Lower glycemic indices and lipid profile among type 2 diabetes mellitus patients who received novel dose of Silybum marianum (L.) Gaertn. (silymarin) extract supplement: A Triple-blinded randomized controlled clinical trial
Graphical abstract
Introduction
Type 2 diabetes mellitus (T2DM) is a metabolic dysfunction of the endocrine system (Marín-Peñalver et al., 2016) which is defined as both inability of insulin to activate the glucose transport system in insulin-dependent tissues and an inappropriate compensatory hyperinsulinemia to overcome this insulin resistance (Henriksen et al., 2011). Diabetes is a global health concern in developing as well as developed countries due to its worldwide increasing prevalence (Marín-Peñalver et al., 2016, Baluchnejadmojarad and Roghani, 2009). The number of patients is expected to increase by 50% in the next 20 years (Rains and Jain, 2011). Maintenance of blood glucose levels within normal range is one of the major goals in diabetes management, because uncontrolled chronic hyperglycemia is responsible for several complications including retinopathy, nephropathy and neuropathy (Evans et al., 2002). Despite the use of appropriate oral hypoglycaemic drugs, majority of patients referred to clinicians have hyperglycaemia. It may be the result of poor adherence to hypoglycaemic drugs, possibly due to their side effects (Chaudhury et al., 2017, Khan and Siddiqui, 2012). The adverse effects of oral hypoglycaemic medications have led to a growing interest among T2DM patients in the use of natural products with anti-diabetes activity (Li et al., 2004). One of such potential remedy is Complementary and Alternative Medicine (CAM), in particular, Silybum marianum (L.) Gaertn (Khan and Siddiqui, 2012). S. marianum (L.) Gaertn. is an ancient medicinal plant which has been used for centuries in the treatment of several diseases such as liver and gastrointestinal disorders (Martinelli et al., 2017, Karimi et al., 2011). Seed extract of S. marianum has many chemical constituents collectively known as silymarin, which has powerful antioxidant properties (Karimi et al., 2011). An important factor that impairs insulin homeostasis and consequently leads to insulin resistance, lipid profile alteration and blood glucose impairment is oxidative stress (Henriksen et al., 2011); favorable effects of antioxidant agents in the treatment of metabolic disorders in diabetes have been reported in several studies (Stolf et al., 2017, Ebrahimpour koujan et al., 2015, Huseini et al., 2006). The authors of the current study reported on the antioxidant potential and anti-inflammatory effect of silymarin on TD2M patients (Ebrahimpour koujan et al., 2015). Moreover, some trials have demonstrated that improving glycemic control does not remarkably improve oxidative stress (Hussain, 2007). Thus, specific therapies directed towards oxidative stress and hyperglycemia are needed. Silymarin prevented both plasma glucose increase and pancreatic lipid peroxidation in alloxan-induced diabetes rats (Soto et al., 1998). Although, several clinical trials were conducted to evaluate the effects of silymarin on some disorders related to diabetes such as blood glucose and lipid profile (Khan and Siddiqui, 2012, Hussain, 2007, Huseini et al., 2006), there were major controversies in the results of these trials. These studies applied different dosages and sample size. Also, their study design and results could not suggest applicable and appropriate dose for clinical practice. Given the inconsistencies in previous findings, it seems that additional data from clinical studies, controlling for a wide range of confounders, are required to shed light on this issue. Therefore, the present placebo-controlled, randomized, triple-blinded, clinical trial was designed to investigate the effects of silymarin on glycemic control and lipid profile of T2DM patients.
Section snippets
Patients
Forty T2DM patients (twenty male and twenty female), aged 25–50 years, participated in this study. All the subjects had been diagnosed of diabetes for at least 6 month prior to enrollment in the study and were recruited from the Iranian Diabetes Society in East Azarbaijan (Tabriz, Iran) and Endocrinology and Metabolism Clinics, Tabriz University of Medical Sciences (Tabriz, Iran). Inclusion criteria for the study comprised of: diagnosis of T2DM based on the World Health Organization guidelines
Outcomes
The primary outcomes of the present clinical trial according the aims of the study were effects of S. marianum (L.) Gaertn. (silymarin) extract supplementation on concentrations of fasting blood sugar (FBS), Insulin, Homeostasis Model Assessment-Insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and TG/HDL-c ratio. The secondary
Intervention
All the patients, researcher, endocrinologist, laboratory staff and the statistical analyst were blinded to the trial grouping. After a week run-out period, they received their treatments. In the run-out period, the patients were asked to adhere to their habitual diet and should not change their diet and physical activity a week before the trial. During this period, they were educated on food table and also how to report their 24 h recalls. Intervention started in run-in period after run-out
Results
All the patients (forty) completed the 45 days clinical trial. Participants did not report any adverse effects or symptoms with the silymarin supplementation during the study and had good compliance with the intervention. There were no significant differences between groups in terms of age, sex, duration of diabetes, dose and duration of metformin, glibenclamide and lipid lowering drugs intake; and anthropometric measures including height, weight, BMI and WC at the start of study. (p ˃ 0.05).
Discussion
There are evidences that silymarin, a powerful antioxidant, can ameliorate metabolic disorders in diabetes (Huseini et al., 2006, Soto et al., 1998). Based on literature review, the present work is the first to investigate the effectiveness of 140 mg silymarin thrice daily supplementation on metabolic status of T2DM patients.
The results showed that adjuvant treatment with silymarin significantly reduced FBS, insulin, HOMA-IR and increased QUICKI in the intervention group as compared to baseline
Conflict of interest
We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.
Acknowledgments
The present study was written based on the data for MS thesis on nutrition and funded by the Vice-Chancellor for Research of Tabriz University of Medical sciences, Tabriz, Iran. Laboratory tests of the study were performed in the Drug Applied Research Center of Tabriz University of Medical Sciences, Tabriz, Iran. We sincerely thank the management of the Iranian Diabetes Society in East Azarbaijan (Tabriz, Iran) as well as Mr. Haghighi for their valuable support. The authors would also like to
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2021, Obesity MedicineCitation Excerpt :The pooled effect size from 6 studies (Ebrahimpour-Koujan et al., 2018; Fallahzadeh et al., 2012; Huseini et al., 2006; Ramezani et al., 2008; Velussi et al., 1997; Elgarf et al., 2015) showed no significant diffrences on TG (MD: 36.40, 95% CI [-89.52, 16.72], P = 0.179), but the studies were significantly heterogeneous (I2 = 94.2%, P = 0.000) (Fig. 5.). The effect of silymarin on LDL-C was evaluated in 5 trials (Ebrahimpour-Koujan et al., 2018; Fallahzadeh et al., 2012; Huseini et al., 2006; Ramezani et al., 2008; Elgarf et al., 2015). Our results showed a significant reduction in LDL-C after the intervention (MD: 23.88, 95% CI [-44.35, −3.41], P = 0.02).
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Chemical compounds: Silymarin (PubChem CID: 31553).