Theobromine supplementation in combination with a low-calorie diet improves cardiovascular risk factors in overweight and obese subjects with metabolic syndrome: a randomized controlled trial.

Background & aims: The beneficial effects of theobromine (TB) on obesity and features of metabolic syndrome (MetS) have been reported in several studies. However, the findings are equivocal. The present study aimed to investigate the effects of 12 week pure TB supplementation (450 mg day-1) combined with a low-calorie diet on the anthropometric and metabolic syndrome indices in overweight and obese adults with MetS. Methods: In a randomized double-blind parallel controlled trial, 80 participants aged 40-55 years were randomly assigned to take 450 mg day-1 TB or placebo along with a low-calorie diet for 12 weeks. Dietary intake, anthropometric indices, blood pressure, lipid profile and glycemic indices were assessed at the start and end of the intervention. Results: Seventy-two participants completed the study. After 12 weeks, TB supplementation significantly decreased the waist circumference (WC) (-0.86 cm; P = 0.045), LDL-c/HDL-c (-0.26; P = 0.008), TG/HDL-c (-0.41; P = 0.001), TC/HDL-c (-0.38; P = 0.006) and increased HDL-c (1.72 mg dl-1; P = 0.036) compared to the placebo group. There were no significant differences regarding body weight, BMI, hip circumference (HC), hip-to-waist circumference ratio (WHR), systolic and diastolic blood pressure, fasting levels of total cholesterol (TC), triacylglycerol (TAG), low-density lipoprotein cholesterol (LDL-c), fasting blood glucose, insulin, homoeostatic model assessment for insulin resistance (HOMA-IR) and homeostasis model assessment of ß-cell function (HOMA-ß) between the two groups (p > 0.05). Conclusion: The results of the current study revealed that TB supplementation along with a low-calorie diet had favorable effects on WC, LDL-c/HDL-c, TG/HDL-c, TC/HDL-c, and serum level of HDL-c in overweight and obese subjects with MetS. Trial registration number: IRCT20091114002709N59. Registration date: 5 March 2022.

A comprehensive insight into the molecular effect of theobromine on cardiovascular-related risk factors: A systematic review of in vitro and in vivo studies.

Theobromine may have beneficial effects on cardiovascular risk factors. This study aimed to find molecular effects of theobromine on lipid profile, glycemic status, inflammatory factors, and vascular function through a comprehensive assessment of all in vitro and in vivo studies. The search process was started at 18 July 2022. Databases including PubMed, Scopus, and Web of Science were searched to find all articles published up to 18 July 2022. Nineteen studies were included in this study. In vitro studies showed the improving effects of theobromine on inflammatory markers. Of four animal studies assessing the effect of theobromine on inflammatory markers, two reported favorable effects. Among five animal studies assessing the effects of theobromine on lipid profile, three reported improving effects on either triglyceride, total cholesterol, low- or high-density lipoprotein cholesterol. Of the three human studies, two revealed that theobromine had improving effects on lipid profile. A favorable effect of theobromine on augmentation index was also reported in two RCTs. The results for other outcomes were inconclusive. Theobromine may have favorable effects on inflammatory factors, lipid profile, and vascular function markers. However, studies with a longer duration and lower, dietary-relevant doses are required for future confirmation.

The effect of resveratrol supplementation on biomarkers of liver health: A systematic review and meta-analysis of randomized controlled trials.

This study aimed to evaluate the effect of resveratrol on liver biomarkers in adult participants, using systematic review and meta-analysis of randomized controlled trials. PubMed, Scopus, Web of Science and Cochran Library was searched, up to October 2021. The pooled effects were calculated using a random-effects model and expressed as weighted mean difference and 95% confidence interval. The methodological quality of studies as well as certainty of evidence were assessed by standard tools. Thirty-seven relevant trials were found. Although overall analysis found no significant change, subgroup analysis showed a significant improvement in alanine aminotransferase (ALT; -7.79 U/L) and glutamyl transferase (-6.0 U/L) in patients with liver disorders, and ALT (-2.22 U/L) in younger adults; however, high-dose supplementation (>1,000 mg/day) appeared to increase alkaline phosphatase concentration (+5.07 U/L). ALT also increased in older adults (+2.33 U/L) following resveratrol supplementation. We found resveratrol did not have a significant effect on liver health in the general population. However, resveratrol could be effective in patients with liver disorders. Our findings also suggest that high-dose resveratrol administration and supplementation in older adults should be performed with caution. Further high-quality clinical trials are also needed to firmly establish the clinical efficacy of resveratrol.

Comparing the effects of docosahexaenoic and eicosapentaenoic acids on cardiovascular risk factors: Pairwise and network meta-analyses of randomized controlled trials.

BACKGROUND: Evidence from clinical trial studies suggests that docosahexaenoic acids (DHA) may have greater potential effects on improving cardiovascular risk factors than eicosapentaenoic acid (EPA). However, this evidence has not yet been meta-analyzed and quantified. The aim of this study was to evaluate and compare the effect of DHA and EPA monotherapy on cardiovascular risk factors based on paired and network meta-analysis. METHODS: Relevant articles published up to January 2022 were systematically retrieved from relevant databases. We included all Randomized Controlled Trials (RCTs) on adults that directly compared the effects of DHA with EPA and RCTs of indirect comparisons (DHA and EPA monotherapy compared to control groups). Data were pooled by pairwise and network meta-analysis and expressed as mean differences (MDs) with 95% CIs. The study protocol was registered with PROSPERO (Registration ID: CRD42022328630). RESULTS: Network meta-analysis of comparisons of DHA and EPA suggested significant comparable effects only on LDL-C (MD EPA versus DHA = -8.51 mg/L; 95% CI: -16.67; -0.35). However, the Network meta-analysis not show a significant effect for other risk factors. Furthermore, pairwise meta-analysis of direct comparisons of DHA and EPA showed significant difference in their effects on plasma glucose (MD EPA versus DHA = -0.31 mg/L; 95% CI: -0.60, -0.02), Insulin (MD EPA versus DHA = -2.14 mg/L; 95% CI: -3.26, -1.02), but the results were not significant for risk factors. CONCLUSION: Our findings suggest that both EPA and DHA act similarly on the markers under study, with slight changes in plasma glucose, insulin, and LDL-C.

The effect of lycopene supplement from different sources on prostate specific antigen (PSA): A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Prostate cancer is a major malignancy, affecting men, worldwide. The protective effect of dietary or supplemental lycopene on prostate cancer has been reported in several studies; however, the findings are equivocal. OBJECTIVE: The aim of this study was to evaluate the effects of supplemental lycopene on PSA level, by conducting a systematic review and meta-analysis of randomized controlled trials. METHODS: We searched online databases, including PubMed, Scopus, and Web of Science, up to 9 Jun 2020, to obtain relevant publications. The publication search was not limited by language or date. RESULTS: A total of 1036 records were identified in the systematic search; from these, 9 were included in the systematic review and 6 in meta-analysis. The pooled analysis of the 6 studies showed no significant differences in PSA levels in subjects treated with lycopene or tomato extract containing lycopene (WMD= -0.12 ng/ml; 95% CI: -0.62, 0.38 ng/ml; P = 0.64) compared to the control. CONCLUSION: Overall, tomato extracts or lycopene treatment yielded no significant effect on PSA level compared to the control. However, more consistent clinical trials, with larger sample sizes, are required to better discern the actual effect of tomato extract or lycopene on PSA level.

Role of whey protein in vascular function: a systematic review and meta-analysis of human intervention studies.

Whey protein (WP) has been heavily appreciated as a rich source of bioactive peptides, with potential benefits for cardiovascular health. This study constitutes a systematic review and meta-analysis summarising the effects of WP consumption on vascular reactivity, arterial stiffness and circulatory biomarkers of vascular function. We searched electronic databases, including PubMed, SCOPUS and Web of science for relevant articles from inception to July 2020. Original clinical trials published in English-language journals that investigated the effects of WP on vascular function were eligible. A total of 720 records were identified in the initial search; from these, sixteen were included in our systematic review and thirteen in meta-analysis. The pooled analysis of six studies showed a significant increase in flow-mediated dilation (FMD) after WP consumption (weighted mean differences (WMD): 1·09 %, 95 % CI: 0·17, 2·01, P= 0·01). Meta-analysis of available data did not show any significant reduction in arterial stiffness measures including augmentation index (effect sizes: 7, WMD: -0·29 %, 95 % CI: -1·58, 0·98, P= 0·64) and pulse wave velocity (effect sizes: 4, WMD: -0·72 m/s, 95 % CI: -1·47, 0·03, P= 0·06). Moreover, the pooled analysis of six effect sizes showed no significant effects on plasma levels of nitric oxide following WP supplementation (WMD: 0·42 µmol/l, 95 % CI: -0·52, 1·36, P= 0·38). The overall results provided evidence supporting a protective effect of WP on endothelial function measured by FMD, but not for arterial stiffness measures and circulatory biomarker of vascular function. Further research is required to substantiate the benefits of WP on vascular function.

Effects of alpha lipoic acid on iron overload, lipid profile and oxidative stress indices in ß-thalassemia major patients: A cross-over randomised controlled clinical trial.

AIMS: ß-Thalassemia major (ß-TM) is associated with iron overload, abnormal lipid levels and oxidative stress. Alpha lipoic acid (ALA) showed anti-oxidant and iron chelating properties, but its effect in ß-TM patients is unclear. We investigated the effects of ALA on iron levels, lipid profile and oxidative stress. METHODS: In this cross-over randomised clinical trial, 26 ß-TM patients were assigned to receive 600 mg/d ALA or placebo (corn starch), for 8 weeks with a 21-days washout period. Serum ferritin, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C, total antioxidant capacity, malondialdehyde (MDA) and MDA/LDL-C were assessed at baseline and the end of each intervention phase. RESULTS: Twenty-two patients completed the study. Serum ferritin (P = .004), MDA (P = .025) and MDA/LDL-C ratio (P =.002) were decreased and HDL-C (P =.035) increased significantly during ALA consumption. In comparison with placebo, ALA decreased the serum ferritin significantly (P = .02). Also, the changes in serum ferritin between ALA and placebo (-123.1 ± 40.0 vs -34.3 ± 21.0, P =.03) was significant in women subgroup. ALA had no significant effects on the other biomarkers. CONCLUSION: The results of this study indicated that supplementation with 600 mg/d ALA may decrease serum ferritin in ß-TM. Further studies are needed to confirm the findings.

The effect of green tea on prostate specific antigen (PSA): A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Prostate cancer is a major malignancy, affecting men, worldwide. The protective effect of green tea consumption on prostate cancer has been reported in several studies; however, the findings are equivocal. OBJECTIVE: The aim of this study was to evaluate the effects of green tea on PSA level, by conducting a systematic review and meta-analysis of randomized controlled trials. METHODS: We searched online databases, including PubMed, Scopus, and Web of Science, up to 11 Aug 2020, to obtain relevant publications. The publication search was not limited by language or date. RESULTS: A total of 2488 records were identified in the systematic search; from these, seven were included in the meta-analysis. The overall analysis showed no significant changes in PSA levels in subjects treated with green tea, (WMD: ‒0.60 ng/mL; 95 % CI: ‒1.32, 0.12 ng/mL; P = 0.104, I2 = 93.80 %, P heterogeneity<0.001). Subgroup analysis based on geographical location showed that green tea significantly reduced PSA level in the USA population (WMD: ‒1.02 pg/mL, 95 % CI: ‒1.30, ‒0.73, P < 0.001) compared to non-USA populations (WMD: ‒0.22 pg/mL, 95 % CI: ‒0.95, 0.50, P = 0.539) (P < 0.001). CONCLUSION: The results of this review show that green tea has no significant effect on PSA level. However, due to the heterogeneity among studies more consistent clinical trials, with larger sample sizes are required.

Effects of Alpha-Lipoic Acid Supplementation on Cardiovascular Disease Risk Factors in ß-Thalassemia Major Patients: A Clinical Trial Crossover Study.

AIM: Thalassemia is one of the most common genetic diseases, and cardiovascular disease (CVD) has been considered as the leading cause of mortality in more than 50% of ß-thalassemia patients. The aim of this study was to determine the effects of alpha-lipoic acid (ALA) on CVD risk factors in ß-thalassemia major patients. METHODS: Twenty ß-thalassemia major patients participated in this randomized crossover clinical trial study. Participants were randomly assigned to ALA (600 mg/day) or placebo groups for two 8-wk interventions that were separated by a 3-wk washout period. The CVD risk factors including serum osteoprotegerin (OPG), homocysteine, lipoprotein-associated phospholipase A2 and trimethylamine N-oxide were measured at the beginning and the end of each intervention phase according to the standard protocol. RESULTS: Serum OPG reduced significantly in the ALA group in all participants (5.38 ± 2.79 to 3.27 ± 2.43 ng/mL, P= .003) and in the male subgroup (5.24 ± 2.56 to 3.13 ± 2.5 ng/mL, P= .015); this reduction was significant in comparison with the placebo group (P= .013). The changes in other CVD risk factors were not significant. CONCLUSION: The results of this study showed that after 8-wk of ALA consumption, the serum OPG reduced significantly in ß-thalassemia major patients. Therefore, controlling the serum OPG level with ALA consumption can be an important complementary therapeutic option to prevent the progression of CVD in ß-thalassemia major patients.