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doi:10.1111/jog.12311

J. Obstet. Gynaecol. Res. 2014

Effects of raw red onion consumption on metabolic features in overweight or obese women with polycystic ovary syndrome: A randomized controlled clinical trial Mehranghiz Ebrahimi-Mamaghani1, Maryam Saghafi-Asl2, Saeed Pirouzpanah3 and Mohammad Asghari-Jafarabadi4 1

Nutrition Research Center, 2Student Research Committee, Talented Students’ Center, 3Department of Nutrition in Community, School of Nutrition, and 4Medical Education Research Center, School of Health, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract Aim: We aimed to evaluate the effects of raw red onion consumption on metabolic features in overweight and obese women with polycystic ovary syndrome. Material and Methods: In this randomized controlled clinical trial, the patients (n = 54) were randomly allocated to the intervention group as ‘high-onion’ (raw red onions: 2 × 40–50 g/day if overweight and 2 × 50–60 g/day if obese) or to the control group as ‘low-onion’ (raw red onions: 2 × 10–15 g/day) along with limited liliaceous vegetables for 8 weeks. Body mass index, dietary record, and metabolic parameters (fasting blood sugar, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and lipoprotein (a)) were evaluated in the follicular phase of the menstrual cycle at baseline and after 8 weeks. Hormonal variables (progesterone, prolactin, and 17-OH progesterone) were also measured at baseline. Results: Onion significantly decreased the levels of total cholesterol within each group; however, these changes were stronger in the high-onion group (weighted mean differences [WMD]: −5.60 [95% confidence interval [CI]: −9.16, −2.03]; P = 0.003) than in the low-onion group (WMD: −6.42 [95%CI: −11.97, −0.87]; P = 0.025). Similarly, low-density lipoprotein cholesterol decreased significantly (WMD: −5.13 [95%CI: −9.46, −0.81); P = 0.022) in the high-onion group, and (WMD: −2.90 [95%CI −5.57, −0.21]; P = 0.035) in the low-onion group after treatment. The levels of fasting blood sugar, triglycerides, high-density lipoprotein cholesterol and lipoprotein (a) did not differ significantly after 8-week onion treatment. Adjustment for confounders did not make any significant changes in any of the parameters in post-treatment levels. Conclusion: Raw red onion consumption appears to be effective as a cholesterol-lowering food agent in women with polycystic ovary syndrome. However, further investigation is warranted. Key words: blood glucose, diabetes, lipid profile, onion, polycystic ovary syndrome.

Introduction Polycystic ovary syndrome (PCOS) is characterized by the manifestation of oligo-/anovulation, clinical or bio-

chemical hyperandrogenism and/or polycystic ovaries.1 It is believed that PCOS is a heterogeneous gynecological syndrome, associated with wideranging endocrine and metabolic abnormalities,

Received: May 10 2013. Accepted: September 26 2013. Reprint request to: Dr Maryam Saghafi-Asl, Student Research Committee, School of Nutrition, Tabriz University of Medical Sciences, Tabriz 5166614711, Iran. Email: [email protected]

© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology

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including hyperinsulinemia, hyperglycemia, glucose intolerance, dyslipidemia, and obesity.2 Insulin resistance (IR) is implicated as the common cause of reproductive and metabolic abnormalities, such as type 2 diabetes mellitus (T2DM) and dyslipidemia in PCOS.3 It is estimated that 70% of women with PCOS have at least one abnormal lipid constituent.4 Atherogenic lipid profile associated with PCOS is usually manifested as high levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) and reduced levels of high-density lipoprotein cholesterol (HDL-C).5 Women with PCOS are 7.4 times more likely to develop ischemic heart disease and myocardial infarction compared with healthy women.6 Therefore, dyslipidemia should be included in the therapeutic strategies of practitioners to prevent further cardiometabolic complications associated with PCOS. The use of standard anti-hyperlipidemic or insulinsensitizing drugs may bring about a patient’s noncompliance due to their side-effects. It is reported that lifestyle modifications can improve metabolic aberrations through amelioration of reproductive abnormalities in PCOS women.7 Therefore, improving lipids and glucose levels with dietary options seems to be favorable. However, despite the possible therapeutic roles of energy restriction, most overweight or obese PCOS women show less tendency to pursue such recommendations.8 Medicinal plants continue to be a treasure of curative agents in medicine. Among these, onion (Allium cepa L.) has been extensively investigated for its curative properties.9 It is commonly used in the daily diet in Iran. Two sets of compounds make up the majority of onion’s known active components: sulfur compounds, such as alkyl sulfoxides and S-methyl cysteine sulfoxide, and flavonoids, such as quercetin. Several, but not all of the studies have established hypolipidemic10–16 and hypoglycemic10,12,14,17 as well as other beneficial properties of onion (in forms of powder, extract, essential oil, fresh or juice) in animal models of chemically induced T2DM or hypercholesterolemia or humanbased studies. Alkyl and alkenyl sulfoxides and their breakdown products, as active components of onion, were shown to lower serum total and LDL-C, increase HDL-C, and protect LDL-C against oxidation.16 Previous studies revealed that S-methyl cysteine sulfoxide (SMCS), a precursor of onion oil, had hypoglycemic as well as hypolipidemic effect in alloxan diabetic rats.12,14 Amelioration of the hyperlipidemic condition was also

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observed when SMCS was administered at a dose of 200 mg/kg bodyweight for 45 days to high-cholesterol fed rats.13 In another study, a diet containing 12.5% bodyweight onion could not reduce the level of blood glucose in alloxan-induced diabetic rats.18 Hwang et al. showed that administration of onion powder to rats fed high-fat and high-cholesterol diet seemed to control weight gain and significantly lower the level of total cholesterol in the liver.11 In another study,19 it was demonstrated that the efficacy of onion consumption depends on its type and dosage. Complementary to animal studies, a cross-over research on 20 well-controlled diabetic patients showed that 20 g of fresh onion, 3 times daily for 1 week could significantly reduce fasting blood sugar (FBS), but not TG or cholesterol level.17 In a preliminary study on healthy male volunteers, administration of 50 g of raw or boiled onion prevented the rise in serum cholesterol induced by consumption of a high-fat meal.15 In another study, this author reported that onion does not reduce blood sugar levels in healthy non-diabetic people.20 Although there have been numerous reports regarding the effects of different forms of garlic and onion and their active principles, little attention has been paid to the effects of whole onion consumption. Many active compounds of a whole onion may not be present in an in vitro or in vivo system. In addition, previous studies have primarily focused upon its effect on metabolic parameters in T2DM or hypercholesterolemic conditions basically in animals and rarely in humans. To the best of our knowledge, no prior study has been published on the effect of onion consumption in PCOS. On the other hand, the number of studies investigating the effects of nutrients on PCOS is scarce. Therefore, this randomized controlled clinical trial was undertaken to evaluate the effects of raw red onion consumption on metabolic features in overweight or obese women with PCOS.

Methods Study subjects This randomized controlled clinical trial was conducted from January 2011 to August 2012 in outpatients of the Gynecology and Endocrinology Clinics of Tabriz University of Medical Sciences, Tabriz, Iran. Fifty-four PCOS patients with overweight or obese characteristics were recruited in this study. The research protocol was approved by the Ethics Committee of Tabriz University of Medical Sciences

© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology

Effects of onion consumption in PCOS

(reference number: 906, IRCT registration number: IRCT201105306652N1). Written informed consent was obtained from all the participants. The diagnosis of PCOS was based on the revised Rotterdam criteria,21 in which the presence of any two out of the three following criteria were required: (i) oligo- and/or anovulation ( 8); and (iii) polycystic ovaries on sonography (i.e., at least one ovary containing 12 or more peripheral follicles measuring 2–9 mm in diameter and/or ovarian volume of at least 10 mL)23 and exclusion of causal comorbidities (congenital adrenal hyperplasia, androgen-secreting tumors, and Cushing’s syndrome). Vaginal or transabdominal pelvic sonography, as appropriate, were performed only on patients who did not fulfill the diagnostic criteria. The inclusion criteria were any PCOS patient diagnosed by the above-mentioned criteria aged 17–37 years, body mass index (BMI) between 25 and 40 kg/m2, taking no medicines at least 2 months before the enrollment, no tendency to become pregnant during the study, applying non-drug methods to prevent pregnancy, and low intake ( 2.08 ng/mL) than those in the highonion group (67% vs 48%, P = 0.271). Around 80% of

Figure 1 Flowchart of the participants’ progress through the phases of the trial.

© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology

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*P-values (within-group comparison, weighted least squares regression). **P-values (between-groups comparison, weighted least squares regression). P-values are not significant after adjustment for BMI, age, and free testosterone as confounders. †For Lp (a), the data are expressed as median (range); high-onion group (n = 15) and low-onion group (n = 20). BMI, body mass index; CI, confidence interval; FBS, fasting blood sugar; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; Lp (a), Lipoprotein (a); SD, standard deviation; TC, total cholesterol; TG, triglyceride; WMD, weighted mean difference.

0.36 (0.22, 0.49) 0.56 (−1.12, 2.25) 5.44 (−12.00, 22.88) −0.33 (−5.14, 4.48) −1.14 (−5.06, 2.78) −0.53 (−2.11, 1.05) 0.010 (−0.004, 0.025) 0.013 0.062 0.081 0.025 0.035 0.421 0.931 −0.15 (−0.26, −0.03) 1.09 (−0.05, 2.25) −7.81 (−16.65, 1.03) −6.42 (−11.97, −0.87) −2.90 (−5.57, −0.21) −0.40 (−1.42, 0.61) −0.008 (−0.043, 0.026) 0.001 0.549 0.697 0.003 0.022 0.135 0.722 0.19 (0.08, 0.30) 0.28 (−0.67, 1.24) 2.74 (−11.53, 17.02) −5.60 (−9.16, −2.03) −5.13 (−9.46, −0.81) −1.16 (−2.71, 0.38) 0.012 (−0.011, 0.034) 31.51 ± 4.10 93.50 ± 10.44 133.37 ± 53.94 181.40 ± 32.33 109.22 ± 28.4 45.48 ± 9.51 0.17 (0.07, 1.02) BMI (Kg/m2) FBS (mg/dl) TG (mg/dl) TC (mg/dl) LDL-C (mg/dl) HDL-C (mg/dl) Lp (a) (g/l)†

30.72 ± 3.75 90.55 ± 6.80 142.25 ± 60.32 183.44 ± 43.09 111.69 ± 39.80 43.30 ± 7.15 0.10 (0.07, 0.70)

P**

the patients in each group had hirsutism. All of the patients in the low-onion group and the majority of those in the high-onion group had oligo-/anovulation (P = 0.118) (Fig. 2). No significant difference was observed in the level of FBS and TG within or between the two groups after the treatment. But there was a significant decrease in TC both in the high-onion group (WMD: −5.60 [95%CI: −9.16, −2.03]; P = 0.003), and in the low-onion group (WMD: −6.42 [95%CI: −11.97, −0.87]; P = 0.025). Similarly, LDL-C decreased significantly both in the highonion group (WMD: −5.13 [95%CI: −9.46, −0.81]; P = 0.022), and in the low-onion group (WMD: −2.90 [−5.57, −0.21]; P = 0.035). Though onion could reduce the levels of TC and LDL-C within each group, no significant difference was observed between the two groups. The levels of HDL-C and LP (a) did not differ significantly within or between the two groups after 8-week onion treatment (Table 2). There was a significant increase in BMI from 31.27 ± 3.90 kg/m2 to 31.51 ± 4.10 kg/m2 (P = 0.001) in the high-onion group, while there was a significant decrease from 30.83 ± 3.92 kg/m2 to 30.72 ± 3.75 kg/m2 (P = 0.013) in low-onion group. After 8-week treatment, the mean BMI also differed significantly between the two groups (P < 0.001). However, adjustment for the confounders (i.e. BMI, age, and free testosterone) did not make any significant changes in any of the parameters in post-treatment levels between the two groups. When we divided the patients into two subgroups, one with unchanged or increased BMI and the other with decreased BMI, the level of cholesterol declined (WMD: −3.20 mg/dL [95%CI: −8.00, −1.60]; P = 0.183)

P*

Figure 2 Comparison of body mass index (BMI), insulin resistance, and clinical characteristics between highand low-onion groups at baseline of the study (P-values are non-significant, using χ2-test). , highonion; , low-onion.

Table 2 Effects of 8-week onion treatment on metabolic features in overweight or obese patients with polycystic ovary syndrome

H irs ut yp is er m an dr og en em O lig ia o/ an ov ul at io n H

BM

I: 25 –2 9. 99 BM kg I: 30 /m 2 –3 4. 99 kg /m 2 BM I: ≥3 5 kg In /m su 2 lin re si st an ce

0

Low-onion group (n = 27) After (Mean ± SD) WMD (95%CI)

20

P*

40

High-onion group (n = 27) After (Mean ± SD) WMD (95%CI)

60

Between-groups changes WMD (95%CI)

80

Variable

Percentage

100

Effects of raw red onion consumption on metabolic features in overweight or obese women with polycystic ovary syndrome: a randomized controlled clinical trial.

We aimed to evaluate the effects of raw red onion consumption on metabolic features in overweight and obese women with polycystic ovary syndrome...
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