Thursday, 29 November 2018

Re: Clinical Trial Reports that Cinnamon Reduces Insulin Resistance in Women with Polycystic Ovary Syndrome

Cinnamon (Cinnamomum verum, Lauraceae) Polycystic Ovary Syndrome Insulin Resistance Date: 11-15-2018 HC# 101831-604 Hajimonfarednejad M, Nimrouzi M, Heydari M, Zarshenas MM, Raee MJ, Jahromi BN. Insulin resistance improvement by cinnamon powder in polycystic ovary syndrome: A randomized double-blind placebo controlled clinical trial. Phytother Res. February 2018;32(2):276-283. doi: 10.1002/ptr.5970. Polycystic ovary syndrome (PCOS), caused by a hormonal imbalance, is diagnosed when a woman has two of the following conditions without other medical explanation: hyperandrogenism, intermittent or absent menstrual cycles, and polycystic ovary indicated by ultrasound. Although its etiology is uncertain, PCOS appears to result from a combination of genetic and environmental factors. Insulin resistance is common in women with PCOS, may play a causal role in its development, and can contribute to the development of obesity, diabetes, and cardiovascular problems. Pharmaceutical treatments for PCOS are limited by contraindications, poor efficacy, and adverse effects. Cinnamon (Cinnamomum verum, Lauraceae) bark is used traditionally to regulate menstrual cycles in patients with PCOS and has been shown to lower blood glucose and reduce the homeostatic model assessment of insulin resistance (HOMA-IR) index in patients with diabetes. These authors conducted a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of cinnamon in patients with PCOS. The study was conducted at Shiraz University of Medical Sciences in Shiraz, Iran. Fresh cinnamon bark, purchased from a local Shiraz market, was washed, dried, and ground into a powder, which was used to fill 500 mg capsules. Placebo capsules contained 450 mg of starch (heated until it turned brown) and 50 mg of cinnamon powder (used to produce similar taste and odor). Patients at the University's Shaheed Motahari Outpatient Clinic who were aged 18 to 45 years, met the Rotterdam Criteria for PCOS, and had a body mass index (BMI) ≥18 kg/m2 were eligible for the study. Exclusion criteria included diabetes, hypertension, hyperprolactinemia, or thyroid problems, pregnancy or lactation, treatment for infertility, or use of hormones or any drug that affects insulin sensitivity. Enrollment took place between January 2016 and July 2016. Of 80 women screened, 66 were enrolled in the trial. For 12 weeks, 33 of those patients were instructed to take one cinnamon capsule three times daily after meals, for a total daily dose of 1500 mg. The remaining 33 patients were to take one placebo capsule three times daily. All patients also took a standard treatment of 10 mg daily of medroxyprogesterone for 10 days per month starting from day 15 of each menstrual cycle. The primary outcome of the study was insulin resistance, as measured by the HOMA-IR index. Secondary outcomes were patients' anthropometric profiles (weight, BMI, and waist circumference); biochemical parameters including fasting blood sugar (FBS), two-hour postprandial blood glucose, and lipid profile; and androgenic hormone assays to measure serum total testosterone and dehydroepiandrosterone sulphate levels. Three patients in the cinnamon group and two in the placebo group were not included in the final analyses because they missed follow-up visits. One patient in the cinnamon group discontinued the treatment because of a rash and itching, and one patient in the placebo group withdrew from the study because of travel plans. Four others, one in the cinnamon group and three in the placebo group, were noncompliant (more than three doses missed) but were included in intention-to-treat analyses. The final analyses included 29 patients in the cinnamon group and 30 patients in the placebo group. Compared with the placebo group, the cinnamon group had significantly greater reductions in fasting insulin (P=0.024), HOMA-IR index (P=0.014), and low-density lipoprotein cholesterol levels (P=0.049). Fasting insulin and HOMA-IR declined substantially over the course of the study in both groups, though significantly more so in the cinnamon group. Improvements were observed in the cinnamon group in body weight, BMI, waist circumference, FBS, two-hour postprandial blood glucose, total cholesterol, triglycerides, and serum androgenic hormone levels. However, the changes were mostly small and final figures were not significantly different from those in the placebo group. Testosterone significantly decreased in the cinnamon group from 0.82 ± 0.82ng/mL at baseline to 0.55 ± 0.28 ng/mL at the conclusion of the study (P=0.001); there was also a smaller significant decrease (P=0.041) in the placebo group. The rash and itching reported by one patient in the cinnamon group disappeared after the treatment was discontinued. No other serious adverse effects were reported. The use of progesterone therapy as standard treatment along with the study intervention in both groups is a limitation of this study, as the authors could not evaluate the effects of cinnamon on the patients' menstrual cycles. The therapy was used, however, because it was considered unethical to deprive any patient of standard medical treatment. Although the first evaluation of androgen was conducted during the follicular phase of all patients, final blood samples were drawn at the end of the study at 12 weeks, when some patients may have been in different phases of their menstrual cycle. According to the authors, this should be considered when interpreting the results of the androgenic hormone assays. Other limitations of this study include the lack of an ultrasound of the patients' ovaries at the end of the study, the small number of study patients, and the short duration. The fact that the placebo contained a small dose of cinnamon might have reduced differences between groups. The authors concluded that "cinnamon supplementation with the daily dose of 1.5 g for 12 weeks in combination with progesterone therapy was well tolerated and significantly improved insulin sensitivity and decreased insulin and LDL level in women with PCOS." The authors declared that they have no conflicts of interest. —Shari Henson