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Life Extension Magazine

LE Magazine January 2003


The Quest for a Better Quercetin

Quercetin and kidney disease

Kidney disease leading to kidney failure is an under-recognized epidemic in the United States. As the population ages, the prevalence of kidney failure is expected to increase dramatically. In numerous experimental studies on both animals and humans, quercetin has been found to protect kidney tissues against age-related insult.

NF-kB activity in the kidneys increases with age and leads to increased oxidative stress. Caloric restriction, which is known to extend life span, has been found to reduce NF-kB activity in the kidneys of rats.13

Researchers tested the effect of quercetin on the activation of NF-kB in cultured rat kidney cells. The cells were proximal tubular cells (PTC's), which play a pivotal role in progressive kidney diseases by regulating the accumulation of macrophages.

They found that quercetin potently inhibited NF-kB activation in PTC.10 Since NF-kB regulates inflammatory signaling and adhesion molecules in PTC, these findings may explain earlier findings that preventive administration of quercetin inhibited tubular injury and the upregulation of inflammatory cytokines in the renal cortex.


Ischemia and reperfusion, discussed earlier in relation to cardiovascular disease, also damages the kidneys. Quercetin protects the kidneys during ischemia and reperfusion by preserving higher levels of the enzyme xanthine dehydrogenase relative to the injurious enzyme xanthine oxidase.14

Quercetin has recently been shown to protect against the kidney damage caused by a well-known nephrotoxic drug. Cyclosporine is a potent immune suppressant, the first-line therapy for solid organ transplant patients and autoimmune disease patients. It causes kidney damage in the form of fibrosis, arterial damage, and cyst formation, among other changes. Such extensive damage is thought to be due to a combination of factors, including increased free radical production, increases in renal nerve activity that cause constriction of renal arteries, blockade of the release of calcium from the mitochondria and a resultant rise in intracellular calcium. (If calcium concentrations rise too high, blood vessels become constricted.)

In a study of cyclosporine's effects on rat kidneys, a 20% to 30% reduction in glomerular filtration rate (the rate at which the kidneys filter wastes from the blood) and up to 40% reduction in renal blood flow were found. Rats given 2 mg/kg of quercetin suffered far less damage to their kidneys when given cyclosporine. Their urinary output increased and markers of free radical damage dropped.15

Quercetin's antioxidant effects and its enhancement of mitochondrial function-including improved intracellular/extracellular calcium balance -likely explain these protective effects. Protecting the kidneys is paramount, for once they are damaged, it becomes difficult, if not impossible to restore healthy function.

Quercetin as antioxidant

The voluminous literature on quercetin's antioxidant effects is beyond the scope of this article. We will focus here on quercetin's ability to quench hydrogen peroxide (H202), an oxidant that is pervasive in the body.4 We have already seen that quercetin reduces platelet aggregation and adhesion by reducing hydrogen peroxide production.

Hydrogen peroxide is normally present in the aqueous humor of the eye, and is thought to be a major oxidant in the formation of cataracts. In the laboratory, hydrogen peroxide causes lens opacification and a pattern of oxidative damage similar to that found in cataracts. Not surprisingly, hydrogen peroxide levels are very high in the aqueous humor of cataract patients.

Researchers studied the effect of quercetin in a model of cataract formation where a rat lens organ culture is exposed to hydrogen peroxide. They found that quercetin is methylated by an enzyme present in the lens, and that both quercetin and this methylated quercetin metabolite protected the lens from opacification and oxidative damage. Their results support the hypothesis that dietary quercetin actively inhibits oxidative damage in the lens and could play an important role in the prevention of cataract.16

Hydrogen peroxide damages neurons by interfering with the cell's ability to regulate calcium levels, as occurs in many neurodegenerative diseases. In particular, hydrogen peroxide increases intracellular calcium levels, and if this condition is sustained too long, mitochondrial function is impaired and irreversible damage and/or cell death can result. Researchers tested the effect of quercetin and other flavonoids on calcium regulation in PC12 cells, commonly used in cellular models of the nervous system. They found that quercetin best protected cells against hydrogen peroxide-induced oxidative stress and calcium dysregulation. The researchers analyzed the chemical structural characteristics that confer these protective effects, and concluded that the quercetin molecule displays precisely the desired characteristics.17

How to obtain water-soluble quercetin

Quercetin, the predominant flavonoid in the human diet, has been unobtainable as a practical dietary supplement due to poor absorption. In fruits and vegetables, quercetin is bound to sugars that make it absorbable. Water-soluble quercetin concentrates the key flavonoid benefit of fruit and vegetable consumption into a convenient, absorbable form. Absorbability helps to bridge the hundreds of studies documenting the health-promoting effects of quercetin from the Petri dish to the vitamin shelf.


Starting in October 2002, Life Extension Super Carnosine and Chronoforte supplements were fortified with the amount of bioavailable quercetin that provides optimal potencies for most individuals. Most Life Extension members already take either Super Carnosine or Chronoforte to inhibit the glycation process.

Glycation is a pathologic mechanism that occurs when a glucose molecule inappropriately binds to a protein molecule. The result of glycation is the formation of non-functioning structures in the body known as advanced glycated end products (AGE). Protein degradation caused by glycation is related to the development of numerous degenerative diseases. The next article describes how carnosine inhibits glycation and why it has become a popular supplement for those seeking to stave off the effects of aging.


1. Middleton E Jr, et al. Effects of flavonoids on immune and inflammatory cell functions. Biochem Pharmacol 1992 Mar 17;43(6):1167-79.

2. Tzeng SH, et al. Inhibition of platelet aggregation by some flavonoids. Thromb Res 1991 Oct 1;64(1):91-100.

3. Yokoyama C, et al. Prostacyclin-deficient mice develop ischemic renal disorders, including nephrosclerosis and renal infarction. Circulation 2002 Oct 29;106(18):2397-403.

4. Pignatelli P, et al. The flavonoids quercetin and catechin synergistically inhibit platelet function by antagonizing the intracellular production of hydrogen peroxide. Am J Clin Nutr 2000;72:1150-5.

5. Hertog MGL, et al, Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly study. Lancet 1993;342:1007-11.

6. Keli SO, et al. Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study. Arch Intern Med 1996 Mar 25;156(6):637-42.

7. Alcocer F, et al. Quercetin inhibits human vascular smooth muscle cell proliferation and migration. Surgery 2002;131:198-204.

8. Yoshizumi M, et al. Quercetin inhibits Shc- and phosphatidylinositol 3-kinase-mediated c-jun N-terminal kinase activation by angiotensin II in cultured rat aortic smooth muscle cells. Mol Pharmacol 2001;60:656-665.

9. Duarte J, et al. Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. Br J Pharmacol 2001;133:117-24.

10. Brookes PS, et al. Mitochondrial function in response to cardiac ischemia-reperfusion after oral treatment with quercetin. Free Rad Biol Med 2002;32(11):1220-8.

11. Hajra L, et al. The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. PNAS 2000 Aug 1;97(16):9052-7.

12. Kimata M, et al. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clin Exp Allergy 2000 Apr;30(4):501-8.

13. Kim H-J, et al. Molecular exploration of age-related NF-kB/IKK downregulation by calorie restriction in rat kidney. Free Rad Biol Med 2002;32(10):991-1005.

14. Sanhueza J, et al. Changes in the xanthine dehydrogenase/xanthine oxidase ratio in the rat kidney subjected to ischemia-reperfusion stress: preventive effect of some flavonoids. Res Commun Chem Pathol Pharmacol 1992 Nov;78(2):211-8.

15. Satyanarayana PSV, et al. Quercetin, a bioflavonoid, protects against oxidative stress-related renal dysfunction by cyclosporine in rats. Methods Find Exp Clin Pharmacol 2001;23(4):175-81.

16. Cornish KM, et al. Quercetin metabolism in the lens: role in inhibition of hydrogen peroxide induced cataract. Free Rad Biol Med 2002;33(1):

17. Wang H, et al. Structure-activity relationships of quercetin in antagonizing hydrogen peroxide-induced calcium dysregulation in cells. Free Rad Biol Med 1999;27(5/6):683-694


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