Abstract
Background:
Quercetin, found abundantly in onion peel, has been known to have anticholesterol, antithrombotic and insulin-sensitizing properties. Here, we investigated the effect of quercetin-rich onion peel extract (OPE) on reactive oxygen species (ROS) production and antioxidative defense in obese woman.
Methods:
This study was randomized, double-blind, placebo controlled study. Thirty-seven healthy obese participants were randomly assigned that eighteen subjects received red soft capsuled OPE (100 mg/d, 50 mg bis in die), while the other nineteen subjects received same capsuled placebo for 12 weeks. ROS production and superoxide dismutase (SOD) activity in plasma were determined by using ROS and SOD assay kits, respectively.
Results:
Baseline characteristics of anthropometric indicators and blood metabolic profiles were not significantly different between the two groups. Compared with baseline values, OPE consumption significantly reduced waist and hip circumference. Plasma ROS level and SOD activity were decreased in both placebo and OPE groups compared with baseline values. However, plasma ROS level in OPE group was significantly lower than in placebo group while plasma SOD activity in OPE group was significantly higher than in placebo group after 12 weeks of consumption.
Conclusions:
These findings indicate that OPE consumption may exert antioxidative effect by preventing the decrease of SOD activity as well as the production of ROS in obese women.
Keywords: Onion peel extract, Quercetin, Reactive oxygen species, Superoxide dismutase
INTRODUCTION
There is considerable evidence linking continued oxidative stress to the development of chronic inflammation, which in turn could mediate most chronic diseases including cancer, diabetes, aging, and vascular disorders.1–3 Oxidative stress is characterized as the disruption of intracellular balance between generation of free radicals and reactive metabolites (often called as oxidants or reactive oxygen species [ROS]), and their destruction by protective systems and mechanisms, referred to as antioxidants.3 Most ROS, generated in cells via the mitochondrial respiration, are products of a normal cellular oxidative metabolism. Under physiologic conditions, cells generate ROS such as superoxide anion radical (O2−), hydroxyl radical (OH •), hydrogen peroxide (H2O2), and organic peroxides as normal products of the biological reduction of molecular oxygen.4 However, under a sustained oxidative stress, ROS are generated over a long time and thus affect cellular viability, metabolism, and function which may lead to the development of chronic diseases including vascular disorders neurodegenerative diseases, diabetes mellitus, and tumor diseases.2,5–8 Even physiological processes such as aging are also defined as an increase in oxidative stress as a results of progressive decrease in the ROS elimination.9 To fight excessive production of these harmful pro-oxidants, the organism has built protective systems such as enzymatic antioxidants (e.g., superoxide dismutase [SOD], glutathione peroxidase [GPX], glutathione reductase, and catalase) and non-enzymatic antioxidants (e.g., glutathione [GSH], vitamins C, and D).10 Disturbances in the balance between the generation of ROS and antioxidant defenses of cells lead to the accumulation of molecular damage in proteins, lipids, and DNA, with potential impact on the whole organism.3 To enhance antioxidant system capable of reducing oxidative stress to eventually prevent chronic diseases associated with continued oxidative stress, the application of food-derived antioxidants has recently become a focus of interest.
The polyphenol quercetin, found abundantly in onion peel, is one of the major plant-derived flavonoid. It has been known to have antiobesity, antidiabetes, and antihypertensive effects in animal models and human studies.11–16 Quercetin could also sensitize resistant cancer cells to chemotherapy and synergize the effect of drugs in nonresistant cancer cell.17 In addition, previous studies have demonstrated that quercetin-rich onion peel extract (OPE) treatment has antiplatelet, antiadipogenic, and anti-inflammatory property in vitro as well as in animal models.18–22 Thus far, there is no study to examine the effect of treatment with OPE on the antioxidant system in obese human. Therefore, in the present study, we evaluated the effect of quercetin-rich OPE supplementation for 12 weeks on ROS production and antioxidative defense in obese woman.
MATERIALS AND METHODS
1. Subjects
This study was randomized, double-blind, placebo controlled study. Thirty-seven healthy obese participants were recruited. The study was approved by the institutional review board of Kyung Hee Medical Center (KMC IRB 1304-03-C1). Subjects who had hypertension and diabetes were excluded from this study. And, subjects with who were taking dietary restriction drugs or were participating diet programs were excluded from this study.
2. Onion peel extract preparation
OPE were prepared from Newfood Co., Changnyung, Korea. OPE were washed, extracted with 60% ethanol, filtered, concentrated, and processed to give a powder. Analyses of total phenol, total flavonoid, and quercetin contents yielded the following values: 681.7, 372.0, and 286.0 mg/g, respectively.
3. Study protocol
Thirty-seven healthy obese participants were randomly assigned using a computerized random allocation sequence that eighteen subjects received red soft capsuled OPE (100 mg/d, 50 mg bis in die), while the other nineteen subjects received same capsuled placebo for 12 weeks. Plasma was obtained by centrifugation of blood at 1,500 ×g for 15 minutes which was stored at −80°C until analyzed.
4. Anthropometric and biochemical analysis
Anthropometric measurements were taken at baseline and at 12 weeks. Body mass index (BMI) was calculated as weight in kilogram divided by height in meters squared; waist and hip circumference were also measured. Fat mass were measured by bioimpedance analysis (Inbody 3.0; Biospace, Seoul, Korea). Systolic blood pressure and diastolic blood pressure (DBP) was measured from the left arm in seated patients with an automatic blood pressure monitor (TM-2654; A&D, Tokyo, Japan) after a 20 minutes rest. Two measurements were taken at least 5 minutes apart, and the mean was used for analysis. Plasma triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein-cholesterol were measured with commercially available kits (Bayers, Tarrytown, NY, USA) using enzymatic methods.
5. Determination of reactive oxygen species concentration
Plasma ROS levels was determined using OxiSelect Intracellular ROS Assay Kit (Cell Biolabs Inc., San Diego, CA, USA), according to the manufacturer’s instructions. Briefly, ROS species react with 2′,7′-dichlorodihydrofluorescein (DCFH), which is rapidly oxidized to the fluorescent DCFH. Its fluorescence intensity is proportional to the total ROS levels within the sample and was quantified by a spectrophotometer (Spectramax M2; Molecular Devices, Sunnyvale, CA, USA) at 480 nm/530 nm with 530 nm cutoff.
6. Determination of superoxide dismutase activity
Plasma SOD activity was determined by a competitive colorimetric inhibition assay using SOD activity kit (ENZO life Sciences, Plymouth Meeting, PA, USA), according to the manufacturer’s instructions. Briefly, samples or standards (25 μL) were incubated with 150 μL reaction mixture containing WST-1 and Xanthine oxidase and then xanthine solution was added. Formazan formation was measured at 450 nm using a 96-well plate reader (Spectramax M2; Molecular Devices). SOD concentration, expressed in units per milligram of protein, was determined using the SOD standard curve.
7. Statistical analysis
Statistical analysis was performed with the SAS ver. 9.1 software package (SAS Institute Inc., Cary, NC, USA). Data were expressed as means ± SD. Significantly different before and after placebo or OPE intakes by paired t-test. The difference between the OPE and placebo groups was analyzed using t-test. Differences were considered significant at P < 0.05.
RESULTS
1. Effects of onion peel extract on anthropometric measurements
Baseline characteristics of anthropometric indicators were not significantly different between the two groups. On assessing body weight, BMI, fat mass, and blood pressure after 12 weeks, no significant difference was found between the placebo and OPE treatment. However, OPE consumption significantly reduced waist and hip circumferences, compared with baseline values (Table 1).
Table 1.
Variable | Placebo (n = 19) | Onion peel extract (n = 18) | ||||
---|---|---|---|---|---|---|
|
|
|||||
Baseline | 12 weeks | Change | Baseline | 12 weeks | Change | |
Age (yr) | 45.4 ± 9.5 | – | – | 44.6 ± 7.6 | – | – |
Height (cm) | 159.0 ± 6.3 | – | – | 159.2 ± 4.1 | – | – |
Weight (kg) | 67.2 ± 6.8 | 67.2 ± 6.6 | 0.02 ± 3.86 | 65.9 ± 9.2 | 65.4 ± 8.9 | −0.68 ± 1.76 |
BMI (kg/m2) | 26.6 ± 2.5 | 26.6 ± 2.4 | 0.02 ± 3.86 | 26.0 ± 3.8 | 25.8 ± 3.6 | −0.68 ± 1.76 |
Waist (cm) | 88.9 ± 7.1 | 88.5 ± 6.9 | −0.46 ± 2.51 | 90.5 ± 8.3 | 88.3 ± 7.8a | −2.33 ± 2.77 |
Hip (cm) | 99.9 ± 5.7 | 99.1 ± 5.3 | −0.58 ± 1.67 | 99.9 ± 5.6 | 98.5 ± 6.1a | −1.37 ± 2.14 |
Fat mass (kg) | 23.6 ± 4.53 | 23.4 ± 4.05 | 0.24 ± 10.57 | 23.7 ± 6.30 | 23.4 ± 5.9 | −1.13 ± 5.52 |
SBP (mmHg) | 117.3 ± 14.7 | 117.7 ± 13.3 | 0.83 ± 8.47 | 110.1 ± 9.3 | 110.1 ± 9.4 | 0.39 ± 8.80 |
DBP (mmHg) | 74.3 ± 9.4 | 75.5 ± 7.8 | 2.20 ± 9.04 | 69.6 ± 8.2 | 68.1 ± 6.5 | −1.04 ± 12.93 |
Values are presented as mean ± SD. BMI, body mass index; Waist, waist circumference; Hip, hip circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure.
P-value < 0.05, significantly different before and after placebo or onion peel extract intakes by paired t-test.
2. Effects of onion peel extract on blood metabolic profiles parameters
As shown in Table 2, characteristics of blood metabolic profiles before and after the 12-week treatment were not significantly different between the two groups.
Table 2.
Variable | Placebo (n = 19) | Onion peel extract (n = 18) | ||||
---|---|---|---|---|---|---|
|
|
|||||
Baseline | 12 weeks | Change | Baseline | 12 weeks | Change | |
Triglyceride (mg/dL) | 108.6 ± 44.4 | 116.9 ± 43.0 | 14.22 ± 36.47 | 98.8 ± 35.5 | 95.0 ± 28.8 | 2.13 ± 28.92 |
TC (mg/dL) | 193.6 ± 37.4 | 187.9 ± 35.6 | −1.56 ± 14.10 | 183.6 ± 34.9 | 193.1 ± 28.7 | 8.25 ± 26.11 |
LDL-C (mg/dL) | 122.2 ± 33.9 | 118.8 ± 31.8 | 0.38 ± 21.87 | 118.3 ± 30.6 | 126.8 ± 29.3 | 12.63 ± 41.72 |
HDL-C (mg/dL) | 55.2 ± 9.2 | 53.5 ± 8.6 | −2.17 ± 11.94 | 51.7 ± 9.9 | 53.6 ± 9.7 | 4.96 ± 16.84 |
Leptin (ng/mL) | 15.2 ± 7.8 | 12.8 ± 6.1 | −12.55 ± 30.86 | 16.9 ± 11.6 | 13.3 ± 7.3 | −7.31 ± 50.95 |
Values are presented as mean ± SD. TC, total cholesterol; LDL-C, low-density lipoprotein-cholesterol; HDL-C, high-density lipoprotein-cholesterol.
3. Effects of onion peel extract on reactive oxygen species level and superoxide dismutase activity
Plasma ROS level and SOD activity changed significantly after 12 weeks of treatment with placebo or OPE (Table 3). However, plasma ROS level in OPE-treated group was significantly lower than in placebo group while plasma SOD activity in OPE-treated group was significantly higher than in placebo group.
Table 3.
Placebo (n = 19) | Onion peel extract (n = 18) | |||||
---|---|---|---|---|---|---|
|
|
|||||
Baseline | 12 weeks | Change | Baseline | 12 weeks | Change | |
ROS (nM) | 147.9 ± 32.7 | 137.8 ± 61.6a | −1.55 ± 52.66 | 158.8 ± 22.8 | 123.5 ± 45.4a | −21.54 ± 31.73b |
SOD (U/mg protein) | 1.96 ± 0.26 | 1.45 ± 0.38a | −23.77 ± 23.20 | 1.95 ± 0.20 | 1.60 ± 0.25a | −17.68 ± 9.42b |
Values are presented as mean ± SD. ROS, reactive oxygen species; SOD, superoxide dismutase.
P < 0.05, significantly different before and after placebo or onion peel extract intakes by paired t-test.
P < 0.05, significantly different in placebo and onion peel extract by t-test.
DISCUSSION
The aim of the present randomized, double-blind, placebo controlled study was to investigate the effect of a 12-week supplementation with quercetin-rich OPE on ROS production and antioxidative defense in obese women. Our major finding was that OPE supplementation significantly prevented the decrease of SOD activity and the production of ROS.
Numerous studies suggest the suppressive effects of quercetin and quercetin-rich OPE against obesity in animal models and cell lines. In mice fed a Western diet or high-fat diet, quercetin reduced liver fat accumulation by regulating the expression of lipid metabolism genes.11,13 In obese Zucker rats, Rivera et al.12 demonstrated that quercetin also had anti-inflammatory effects in the visceral adipose tissue and reduced body weight gain. In 3T3-L1 cells, quercetin and quercetin-rich OPE were reported to attenuate adipogenesis.19,22,23 Recently, Yang and Kim24 demonstrated that the obesity index (% fat, BMI, waist circumstance) were significantly decreased by OPE intake for 12 weeks in obese university women. However, another study reported that no changes were observed in body weight and BMI in healthy young women with OPE supplementation for 2 weeks.25 In the current study, we also found that OPE supplementation significantly reduced waist and hip circumferences, compared with baseline values. However, the changes observed in body weight and BMI were not statistically significant after 12 weeks of OPE supplementation. Since abdominal obesity has been identified as an independent risk factor for metabolic diseases and waist circumference as well as waist-to-hip ratio has been shown to be better markers of metabolic risk than BMI among many anthropometric measures for central body fat assessment,26–28 our results are in line with the previous studies showing antiobesity effects of OPE.
Recently, Egert et al.16 have shown that quercetin for 6 weeks in people with metabolic syndrome compared with the placebo group significantly decreased the systolic and DBPs. In addition, Edwards et al.29 have demonstrated that quercetin supplementation for 4 weeks in pre-hypertensives and stage 1 hypertensive individuals significantly reduced systolic and DBPs only in stage 1 hypertensive subjects while no significant differences were found between two groups. In our study, OPE supplementation did not attenuate the blood pressure in obese women with normal blood pressure. This finding is consistent with the study conducted by Conquer et al.30 which examined the effect of quercetin supplementation on blood pressure in healthy subjects and reported that quercetin for 4 weeks could not have a significant effect on systolic and DBP. It seems likely that the blood pressure-lowering effect of quercetin is related to the degree of hypertension. Indeed, Lee et al.31 reported that daily quercetin-rich supplementation from OPE for 10 weeks significantly decreased both systolic and DBP in pre-hypertentive male smokers.
In many animal studies, quercetin is known to have antioxidant properties. Pre-treatment of quercetin may protect against ethanol-induced oxidative stress in mouse liver by directly quenching lipid peroxides and indirectly by enhancing the production of the endogenous antioxidant GSH.32 Galisteo et al.33 investigated the potential of chronic administration of dietary flavonoid quercetin to prevent hypertension as well as oxidative stress induced by deoxycorticosterone acetate-salt in rats and found that antihypertensive effect of quercetin accompanied by normalization of plasma thiobarbituric acid reactive substances (TBARS) values, improvement of the antioxidant defense system in heart and liver, restoring total GSH levels in both organs and altered liver glutathione S-transferase and GPX activities. However, human studies to investigate the antioxidative effect of quercetin have shown contradictory results which may associated with difference of physiology in humans and animals as well as levels of oxidative status.29,34 In addition, there are only few studies that examined the effect of OPE supplementation on ROS production and antioxidative defense in animals and humans. Park et al.35 demonstrated that dietary onion flesh or onion peel supplementation was beneficial for lowering lipid peroxides levels such as plasma total antioxidant status, liver TBARS, and brain 8-isoprrostance levels in aged rats. Previously, Kim et al.25 reported that OPE supplementation for 2 weeks significantly modified the lipid profile and atherogenic index while no changes observed in activities of antioxidant enzymes or levels of lipid peroxidation markers in healthy young women. In the current study, we observed that plasma ROS level and SOD activity changed significantly after 12 weeks of treatment with placebo or OPE; however, plasma ROS level in OPE-treated group was significantly lower than in placebo group while plasma SOD activity in OPE-treated group was significantly higher than in placebo group. These results can be attributed to the difference of subjects (healthy normal-weight women vs. obese women) and study design (2 weeks vs. 12 weeks of supplementation with OPE).
In conclusion, our findings demonstrate that OPE supplementation may exert antioxidative effect by preventing the decrease of SOD activity and the production of ROS in obese women. To the best of our knowledge, there is no study to investigate the antioxidative effect of quercetin-rich OPE in obese women. Since free radicals and their reactive metabolites including ROS have emerged as important regulators of many physiological and pathological processes, OPE consumption may be beneficial for obese individuals as a means of reducing oxidative stress to eventually prevent chronic diseases associated with continued oxidative stress.
Acknowledgments
This research is financially supported by Changwon National University in 2015–2016.
Footnotes
CONFLICTS OF INTEREST
No potential conflicts of interest were disclosed.
REFERENCES
- 1.Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010;49:1603–16. doi: 10.1016/j.freeradbiomed.2010.09.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Kim YW, West XZ, Byzova TV. Inflammation and oxidative stress in angiogenesis and vascular disease. J Mol Med (Berl) 2013;91:323–8. doi: 10.1007/s00109-013-1007-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Duracková Z. Some current insights into oxidative stress. Physiol Res. 2010;59:459–69. doi: 10.33549/physiolres.931844. [DOI] [PubMed] [Google Scholar]
- 4.Fridovich I. The biology of oxygen radicals. Science. 1978;201:875–80. doi: 10.1126/science.210504. [DOI] [PubMed] [Google Scholar]
- 5.Cherubini A, Ruggiero C, Polidori MC, Mecocci P. Potential markers of oxidative stress in stroke. Free Radic Biol Med. 2005;39:841–52. doi: 10.1016/j.freeradbiomed.2005.06.025. [DOI] [PubMed] [Google Scholar]
- 6.Aruoma OI, Neergheen VS, Bahorun T, Jen LS. Free radicals, antioxidants and diabetes: embryopathy, retinopathy, neuropathy, nephropathy and cardiovascular complications. Neuroembryol Aging. 2007;4:117–37. doi: 10.1159/000109344. [DOI] [Google Scholar]
- 7.Muchová J, Liptáková A, Országhová Z, Garaiová I, Tison P, Cársky J, et al. Antioxidant systems in polymorphonuclear leucocytes of Type 2 diabetes mellitus. Diabet Med. 1999;16:74–8. doi: 10.1046/j.1464-5491.1999.00015.x. [DOI] [PubMed] [Google Scholar]
- 8.Schraufstätter I, Hyslop PA, Jackson JH, Cochrane CG. Oxidant-induced DNA damage of target cells. J Clin Invest. 1988;82:1040–50. doi: 10.1172/JCI113660. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Minelli A, Bellezza I, Conte C, Culig Z. Oxidative stress-related aging: A role for prostate cancer? Biochim Biophys Acta. 2009;1795:83–91. doi: 10.1016/j.bbcan.2008.11.001. [DOI] [PubMed] [Google Scholar]
- 10.Sies H. Oxidative stress: from basic research to clinical application. Am J Med. 1991;91:31S–8S. doi: 10.1016/0002-9343(91)90281-2. [DOI] [PubMed] [Google Scholar]
- 11.Jung CH, Cho I, Ahn J, Jeon TI, Ha TY. Quercetin reduces high-fat diet-induced fat accumulation in the liver by regulating lipid metabolism genes. Phytother Res. 2013;27:139–43. doi: 10.1002/ptr.4687. [DOI] [PubMed] [Google Scholar]
- 12.Rivera L, Morón R, Sánchez M, Zarzuelo A, Galisteo M. Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese Zucker rats. Obesity (Silver Spring) 2008;16:2081–7. doi: 10.1038/oby.2008.315. [DOI] [PubMed] [Google Scholar]
- 13.Kobori M, Masumoto S, Akimoto Y, Oike H. Chronic dietary intake of quercetin alleviates hepatic fat accumulation associated with consumption of a Western-style diet in C57/BL6J mice. Mol Nutr Food Res. 2011;55:530–40. doi: 10.1002/mnfr.201000392. [DOI] [PubMed] [Google Scholar]
- 14.Kobori M, Masumoto S, Akimoto Y, Takahashi Y. Dietary quercetin alleviates diabetic symptoms and reduces streptozotocin-induced disturbance of hepatic gene expression in mice. Mol Nutr Food Res. 2009;53:859–68. doi: 10.1002/mnfr.200800310. [DOI] [PubMed] [Google Scholar]
- 15.Duarte J, Pérez-Palencia R, Vargas F, Ocete MA, Pérez-Vizcaino F, Zarzuelo A, et al. Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. Br J Pharmacol. 2001;133:117–24. doi: 10.1038/sj.bjp.0704064. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Egert S, Bosy-Westphal A, Seiberl J, Kürbitz C, Settler U, Plachta-Danielzik S, et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. Br J Nutr. 2009;102:1065–74. doi: 10.1017/S0007114509359127. [DOI] [PubMed] [Google Scholar]
- 17.Miles SL, McFarland M, Niles RM. Molecular and physiological actions of quercetin: need for clinical trials to assess its benefits in human disease. Nutr Rev. 2014;72:720–34. doi: 10.1111/nure.12152. [DOI] [PubMed] [Google Scholar]
- 18.Ro JY, Ryu JH, Park HJ, Cho HJ. Onion (Allium cepa L.) peel extract has anti-platelet effects in rat platelets. Springerplus. 2015;4:17. doi: 10.1186/s40064-015-0786-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Bae CR, Park YK, Cha YS. Quercetin-rich onion peel extract suppresses adipogenesis by down-regulating adipogenic transcription factors and gene expression in 3T3-L1 adipocytes. J Sci Food Agric. 2014;94:2655–60. doi: 10.1002/jsfa.6604. [DOI] [PubMed] [Google Scholar]
- 20.Kim J, Kim JS, Park E. Cytotoxic and anti-inflammatory effects of onion peel extract on lipopolysaccharide stimulated human colon carcinoma cells. Food Chem Toxicol. 2013;62:199–204. doi: 10.1016/j.fct.2013.08.045. [DOI] [PubMed] [Google Scholar]
- 21.Lee SM, Moon J, Chung JH, Cha YJ, Shin MJ. Effect of quercetin-rich onion peel extracts on arterial thrombosis in rats. Food Chem Toxicol. 2013;57:99–105. doi: 10.1016/j.fct.2013.03.008. [DOI] [PubMed] [Google Scholar]
- 22.Moon J, Do HJ, Kim OY, Shin MJ. Antiobesity effects of quercetin-rich onion peel extract on the differentiation of 3T3-L1 preadipocytes and the adipogenesis in high fat-fed rats. Food Chem Toxicol. 2013;58:347–54. doi: 10.1016/j.fct.2013.05.006. [DOI] [PubMed] [Google Scholar]
- 23.Ahn J, Lee H, Kim S, Park J, Ha T. The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochem Biophys Res Commun. 2008;373:545–9. doi: 10.1016/j.bbrc.2008.06.077. [DOI] [PubMed] [Google Scholar]
- 24.Yang YK, Kim SP. The effect of onion extract intake for 12 weeks on blood lipid and obesity index in obese university women. Korean J Sports Sci. 2013;22:955–62. [Google Scholar]
- 25.Kim J, Cha YJ, Lee KH, Park E. Effect of onion peel extract supplementation on the lipid profile and antioxidative status of healthy young women: a randomized, placebo-controlled, double-blind, crossover trial. Nutr Res Pract. 2013;7:373–9. doi: 10.4162/nrp.2013.7.5.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Bergman RN, Kim SP, Hsu IR, Catalano KJ, Chiu JD, Kabir M, et al. Abdominal obesity: role in the pathophysiology of metabolic disease and cardiovascular risk. Am J Med. 2007;120:S3–8. doi: 10.1016/j.amjmed.2006.11.012. discussion S29–32. [DOI] [PubMed] [Google Scholar]
- 27.Han TS, van Leer EM, Seidell JC, Lean ME. Waist circumference action levels in the identification of cardiovascular risk factors: prevalence study in a random sample. BMJ. 1995;311:1401–5. doi: 10.1136/bmj.311.7017.1401. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Ashwell M, Gunn P, Gibson S. Waist-to-height ratio is a better screening tool than waist circumference and BMI for adult cardiometabolic risk factors: systematic review and meta-analysis. Obes Rev. 2012;13:275–86. doi: 10.1111/j.1467-789X.2011.00952.x. [DOI] [PubMed] [Google Scholar]
- 29.Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T. Quercetin reduces blood pressure in hypertensive subjects. J Nutr. 2007;137:2405–11. doi: 10.1093/jn/137.11.2405. [DOI] [PubMed] [Google Scholar]
- 30.Conquer JA, Maiani G, Azzini E, Raguzzini A, Holub BJ. Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects. J Nutr. 1998;128:593–7. doi: 10.1093/jn/128.3.593. [DOI] [PubMed] [Google Scholar]
- 31.Lee KH, Park E, Lee HJ, Kim MO, Cha YJ, Kim JM, et al. Effects of daily quercetin-rich supplementation on cardiometabolic risks in male smokers. Nutr Res Pract. 2011;5:28–33. doi: 10.4162/nrp.2011.5.1.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Molina MF, Sanchez-Reus I, Iglesias I, Benedi J. Quercetin, a flavonoid antioxidant, prevents and protects against ethanol-induced oxidative stress in mouse liver. Biol Pharm Bull. 2003;26:1398–402. doi: 10.1248/bpb.26.1398. [DOI] [PubMed] [Google Scholar]
- 33.Galisteo M, García-Saura MF, Jiménez R, Villar IC, Zarzuelo A, Vargas F, et al. Effects of chronic quercetin treatment on antioxidant defence system and oxidative status of deoxycorticosterone acetate-salt-hypertensive rats. Mol Cell Biochem. 2004;259:91–9. doi: 10.1023/B:MCBI.0000021360.89867.64. [DOI] [PubMed] [Google Scholar]
- 34.Young JF, Nielsen SE, Haraldsdóttir J, Daneshvar B, Lauridsen ST, Knuthsen P, et al. Effect of fruit juice intake on urinary quercetin excretion and biomarkers of antioxidative status. Am J Clin Nutr. 1999;69:87–94. doi: 10.1093/ajcn/69.1.87. [DOI] [PubMed] [Google Scholar]
- 35.Park J, Kim J, Kim MK. Onion flesh and onion peel enhance antioxidant status in aged rats. J Nutr Sci Vitaminol (Tokyo) 2007;53:21–9. doi: 10.3177/jnsv.53.21. [DOI] [PubMed] [Google Scholar]