Neuroprotective Effect of Quercetin Against Glaucoma Damage

What is Quercetin?

Quercetin is a member of the flavonoid family of naturally occurring compounds. It can be found in apples, asparagus, berries (such as bilberries, black currants, and alpine cranberries) broccoli, Ginkgo biloba,[1] green beans, kale, onions, red wine, tea, and tomatoes.[2] It is most concentrated in the leaves and skin of fruits and vegetables. When modified by the addition of rutinose (a sugar) Quercetin is known as Rutin.[3]

There is laboratory evidence that it has antioxidant[4] and anti-inflammatory[5] properties. At higher doses, however, it may also increase oxidative damage.[6] Additionally, the anti-inflammatory properties noted in the laboratory may not be active in the body.[7] Its potential benefit as an oral supplement, however, is limited by low bioavailability (the amount ingested that is actually absorbed into the bloodstream).

Once in the bloodstream evidence suggests that only a small percentage of it crosses the blood-brain barrier.[8] However, once in the brain it appears to have both an anti-inflammatory[9] and neuroprotective[10] effect, at least in concentrations expected from moderate oral supplementation.[11] In higher concentrations, however, Quercetin may be toxic to neurons.[12]

Neuroprotective Effect of Quercetin. Evidence that Quercetin can be effective in the treatment of Glaucoma

There is no direct evidence that Quercetin could have an IOP lowering effect on the eye. Its purported benefit to patients with glaucoma is related to its neuroprotective effect.[13] The eye naturally produces enzymes called Peroxiredoxins (PRDXs) which neutralize hydrogen peroxide.  Quercetin has been shown in the laboratory to increase the production of Peroxiredoxins by trabecular meshwork cells.[14]

Potential Side Effects and Risks:

Quercetin appears to be safe when used orally in amounts up to 1,000mg per day for up to three months.[15]  Longer term studies are not available so chronic, ongoing use may or may not be safe. Additionally, intravenous (IV) quercetin has been associated with kidney damage.[16] Side effects of oral Quercetin include headaches and tingling of the arms and/or legs.[17] There is some evidence that Quercetin may worsen memory performance.[18]

Potential Drug Interactions

Blood Thinners

Research suggests that Quercetin may limit the ability of platelets to clump.[19]This could increase the risk of bleeding when used with ”blood thinning” medications.  Therefore, use of Quercetin may result in undesirable bleeding in those who are already taking anticoagulant medications such as aspirin, apixaban (Eliquis), clopidogrel (Plavix), dabigatran (Pradaxa), rivaroxaban (Xarelto) and warfarin (Coumadin).

Anti-Hypertensive Medications

Quercetin may lower blood pressure.[20] In those whose blood pressure is not well-controlled this could be a good thing. However, care should be taken when used along with other blood-pressure lowering medications such as captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), amlodipine (Norvasc), hydrochlorothiazide (HydroDIURIL), furosemide (Lasix), as well as many others.

Potential Interactions with Other Supplement

Resveratrol

Quercetin can increase the intestinal absorption of Resveratrol.[21] For those taking Resveratrol this interaction is most likely desirable.

Green Tea Catechins

Quercetin can increase the intestinal absorption of Green Tea Catechins. For those taking Green Tea Catechins this interaction is most likely desirable.

Recommended Dosage

As no human glaucoma studies have been done looking at the role of quercetin, it is not possible to recommend a proper dosage. For those who desire to take this supplement, however, it is worth noting that the dihydrate form of Quercetin appears to have the best bioavailability. Another option would be to take Rutin instead of Quercetin.

References

1) Wang FM, Yao TW, Zeng S. Determination of quercetin and kaempferol in human urine after orally administrated tablet of ginkgo biloba extract by HPLC. J Pharm Biomed Anal. (2003)

2) Anon. Quercetin. Alt Med Rev 1998;3:140-3.

Nemeth K, Piskula MK. Food content, processing, absorption and metabolism of onion flavonoids. Crit Rev Food Sci Nutr 2007;47:397-409.

3) Murota K, et al. alpha-Oligoglucosylation of a sugar moiety enhances the bioavailability of quercetin glucosides in humans. Arch Biochem Biophys. (2010)

4) Lean ME, Noroozi M, Kelly I. Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA. Diabetes 1999;48:176-81.

5) Anon. Quercetin. Alt Med Rev 1998;3:140-3.

Nieman DC, Henson DA, Davis JM, et al. Quercetin’s influence on exercise-induced changes in plasma cytokines and muscle and leukocyte cytokine mRNA. J Appl Physiol 2007;103:1728-35.

6) Harwood M, Danielewska-Nikiel B, Borzelleca JF, et al. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic / carcinogenic properties. Food Chem Toxicol 2007;45:2179-205.

7) de Pascual-Teresa S, Johnston KL, DuPont MS, et al. Quercetin metabolites downregulate cyclooxygenase-2 transcription in human lymphocytes ex vivo but not in vivo. J Nutr 2004;134:552-7.

8) Faria A, et al. Flavonoid transport across RBE4 cells: A blood-brain barrier model. Cell Mol Biol Lett. (2010)

Ren SC, et al. {Quercetin permeability across blood-brain barrier and its effect on the viability of U251 cells}. Sichuan Da Xue Xue Bao Yi Xue Ban. (2010)

Dan H, Du WT, Fan XJ. {Study of flavanoids extracted from onion on the blood-brain barrier permeation and neuroprotective effects}. Zhongguo Zhong Xi Yi Jie He Za Zhi. (2011)

9) Chen JC, et al. Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of IkappaB kinase, nuclear factor-kappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia. Eur J Pharmacol. (2005)

Kwon YS, et al. Modulation of suppressive activity of lipopolysaccharide-induced nitric oxide production by glycosidation of flavonoids. Arch Pharm Res. (2004)

Bureau G, Longpré F, Martinoli MG. Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation. J Neurosci Res. (2008)

10) Protective Effects of Quercetin and Vitamin C against Oxidative Stress-Induced Neurodegeneration

Sasaki N, et al. Protective effects of flavonoids on the cytotoxicity of linoleic acid hydroperoxide toward rat pheochromocytoma PC12 cells. Chem Biol Interact. (2003)

11) Shirai M, et al. Effect of a conjugated quercetin metabolite, quercetin 3-glucuronide, on lipid hydroperoxide-dependent formation of reactive oxygen species in differentiated PC-12 cells. Free Radic Res. (2006)

12) Jakubowicz-Gil J, et al. Cell death and neuronal arborization upon quercetin treatment in rat neurons. Acta Neurobiol Exp (Wars). (2008)

13) Dok-Go H, Lee KH, Kim HJ, et al. Neuroprotective effects of anti-oxidative ?avonoids, quercetin, (+)-dihydroquercetin and quercetin 3-methyl ethe, isolated from Opuntia ?cus-indica va. saboten. Brain Res. 2003;965:130–136.

14) Miyamoto M, Izumi H, Miyamoto R, et al. Quercetin Induces the Expression of Peroxiredoxins 3 and 5 via the Nrf2/NRF1 Transcription Pathway. Invest Ophthalmol Vis Sci. 2011;52:1055–1063.

15) Harwood M, Danielewska-Nikiel B, Borzelleca JF, et al. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic / carcinogenic properties. Food Chem Toxicol 2007;45:2179-205.

16) Ferry DR, Smith A, Malkhandi J, et al. Phase I clinical trial of the flavonoid quercetin: Pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res 1996;2:659-67.

17) Shoskes DA, Zeitlin SI, Shahed A, Rajfer J. Quercetin in men with category III chronic prostatitis: A preliminary prospective, double-blind, placebo-controlled trial. Urol 1999;54:960-3.

18) Jung WY, et al. Quercetin impairs learning and memory in normal mice via suppression of hippocampal phosphorylated cyclic AMP response element-binding protein expression. Toxicol Lett. (2010)

19) Janssen K, Mensink RP, Cox FJ, et al. Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study. Am J Clin Nutr 1998;67:255-62.

Hubbard GP, Wolffram S, Lovegrove JA, Gibbins JM. Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans. J Thromb Haemost 2004;2:2138-45.

20) Perez-Vizcaino F, Duarte J, Andriantsitohaina R. Endothelial function and cardiovascular disease: effects of quercetin and wine polyphenols. Free Radic Res 2006;40:1054-65. Edwards RL, Lyon T, Litwin SE, et al. Quercetin reduces blood pressure in hypertensive subjects. J Nutr 2007;137:2405-11.

21) Harris RM, Waring RH. Sulfotransferase inhibition: potential impact of diet and environmental chemicals on steroid metabolism and drug detoxification. Curr Drug Metab. (2008)

Don’t delay getting checked for glaucoma.

Make an appointment with an eye doctor in your area now.  If you live in the greater Los Angeles area and would like Dr. Richardson to evaluate your eyes for glaucoma call 626-289-7856 now. No referral required. Same day or next day appointments are available, Tuesday through Saturday.

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