Life Extension Magazine December 2006
Vitamin C and Dihydroquercetin
By Mark J. Neveu, PhD
By Mark J. Neveu, PhD
Dihydroquercetin Inhibits Oxidative Stress and Inflammation
Because of its forceful antioxidant abilities, dihydroquercetin can search for and destroy two of the most dangerous types of free radicals in the body: the superoxide and peroxide radicals. Dihydroquercetin also works overtime to protect red and white blood cells. Studies show that it protects white blood cells from environmental injury and prevents oxidative cell death in red blood cells. The result is a stronger, more vigorous immune system that can aggressively police and protect critical cell units throughout the body.24-26
As Life Extension readers know, inflammation is a key culprit in degenerative diseases such as arthritis, cardiovascular disease, and cancer. Dihydroquercetin has shown its ability to reduce inflammation-producing enzymes such as cyclooxygenase-2 (COX-2) and to inhibit inflammatory mediators, including cytokines.27-30 The COX-2 enzyme has been the focus of extensive pharmaceutical research that has produced drugs such as Vioxx® and Celebrex®. These drugs went on to be implicated in the creation of lethal heart disease. Dihydroquercetin may provide a safe alternative to certain pharmaceuticals used to address inflammation.
Inflammation also makes its presence known through allergic reactions. Histamines are widely recognized as the trigger of most allergic episodes. Dihydroquercetin suppresses the release of histamines, thereby reducing the severity of allergic occurrences.31
Studies Confirm Safety and Efficacy
Studies indicate that dihydroquercetin is highly safe and efficacious. In fact, research suggests that dihydroquercetin is even safer than its nutritional cousin, quercetin.61,62 No toxic effects were observed in rats that were treated with high levels of dihydroquercetin for long periods of time.63
While people in Russia require a prescription to acquire the many benefits of dihydroquercetin and vitamin C, this broad-spectrum nutrient combination is now readily available as a low-cost dietary supplement to Americans seeking to enhance their health and well-being. By protecting and enhancing vitamin C as it courses through the body, dihydroquercetin dramatically increases the benefits of this important nutrient.
Substantial scientific evidence suggests that this novel combination of nutrients confers powerful, synergistic protection against some of the most common and dangerous diseases of aging, including cardiovascular, neurological, and diabetic disorders. Incorporating vitamin C and dihydroquercetin in a daily supplementation program is a simple, low-cost way to further strengthen the body’s natural antioxidant defenses.
1. Kregel KC, Zhang HJ. An integrated view of oxidative stress in aging: basic mechanisms, functional effects and pathological considerations. Am J Physiol Regul Integr Comp Physiol. 2006 Aug 17.
2. Harman D. Free radical theory of aging: an update: increasing the functional life span. Ann NY Acad Sci. 2006 May;1067:10-21.
3. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2006 Aug 4; [Epub ahead of print]
4. Halvorsen BL, Carlsen MH, Phillips KM, Bohn SK, Holte K, Jacobs DR Jr, Blomhoff R. Content of redox-active compounds (ie, antioxidants) in foods consumed in the United States. Am J Clin Nutr. 2006 Jul;84(1):95-135.
5. Available at: http://en.wikipedia.org/wiki/Bioflavonoids. Accessed October 10, 2006.
6. Ross JA, Kasum CM. Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr. 2002;22:19-34.
7. Hertog MG, Kromhout D, Aravanis C, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med. 1995 Feb 27;155(4):381-6.
8. Knekt P, Kumpulainen J, Jarvinen R, et al. Flavonoid intake and risk of chronic diseases. Am J Clin Nutr. 2002 Sep;76(3):560-8.
9. Landrault N, Larronde F, Delaunay JC, et al. Levels of stilbene oligomers and astilbin in French varietal wines and in grapes during noble rot development. J Agric Food Chem. 2002 Mar 27;50(7):2046-52.
10. Available at: http://en.wikipedia.org/wiki/Vitamin_c. Accessed October 10, 2006.
11. Vinson JA, Bose P. Comparative bioavailability to humans of ascorbic acid alone or in a citrus extract. Am J Clin Nutr. 1988 Sep;48(3):601-4.
12. Harper KA, Morton AD, Rolfe EJ. Phenolic compounds of black currant juice and their effect on ascorbic acid. III Mechanism of ascorbic acid oxidation and its inhibition by flavonoids. J Food Tech. 1969;4:255-67.
13. Nijveldt RJ, van NE, van Hoorn DE, et al. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr. 2001 Oct;74(4):418-25.
14. van der LB, Bachschmid M, Spitzer V, et al. Decreased plasma and tissue levels of vitamin C in a rat model of aging: implications for antioxidative defense. Biochem Biophys Res Commun. 2003 Apr 4;303(2):483-7.
15. Jacob RA, Sotoudeh G. Vitamin C function and status in chronic disease. Nutr Clin Care. 2002 Mar;5(2):66-74.
16. Bsoul SA, Terezhalmy GT. Vitamin C in health and disease. J Contemp Dent Pract. 2004 May 15;5(2):1-13.
17. Logvinov SV, Pugachenko NV, Potapov AV, et al. Ischemia-induced changes in synaptoarchitectonics of brain cortex and their correction with ascovertin and Leuzea extract. Bull Exp Biol Med. 2001 Oct;132(4):1017-20.
18. Plotnikov MB, Logvinov SV, Pugachenko NV, et al. Cerebroprotective effects of diquertin and ascorbic acid. Bull Exp Biol Med. 2000 Nov;130(11):1080-3.
19. Plotnikov MB, Plotnikov DM, Aliev OI, et al. Hemorheological and antioxidant effects of Ascovertin in patients with sclerosis of cerebral arteries. Clin Hemorheol Microcirc. 2004;30(3-4):449-52.
20. Plotnikov MB, Plotnikov DM, Alifirova VM, et al. Clinical efficacy of a novel hemorheological drug ascovertin in patients with vascular encephalopathy. Zh Nevrol Psikhiatr Im SS Korsakova. 2004;104(12):33-7.
21. Plotnikov MB, Aliev OI, Maslov MJ, Vasiliev AS, Tjukavkina NA. Correction of the high blood viscosity syndrome by a mixture of Diquertin and ascorbic acid in vitro and in vivo. Phytother Res . 2003 Mar;17(3):276-8.
22. Plotnikov MB, Aliev OI, Maslov MJ, Vasiliev AS, Tjukavkina NA. Correction of haemorheological disturbances in myocardial infarction by diquertin and ascorbic acid. Phytother Res. 2003 Jan;17(1):86-8.
23. Logvinov SV, Plotnikov MB, Varakuta EY, et al. Effect of ascovertin on morphological changes in rat retina exposed to high-intensity light. Bull Exp Biol Med. 2005 Nov;140(5):578-81.
24. Potapovich AI, Kostyuk VA. Comparative study of antioxidant properties and cytoprotective activity of flavonoids. Biochemistry (Mosc.). 2003 May;68(5):514-9.
25. Haraguchi H, Mochida Y, Sakai S, et al. Protection against oxidative damage by dihydroflavonols in Engelhardtia chrysolepis. Biosci Biotechnol Biochem. 1996 Jun;60(6):945-8.
26. Kostyuk VA, Potapovich AI. Antiradical and chelating effects in flavonoid protection against silica-induced cell injury. Arch Biochem Biophys. 1998 Jul 1;355(1):43-8.
27. Wang YH, Wang WY, Chang CC, et al. Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-oxidative effect and modulation of NF-kappa B activation. J Biomed Sci. 2006 Jan;13(1):127-41.
28. Soliman KF, Mazzio EA. In vitro attenuation of nitric oxide production in C6 astrocyte cell culture by various dietary compounds. Proc Soc Exp Biol Med. 1998 Sep;218(4):390-7.
29. Bito T, Roy S, Sen C,K et al. Flavonoids differentially regulate IFN gamma-induced ICAM-1 expression in human keratinocytes: molecular mechanisms of action. FEBS Lett. 2002 Jun 5;520(1-3):145-52.
30. Devi MA, Das NP. In vitro effects of natural plant polyphenols on the proliferation of normal and abnormal human lymphocytes and their secretions of interleukin-2. Cancer Lett. 1993 May 14;69(3):191-6.
31. Bronner C, Landry Y. Kinetics of the inhibitory effect of flavonoids on histamine secretion from mast cells. Agents Actions. 1985 Apr;16(3-4):147-51.
32. Kravchenko LV, Morozov SV, Tutel’yan VA. Effects of flavonoids on the resistance of microsomes to lipid peroxidation in vitro and ex vivo. Bull Exp Biol Med. 2003 Dec;136(6):572-5.
33. Teselkin YO, Babenkova IV, Tjukavkina NA, et al. Influence of dihydroquercetin on the lipid peroxidation of mice during post-radiation period. Phytotherapy Research. 1998;12:517-9.
34. Vasiljeva OV, Lyubitsky OB, Klebanov GI, Vladimirov YA. Effect of the combined action of flavonoids, ascorbate and alpha-tocopherol on peroxidation of phospholipid liposomes induced by Fe2+ ions. Membr Cell Biol. 2000;14(1):47-56.
35. Kostyuk VA, Kraemer T, Sies H, Schewe T. Myeloperoxidase/nitrite-mediated lipid peroxidation of low-density lipoprotein as modulated by flavonoids. FEBS Lett. 2003 Feb 27;537(1-3):146-50.
36. Casaschi A, Rubio BK, Maiyoh GK, Theriault AG. Inhibitory activity of diacylglycerol acyltransferase (DGAT) and microsomal triglyceride transfer protein (MTP) by the flavonoid, taxifolin, in HepG2 cells: potential role in the regulation of apolipoprotein B secretion. Atherosclerosis. 2004 Oct;176(2):247-53.
37. Igarashi K, Uchida Y, Murakami N, Mizutani K, Masuda H. Effect of astilbin in tea processed from leaves of Engelhardtia chrysolepis on the serum and liver lipid concentrations and on the erythrocyte and liver antioxidative enzyme activities of rats. Biosci Biotechnol Biochem. 1996 Mar;60(3):513-5.
38. Chen TH, Liu JC, Chang JJ, et al. The in vitro inhibitory effect of flavonoid astilbin on 3-hydroxy-3-methylglutaryl coenzyme A reductase on Vero cells. Zhonghua Yi Xue Za Zhi (Taipei). 2001 Jul;64(7):382-7.
39. Tikhonov VP, Makarova MN, Zajtseva MA, Makarov VG. Efficacy of (±)-taxifolin from Larix sibirica (Mûnchh.) Ledeb. on blood pressure in experiments in vivo. Planta Med. 2006;72:174.
40. Wang YH, Wang WY, Liao JF, et al. Prevention of macrophage adhesion molecule-1 (Mac-1)-dependent neutrophil firm adhesion by taxifolin through impairment of protein kinase-dependent NADPH oxidase activation and antagonism of G protein-mediated calcium influx. Biochem Pharmacol. 2004 Jun 15;67(12):2251-62.
41. Dok-Go H, Lee KH, Kim HJ, et al. Neuroprotective effects of antioxidative flavonoids, quercetin, (+)-dihydroquercetin and quercetin 3-methyl ether, isolated from Opuntia ficus-indica var. saboten. Brain Res. 2003 Mar 7;965(1-2):130-6.
42. van Oostrom AJ, van Wijk JP, Sijmonsma TP, Rabelink TJ, Castro CM. Increased expression of activation markers on monocytes and neutrophils in type 2 diabetes. Neth J Med. 2004 Oct;62(9):320-5.
43. Fedosova NF, Alisievich SV, Lyadov KV, et al. Mechanisms underlying diquertin-mediated regulation of neutrophil function in patients with non-insulin-dependent diabetes mellitus. Bull Exp Biol Med. 2004 Feb;137(2):143-6.
44. Haraguchi H, Ohmi I, Fukuda A, et al. Inhibition of aldose reductase and sorbitol accumulation by astilbin and taxifolin dihydroflavonols in Engelhardtia chrysolepis. Biosci Biotechnol Biochem. 1997 Apr;61(4):651-4.
45. Haraguchi H, Ohmi I, Masuda H, et al. Inhibition of aldose reductase by dihydroflavonols in Engelhardtia chrysolepis and effects on other enzymes. Experientia. 1996 Jun 15;52(6):564-7.
46. Batt AM, Ferrari L. Manifestations of chemically induced liver damage. Clin Chem. 1995 Dec;41(12 Pt 2):1882-7.
47. Teselkin YO, Babenkova IV, Kolhir VK, et al. Dihydroquercetin as a means of antioxidative defence in rats with tetrachloromethane hepatitis. Phytother Res. 2000 May;14(3):160-2.
48. Wang J, Zhao Y, Xu Q. Astilbin prevents concanavalin A-induced liver injury by reducing TNF-alpha production and T lymphocytes adhesion. J Pharm Pharmacol. 2004 Apr;56(4):495-502.
49. Xu Q, Wu F, Cao J, et al. Astilbin selectively induces dysfunction of liver-infiltrating cells—novel protection from liver damage. Eur J Pharmacol. 1999 Jul 14;377(1):93-100.
50. Closa D, Torres M, Hotter G, et al. Prostanoids and free radicals in Cl4C-induced hepatotoxicity in rats: effect of astilbin. Prostaglandins Leukot Essent Fatty Acids. 1997 Apr;56(4):331-4.
51. Biziagos E, Crance JM, Passagot J, Deloince R. Effect of antiviral substances on hepatitis A virus replication in vitro. J Med Virol. 1987 May;22(1):57-66.
52. Gupta MB, Bhalla TN, Gupta GP, Mitra CR, Bhargava KP. Anti-inflammatory activity of taxifolin. Jpn J Pharmacol. 1971 Jun;21(3):377-82.
53. Cai Y, Chen T, Xu Q. Astilbin suppresses collagen-induced arthritis via the dysfunction of lymphocytes. Inflamm Res. 2003 Aug;52(8):334-40.
54. Yan R, Xu Q. Astilbin selectively facilitates the apoptosis of interleukin-2-dependent phytohemagglutinin-activated Jurkat cells. Pharmacol Res. 2001 Aug;44(2):135-+9.
55. Cechinel-Filho V, Vaz ZR, Zunino L, Calixto JB, Yunes RA. Antinociceptive and anti-oedematogenic properties of astilbin, taxifolin and some related compounds. Arzneimittelforschung. 2000 Mar;50(3):281-5.
56. Kolhir VK, Bykov VA, Teselkin YO, et al. Use of a new antioxidant diquertin as an adjuvant in the therapy of patients with acute pneumonia. Phytotherapy Research. 1998;12:606-8.
57. Min BS, Lee HK, Lee SM, et al. Anti-human immunodeficiency virus-type 1 activity of constituents from Juglans mandshurica. Arch Pharm Res. 2002 Aug;25(4):441-5.
58. Chu SC, Hsieh YS, Lin JY. Inhibitory effects of flavonoids on Moloney murine leukemia virus reverse transcriptase activity. J Nat Prod. 1992 Feb;55(2):179-83.
59. Fei M, Wu X, Xu Q. Astilbin inhibits contact hypersensitivity through negative cytokine regulation distinct from cyclosporin A. J Allergy Clin Immunol. 2005 Dec;116(6):1350-6.
60. Cai Y, Chen T, Xu Q. Astilbin suppresses delayed-type hypersensitivity by inhibiting lymphocyte migration. J Pharm Pharmacol. 2003 May;55(5):691-6.
61. Bjeldanes LF, Chang GW. Mutagenic activity of quercetin and related compounds. Science. 1977 Aug 5;197(4303):577-8.
62. Nagao M, Morita N, Yahagi T, et al. Mutagenicities of 61 flavonoids and 11 related compounds. Environ Mutagen. 1981;3(4):401-19.
63. Booth AN, Deeds F. The toxicity and metabolism of dihydroquercetin. J Am Pharm Assoc Am Pharm Assoc (Baltim.). 1958 Mar;47(3, Part 1):183-4.
64. Available at: http://lpi.oregonstate.edu/infocenter/vitamins/vitaminC/. Accessed October 11, 2006.
65. Li W, Maeda N, Beck MA. Vitamin C deficiency increases the lung pathology of influenza virus-infected gulo-/- mice. J Nutr. 2006 Oct;136(10):2611-6.
66. Chen Q, Espey MG, Krishna MC, et al. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci USA. 2005 Sep 20;102(38):13604-9.
67. Riordan HD, Casciari JJ, Gonzalez MJ, et al. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. PR Health Sci J. 2005 Dec;24(4):269-76.
68. Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. Inhibition of malignant mesothelioma cell matrix metalloproteinase production and invasion by a novel nutrient mixture. Exp Lung Res. 2006 Mar;32(3-4):69-79.
69. Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. Antitumor effect of ascorbic acid, lysine, proline, arginine, and green tea extract on bladder cancer cell line T-24. Int J Urol. 2006 Apr;13(4):415-9.
70. Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. In vivo and in vitro antitumor effect of ascorbic acid, lysine, proline, arginine, and green tea extract on human fibrosarcoma cells HT-1080. Med Oncol. 2006;23(1):105-11.
71. Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. Inhibition of matrix metalloproteinase-2 secretion and invasion by human ovarian cancer cell line SK-OV-3 with lysine, proline, arginine, ascorbic acid and green tea extract. J Obstet Gynaecol Res. 2006 Apr;32(2):148-54.
72. Roomi MW, Ivanov V, Netke S, et al. In vivo and in vitro antitumor effect of ascorbic acid, lysine, proline and green tea extract on human melanoma cell line A2058. In Vivo. 2006 Jan;20(1):25-32.
73. Roomi MW, Roomi N, Ivanov V, et al. Inhibitory effect of a mixture containing ascorbic acid, lysine, proline and green tea extract on critical parameters in angiogenesis. Oncol Rep.2005 Oct;14(4):807-15.
74. Roomi MW, Roomi NW, Ivanov V, et al. Modulation of N-methyl-N-nitrosourea induced mammary tumors in Sprague-Dawley rats by combination of lysine, proline, arginine, ascorbic acid and green tea extract. Breast Cancer Res. 2005;7(3):R291-5.
75. Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. In vitro and in vivo antitumorigenic activity of a mixture of lysine, proline, ascorbic acid, and green tea extract on human breast cancer lines MDA-MB-231 and MCF-7. Med Oncol. 005;22(2):129-38.
76. Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. Antitumor effect of a combination of lysine, proline, arginine, ascorbic acid, and green tea extract on pancreatic cancer cell line MIA PaCa-2. Int J Gastrointest Cancer. 2005;35(2):97-102.
77. Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. In vivo antitumor effect of ascorbic acid, lysine, proline and green tea extract on human prostate cancer PC-3 xenografts in nude mice: evaluation of tumor growth and immunohistochemistry. In Vivo. 2005 Jan;19(1):179-83.
78. Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. In vivo antitumor effect of ascorbic acid, lysine, proline and green tea extract on human colon cancer cell HCT 116 xenografts in nude mice: evaluation of tumor growth and immunohistochemistry. Oncol Rep. 2005 Mar;13(3):421-5.
79. Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. Antitumor effect of nutrient synergy on human osteosarcoma cells U-2OS, MNNG-HOS and Ewing’s sarcoma SK-ES.1. Oncol Rep. 2005 Feb;13(2):253-7.