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Relation
N. Rezvan, A. Moini, L. Janani et al. Effects of quercetin on adiponectin-mediated insulin sensitivity in polycystic ovary syndrome: a randomized placebo-controlled double-blind clinical trial.Horm Metab Res. 2017;49:115-121.
Draft
A 12-week randomized placebo-controlled double-blind clinical trial was conducted to determine the effect of quercetin supplementation on serum adiponectin levels in women with polycystic ovary syndrome (PCOS).
Participant
A total of 84 women with PCOS diagnosed according to the Rotterdam criteria, aged 20 to 40 years, with a BMI between 25 and 40 kg/m2were included in the study. Individuals with concomitant endocrine or metabolic diseases (hypothyroidism, hyperthyroidism, androgen-secreting tumors, diabetes mellitus, adrenal hyperplasia, Cushing's syndrome) and those taking confounding medications (metformin, contraceptives, antihypertensives, lipid-lowering agents, anti-inflammatories) were excluded.
intervention
Participants in the experimental group (n=42) received a total of 1 g of quercetin (Jarrow, USA) daily, with one 500 mg capsule taken orally after breakfast and lunch. The control group (n=42) followed the same dosing regimen but with placebo capsules containing starch. Adherence was monitored by weekly telephone checks and by counting the number of capsules returned every 2 weeks.
Target parameters
Primary outcome measures included changes in serum levels of total and high molecular weight (HMW) adiponectin. Additionally, the following anthropometric, metabolic, and hormonal measures were assessed: weight, BMI, waist-to-hip ratio (WHR), serum testosterone, luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and homeostatic model assessment of insulin resistance (HOMA-IR). Assessments were conducted at baseline and week 12.
Key insights
Of the 84 enrolled participants, only 2 participants, both in the control group, were unable to complete the study. One discontinued the intervention due to reported diarrhea and the other was lost to follow-up.
While the results of this study have elucidated the role of adiponectin in insulin resistance, it is still unclear whether and how PCOS symptoms are influenced by rising levels.
In the experimental group, total and HMW adiponectin levels were significantly higher (8.6% and 7.4%;P<0.001 for both) at the end of the study compared to baseline. Notable and significant improvements in HOMA-IR (17.5%;P<0.001), serum testosterone and LH were also observed. Quercetin had a marginal effect on SHBG. Placebo provided no therapeutic benefit with regard to these measures. Changes in weight, BMI, and WHR were not significantly different between the two groups. An inverse correlation between adiponectin levels and HOMA-IR, BMI and WC was found and considered statistically significant.
Practice implications
Insulin resistance and subsequent hyperinsulinemia are common clinical features of PCOS. With an estimated prevalence of 50% to 70%, insulin resistance is considered a major factor contributing to the pathophysiology of the disease.1One proposed mechanism of PCOS involves stimulation of ovarian theca cells by insulin, leading to testosterone production and ultimately androgen excess.1Treatment protocols for PCOS, both conventional and naturopathic, typically include insulin sensitization as a primary goal. At least lowering insulin levels reduces the risk of type 2 diabetes mellitus and cardiovascular disease. At best, it can also help to control the symptoms.
The gold standard for diagnosing insulin resistance is the hyperinsulinemic-euglycemic clamp, although it is not commonly used. Instead, diagnosis and management are usually based on clinical presentation and fasting blood glucose and hemoglobin A1clevels. Measuring adiponectin, a protein derived from adipose tissue, can improve diagnostic accuracy because it is a strong predictor of insulin resistance.2Unlike other adipokines, its effects are protective (anti-inflammatory, antidiabetic, antiatherogenic, cardioprotective) and levels are inversely related to metabolic dysregulation.3
The first clinical trial investigating adiponectin and its role in PCOS-related metabolic syndrome was published in 2003. She identified a direct correlation between adiponectin levels and the rate of glucose catabolism (P=0.043) and an inverse correlation with WHR (P=0.024). It also recognized adiponectin levels as a valid indicator of abdominal fat mass.4
Trolle et al. confirmed the inverse correlation between adiponectin levels and WHR and found the same to be true for insulin and HOMA-IR. Also in this study, metformin was tested to determine its ability to increase adiponectin levels.5No significant changes were observed, and several other papers documented the same result.6.7Conversely, there are several reports of success with other insulin-sensitizing drugs such as pioglitazone,8rosiglitazone,9and the combination of flutamide plus metformin.10
In the studies using the above medications, researchers also reported significantly lower baseline adiponectin levels in patients with PCOS compared to people without PCOS of the same weight. The results suggest that obesity leads to changes in values even without obesity. However, lean PCOS patients may still be at risk for low adiponectin and insulin resistance depending on their body composition.
This study was the first to evaluate the effect of quercetin on PCOS, although previous research has demonstrated therapeutic benefits for numerous conditions and highlighted the antioxidant effects of quercetin11and anti-inflammatory12Characteristics. A study published in September 2017 found that women with PCOS experience higher levels of oxidative stress and inflammation than women without PCOS. Therefore, it is not surprising that quercetin is currently of interest to researchers.13It's also worth noting that PCOS can put women at higher risk of ovarian cancer.14In vitro and animal studies suggest that quercetin may have a protective effect against the development of ovarian cancer.fifteen
While the results of this study have elucidated the role of adiponectin in insulin resistance, it is still unclear whether and how PCOS symptoms are influenced by increasing levels. Further research examining the long-term outcomes of supplementation is needed to better understand its use in the treatment of PCOS. Until then, quercetin is a low-risk intervention that may serve as a beneficial adjunctive treatment.