,000 mg per day and above) currently lacks safety data and we don’t recommend such high doses. For example, one trial in overweight but otherwise healthy older adults found that 1,000 mg per day actually increased certain cardiovascular risk biomarkers, prompting the trial authors to caution against very high doses in older patients with metabolic syndrome-like features. Since menopausal women often have some of these same risks— altered lipid profiles, insulin resistance, middle and upper body fat— it is important to be cautious on doses.
I also recommend following a Mediterranean-style diet which delivers polyphenols including low-dose resveratrol from whole food sources like grapes, berries, and olive products that further support supplementation.
I selected TruResveratrol™ Complex for our Truth for Health Store because it is unique in providing a complete bioflavonoid complex with resveratrol, quercetin, and pterostilbene. These three antioxidants work together synergistically. Pterostilbene is methylated resveratrol, a bio-optimized form that complements resveratrol and quercetin. This methylation results in dramatically higher metabolic stability in the liver, improves intestinal absorption and facilitates membrane transport compared to unmethylated resveratrol and quercetin. All of these properties aid in the absorption of resveratrol.
Together this combination and improved bioavailability pack quite a punch! That’s why I am pleased to be able to provide TruResveratrol™ Complex for an exceptionally high-quality resveratrol formulation as part of our commitment to help you improve your health and resilience.
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