Riboflavin is an antioxidant: a review update.

Aerobic organisms need antioxidant defense systems to deal with free radicals which either are produced during aerobic respiration or may have an external origin. Oxidative stress, which is resulted from an imbalance between the production of free radicals and the ability of antioxidant defense mechanism to deactivate them, is involved in the development of many chronic diseases such as cancer, diabetes, CVD and some neurodegenerative diseases. Reinforcing the antioxidant potential of the body has been considered as a strategy that could prevent and manage such conditions. In the previous review article published by British Journal of Nutrition, in 2014, for the first time, we concluded that riboflavin could alleviate oxidative stress. Although riboflavin can serve as a prooxidant when exposed to ultraviolet irradiation, the literature is replete with studies that support its antioxidant properties. Furthermore, recent evidence suggests that riboflavin may have a therapeutic potential in many conditions in which oxidative stress is involved, although the therapeutic efficacy of riboflavin as an antioxidant requires further study under conditions of wellness and clinical disease.

The association between zinc and endothelial adhesion molecules ICAMs and VCAM-1 and nuclear receptors PPAR-ɑ and PPAR-γ: A systematic review on cell culture, animal and human studies.

BACKGROUND: Cardiovascular health is strongly influenced by diet. The levels of inflammatory factors like ICAM-1 and VCAM-1 are high in patients with atherosclerosis or predisposing factor for heart disease. Antioxidant and anti-inflammatory functions are attributed to zinc. We systematically reviewed cell culture, human or animal studies for determining the relationship between zinc status and ICAMs or VCAM-1 levels. METHODS: PubMed, Google Scholar, Scopus, and Cochrane databases from database inception till 30th August 2020 were systematically searched to obtain any possible article for inclusion. RESULTS: After screening and removing unrelated or duplicate articles by the title and abstract by two independent reviewers, 15 articles were included. Results indicating an inverse relationship between zinc status with ICAM-1 or VCAM-1 levels and the development of endothelial inflammation, plaque formation, or atherosclerosis. A direct relationship between zinc status and PPAR-α or γ levels was also observed. Zinc oxide (ZnO), zinc nanoparticles, or ions can cause endothelial activation and increased levels of ICAM-1 and VCAM-1. CONCLUSION: Normal function of the endothelium is linked with zinc level. Zinc deficiency causes atherosclerosis, most probably via increased production of ICAM-1 and VCAM-1; and decreased expression of PPAR-ɑ and PPAR-γ receptors. Contrarily, endothelial activation and increased ICAM-1 and VCAM-1 levels can be caused by ZnO, zinc nanoparticles, or zinc ions.

The effect of obesity, macronutrients, fasting and nutritional status on drug-metabolizing cytochrome P450s: a systematic review of current evidence on human studies.

BACKGROUND: Cytochrome P450s (CYPs) are a class of hemoproteins involved in drug metabolism. It has been reported that body composition, proportion of dietary macronutrients, fasting and nutritional status can interfere with the activity of drug-metabolizing CYPs. OBJECTIVES: The present systematic review was conducted to summarize the effect of obesity, weight reduction, macronutrients, fasting and malnutrition on the CYP-mediated drug metabolism. METHODS: PubMed (Medline), Scopus, Embase and Cochrane Library databases and Google Scholar were searched up to June 2020 to obtain relevant studies. The PRISMA guidelines were employed during all steps. Two reviewers independently extracted the information from the included studies. Studies investigating CYPs activity directly or indirectly through pharmacokinetics of probe drugs, were included. Increase in clearance (CL) or decrease in elimination half-life (t½) and area under the curve (AUC) of probe drugs were considered as increase in CYPs activity. RESULTS: A total of 6545 articles were obtained through searching databases among which 69 studies with 126 datasets fully met the inclusion criteria. The results indicated that obesity might decrease the activity of CYP3A4/5, CYP1A2 and CYP2C9 and increase the activity of CYP2E1. The effect of obesity on CYP2D6 is controversial. Also, weight loss increased CYP3A4 activity. Moreover, CYP1A2 activity was decreased by high carbohydrate diet, increased by high protein diet and fasting and unchanged by malnutrition. The activity of CYP2C19 was less susceptible to alterations compared to other CYPs. CONCLUSION: The activity of drug-metabolizing CYPs are altered by body composition, dietary intake and nutritional status. This relationship might contribute to drug toxicity or reduce treatment efficacy and influence cost-effectiveness of medical care.

Dietary Glycemic Index and Glycemic Load and the Risk of Prostate Cancer: An Updated Systematic Review and Dose-Response Meta-Analysis.

A meta-analysis in 2015 revealed no significant association between glycemic index (GI), glycemic load (GL), and prostate cancer. Moreover, until now, no study has examined the dose-response association of GI, GL, and prostate cancer yet. The online databases were searched by two independent researchers for relevant publications up to Jan. 2019, using relevant keywords. Nine studies including five prospective and four case-control studies were included in the current systematic review and meta-analysis. These studies have included 290,911 individuals. We found a significant positive dose-response association between dietary GI and prostate cancer (Pnonlinearity = 0.03). Comparing individuals in the highest category of GI with those in the lowest category, no significant association was found between GI and prostate cancer (combined effect size: 1.08, 95% CI: 0.97-1.19, P = 0.17). Furthermore, no significant association was seen between dietary GL and prostate cancer in both dose-response analysis and when comparing the highest versus lowest categories of GL (combined effect size: 1.03, 95% CI: 0.91-1.16, P = 0.65). In conclusion, we found a significant positive dose-response association between dietary GI and prostate cancer. However, significant association was not seen for dietary GL.

Melatonin supplementation and pro-inflammatory mediators: a systematic review and meta-analysis of clinical trials.

BACKGROUND: Inflammatory processes are involved in chronic diseases. It has been suggested that melatonin reduces inflammation by its radical scavenging properties; however, the results of the previous studies are inconclusive. The objective of the present meta-analysis is to determine the direction and magnitude of melatonin supplementation effect on inflammatory biomarkers. METHODS: Databases including PubMed, Scopus, Cochran Library, Embase, and Google Scholar were searched up to April 2019. Meta-analysis was performed using random-effect model. Subgroup analysis, sensitivity analysis, and meta-regression were also carried out. RESULTS: Thirteen eligible studies with 22 datasets with total sample size of 749 participants were included in the meta-analysis. Melatonin supplementation significantly decreased TNF-α and IL-6 levels [(WMD = - 2.24 pg/ml; 95% CI - 3.45, - 1.03; P < 0.001; I2 = 96.7%, Pheterogeneity < 0.001) and (WMD = - 30.25 pg/ml; 95% CI - 41.45, - 19.06; P < 0.001, I2 = 99.0%; Pheterogeneity < 0.001)], respectively. The effect of melatonin on CRP levels was marginal (WMD = - 0.45 mg/L; 95% CI - 0.94, 0.03; P = 0.06; I2 = 96.6%, Pheterogeneity < 0.001). CONCLUSION: The results of the present meta-analysis support that melatonin supplementation could be effective on ameliorating of inflammatory mediators.

The effect of weight loss on HDL subfractions and LCAT activity in two genotypes of APOA-II -265T>C polymorphism.

BACKGROUND: People may have different responses to the same environmental changes. It has been reported that genome variations may be responsible for these differences. Also, HDL subfractions may be influenced by different genetic variations. The aim of the present study was to determine gene-diet interactions and to evaluate the influence of weight loss on HDL subfractions between two genotypes of -265 T>C APOA-II polymorphism. METHODS: In the present study, 56 overweight and obese patients with type 2 diabetes mellitus were selected from 697 genotype-specified subjects. After matching for gender, age and BMI at the beginning of the study, an equal number of patients remained on each genotype of APOA-II (TT/TC and CC group). After a 6-week calorie restriction program, 44 patients completed the study. Serum HDL subfractions, including HDL2 and HDL3 and LCAT activity, were compared between the two genotypes and, before and after the intervention, were separated in each genotype. RESULTS: Serum concentration of HDL and its subfractions decreased significantly due to the weight loss. A comparison of the mean changes between the genotypes showed that HDL3 significantly decreased in the CC genotype while, in the TT/TC group, the serum concentration of HDL2 was significantly reduced. However, the increase of LCAT activity was not significant among the two genotypes. CONCLUSION: A comparison of mean changes of variables within two genotype groups showed that C homozygote carriers lead to a general shift toward larger size HDL subfractions and T allele carriers shift toward smaller size HDL subfractions after weight loss.

Beneficial Effects of n-3 Fatty Acids on Cardiometabolic and Inflammatory Markers in Type 2 Diabetes Mellitus: A Clinical Trial.

OBJECTIVE: To determine the effect of supplementation with n-3 polyunsaturated fatty acids (PUFAs) on circulatory resistin and monocyte chemoattractant protein 1 (MCP-1) levels in type 2 diabetes mellitus (T2DM) patients. SUBJECTS AND METHODS: This was a 10-week, placebo-controlled, double-blind, randomized trial of n-3 PUFAs (2,700 mg/day) versus placebo (soft gels containing 900 mg of edible paraffin). Forty-four T2DM patients were supplemented with n-3 PUFAs and another 44 patients received placebo (3 patients discontinued the trial). Serum resistin, MCP-1, and the lipid profile were measured before and after supplementation. The adiponectin-resistin index (1 + log10 [resistin] - log10 [adiponectin]) and atherogenic index (log10 triglyceride/high-density lipoprotein cholesterol) of plasma (an indicator of cardiovascular complications) were assessed. The independent Student t test was used to assess the differences between the supplement and placebo groups and the paired t test to analyze the before/after changes. RESULTS: In this study, n-3 PUFAs reduced serum MCP-1 levels (from 260.5 to 230.5 pg/mL; p = 0.002), but they remained unchanged in the placebo group. n-3 PUFAs could not decrease serum resistin levels. The adiponectin-resistin index was significantly reduced after supplementation with n-3 PUFAs when compared to the placebo. The atherogenic index was also significantly improved after supplementation with n-3 PUFAs (from 1.459 to 1.412; p = 0.006). CONCLUSIONS: The MCP-1 levels and lipid profile were improved after supplementation with n-3 PUFAs, but resistin serum levels were not changed. Hence, the anti-inflammatory effects of n-3 PUFAs might be mediated by targeting MCP-1.

Dietary Intake and Serum Level of Carotenoids in Lung Cancer Patients: A Case-Control Study.

The aim of this study was to compare the dietary intake and serum levels of some selected carotenoids of lung cancer patients with healthy subjects. Thirty-five lung cancer patients and 33 healthy people were enrolled into this case-control study. Daily intake of nutrients was estimated using a semiquantitative food frequency questionnaire and a 3-day 24-h food recall questionnaire. The concentration of serum beta-carotene and lycopene were analyzed using a high performance liquid chromatography method. Case and control groups did not differ by the means of age, gender, smoking habits, weight, body mass index, mean daily energy intake, mean daily fat intake, and the percentage of daily energy provided by fat to total daily energy intake. The beta-carotene and lycopene intake of the case subjects was 96% and 195% greater than that of the control subjects. Daily intake of fruits and vegetables in the cancer group was higher than the control group. However, the serum concentration of 118% beta-carotene and 60% lycopene were higher in the control group. Despite a higher daily dietary intake of beta-carotene and lycopene by lung cancer patients, serum beta-carotene and lycopene concentrations were significantly lower than the group without cancer.

The Effect of Tomato Juice Consumption on Antioxidant Status in Overweight and Obese Females.

Tomatoes and their products are the main source of lycopene, a powerful potent antioxidant. Tomato products improve antioxidant defenses and reduce the risk of oxidative stress, at least partly, due to the presence of lycopene. Lycopene, as an antioxidant, induces the upregulation of antioxidant enzymes and reinforces the total enzyme capacity of the human body. Obesity is a chronic condition in which destructive mechanisms increase the reactive oxygen species and attenuation of antioxidant status. We hypothesized that the consumption of a lycopene-rich food would improve the antioxidant defense of women who were overweight or obese. A total of seventy-five overweight or obese female students of the Tehran University of Medical Sciences were enrolled and randomly allocated to one of two groups, intervention (n = 40) or control (n = 35), consuming 330 ml/d of tomato juice or water, respectively, for a 20-day period. At baseline and day 20, total antioxidant capacity and antioxidant enzyme activity (superoxide dismutase, glutathione peroxidase, and catalase) were analyzed using ELISA kits and spectrophotometric methods and then compared between the two groups. Lycopene consumption had no effect on these aforementioned variables. Therefore, it seems that more research with longer duration and more sensitive indicators will be required.

Riboflavin (vitamin B2) and oxidative stress: a review.

Oxidative stress is involved in the development of many chronic diseases. One of the main factors involved in oxidative stress reduction is increased antioxidant potential. Some nutrients such as vitamin C, vitamin E and carotenoids are known to act as antioxidants; however, riboflavin is one of the neglected antioxidant nutrients that may have an antioxidant action independently or as a component of the glutathione redox cycle. Herein, studies that have examined the antioxidant properties of riboflavin and its effect on oxidative stress reduction are reviewed. The results of the reviewed studies confirm the antioxidant nature of riboflavin and indicate that this vitamin can protect the body against oxidative stress, especially lipid peroxidation and reperfusion oxidative injury. The mechanisms by which riboflavin protects the body against oxidative stress may be attributed to the glutathione redox cycle and also to other possible mechanisms such as the conversion of reduced riboflavin to the oxidised form.

Tomato juice consumption reduces systemic inflammation in overweight and obese females.

Tomatoes are the richest source of lycopene, a potent antioxidant. Tomato products improve antioxidant defences and reduce the risk of inflammatory diseases, at least partly, due to the presence of lycopene. Lycopene, as an anti-inflammatory agent, prevents the production of inflammatory cytokines. Obesity is a chronic inflammatory condition in which the increased level of body fat leads to an increase in circulating inflammatory mediators. We hypothesised that the consumption of a lycopene-rich food would reduce inflammation in people who are overweight or obese. A total of 106 overweight or obese female students of the Tehran University of Medical Sciences were enrolled and randomly allocated to an intervention group (n 53) or a control group (n 53) consuming 330 ml/d of tomato juice or water, respectively, for 20 d. At baseline and day 20, serum concentrations of IL-6, IL-8, high-sensitivity C-reactive protein and TNF-α were analysed by ELISA and compared between the groups. Serum concentrations of IL-8 and TNF-α decreased significantly in the intervention group compared with the control group and with baseline. Subgroup analysis indicated that this effect was confined to subjects who were overweight. Among obese subjects, serum IL-6 concentration was decreased in the intervention group compared with the control group, with no differences in IL-8 and TNF-α observed. Tomato juice reduces inflammation in overweight and obese females. Thus, increasing tomato intake may provide a useful approach for reducing the risk of inflammatory diseases such as CVD and diabetes, which are associated with obesity.

Quercetin prevents experimental glucocorticoid-induced osteoporosis: a comparative study with alendronate.

Glucocorticoid-induced osteoporosis (GIO) is the most common type of secondary osteoporosis. The aim of this study was to compare the efficacy of quercetin, a plant-derived flavonoid, with alendronate in the prevention of GIO. Fifty-six Sprague-Dawley rats were randomly distributed among 7 groups (8 rats per group) and treated for 6 weeks with one of the following: (i) normal saline; (ii) 40 mg methylprednisolone sodium succinate (MP)/kg body mass; (iii) MP + 40 µg alendronate/kg; (iv) MP + 50 mg quercetin/kg; (v) MP + 40 µg alendronate/kg + 50 mg quercetin/kg; (vi) MP + 150 mg quercetin/kg; and (vii) MP + 40 µg alendronate/kg + 150 mg quercetin/kg. MP and alendronate were injected subcutaneously and quercetin was administered by oral gavage 3 days a week. At the end of the study, femur breaking strength was significantly decreased as a consequence of MP injection. This decrease was completely compensated for in groups receiving 50 mg quercetin/kg plus alendronate, and 150 mg quercetin/kg with or without alendronate. Quercetin noticeably elevated osteocalcin as a bone formation marker, while alendronate did not show such an effect. In addition, administration of 150 mg quercetin/kg increased femoral trabecular and cortical thickness by 36% and 22%, respectively, compared with the MP-treated group. These data suggest that 150 mg quercetin/kg, alone or in combination with alendronate, can completely prevent GIO through its bone formation stimulatory effect.

Dietary pattern in autism increases the need for probiotic supplementation: A comprehensive narrative and systematic review on oxidative stress hypothesis.

Autism spectrum disorders (ASDs) are associated with specific dietary habits, including limited food selection and gastrointestinal problems, resulting in an altered gut microbiota. Autistic patients have an elevated abundance of certain gut bacteria associated with increased oxidative stress in the gastrointestinal tract. Probiotic supplementation has been shown to decrease oxidative stress in a simulated gut model, but the antioxidant effects of probiotics on the oxidative stress of the gut in autistic patients have not been directly studied. However, it is speculated that probiotic supplementation may help decrease oxidative stress in the gastrointestinal tract of autistic patients due to their specific dietary habits altering the microbiota. PubMed, Scopus and Web of Science databases and Google Scholar were searched up to May 2023. This systematic-narrative review aims to present the latest evidence regarding the changes in eating habits of autistic children which may further increase the gut microbiota induced oxidative stress. Additionally, this review will assess the available literature on the effects of probiotic supplementation on oxidative stress parameters.

The effectiveness of treatment with probiotics in Helicobacter pylori eradication: results from an umbrella meta-analysis on meta-analyses of randomized controlled trials.

Background and aims: The purpose of this umbrella meta-analysis was to quantitatively summarize meta-analyses of randomized controlled trial (RCT) studies regarding the effects of probiotic supplementation on Helicobacter pylori (H. pylori) eradication. Methods: A thorough search of the electronic databases including PubMed, Web of Science, Embase, Scopus, and Google Scholar was carried out from the inception up to May 2022. For the evaluation of overall effect sizes, the pooled relative risk (RR) or odds ratio (OR) and their corresponding 95% confidence intervals (CI) were calculated. The random-effects model was used for the meta-analysis. Results: Overall, 18 eligible studies (47 278 participants in total) were included in the study. The findings revealed that probiotics have a beneficial impact on H. pylori eradication (pooled ESRR: 1.13; 95% CI: 1.11, 1.14, p < 0.01, and ESOR = 1.86, 95% CI: 1.70, 2.03, p < 0.01). Greater effects on H. pylori eradication were observed when higher doses (>10 × 1010 CFU) and mixed strains were supplemented. Conclusion: The present umbrella meta-analysis suggests that supplementation with probiotics may be considered as an efficient approach to ameliorate H. pylori complications, particularly probiotics with higher CFUs and mixed strains.

Anti-cancer potential of synergistic phytochemical combinations is influenced by the genetic profile of prostate cancer cell lines.

Introduction: Despite strong epidemiological evidence that dietary factors modulate cancer risk, cancer control through dietary intervention has been a largely intractable goal for over sixty years. The effect of tumour genotype on synergy is largely unexplored. Methods: The effect of seven dietary phytochemicals, quercetin (0-100 µM), curcumin (0-80 µM), genistein, indole-3-carbinol (I3C), equol, resveratrol and epigallocatechin gallate (EGCG) (each 0-200 µM), alone and in all paired combinations om cell viability of the androgen-responsive, pTEN-null (LNCaP), androgen-independent, pTEN-null (PC-3) or androgen-independent, pTEN-positive (DU145) prostate cancer (PCa) cell lines was determined using a high throughput alamarBlue® assay. Synergy, additivity and antagonism were modelled using Bliss additivism and highest single agent equations. Patterns of maximum synergy were identified by polygonogram analysis. Network pharmacology approaches were used to identify interactions with known PCa protein targets. Results: Synergy was observed with all combinations. In LNCaP and PC-3 cells, I3C mediated maximum synergy with five phytochemicals, while genistein was maximally synergistic with EGCG. In contrast, DU145 cells showed resveratrol-mediated maximum synergy with equol, EGCG and genistein, with I3C mediating maximum synergy with only quercetin and curcumin. Knockdown of pTEN expression in DU145 cells abrogated the synergistic effect of resveratrol without affecting the synergy profile of I3C and quercetin. Discussion: Our study identifies patterns of synergy that are dependent on tumour cell genotype and are independent of androgen signaling but are dependent on pTEN. Despite evident cell-type specificity in both maximally-synergistic combinations and the pathways that phytochemicals modulate, these combinations interact with similar prostate cancer protein targets. Here, we identify an approach that, when coupled with advanced data analysis methods, may suggest optimal dietary phytochemical combinations for individual consumption based on tumour molecular profile.Graphical abstract.

Influence of Vitamin A supplementation on inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials.

Vitamin A is an anti-oxidant which has been presumed to act as an anti-infective vitamin in many studies. This study aimed to evaluate the association between vitamin A supplementation and c-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) levels in randomized control trials (RCTs) studies on adults. A systematic search was performed on databases including PUBMED, SCOPUS, and the Cochrane library. The studies included were considered for data extraction and subsequently assessed for effect. Weighted mean differences (WMD) and 95% confidence intervals (CIs) were evaluated. Among 13,219 articles 13 studies were included for analysis of CRP and TNF-α, as well as 9 studies included for IL-6 in quality and quantity. The pooled WMD analysis of CRP demonstrated that vitamin A supplementation significantly increased CRP concentration with (WMD: 0.84 mg/L; 95% CI 0.29-1.39, I2 = 0.96.2% and p value < 0.003). However, there was no significant correlation between vitamin A supplementation and lower plasma TNF-α (p < 0.45)). Subgroup analysis by dosage demonstrate significant association between vitamin A supplementation and IL-6 in dosage with 50,000 with (WMD: - 1.53 mg/L; 95% CI - 2.36 to - 0.71, p value < 0.00001) as well as a negative significant association was seen at 44 weeks of supplementation with 50,000 IU/day retinyl palmitate and TNF-a in chronic hepatitis B conditions with (- 0.94 (- 1.19, - 0.69) p < 0.0001). The result of this study demonstrates that supplementation of vitamin A at low and high dosages for short and long durations increases the CRP plasma concentrations on adults and vitamin A supplementation decreases the TNF-α concentrations in chronic hepatitis B on adults. Therefore, there is an inverse association between vitamin A supplementation and plasma and fecal IL-6 concentrations in many infection conditions.

The Effect of Green Coffee Supplementation on Lipid Profile, Glycemic Indices, Inflammatory Biomarkers and Anthropometric Indices in Iranian Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial.

Polycystic ovary syndrome (PCOS) is a heterogeneous clinical syndrome. Recent studies examine different strategies to modulate its related complications. Chlorogenic acid, as a bioactive component of green coffee (GC), is known to have great health benefits. The present study aimed to determine the effect of GC on lipid profile, glycemic indices, and inflammatory biomarkers. Forty-four PCOS patients were enrolled in this randomized clinical trial of whom 34 have completed the study protocol. The intervention group (n = 17) received 400 mg of GC supplements, while the placebo group (n = 17) received the same amount of starch for six weeks. Then, glycemic indices, lipid profiles, and inflammatory parameters were measured. After the intervention period, no significant difference was shown in fasting blood sugar, insulin level, Homeostasis model assessment of insulin resistance index, low-density lipoprotein, high-density lipoprotein, Interleukin 6 or 10 between supplementation and placebo groups. However, cholesterol and triglyceride serum levels decreased significantly in the intervention group (p < 0.05). This research confirmed that GC supplements might improve some lipid profiles in women with PCOS. However, more detailed studies with larger sample sizes are required to prove the effectiveness of this supplement.

Commensal and Pathogenic Bacterial-Derived Extracellular Vesicles in Host-Bacterial and Interbacterial Dialogues: Two Sides of the Same Coin.

Extracellular vesicles (EVs) cause effective changes in various domains of life. These bioactive structures are essential to the bidirectional organ communication. Recently, increasing research attention has been paid to EVs derived from commensal and pathogenic bacteria in their potential role to affect human disease risk for cancers and a variety of metabolic, gastrointestinal, psychiatric, and mental disorders. The present review presents an overview of both the protective and harmful roles of commensal and pathogenic bacteria-derived EVs in host-bacterial and interbacterial interactions. Bacterial EVs could impact upon human health by regulating microbiota-host crosstalk intestinal homeostasis, even in distal organs. The importance of vesicles derived from bacteria has been also evaluated regarding epigenetic modifications and applications. Generally, the evaluation of bacterial EVs is important towards finding efficient strategies for the prevention and treatment of various human diseases and maintaining metabolic homeostasis.

FruHis significantly increases the anti-benign prostatic hyperplasia effect of lycopene: A double-blinded randomized controlled clinical trial.

Background: For decades, lycopene was considered the main compound of tomato protecting benign prostatic hyperplasia (BPH). Recent animal studies suggest that a newly discovered compound "FruHis" boosts lycopene for its action. This study aimed to determine whether FruHis enhances the action of lycopene to modify the laboratory parameters and clinical outcomes of patients with BPH. Materials and methods: Current study was conducted on 52 BPH patients, who were randomly assigned into four groups of treatments: lycopene plus FruHis (n = 11, 25 mg/day lycopene and 10 mg/day FruHis), lycopene (n = 12, 25 mg/day lycopene), FruHis (n = 12, 10 mg/day FruHis), and placebo (n = 13). Patients received these supplements for 8 weeks. Results: FruHis intake strengthened the reducing effects of lycopene on insulin-like growth factor-1 (IGF-1) (-54.47 ± 28.36 ng/mL in the lycopene + FruHis group vs. -30.24 ± 46.69 ng/mL in the lycopene group), total prostate-specific antigen (TPSA) (-1.49 ± 4.78 ng/mL in the lycopene + FruHis group vs. -0.64 ± 2.02 ng/mL in the lycopene group), and symptom score (-4.45 ± 4.03 in the lycopene + FruHis group vs. -1.66 ± 5.41 in the lycopene group) in BPH patients. Such findings were also seen for body mass index (BMI) and waist circumference (WC). However, except for IGF-1, these reductions were not statistically significant compared with the placebo, and the intakes of lycopene and FruHis alone, however, were clinically important. Such effects of lycopene and FruHis were not seen for free PSA (FPSA) and FPSA/TPSA ratio. Conclusion: Despite the non-significant effects of lycopene and FruHis, it seems that FruHis intake strengthens the beneficial effects of lycopene on IGF-1, TPSA, and symptom scores among BPH patients. Clinical trial registration: [www.irct.ir], identifier [IRCT20190522043669N1].

Probiotic Supplementation and Micronutrient Status in Healthy Subjects: A Systematic Review of Clinical Trials.

Micronutrient deficiencies are a worldwide public health concern. Emerging evidence supports the ability of probiotics to enhance micronutrient status, which could aid in the prevention of non-communicable disease-associated malnutrition. This systematic review evaluated evidence of the efficacy of probiotic supplementation to improve micronutrient status in healthy subjects. The authors searched for published English language peer-reviewed journal articles in PubMed, Scopus, Embase, and Google Scholar databases from inception to July 2020 using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of eligible studies was assessed using the Revised Cochrane Risk-of-Bias tool (RoB)2 and Risk of Bias in Non-Randomized Studies of Interventions tool (ROBINS-I tool). Fourteen original studies out of 2790 met the inclusion criteria. The results indicated that, despite varying degrees of efficacy, the intake of certain probiotics in healthy subjects was associated with a positive impact on the status of certain micronutrients (vitamin B12, calcium, folate, iron and zinc). A limitation was that studies were widely heterogeneous in terms of participant age, probiotic strain, species, dosage, intervention duration, and form of administration. Additional clinical trials are warranted to determine the most effective strains of probiotics, doses and durations of interventions.