Healing of diabetic foot ulcer with topical and oral administrations of herbal products: A systematic review and meta-analysis of randomized controlled trials.

This systematic review aimed to qualitatively synthesize recent randomized controlled trials (RCTs) regarding the effect of topical application and oral intake of herbal products on the healing of diabetic foot ulcer (DFU). Also, we sought to pool the obtained findings in a meta-analysis using a random-effects model, if RCTs were relatively comparable and homogenous. A comprehensive search was performed on five electronic data sources from their inception through 23 January 2024. The RCTs, without restriction on the country of origin, were included if they compared the effect of administering standard treatments and/or placebo (i.e. control condition) to applying standard treatments and/or herbal products in topical or oral routes (i.e. experimental condition). Out of 1166 retrieved records, 28 RCTs were included. Studies used different poly and single herbal formulations. Based on the meta-analysis, administration of standard care plus daily dressing of the ulcer site with olive oil for 28 days significantly increased the total ulcer healing score (3 RCTs; weighted mean difference [WMD] = 89.30; p < 0.001), raised frequency of complete ulcer healing (2 RCTs; risk ratio [RR] = 12.44; p = 0.039) and declined ulcer degree (3 RCTs; WMD = -22.28; p = 0.002). Also, daily use of the bitter melon leaf extract in oral form for 28 days significantly increased the total ulcer healing score (2 RCTs; WMD = 0.40; p = 0.001). Additionally, based on qualitative synthesis, the adjuvant use of herbal agents seems an intriguing choice to manage DFU. Nonetheless, considering the undesirable methodological quality of most studies and the high heterogeneity in administered herbal formulations, more robust trials are required to build a solid conclusion regarding the use of herbal products for healing DFU.

Curcumin and zinc co-supplementation along with a loss-weight diet can improve lipid profiles in subjects with prediabetes: a multi-arm, parallel-group, randomized, double-blind placebo-controlled phase 2 clinical trial.

BACKGROUND: Diabetes is one of the major public health concerns. Prediabetes can increase the risk of developing some non-communicable diseases such as type 2 diabetes. Given the increasing trend of prediabetes, it is critical to control it and prevent its complications. Curcumin is a major bioactive component of turmeric. Zinc is an antioxidant nutrient. The present trial aimed to evaluate the effect of curcumin and zinc co-supplementation along with a loss-weight diet on serum lipid profiles in overweight or obese patients with prediabetes. METHODS: Eighty-four participants were randomized to four groups (curcumin (500 mg/day), zinc (30 mg/day), "curcumin and zinc", and placebo) for 90 days. Serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), non-HDL, HDL/LDL ratio, weight, BMI, waist circumstance (WC), hip circumstance (HC), physical activity (PA) and dietary intake were determined pre and post-intervention. This study will be conducted at Yazd Diabetes Research Clinic, Shahid Sadoughi University of Medical Sciences. RESULTS: Totally, 82 participants were included in the final analysis. After the adjusted PA effect, changes in serum TG (adjusted p = 0.001), LDL (adjusted p = 0.035), non-HDL (adjusted p = 0.003), HDL/LDL ratio (adjusted p = 0.002), and HDL (adjusted p < 0.0001) revealed a significant difference between the groups. However, the changes in weight (adjusted p = 0.004) and BMI (adjusted p = 0.006) were significant but the changes in dietary intake, PA, WC, and HC were non-significant (adjusted p ≥ 0.05). Despite that there was a significant difference for post-intervention HDL levels (adjusted p = 0.016), other lipid profiles showed no significant difference (adjusted p ≥ 0.05). CONCLUSION: The beneficial effects of "curcumin and zinc" co-supplementation was reported for the changes of some lipid profiles (TG, LDL, HDL, non-HDL, and HDL to LDL ratio), BMI, and weight with no positive effects on TC, dietary intake, PA, WC, and HC. Therefore, it may play a potential role in the prevention of macro and microvascular complications. Trial registration The project is a registered clinical trial (Registration number: IRCT20190902044671N1, Iranian Registry of Clinical Trials (IRCT), registered October 11, 2019.

The effect of different doses of vitamin D on the prognosis of patients undergoing carpal tunnel syndrome surgery.

Background and Objective: Vitamin D accelerates myelin repair and recovery after nerve damage. This study aimed to evaluate the effect of vitamin D on the prognosis of patients with carpal tunnel syndrome (CTS). Methods: A randomized clinical trial was conducted in the orthopedic ward of Golestan and Imam Khomeini hospitals in Ahvaz for 2 years (from October 2018 to October 2020). Patients were divided into three groups: the first group received 1,000 units of vitamin D daily, the second group received 4,000 units of vitamin D per week for the first 4-6 weeks and then 2,000 units per month, and the third group received no vitamin D supplementation. The results were compared before and after 6 months between the study groups. Results: A total of 105 patients were included in the study, who were divided into three groups. The mean age of the patients was 39.24 ± 7.01 years (25-52 years). The mean level of the vitamin D in the control group was 25.40 ± 8.37 ng/mL, the group receiving 1,000 units/day was 26.71 ± 8.70 ng/mL, and the group receiving 50,000 units per week was 26.17 ± 8.63 ng/mL. The mean values of preoperative pain intensity, symptom severity, and functional status were almost the same in the three groups. These values were reduced after surgery in the two groups receiving the drug compared to the control group. Conclusions: The findings of the study showed that the administration of vitamin D supplementation in patients with CTS can significantly improve the postoperative symptoms of patients who underwent tendon release surgery and further improve the severity of symptoms and dysfunction of patients.

The effect of curcumin and zinc co-supplementation on glycemic parameters in overweight or obese prediabetic subjects: A phase 2 randomized, placebo-controlled trial with a multi-arm, parallel-group design.

Management of prediabetes is a critical step to prevent type-2 diabetes. Curcumin and zinc have been studied as an antioxidant, antiinflammatory, and antidiabetic agents. In this clinical trial, 84 subjects were randomized into curcumin (500 mg), zinc (30 mg), zinc and curcumin, and placebo groups for 90 days. At the baseline and the end of the study, the outcomes (fasting plasma glucose (FPG), 2-hour postprandial glucose (2hpp), HbA1 C, insulin, insulin sensitivity (IS), insulin resistance (IR), ß-cell function (BCF), weight, body mass index (BMI), dietary intake, and physical activity (PA)) were measured. A hypocaloric diet and PA were recommended for all subjects. In total, 82 subjects completed the study. After the intervention, dietary intake, PA, weight, and BCF% did not show a significant difference among the groups. However, subjects taking only zinc and zinc and curcumin groups experienced decreased BMI compared to the placebo (p = .01 and .007, respectively). The three treated groups had improved FPG (p = .01), 2hpp (p = .003), HbA1C (p = .004), insulin (p = .001), IS% (p = .001), and IR (p < .001) compared to the placebo. Based on these results, zinc and curcumin supplementation exerted a beneficial effect on several key glycemic parameters.

Evaluation of the effect of curcumin and zinc co-supplementation on glycemic measurements, lipid profiles, and inflammatory and antioxidant biomarkers in overweight or obese prediabetic patients: a study protocol for a randomized double-blind placebo-controlled phase 2 clinical trial.

BACKGROUND: The prevalence of prediabetes is increasing worldwide. Unfortunately, prediabetes is related to non-communicable diseases. A high risk of developing type 2 diabetes mellitus (T2DM) is reported in people with prediabetes. Curcumin, a polyphenol, might lead to its therapeutic role in obesity and some obesity-related metabolic diseases. Zinc is a trace element that plays a key role in the synthesis and action of insulin, carbohydrate metabolism, and decreasing inflammation. There has been no clinical trial of zinc and curcumin co-supplementation in patients with prediabetes. In previous studies, the single administration of zinc or curcumin has not been conducted on many of the studied markers in prediabetic patients. METHODS: The purpose of this randomized double-blind placebo-controlled clinical trial is to investigate the effect of curcumin and zinc co-supplementation on glycemic measurements, lipid profiles, and inflammatory and antioxidant biomarkers among 84 prediabetic patients with body mass index (BMI) between 25 and 35. Also, liver enzyme, serum zinc, urine zinc, blood pressure, anthropometric parameters, quality of life, adherence to co-supplementation, the side effects of co-supplementation, physical activity, and dietary intake will be assessed. Women or men (18-50 years old for men and 18 years to before menopause for women) will be followed for 3 months (90 days). This study will be conducted at Yazd Diabetes Research Clinic, Shahid Sadoughi University of Medical Sciences. DISCUSSION: A diet rich in antioxidants, polyphenols, and phytochemicals has been shown to have a beneficial role in prediabetes. According to the beneficial properties of curcumin or zinc and inadequate evidence, RCTs are needed to assess the effect of curcumin and zinc co-supplementation in native prediabetes patients. We hope the results of the present trial, negative or positive, fill this gap in the literature and facilitate the approach for a much larger, multi-center clinical trial. In conclusion, a synergic effect of co-supplementation along with a weight-loss diet may delay the progression to type 2 diabetes mellitus. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT) IRCT20190902044671N1 . Registered on 11 October 2019.

The effects of vitamin D supplementation on adiponectin level and insulin resistance in first-degree relatives of subjects with type 2 diabetes: a randomized double-blinded controlled trial.

BACKGROUND: Despite the certain role of both vitamin D and adiponectin in the regulation of insulin sensitivity, the interaction between these two agents has remained uncertain. OBJECTIVE: The present study aimed to determine whether vitamin D is able to change plasma adiponectin and affect glucose homeostasis and insulin sensitivity in first-degree relatives of subjects with type 2 diabetes. METHODS: This randomized clinical trial was conducted at Clinic of Shahid Sadoughi Hospital in Yazd, Iran, from January 25, 2012 to December 25, 2014. In this randomized, double-blinded controlled trial, 64 first-degree relatives of type 2 diabetic patients were assigned randomly to receive either vitamin D supplement (50000 IU vitamin D tablet weekly) plus lifestyle change as the intervention group (n = 32) or placebo plus lifestyle change as the control group (n = 32) for twelve weeks (three months). RESULTS: Fifty-three patients (28 in the intervention group and 25 in the control group) completed the study. Serum levels of vitamin D increased while insulin level and consequently insulin resistance (calculated by HOMA formula) significantly decreased in the case group (p-value <0.001 for all variables). Although the values of these three biomarkers showed a slight increase in control group, the changes were not statistically significant. The levels of the changes in other markers including adiponectin, Fasting Blood Sugar (FBS), triglyceride, and total cholesterol remained insignificant in both study groups after completing interventions compared with before interventions. CONCLUSION: This study showed that decreased insulin resistance is expected by administrating vitamin D supplement in first-degree relatives of the patients with diabetes mellitus. TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: 201105176430N1. FUNDING: The authors received no financial support for the research or publication of this article.