Life Extension Magazine®

Issue: Sep 2014

Quercetin’s Unique Protective Mechanisms

People with high intakes of quercetin have significantly lower risk for cardiovascular diseases. Quercetin provides multimodal cardiac protection such as triggering reverse cholesterol transport and improving after-meal endothelial function by 31.4%.

By Michael Enders

Quercetin’s Unique Protective Mechanisms  

In our quest to identify cutting-edge therapies to protect against age-related disorders, we sometimes overlook the basics.

Found in certain fruits and vegetables, quercetin has been studied for decades and evidence supporting its biological properties is substantial.

Recent lab and human studies are confirming that quercetin can prevent many of the underlying factors that are destructive to our health. These deleterious biological events are often unnoticed by medical doctors until they manifest as major diseases.

Quercetin fits nicely into a broad-based anti-aging strategy and has long been included in nutrient formulas used by health-conscious individuals.

Protecting Hardworking Heart Muscle

People with high intakes of dietary flavonols and flavones such as quercetin have a demonstrably lower risk for cardiovascular diseases.1,2 Exciting new research suggests that a big part of the reason for this protection is quercetin’s effects on mitochondria.

Proof of the impact of quercetin’s mitochondrial “boost” can be seen in a pair of animal and human exercise studies. Untrained mice supplemented with quercetin for seven days increased both their maximal endurance capacity on a treadmill and their voluntary use of the treadmill, while biopsies showed formation of new mitochondria in their muscles and brains.3

In the companion human trial, untrained volunteers took 500 mg/day of quercetin, or placebo, for seven days, with their exercise performance measured before and after the trial period.4 Subjects taking quercetin modestly increased their oxygen consumption by 3.9%, but increased their riding time to fatigue by 13.2%, entirely without additional training!

In a similar trial, untrained young men who took 1,000 mg/day of quercetin for two weeks also increased the distance they could run on a treadmill by 2.9%, while placebo subjects lost 1.2%; muscle mitochondrial numbers grew by 4.1% in supplemented subjects, while falling 6% in placebo recipients.5

Plaque Regression

Plaque Regression  

Quercetin has been analyzed for its ability to counteract atherosclerosis—the gradual blockage of blood flow through arteries. Atherosclerotic plaques are a major cause of heart attack and stroke, two of the top killers of Americans.

In a study of rabbits fed a high-cholesterol diet, quercetin prevented the oxidative and inflammatory effects of the diet on arterial walls, as expected. But it also promoted regression of atherosclerotic plaque, a direct effect of its inhibition of inflammatory enzymes such as COX and 5-LOX (these enzymes produce pro-inflammatory molecules called prostaglandins and leukotrienes).6

This plaque regression is likely driven by a recently discovered property of quercetin. Scientists found that quercetin triggers reverse cholesterol transport, which is the removal of cholesterol from the arterial wall by HDL for transport to the liver for safe disposal.7-9

Quercetin has additional benefits for the endothelial cells lining the blood vessels that normally control blood flow and pressure. Quercetin restores normal production of the relaxation-signaling molecule nitric oxide, and has been shown to produce relaxation of major arteries to promote improved blood flow.10-12 This played out in an impressive fashion in a human study showing that a quercetin-containing food improved after-meal endothelial function by 31.4%.13

New data on quercetin’s many cardiovascular benefits are being published regularly. Here are just a few highlights from the recent literature:

  • Quercetin counteracts the development of tolerance to nitroglycerin and related drugs used in treatment of angina.14
  • Quercetin reduces abnormal heart rhythms in patients with ischemic heart disease who were already on standard medical therapy.15
  • Quercetin reduces the incidence of abdominal aortic aneurysms in animal models; these deadly defects in the wall of the aorta can lead to sudden death.16
  • Quercetin helps to slow platelet aggregation, which can lead to blood clots that produce heart attacks and strokes.17,18
What You Need To Know
Quercetin Can Restore and Refurbish Mitochondria

Quercetin Can Restore and Refurbish Mitochondria

  • Studies show that quercetin triggers reverse cholesterol transport, which results in the removal of cholesterol from the arterial wall by HDL for transport to the liver for safe disposal.
  • Excitingly, quercetin has been found to activate the brain’s powerful natural antioxidant defense system (called Nrf2) that upgrades cellular defenses such as glutathione and prevents brain cell death.
  • As a neuroprotective agent, quercetin protects brain cells against excitotoxicity, the damage done by repeated excitatory electrical impulses observed in Alzheimer’s and other neurodegenerative diseases.
  • Quercetin, found in onions and apples, has now been shown to preserve mitochondria in the heart, brain, liver, and skeletal muscles.
  • Quercetin boosts cardiovascular function, muscular endurance and performance, protects against loss of brain cells, corrects blood glucose and lipid abnormalities in metabolic syndrome, and shows evidence of anticancer and bone health-promoting properties.

Potent Neuroprotection

Like the heart, the human brain is a major consumer of energy. That means it depends heavily upon its mitochondria to deliver the power needed for normal thought, memory, and cognition. Aging reduces mitochondrial function in the brain, mainly as a result of the strong oxidant impact of electrical and chemical activity.19

Quercetin is showing real promise as a neuroprotective nutrient. Studies show that quercetin protects brain cells against excitotoxicity, the damage done by repeated excitatory electrical impulses observed in Alzheimer’s and other neurodegenerative diseases.20-23 Acting through its antioxidant mechanisms, quercetin may reduce toxicity of the dangerous and abnormal amyloid-beta proteins that accumulate in the brain, eventually producing symptoms of memory loss and dementia.24 In fact, quercetin has now been found to prevent brain cell death in animal models of Parkinson’s disease.25

Excitingly, quercetin has been found to activate the brain’s powerful natural antioxidant defense system (called Nrf2) that upgrades cellular defenses such as glutathione and prevents brain cell death.26 Quercetin also increases brain mitochondrial expression of the protective paraoxonase 2 (PON2), which scavenges the free radicals that break down mitochondrial membranes and cause them to lose their electrical potential.27-29

Chronic oxidation leads to chronic inflammation in the brain as it does in the rest of the body, eventually producing changes that can lead to both Alzheimer’s and Parkinson’s diseases.30 Quercetin is among the nutrient molecules capable of preserving vital brain cell function in the face of those changes, limiting the cell death that produces neurodegenerative diseases.31

Obesity And Metabolic Syndrome

Obesity is best thought of in relation to other metabolic disturbances, such as blood lipid abnormalities, elevated blood sugar, insulin resistance, and hypertension. Together, these problems define metabolic syndrome, which is strongly associated with poor health outcomes and sudden death.32,33 A prospective study assessing the mortality status of 6,678 healthy middle-aged men concluded that metabolic syndrome increased the risk of sudden death from heart attack by 68%.33

It is widely recognized that plant flavonoids, especially quercetin, can play important roles in fighting individual components of metabolic syndrome, and may work to reduce the impact of the syndrome as a whole.34,35 In a laboratory animal model, quercetin completely abolished glucose-induced life span reduction by enhancing natural cellular “clean-up” mechanisms that prevented loss of function.36

Lab studies show that quercetin is effective at suppressing fat accumulation in the liver,37 leading to a reduction in fat-induced inflammation triggered by high levels of leptin, the hormone produced in excess in fat tissue deposits.38-41 An eight-week study demonstrated that quercetin-rich onion skin extracts led to reduced internal fat accumulation while increasing levels of the hormone adiponectin, thus improving insulin sensitivity and promoting weight loss.42

Increased amounts of fat tissue lead directly to insulin resistance, which produces high blood sugar while at the same time starving cells of the glucose they need for normal function.43 In fact, even mild elevations of blood sugar, over a lifetime, can accelerate aging.36 In rats fed a high-fat, high-sugar diet, quercetin reduced blood sugar and insulin release, improving insulin resistance.44 Other studies show that quercetin-supplemented rats fed a high-fat, high-carbohydrate diet had less abdominal fat, lower blood pressure, and reduced heart and liver fat accumulations, likely due to antioxidant and anti-inflammatory mechanisms.32 Similar findings were made in diabetic and insulin-resistant rats.45

But these exciting results are not limited to lab and animal studies. In a group of overweight and obese adults with early metabolic syndrome, just 150 mg of quercetin daily reduced blood pressure and levels of oxidized LDL cholesterol, two major components of metabolic syndrome.46 Another human study found that the same dose of quercetin (150 mg/day) for eight weeks decreased waist circumference and after-meal systolic blood pressure, while also lowering after-meal triglyceride levels in a group of otherwise healthy men.35 Another study showed women with type II diabetes reduced systolic blood pressure nearly nine points after taking quercetin.47

In other words, quercetin supplementation in animal and now in human studies proved capable of reversing the major components of metabolic syndrome.

Cancer Protection From Quercetin

Cancer Protection From Quercetin  

Quercetin has been shown to possess numerous anticancer properties, including the ability to interrupt the rapid cell proliferation cycle in growing cancers, and to induce apoptosis, the programmed cell death that cancer cells have lost.48,49 Quercetin’s actions appear to be cancer type- and site-specific, with its most aggressive action on the most aggressive and rapidly growing cancers of the blood (leukemia), brain, lung, uterus, and skin (melanoma).50

Additional data suggest that quercetin is highly effective in preventing the division of colon cancer cells as well.51 Indeed, one small human study has already shown that the combination of quercetin with curcumin, another potent anti-inflammatory nutrient, can slow the growth of precancerous colonic polyps in patients with familial polyposis, a condition always associated with colorectal cancers.52

Estrogen receptors present on the surface of cells can serve as growth stimulators in many cancer types, including lung cancer.53 A unique property of quercetin is its ability to modulate the activity of estrogen receptors,54 and in a lab study, this attribute was shown to reduce the proliferation of lung cancer cells.55 It was also demonstrated that quercetin binds to estrogen receptors just as tightly as tamoxifen, the drug most commonly used in breast cancer therapy.55 As a result, quercetin effectively inhibited proliferation of dangerous drug-resistant breast cancer cells, while also preventing their accumulation into lump-like clusters capable of growth and invasion.56

Quercetin Fights Mitochondrial Threats To Bone And Joint Health

Quercetin Fights Mitochondrial Threats To Bone And Joint Health  

Quercetin has powerful bone health-promoting effects, some of which were superior to the prescription anti-osteoporosis drug alendronate in preclinical research. Unlike such drugs, quercetin promotes new bone formation, rather than simply slowing bone degradation.57-60 This is important because alendronate and similar drugs act by essentially inhibiting the bone-resorbing cells61 in the hope that the bone-forming cells that remain intact will predominate and keep bones strong. Quercetin, by contrast, works by stimulating new bone production by bone-forming cells, allowing bones to retain their normal responses to physical stress.62

“Secondary” osteoporosis and osteopenia (a condition where bone mineral density is lower than normal) can occur with certain diseases and drug treatments, most commonly chronic steroid use. Lab studies show that both quercetin and alendronate could completely reverse steroid-induced osteoporosis, but quercetin also stimulated new bone formation in rat femurs by up to 36%, while alendronate did not.59 Very similar results were shown in animals with steroid-induced osteoporosis and osteopenia secondary to diabetes, both of which commonly cause bone loss.58,59

In the management of arthritis, quercetin has demonstrated superior anti-inflammatory properties. When a group of flavonoids was studied, quercetin showed the strongest specific inhibitory effects on the pro-inflammatory enzymes COX-1 and 15-LOX, both of which produce powerful pro-inflammatory signaling molecules in arthritis.63 Recent studies suggest that quercetin may also reduce accumulation of stiff, fibrous tissue in inflamed joints, potentially improving their function.64,65

Quercetin may also be effective in ameliorating the intensely painful arthritis caused by gout, in which crystals of uric acid accumulate in the joint and induce vigorous inflammation.65 Animals with gouty arthritis showed reduced joint swelling, reduced white blood cell infiltration, lower oxidant levels, and lower levels of inflammatory cytokines following supplementation with quercetin.66

Human studies of quercetin in osteoarthritis are encouraging, especially given the lack of any known drug that can effectively modify or slow the disease’s progress. Added to a standard joint supplement containing glucosamine and chondroitin, 45 mg/day of quercetin for 12 or 16 weeks significantly improved joint pain and function scores compared with placebo, while laboratory markers of new collagen formation (important in preserving joint function) were increased.67,68

Summary

Studies show that quercetin preserves and improves cardiovascular health, slows neurodegeneration, and fights metabolic syndrome. Moreover, quercetin may offer protection against cancer, osteoporosis, and osteoarthritis through its multiple beneficial mechanisms.

The beneficial effects of whole fruits and vegetables in the human diet may be partially explained by the quercetin they contain. Those who don’t consume enough healthy fruits and vegetables can obtain this multi-faceted polyphenol (quercetin) in low-cost supplements.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

References

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