The effects of Chlorella vulgaris on cardiovascular risk factors: A comprehensive review on putative molecular mechanisms.

High incidence rate of cardiovascular disease (CVD) make this condition as an important public health concern. The use of natural products in treating this chronic condition has increased in recent years one of which is the single-celled green alga Chlorella. Chlorella vulgaris (CV) has been studied for its potential benefits to human health due to its biological and pharmacological features. CV contains a variety of macro and micronutrients, including proteins, omega-3, polysaccharides, vitamins, and minerals. Some studies have indicated that taking CV as a dietary supplement can help reduce inflammation and oxidative stress. In some studies, cardiovascular risk factors that are based on hematological indices did not show these benefits, and no molecular mechanisms have been identified. This comprehensive review summarized the research on the cardio-protective benefits of chlorella supplementation and the underlying molecular processes.

The role of Pycnogenol in the control of inflammation and oxidative stress in chronic diseases: Molecular aspects.

The prevalence of chronic diseases has increased significantly with the rising trend of sedentary lifestyles, reduced physical activity, and dietary modifications in recent decades. Inflammation and oxidative stress play a key role in the pathophysiology of several chronic diseases, such as type II diabetes, cardiovascular diseases, and hepatic conditions. Therefore, reducing inflammation and oxidative stress may be beneficial in the prevention and treatment of various chronic disorders. Since chronic diseases are not completely curable, various methods have been proposed for their control. Complementary therapies and the use of natural antioxidant and antiinflammatory compounds are among these novel approaches. Pycnogenol (PYC) is a natural compound that could control inflammation and oxidative stress. Furthermore, some previous studies have shown that PYC could effectively reduce inflammation through signaling the downstream of insulin receptors, inhibiting the phosphorylation of the serine residues of insulin receptor substrate-1, reducing pro-inflammatory cytokines and oxidative stress indices through the stimulation of antioxidant pathways, increasing free radical scavenging activities, preventing lipid peroxidation, and protecting the erythrocytes in glucose-6-phosphate dehydrogenase-deficient individuals, although these effects have not been fully proved. The present study aimed to comprehensively review the evidence concerning the positive physiological and pharmacological properties of PYC, with an emphasis on the therapeutic potential of this natural component for enhancing human health.

Does propolis have any effect on rheumatoid arthritis? A review study.

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which inflammation and oxidative stress play a key role in its pathophysiology. Complementary therapies along with medications may be effective in the control of RA. Propolis is a natural substance extracted from beehives, which have confirmed anti-inflammatory and antioxidant effects. The present study aimed to review the possible effects of propolis on inflammation, oxidative stress, and lipid profile in patients with RA. English articles in online databases such as PubMed­Medline, AMED, Google Scholar, EMBASE, Scopus, and Web of Science databases were searched. Pieces of evidence show that supplementation with propolis may have therapeutic effects on RA patients. Due to increased inflammation and oxidative stress in the affected joints of RA patients, propolis could inhibit the inflammatory cascades by inhibiting the nuclear factor kappa B pathway and reducing reactive oxygen species, malondialdehyde, and interleukin-17 by increasing some antioxidants. Therefore, inflammation and pain reduce, helping improve and control RA in patients. Further investigations are required with larger sample sizes and different doses of propolis to demonstrate the definite effects of propolis on various aspects of RA.

Effects of Melatonin and Propolis Supplementation on Inflammation, Oxidative Stress, and Clinical Outcomes in Patients with Primary Pneumosepsis: A Randomized Controlled Clinical Trial.

BACKGROUND AND OBJECTIVE: The present study aimed to investigate the effects of propolis and melatonin supplementation on inflammation, clinical outcomes, and oxidative stress markers in patients with primary pneumosepsis. MATERIALS AND METHODS: This pilot randomized controlled trial was conducted on 55 patients with primary pneumosepsis who were randomly assigned to the intervention and control groups. In the three intervention groups, the patients received propolis alone (1,000 mg/day), propolis (1,000 mg/day) plus melatonin (20 mg/day), and melatonin alone (20 mg/day). The control group received placebo. The inflammatory and oxidative stress markers as well as clinical outcomes were evaluated before and after the intervention, and the 28-day survival rate was also recorded. RESULTS: After the intervention, the combination of propolis and melatonin significantly reduced interleukin-6 (-55.282 pg/mL) and C-reactive protein (-21.656 mg/L) levels, while increasing gavage intake (326.680 mL/day) and improving some clinical outcomes (APACHE II, SOFA, and NUTRIC scores) compared to the control group. However, no significant difference was observed between the groups in terms of oxidative stress and hematological indices. In addition, there was no significant difference in the 28-day survival rate between the groups (p = 0.07). CONCLUSION: Supplementation with propolis and melatonin may improve clinical outcomes by reducing inflammation. Further investigations are required to confirm these findings.

Effects of zinc supplementation on inflammatory biomarkers and oxidative stress in adults: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & OBJECTIVE: Current evidence is debatable regarding the feasible effects of zinc supplementation on the inflammation and oxidative stress status of adults. This systematic review and meta-analysis aimed to clarify this inconclusiveness. MATERIALS AND METHODS: Literature search was conducted via online databases such as PubMed, Scopus, ISI Web of Science, Cochrane Library, and Google Scholar until June 2020. The overall effect was presented as the weighted mean difference (WMD) at 95 % confidence interval (CI) in a random-effects meta-analysis model. Publication bias was also assessed using Egger's and Begg's statistics. RESULTS: In total, 25 clinical trials (n = 1428) were reviewed, which indicated that zinc supplementation significantly affects the concentration of C- reactive protein (WMD: -0.03 mg/l; 95 % CI: -0.06, 0.0; P = 0.029), interlukin-6 (WMD: -3.81 pg/mL; 95 % CI: -6.87, -0.76; P = 0.014), malondialdehyde (WMD: -0.78 µmol/l; 95 % CI: -1.14, -0.42; P < 0.001), and total antioxidant capacity (WMD: 95.96 mmol/l; 95 % CI: 22.47, 169.44; P = 0.010). In addition, a significant between-study heterogeneity and a non-significant increment was reported in nitric oxide (WMD: 1.47 µmol/l; 95 % CI: -2.45, 5.40; P = 0.461) and glutathione (WMD: 34.84 µmol/l; 95 % CI: -5.12, 74.80; P = 0.087). CONCLUSION: According to the results, zinc supplementation may have beneficial anti-inflammatory and anti-oxidative effects in adults.

Protective effects of propolis on hepatic steatosis and fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) evaluated by real-time two-dimensional shear wave elastography: A randomized clinical trial.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, while no drugs have been approved for its treatment. The pieces of evidence indicate that propolis as a novel anti-inflammatory agent might be a promising candidate to treat NAFLD. We aimed to evaluate the efficacy of propolis on hepatic steatosis and fibrosis in patients with NAFLD. This randomized clinical trial was conducted on 54 patients with NAFLD. Patients were randomly assigned to receive propolis tablets at a dose of 250 mg twice daily for 4 months or placebo. The improvement in hepatic steatosis and fibrosis was evaluated using two-dimensional shear wave elastography. Improvement in the hepatic steatosis was significantly higher in the propolis group than the placebo group, even after adjustment for baseline value and changes in weight, energy intake, and physical activity (odds ratio [OR]: 5.67; 95% confidence intervals [CI]: 1.41-22.8; p = .014). A significant reduction was observed on the liver stiffness in the propolis group (-0.65 ± 0.56 kPa; p = .001), whereas it increased in the placebo group (0.27 ± 0.59 kPa; p = .037). Also, the intake of propolis significantly decreased high-sensitivity C-reactive protein (hs-CRP) levels compared with the placebo group (-0.371; 95%CI: -0.582 to -0.16 mg/L; p = .01). Changes in serum levels of fasting blood sugar, alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, cholesterol, and triglyceride did not differ significantly between the two groups (p > .05). There was no significant improvement in insulin resistance in both groups (p > .05). Propolis seems to have protective effects on hepatic steatosis and fibrosis and to reduce the serum levels of hs-CRP in patients with NAFLD.

Vitamin D supplementation effects on the clinical outcomes of patients with coronary artery disease: a systematic review and meta-analysis.

In this systematic review and meta-analysis our aim was to assess the effect of vitamin D supplementation on cardiac outcomes in patients with coronary artery disease (CAD). The search terms were performed from January 2000 to January 2018, only randomized clinical trials (RCT) in human subjects were considered, with no language restrictions. The electronic databases used in this study were: PubMed; Cochran library; Embase; and Scopus. Two independent expert reviewers carried out data extraction according to Cochrane recommendations. Only four RCTs were found in relation to the effects of vitamin D supplementation on the coronary artery disease. In these 299 patients, vitamin D supplementation had significant favorable effects on Diastolic Blood Pressure (DBP) (- 2.96, p = 0.02) and Parathyroid hormone (PTH) (- 4.05, p < 0.001). However, it had no significant effects on hs-CRP mean difference (- 0.04, p = 0.25), total cholesterol (TC) (- 0.46, p = 0.83), triglyceride (TG) (0.68, p = 0.89), low-density lipoproteins (LDL) (2.08, p = 0.56), and high-density lipoproteins (HDL) (- 2.59, p = 0.16). In conclusion, the use of vitamin D was associated with improvements in some cardiac outcomes of CAD patients with vitamin D deficiency. Also, further research is needed to clarify these results.

Association of Zinc and Copper Status with Cardiovascular Diseases and their Assessment Methods: A Review Study.

Cardiovascular disease (CVD) is the leading cause of mortality, morbidity, and financial losses and has a high prevalence across the world. Several studies have investigated the association between various CVD types with zinc and copper status as the essential minerals for the human body, proposing contradictory and similar results. This narrative review aimed to survey the correlations between zinc and copper status in the human body and some risk factors of CVD, as well as the assessment methods of zinc and copper status in the human body. According to the reviewed articles, zinc and copper deficiency may increase the risk of coronary heart disease, valvular regurgitation, and myocardial lesions, cardiac hypertrophy. Furthermore, it could lead to the expanded mitochondrial compartments of the heart, acute and chronic heart failure, and elevation of inflammation markers, such as interleukin-1 (IL-1) and IL-6. Two methods are primarily used for the assessment of zinc and copper in the human body, including the direct method (measurement of their concentrations) and indirect method (determining the activity of zinc- and copper-containing enzymes). Both these methods are considered reliable for the assessment of the zinc and copper levels in healthy individuals. Serum or plasma levels of these elements are also commonly used for the assessment of the correlation between zinc and copper status and CVD. But, which one is a more accurate indicator in relation to CVD is not yet clear; therefore, further studies are required in this field.

Efficacy of high-dose versus low-dose vitamin D supplementation on serum levels of inflammatory factors and mortality rate in severe traumatic brain injury patients: study protocol for a randomized placebo-controlled trial.

BACKGROUND: Traumatic brain injury (TBI) is the most common trauma worldwide and is a leading cause of injury-related death and disability. Inflammation is initiated as a result of the TBI, which is in association with severity of illness and mortality in brain trauma patients, especially in subdural hemorrhage and epidural hemorrhage cases. A high percentage of adults admitted to the intensive care unit with TBI are diagnosed with vitamin D deficiency; this deficiency may induce impaired immune responses and increase the risk of infections. Vitamin D intervention has been shown to modulate pro- and anti-inflammatory cytokines in non-critically ill patients, but to date, there is no substantial data on the effectiveness of vitamin D for the improvement of immune function in traumatic brain injury patients. METHODS/DESIGN: A randomized clinical trial (RCT) will be performed on 74 Iranian adults 18-65 years old with brain trauma and will be treated daily with vitamin D supplements (100,000 IU oral drop) or a similar placebo (1000 IU) for 5 days. DISCUSSION: If this randomized clinical trial demonstrates reductions in inflammatory cytokines, it would provide evidence for a multicenter clinical trial to evaluate the efficacy of vitamin D supplementation in neurocritically ill patients. Since vitamin D supplements are inexpensive and safe, this clinical trial could have the potential to improve clinical outcomes in traumatic brain injury patients through reduction of inflammation and infection-associated morbidity and mortality rates. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT20180619040151N3 . Registered on 10 August 2019.

The effect of vitamin D supplementation on hemoglobin concentration: a systematic review and meta-analysis.

AIMS: The purpose of this review was to investigate the effect of vitamin D supplements on hemoglobin concentration in subjects aged 17.5-68 years old; using randomized controlled trials (RCTs). METHODS: Relevant RCT studies were identified from January 2000 to January 2019 by using MeSH terms in PubMed, Embase, Cochrane Library, Clinical trials, Scopus databases and gray literature. The studies were reviewed systematically, and quality assessments were evaluated by the guidelines of the Cochrane risk of bias. The effect of vitamin D supplements (n = 14) on hemoglobin concentration was considered as primary outcome, while its effects on the levels of ferritin, transferrin saturation and iron status were derived as secondary outcomes. In total, 1385 subjects with age range of 17.5 to 68 years old were examined for 3 h to 6 months; Mean (standard deviation) or median interquartile changes in the hemoglobin concentration in each treatment group was recorded for meta-analysis. RESULTS: Fourteen RCTs met the inclusion criteria. Current study findings propose that vitamin D supplementation leads to a non-significant reduction in hemoglobin levels in subjects (17.5-68 years old) [std. mean difference (SMD): 0.01; 95% CI: - 0.28, 0.29; P = 0.95], also it has no significant effect on ferritin concentrations [std. mean difference (SMD): -0.01; 95% CI: [- 0.20, 0.18; P = 0.91]. However, vitamin D supplementation demonstrated positive effects on transferrin saturation [mean difference (MD): 1.54; 95% CI: 0.31, 2.76; P = 0.01] and iron status [std. mean difference (SMD): 0.24; 95% CI: - 0.09, 0.39; P = 0.002]. CONCLUSION: Current review concluded that supplementation with vitamin D had no significant effect on hemoglobin and ferritin levels while positive effects on transferrin saturation and iron status were observed. Further clinical studies are required to determine the actual effect of this intervention on hemoglobin levels.