Effects of dried okra extract on lipid profile, renal function and some RAGE-related inflammatory genes expression in patients with diabetic nephropathy: A randomized controlled trial.

BACKGROUND: Diabetic nephropathy (DN) is a common complication of type 2 diabetes. Okra (Abelmoschus esculentus L) is reported to have anti-diabetic effects. The present study aimed to investigate the effects of dried okra extract (DOE) supplementation on lipid profile, renal function indices, and expression of inflammatory genes, as well as serum level of soluble Receptor for Advanced glycation end products (sRAGE) in patients with DN. METHODS: In this triple-blind randomized placebo-controlled clinical trial, 64 eligible patients with DN received either 125 mg of DOE or placebo daily along with DN-related nutritional recommendations for 10 weeks. Changes in kidney indices including proteinuria and estimated glomerular filtration rate (eGFR), lipid profile, serum SRAGE, as well as the expression of RAGE, ICAM-1, and IL-1 genes were measured over 10 weeks. RESULTS: After adjustment for the potential confounders, between-group analyses showed no significant differences in terms of lipid profile, kidney function indices, sRAGE, and RAGE-related inflammatory genes expression after 10 weeks. CONCLUSION: Daily 125 mg DOE along with nutritional recommendations on top of usual care did not lead to significant changes in renal function indices, lipid profile, and inflammatory genes expression in patients with DN.

Exploring the impact of stage and tumor site on colorectal cancer survival: Bayesian survival modeling.

Colorectal cancer is a prevalent malignancy with global significance. This retrospective study aimed to investigate the influence of stage and tumor site on survival outcomes in 284 colorectal cancer patients diagnosed between 2001 and 2017. Patients were categorized into four groups based on tumor site (colon and rectum) and disease stage (early stage and advanced stage). Demographic characteristics, treatment modalities, and survival outcomes were recorded. Bayesian survival modeling was performed using semi-competing risks illness-death models with an accelerated failure time (AFT) approach, utilizing R 4.1 software. Results demonstrated significantly higher time ratios for disease recurrence (TR = 1.712, 95% CI 1.489-2.197), mortality without recurrence (TR = 1.933, 1.480-2.510), and mortality after recurrence (TR = 1.847, 1.147-2.178) in early-stage colon cancer compared to early-stage rectal cancer. Furthermore, patients with advanced-stage rectal cancer exhibited shorter survival times for disease recurrence than patients with early-stage colon cancer. The interaction effect between the disease site and cancer stage was not significant. These findings, derived from the optimal Bayesian log-normal model for terminal and non-terminal events, highlight the importance of early detection and effective management strategies for colon cancer. Early-stage colon cancer demonstrated improved survival rates for disease recurrence, mortality without recurrence, and mortality after recurrence compared to other stages. Early intervention and comprehensive care are crucial to enhance prognosis and minimize adverse events in colon cancer patients.

Effect of Zingiber officinale on Lipid Profile and Some Inflammatory Markers in Diabetic Hemodialysis Patients: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

Background: Diabetes, inflammation, and abnormal lipid levels are the main risk factors for mortality in end-stage renal disease (ESRD). The present study aimed to investigate the effects of ginger supplementation on inflammatory markers and lipid profile in diabetic patients with ESRD undergoing hemodialysis. Methods: In this study, 44 patients were randomly assigned to either the ginger or the placebo group. The patients in the ginger group received 2000 mg/d ginger for eight weeks, while the control group received the placebo with the same protocol. The serum concentrations of triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), high-density lipoprotein-cholesterol (HDL-c), albumin, and high-sensitivity C-reactive protein (hs-CRP) were measured after a 12- to 14-hours fast at the baseline and the end of the study, as along with the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and Glasgow prognostic score (GPS). Results: Forty-one subjects were analyzed based on the intention-to-treat method of all included patients. Serum levels of TG (p=0.003), hs-CRP (p=0.022), and NLR (p=0.001) decreased significantly in the ginger group compared to the placebo group, while albumin concentration in serum was elevated (p=0.022). However, there were no significant differences in GPS, levels of TC, LDL-C, HDL-C, and PLR within and between the groups (p > 0.05). Conclusion: Ginger administration reduced NLR, hs-CRP, and TG serum levels and increased serum albumin levels in included patients. Thus, ginger can be considered an effective complementary treatment for these patients. This trail is registered with IRCT20191109045382N3.

Effects of vitamin D supplementation on metabolic parameters, serum irisin and obesity values in women with subclinical hypothyroidism: a double-blind randomized controlled trial.

Purpose: Subclinical hypothyroidism is an early, mild form of hypothyroidism that may progress to overt hypothyroidism if untreated. The current study aimed to assess the effects of vitamin D supplementation on hormonal (thyroid stimulating hormone [TSH], triiodothyronine, thyroxine, and free thyroxine) parameters, lipid profiles, serum irisin, and obesity indices in women with subclinical hypothyroidism. Methods: The present randomized, double-blind, placebo-controlled clinical trial was carried out on 44 women with subclinical hypothyroidism. The participants were allocated to two groups (22 patients in each group) that received vitamin D (50,000 IU/week) or placebo for 12 weeks. Fasting blood samples, anthropometric and body composition measurements, physical activity levels, and dietary intakes were collected at baseline and at the end of the study. Results: Vitamin D supplementation significantly decreased TSH, total cholesterol, and fat mass percentage, and significantly increased serum vitamin D and irisin levels and fat-free mass percentage compared to the control group (all, p<0.05). Changes in thyroid hormones, other lipid profiles, and anthropometric indices were not significantly different between the groups. Conclusion: Our study indicates that vitamin D administration improves serum TSH, total cholesterol, irisin, and body composition in women with subclinical hypothyroidism. More well-designed clinical trials are required to confirm these findings and clarify the effects of vitamin D supplementation on both genders of patients.Clinical trial registration: https://www.irct.ir/trial/57482, Identifier IRCT20100408003664N25.

The Effect of Ginger (Zingiber officinale) on Improving Blood Lipids and Body Weight; A Systematic Review and Multivariate Meta-analysis of Clinical Trials.

BACKGROUND: Beneficial effects of ginger consumption on metabolic biomarkers has been reported previously. The current research aimed to investigate the effects of ginger supplementation on lipid profile and body weight using a meta-analysis of randomized, controlled trials. METHODS: Online databases PubMed, Embase, Web of Science, and Science Direct were searched until December 2021 to identify eligible articles. Twenty-six trials were included. RESULTS: The results showed that ginger consumption could significantly improve lipid profile including total triglyceride (-12.54 (-20.01 to -5.08)), cholesterol (-6.53 (-10.76 to -2.31)), LDL (-5.14 (-8.79 to -1.50)), and HDL (1.13 (0.35 to 1.91)). Moreover, ginger supplementation could significantly decrease body mass index (BMI) (-0.49 (-0.79 to -0.18)). However, the small number of sample studies that investigated reductions in body weight (-0.52 (-1.48 to 0.43)) were not statistically significant. Sub-group analysis of treatment dose and duration showed that in most of the analyzed lipid profiles, both ≤1500 and >1500 mg/d for both of ≤8 and >8 weeks could be effective; however, in the case of weight control dose of >1500 mg/d for more than 8 weeks was more effective. Besides, the results of multivariate meta-analysis revealed the effect of the intervention on all lipid profiles simultaneously. CONCLUSION: The present meta-analysis and review revealed that ginger supplementation can improve lipid profile and body weight if used at the appropriate dose and duration. More studies are needed to fully evaluate the effect of ginger supplements' different doses and duration on lipid profile and BMI.

The effects of butyrate supplementation on glycemic control, lipid profile, blood pressure, nitric oxide level and glutathione peroxidase activity in type 2 diabetic patients: A randomized triple -blind, placebo-controlled trial.

BACKGROUND: This study aimed to investigate the effects of oral NaBut on metabolic parameters, blood pressure, and oxidative stress indices including glutathione peroxidase (GPx) and nitric oxide (NO) status in type 2 diabetic patients. METHODS: In the current interventional trial, 42 patients with type 2 diabetes mellitus (T2DM) were randomly allocated into either NaBut (n = 21) or placebo (n = 21) group for six weeks. Serum concentrations of metabolic parameters, GPx, NO as well as blood pressure were assessed before and after the intervention. RESULTS: Within-group findings demonstrated that NaBut administration significantly reduced systolic and diastolic blood pressure (p = 0.016 and p = 0.002, respectively). Blood sugar 2-hr postprandial (BS2hpp) was also significantly decreased in the intervention and placebo groups (p = 0.016 and p = 0.019, respectively), but the between-group differences were not statistically significant. Differences in homeostatic model assessment of insulin resistance (HOMA-IR) were not significant between groups after adjustment for potential confounders (p = 0.061). NaBut supplementation was also found to significantly increase total cholesterol (p = 0.001), low-density lipoprotein cholesterol (p = 0.005), and insulin levels (p = 0.047) compared to the baseline, while decreased NO levels (p = 0.040). However, there were no significant between-group differences in these parameters. No significant differences were also found in other parameters. CONCLUSIONS: We observed significant within-group decreases in systolic and diastolic blood pressure as well as BS2hpp following oral butyrate treatment. While no or even adverse changes in other biochemical parameters were found. Further investigations with longer durations are warranted to more vividly elucidate the effects of NaBut supplementation on patients with T2DM. Registered under Iranian Registry of Clinical Trials website (http://www.irct.ir), Identifier no. IRC T20090609002017N33.

Effect of Oral and parenteral routes of vitamin D supplementation on serum 25(OH) vitamin D levels in patients with non-alcoholic fatty liver disease.

BACKGROUND: Due to the interruption of the EHC pathway in NAFLD patients, we hypothesized that parenteral vitamin D supplementation is superior to oral in vitamin D insufficient patients with NAFLD. Therefore, this study aimed to compare the efficacy of oral and parenteral routes of vitamin D supplementation on serum 25(OH) vitamin D levels in patients with NAFLD. METHODS: In this prospective randomized trial, 66 NAFLD cases with vitamin D deficiency were studied. For 33 cases, oral vitamin D was supplemented, whereas the other 33 patients were given an intramuscular injection of vitamin D. Laboratory tests and liver ultrasound were performed at the beginning and the end of the trial for each subject. RESULTS: Regardless of the drug administration route, at the end of this trial the mean of serum 25-hydroxy vitamin D level increased from 8.74±2.47 to 33.16±17.61 (P=0.00), and the mean±SD for serum triglyceride decreased from 191.46±92.79 to 166.00±68.30 (P=0.02), both were statistically significant. Liver ultrasound reported statistically significant changes in the grade of fatty liver disease (P=0.003). In the comparison between the two groups, serum 25-hydroxy vitamin D level changes were not statistically significant (P=0.788). CONCLUSION: The intramuscular method of supplementation was not better than the oral route in improving serum 25(OH) vitamin D levels in NAFLD patients. In this study, the impaired EHC and vitamin D absorption inhibitor factors in NAFLD patients did not affect the final result of serum vitamin D levels significantly.

Effects of curcumin supplementation on metabolic parameters, inflammatory factors and obesity values in women with rheumatoid arthritis: A randomized, double-blind, placebo-controlled clinical trial.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to cartilage damage with mostly accompanied by metabolic disorders. This study aimed to investigate the effects of curcumin supplementation on metabolic parameters (lipid profile and glycemic indices), inflammatory factors, visfatin levels, and obesity values in women with RA. This randomized, double-blind, placebo-controlled clinical trial was conducted on 48 women with RA. The patients were treated with curcumin (500 mg once a day) or placebo for 8 weeks. Fasting blood samples, anthropometric measurements, dietary intakes, and physical activity levels of subjects were collected at baseline and the end of the study. Curcumin supplementation significantly decreased homeostatic model assessment for insulin resistance (HOMA-IR), erythrocyte sedimentation rate, serum levels of high-sensitivity C-reactive protein and triglycerides, weight, body mass index, and waist circumference of patients compared with the placebo at the end of the study (p < .05 for all). HOMA-IR and triglyceride levels significantly increased within the placebo group. Changes in fasting blood sugar, insulin, other lipids profile, and visfatin levels were not significant in any of the groups (p > .05). These results support the consumption of curcumin, as a part of an integrated approach to modulate metabolic factors, inflammation, and adiposity in women with RA.

Effects of Melatonin and/or Magnesium Supplementation on Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial.

Magnesium and melatonin are known to exert multiple beneficial effects including anti-inflammatory and antioxidant actions. This study was designed to determine the effects of magnesium and/or melatonin supplementation on metabolic profiles in women with polycystic ovary syndrome (PCOS). This randomized double-blind, placebo-controlled trial was conducted among 84 subjects with PCOS aged 18-40 years old. Patients were randomly assigned based on the random block procedure to take magnesium, melatonin, magnesium plus melatonin, or placebo for 8 weeks. Fasting blood samples were taken at baseline and after the intervention to quantify related variables. After the 8-week intervention, an insignificant marginal difference was seen in waist circumference (WC) between groups (P = 0.085). Magnesium-melatonin co-supplementation resulted in more reductions in hirsutism compared with other groups (P < 0.001). Serum levels of tumor necrosis factor-α (TNF-α) declined significantly in the melatonin and co-supplementation groups compared to baseline (P < 0.05). Also, magnesium plus melatonin was associated with a more increase in total antioxidant capacity (TAC) levels, as compared to the other treatment groups (P = 0.001). Overall, we found a favorable effect of co-supplementation of magnesium and melatonin for 8 weeks in women with PCOS on hirsutism, serum TNF-α, and TAC levels. Furthermore, melatonin independently contributed to decreased serum values of TNF-α.Clinical trial registration number http://www.irct.ir : IRCT20191130045556N1, January 2020.

Metabolic and hormonal effects of melatonin and/or magnesium supplementation in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. This study was designed to investigate the effects of melatonin and/or magnesium supplementation on metabolic profile and levels of sex hormones in PCOS women. METHODS: In an 8-week randomized double-blind placebo-controlled trial, 84 subjects with PCOS aged 18-40 years were randomly assigned based on the random block procedure to take magnesium, melatonin, magnesium plus melatonin, and placebo. Fasting blood samples were obtained at the beginning and end of the study. RESULTS: After intervention, the mean Pittsburg Sleep Quality Index score decreased significantly in both co-supplementation and melatonin groups (P < 0.001). Magnesium supplementation in combination with melatonin resulted in a significant greater decrease in testosterone concentrations compared with the placebo (P < 0.05). Co-supplementation of magnesium-melatonin had significantly reduced serum insulin levels (geometric means difference: - 1.11 (mIU/mL) (percent change: - 15.99)), homeostasis model of assessment-insulin resistance (HOMA-IR) (- 0.28 (- 18.66)), serum cholesterol (mean difference: - 16.08 (mg/dl) [95% CI - 24.24, - 7.92]), low-density lipoprotein cholesterol (LDL-C) - 18.96 (mg/dl) [- 28.73, - 9.20]) and testosterone levels (- 0.09 (ng/ml) (- 25.00)), as compared to the baseline values (P < 0.05). An increase in serum high-density lipoprotein cholesterol (HDL-C) levels was also observed following the administration of the melatonin alone (2.76 (mg/dl) [0.57, 4.95]) or in combination with magnesium (2.19 (mg/dl) [0.61, 3.77]) (P < 0.05). CONCLUSIONS: Co-supplementation with magnesium and melatonin had beneficial effects on sleep quality and total testosterone. Additionally, melatonin supplementation alone was found to be associated with a significant reduction in PSQI score. Moreover, combined melatonin and magnesium supplementation was more effective in improving serum levels of cholesterol, LDL-C, HDL-C and insulin, and HOMA-IR. TRIAL REGISTRATION: Iranian Registry of Clinical Trial. http://www.irct.ir : IRCT20191130045556N1, January 2020.

Effect of French maritime pine bark extract supplementation on metabolic status and serum vascular cell adhesion molecule-1 levels in patients with type 2 diabetes and microalbuminuria.

OBJECTIVES: This study investigated the effect of French maritime pine bark extract (PBE) supplementation on metabolic parameters, vascular cell adhesion molecule 1 (VCAM-1), urinary albumin-to-creatinine ratio (UACR), and anthropometric indexes in patients with type 2 diabetes (T2DM) and microalbuminuria. DESIGN: This randomized, double-blind, placebo-controlled clinical trial was conducted on 46 patients with T2DM and the evidence of microalbuminuria aged 30-65 years. SETTING: Patients were recruited from the endocrinology clinic of Sina hospital (Tabriz, Iran) from March 2018 to April 2019. INTERVENTIONS: The subjects were randomly assigned to receive two capsules/day each containing 50mg of PBE or placebo for eight weeks. MAIN OUTCOME MEASURES: Glycemic parameters, serum VCAM-1 and lipid profile, UACR, and anthropometric indexes were measured for all patients at baseline and the end of the study. RESULTS: PBE supplementation significantly reduced glycosylated hemoglobin, VCAM-1, total cholesterol, UACR, waist circumference, and waist-to-height ratio compared to the placebo group at the end of the study (all P < 0.05). Changes in fasting blood glucose, insulin, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were not significant between the two groups (all P > 0.05). CONCLUSIONS: The study findings demonstrated some favorable effects of PBE supplementation on glycemic control, serum VCAM-1 and total cholesterol levels, and microalbuminuria, as well as abdominal obesity in patients with T2DM.

Nonpharmacological approaches to improve women's childbirth experiences: a systematic review and meta-analysis.

Background: Childbirth is considered a significant experience in women's life. Different models of care and interventions without pharmacological approaches have been used to enhance women's positive childbirth experiences, but the most effective interventions have not been clearly identified.Objective: To assess the effectiveness of nonpharmacological approaches in improving women's childbirth experiences.Methods: We searched Cochrane Library, Medline, Web of Science, Embase, Scopus, ProQuest, Google Scholar, and Persian databases (Magiran, Scientific Information Database, and Barakat) from inception until December 2017. Randomized controlled trials and quasi-randomized controlled trials comparing interventions designed to improve women's childbirth experiences with standard cares were included in this review. Pharmacological interventions were excluded from the study. The outcome measure was women's childbirth experience. Heterogeneity was determined using the Cochrane's test and I2 index. The standardized mean differences were pooled based on random effect models.Results: We included 19 studies (10,141 women) in the review. Results of the meta-analysis of 18 studies (8487 women) demonstrated that all the interventions with nonpharmacological approaches improved childbirth experiences (standardized mean difference: 0.49; 95% confidence interval: 0.33-0.66). But, subgroup meta-analysis showed that different models of midwifery care, support during labor and natural therapies were the most effective interventions in improving women's childbirth experience.Conclusions: Nonpharmacological interventions that enable women to feel supported, safe and respected can lead to improved childbirth experiences. However, there is a need for further studies with larger sample sizes and standardized tool to better assess the effectiveness of specific interventions on women's childbirth experiences.

Expression of NF-κB, IL-6, and IL-10 genes, body composition, and hepatic fibrosis in obese patients with NAFLD-Combined effects of oleoylethanolamide supplementation and calorie restriction: A triple-blind randomized controlled clinical trial.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common noncommunicable diseases worldwide. The present study aimed to investigate the effects of oleoylethanolamide (OEA) supplementation combined with calorie restriction on inflammation, body composition, and hepatic fibrosis among obese patients with NAFLD. In this 12-week randomized clinical trial, 76 obese patients newly diagnosed with NAFLD were randomly allocated into either OEA or placebo group. The weight-loss diet was also designed for both groups. Pre- and postintervention messenger RNA expression levels of the transcription factor nuclear factor-κB (NF-κB), interleukin-6 (IL-6) and IL-10, body composition, and NAFLD fibrosis score were assessed. At the end of the study, the OEA group showed lower NF-κB and IL-6 expression levels compared to the placebo (p < .01). However, IL-10 expression level was approximately twofold higher in the OEA group compared to the placebo group (p = .008). A significant reduction was observed in the fat mass of the OEA group compared to the placebo (p = .044) postintervention. In addition, OEA supplementation led to a significant increase in fat-free mass in the OEA group compared to the placebo (p = .032). A remarkable increase was observed in resting metabolic rate (RMR) in the OEA group (p = .009); however, it was not found in the placebo group. There were no significant between-group differences in RMR postintervention. In addition, no significant within-and between-group differences were observed in the NAFLD fibrosis score at the end of the trial. Treatment with OEA along with weight-loss intervention could significantly improve inflammation and body composition in patients with NAFLD.

The effects of royal jelly and tocotrienol-rich fraction on impaired glycemic control and inflammation through irisin in obese rats.

The effects of royal jelly (RJ) and tocotrienol-rich fraction (TRF) on obesity-induced glucose intolerance and inflammation were assessed in the current study. Regarding irisin as an important adipomyokine that attenuates obesity-induced disorders, we evaluated whether RJ and TRF could exert their metabolism regulatory effects through irisin. Obese rats were fed a high-fat diet (HFD) with or without supplementation of RJ, TRF, or both, for 8 weeks. At the end of the intervention, weight, irisin, glycemic, and inflammatory indices were measured. The weight of the rats did not remarkably reduce in any of the groups. Glucose homeostasis and inflammation were improved when we added RJ and TRF to HFD. RJ elevated irisin concentration, but the effect of TRF on irisin was not noticeable. Our results indicated that, despite the lack of significant weight loss, RJ and TRF promoted healthy obesity. This improvement was mediated by irisin in RJ consuming rats. PRACTICAL APPLICATIONS: Obesity is a public health concern associated with several chronic disorders. The beneficial effects of irisin on obesity-related disorders are well-established. It is the first study assessing the effect of RJ and TRF as functional foods, with pharmacological and nutritional activities on obesity complications, through irisin mediation. Our study demonstrated that RJ exerts its metabolic regulatory effects by irisin as a mediator. Our investigation makes a remarkable contribution to the literature, because it suggests a new mechanism for the anti-obesity properties of RJ and TRF.

The effect of royal jelly and tocotrienol-rich fraction along with calorie restriction on hypothalamic endoplasmic reticulum stress and adipose tissue inflammation in diet-induced obese rats.

OBJECTIVES: Endoplasmic reticulum (ER) stress causes adipose tissue dysfunction and chronic inflammation in obesity. Royal jelly (RJ) and tocotrienol-rich fraction (TRF) are reported to ameliorate inflammation. However, the improving effects of RJ and TRF on inflammation from ER stress modulating view have not been assessed so far. Hence, we investigated the effect of RJ and TRF on ER stress and some adipose tissue-derived inflammatory markers in the high-fat diet (HFD)-induced obesity. Wistar obese rats randomly allocated into 5 groups: HFD, calorie restriction diet (CRD), RJ + CRD, TRF + CRD, RJ + TRF + CRD. After 8-week intervention, adipose tissues and hypothalamus were dissected and serum was collected. RESULTS: RJ reduced glucose-regulated protein-78 (GRP78) expression as ER stress indicator in WAT and hypothalamus compared to CRD. Besides, RJ diminished the expression of inflammatory markers in white adipose tissue (WAT) and also decreased the serum concentration of them. TRF reduced inflammatory markers in the serum without remarkable effects on ER stress. Overall, RJ has protective effect against adipose tissue dysfunction and inflammation then suggested as a therapeutic approach to reduce some obesity-related complications. The impact of TRF in this regard is lower than RJ and limited to systemic inflammation improvement without remarkable changes in adipose tissue inflammation.

Whey protein supplementation reducing fasting levels of anandamide and 2-AG without weight loss in pre-menopausal women with obesity on a weight-loss diet.

BACKGROUND: Despite the importance of dairy proteins in modifying of metabolic abnormalities, no attention has been given to their effects on endocannabinoids. METHODS: A total number of 60 obese women were recruited in a 2-month randomized clinical trial. Following random allocation, they were assigned to one of the two groups: control (n = 30) and intervention (n = 30). Then, all the subjects followed a hypocaloric diet of 800 kcal below estimated energy needs. The intervention group received isocaloric weight-loss diet and whey protein powders (30 g/day). Baseline and 2-month fasting anthropometric, blood glucose, serum insulin, insulin resistance, lipid profile, AEA, and 2-AG were measured. RESULTS: The study groups were homogenous in terms of baseline characteristics (p > 0.05) except for MUFA intake (p = 0.021). There were no significant differences in energy and macronutrient intakes in the intervention group compared to the control group at the end of the study (p > 0.05). The results of the ANCOVA did not show significant reductions in body weight and BMI of the intervention group compared to the control group (p > 0.05); however, WC, body fat, FBS, AEA, 2-AG, total cholesterol, and triglyceride decreased and HDL-c significantly increased in the intervention group compared to the control group (p < 0.05). CONCLUSIONS: In this study, the effects of simultaneous weight-loss diet and whey protein supplementation on the reduction of endocannabinoids were determined. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT2017021410181N8 . Registered on March 2017.

Effects of Royal Jelly and Tocotrienol Rich Fraction in obesity treatment of calorie-restricted obese rats: a focus on white fat browning properties and thermogenic capacity.

BACKGROUND: Obesity has reached an alarming rate worldwide. Promoting thermogenesis via increasing the function of brown adipose tissue (BAT) or white adipose tissue (WAT) browning has been proposed as a new protective approach against obesity. The goal of this study was to evaluate the effects of Royal Jelly (RJ) and tocotrienol rich fraction (TRF) on BAT activation and WAT browning during calorie restriction diet (CRD) in obesity model. METHODS: In this experimental study, 50 obese Wistar rats were randomly divided into 5 groups and then received one of the following treatments for a period of 8-week: High-fat diet (HFD), CRD, RJ + CRD, TRF + CRD, and RJ + TRF + CRD. Effects of RJ and TRF, individually and in combination on body weight and the expression of key thermoregulatory genes in WAT and BAT were examined by quantitative real-time (qRT-PCR). Also, morphological alterations were assessed by hematoxylin and eosin staining. RESULTS: RJ (- 67.21 g ±4.84 g) and RJ + TRF (- 73.29 g ±4.51 g) significantly reduced weight gain relative to the CRD group (- 40.70 g ±6.50 g, P < 0.001). In comparison with the CRD group, RJ and RJ + TRF remarkably enhanced the uncoupling protein1 (UCP1) expression in WAT (5.81, 4.72 fold, P < 0.001) and BAT (4.99, 4.75 fold, P < 0.001). The expression of PR domain containing 16(PRDM 16), cAMP response element-binding protein1 (CREB1), P38 mitogen-activated protein kinases (P38MAPK), and Bone morphogenetic protein8B (BMP8B) have significantly increased following RJ and RJ + TRF treatments (P < 0.001). However, the expression levels of CCAAT/enhancer-binding protein beta (CEBPß) and Bone morphogenetic protein7 ( BMP7) did not remarkably change. Multilocular beige cells in WAT and compacted dense adipocytes were also observed in BAT of RJ and RJ + TRF received groups. TRF showed no substantial effects on the expression of the mentioned thermoregulatory genes and brown fat-like phenotype. CONCLUSION: Our results suggest that, Royal Jelly promotes thermogenesis and browning of WAT, contributing to an increase in energy expenditure. Thus, Royal Jelly may give rise to a novel dietary choice to attenuate obesity.

Oleoylethanolamide supplementation in obese patients newly diagnosed with non-alcoholic fatty liver disease: Effects on metabolic parameters, anthropometric indices, and expression of PPAR-α, UCP1, and UCP2 genes.

The effects of oleoylethanolamide (OEA) on NAFLD are yet to be examined in human. The objective of the present study was to examine the effects of OEA supplementation along with weight loss intervention on the expression of PPAR-α, uncoupling proteins 1and 2 (UCP1 and UCP2) genes in the peripheral blood mononuclear cells (PBMCs), metabolic parameters, and anthropometric indices among obese patients with NAFLD. In this triple-blind placebo-controlled randomized clinical trial, 76 obese patients newly diagnosed with NAFLD were randomly allocated into either OEA or placebo group along with calorie-restricted diets for 12 weeks. At pre-and post-intervention phase, mRNA expression levels of PPAR-α, UCP1, and UCP2 genes in the PBMCs, serum levels of metabolic parameters as well as diet and appetite sensations were assessed. There was a significant increase in the expression levels of PPAR-α, UCP1, and UCP2 genes in the PBMCs, compared to the placebo at the endpoint. A significant decrease in the anthropometric indices, energy and carbohydrate intakes, glycemic parameters, except for hemoglobin A1c concentration was also observed in the OEA group, compared to the placebo group. OEA treatment significantly resulted in decreased serum levels of triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, increased serum levels of high-density lipoprotein cholesterol (HDL-C), and improved appetite sensations. Importantly, a significant improvement in TG, ALT, AST, ALT/AST, HDL-C levels as well as appetite sensations by OEA were under the influence of body mass index (BMI). Although liver steatosis severity was significantly reduced in both groups, the between-group differences did not reach statistical significance (P = 0.061). In conclusion, the present study, for the first time, revealed that OEA supplementation significantly improved anthropometric and metabolic risk factors related to NAFLD.

Effect of green coffee extract supplementation on serum adiponectin concentration and lipid profile in patients with non-alcoholic fatty liver disease: A randomized, controlled trial.

OBJECTIVES: The current study evaluated the effects of green coffee extract (GCE) on serum lipid profile and adiponectin levels in patients with nonalcoholic fatty liver disease (NAFLD). DESIGN: This randomized, double-blind, placebo-controlled clinical trial was conducted on NAFLD patients aged 20-60 years and body mass index (BMI) of 25-35 kg/m2. SETTING: Patients were recruited from the Bahman poly-clinic (Neyshabur, Iran) between January and June 2016. INTERVENTIONS: The study subjects were randomly assigned to receive a daily dose of 400 mg GCE (n = 24) or placebo (n = 24) for eight weeks. MAIN OUTCOME MEASURES: Serum liver enzyme levels, lipid profile, adiponectin concentrations, and hepatic steatosis grade were measured for all patients at baseline and the end of the trial. RESULTS: GCE supplementation significantly reduced BMI [mean difference (MD): -0.57 and 95 % confidence interval (CI): -0.84 to -0.29, P < 0.001] and increased serum high-density lipoprotein cholesterol (MD: 7.06, 95 % CI: 0.25-13.87, P < 0.05) compared to the control group. Serum total cholesterol decreased significantly within the GCE group (MD: -13.33, 95 % CI: -26.04 to -0.61, P < 0.05). Triglyceride levels reduced significantly in GCE group compared to the placebo group (MD: -37.91; 95 % CI: -72.03 to -3.80; P = 0.03). However, this reduction was not significant when was further adjusted for mean changes in BMI and daily energy intake (MD: -23.43; 95 % CI: -70.92 to 24.06; P = 0.32). Hepatic steatosis grade, liver enzymes, and adiponectin levels did not show significant differences between the two groups after the intervention. CONCLUSIONS: GCE supplementation improved serum lipid profile and BMI in individuals with NAFLD. GCE may be useful in controlling NAFLD risk factors.

The effect of crocetin supplementation on markers of atherogenic risk in patients with coronary artery disease: a pilot, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND AND PURPOSE: Molecular mechanisms of atherogenesis are considered to be emerging therapeutic targets for atherosclerosis prevention. Cell and animal studies have shown that crocetin can decelerate atherogenesis. However, the anti-atherogenic properties of crocetin in humans are still ambiguous. METHODS AND RESULTS: Fifty clinically diagnosed CAD patients were randomly divided into two parallel groups, crocetin and placebo, who received one capsule of crocetin (10 mg) and placebo per day, respectively, for two months. Serum circulating homocysteine (Hcy) [-1.09 (-1.64 to -0.54) µM, P = 0.001], heart-type fatty acid binding protein (h-FABP) [-2.07 (-2.72 to -1.43) ng mL-1, P = 0.001], intercellular adhesion molecule 1 [-14.92 (-21.92 to -7.92) ng mL-1, P = 0.001], vascular cell adhesion molecule 1 [-18.61 (-29.73 to -7.49) ng mL-1, P = 0.002], and monocyte chemoattractant protein 1 [-4.67 (-6.50 to -2.83) pg mL-1, P = 0.001] decreased significantly after the trial in the crocetin group, while high-density lipoprotein (HDL) significantly increased [+4.21 (0.68 to 7.73) mg mL-1, P = 0.021]. Also, systolic [-0.21 (-0.32 to -0.10) mmHg, P = 0.001] and diastolic [-0.20 (-0.34 to -0.07) mmHg, P = 0.004] blood pressures decreased significantly in the crocetin group. Nevertheless, clinically significant percentage changes were only observed in Hcy (-15.25 ± 3.15, µM), HDL (-10.70 ± 5.06, mg dL-1), and h-FABP (-21.10 ± 3.09, ng mL-1) in the crocetin group. Furthermore, the relative increase in the gene expressions of sirtuin1 and AMP-activated protein kinase and a decrease in the lectin-type oxidized LDL receptor 1 and nuclear factor-kappa B expression in isolated peripheral blood mononuclear cells in the crocetin group were significant at the end of the trial in comparison with the placebo. CONCLUSION: As the first human study, we showed the ability of crocetin to alter the expression of atherogenic genes and endothelial cell adhesion molecules in CAD patients. It appears that crocetin could be considered as a promising anti-atherogenic candidate for future studies.