Curcumin effects on glycaemic indices, lipid profile, blood pressure, inflammatory markers and anthropometric measurements of non-alcoholic fatty liver disease patients: A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVES: Curcumin has antioxidant properties and has been proposed as a potential treatment for NAFLD. The aim of current systematic review and meta-analysis was to evaluate previous findings for the effect of curcumin supplementation on glycaemic indices, lipid profile, blood pressure, inflammatory markers, and anthropometric measurements of NAFLD patients. METHODS: Relevant studies published up to January 2024 were searched systematically using the following databases: PubMed, SCOPUS, WOS, Science Direct, Ovid and Cochrane. The systematic review and meta-analysis were conducted according to the 2020 PRISMA guidelines. The quality of the papers was assessed the using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Pooled effect sizes were calculated using a random-effects model and reported as the WMD and 95% CI. Also, subgroup analyses were done to find probable sources of heterogeneity among studies. RESULTS: Out of 21010 records initially identified, 21 eligible RCTs were selected for inclusion in a meta-analysis. Overall, 1191 participants of both genders, 600 in the intervention and 591 in the control group with NAFLD were included. There are several limitations in the studies that were included, for instance, the results are weakened substantially by potential bias or failure to account for potential adulteration (with pharmaceuticals) or contamination (with other herbs) of the curcumin supplements that were tested. However, previous studies have reported curcumin to be a safe complementary therapy for several conditions. Our study indicated that curcumin supplementation in doses of 50-3000 mg/day was associated with significant change in FBG [WMD: -2.83; 95% CI: -4.61, -1.06), I2 = 51.3%], HOMA-IR [WMD: -0.52; 95% CI: -0.84, -0.20), I2= 82.8%], TG [WMD: -10.31; 95% CI: -20.00, -0.61), I2 = 84.5%], TC [WMD: -11.81; 95% CI: -19.65, -3.96), I2 = 94.6%], LDL [WMD: -8.01; 95% CI: -15.79, -0.24), I2 = 96.1%], weight [WMD: -0.81; 95% CI: -1.28, -0.35), I2= 0.0%] and BMI [WMD: -0.35; 95% CI: -0.57, -0.13), I2= 0.0%] in adults with NAFLD. There was no significant change in HbA1C, plasma insulin, QUICKI, HDL, SBP, DBP, CRP, TNF-α and WC after curcumin therapy. Subgroup analysis suggested a significant changes in serum FBG, TG, SBP, WC in RCTs for intervention durations of ≥ 8 weeks, and SBP, TG, LDL, HDL, BMI, WC in RCTs with sample size > 55 participants. CONCLUSION: Curcumin supplementation in doses of 50-3000 mg/day over 8-12 weeks was associated with significant reductions in levels of FBG, HOMA-IR, TG, TC, LDL, weight and BMI in patients with NAFLD. Previous studies have reported curcumin as a safe complementary therapy for several diseases. We would suggest that should curcumin supplements be used clinically in specific conditions, it should be used with caution. Also, difference in grades of NAFLD may effect the evaluated outcomes, so it is suggested that future studies be conducted with an analyses on subgroups according to their NAFLD grade. Furthermore, because of the failure to conduct independent biochemical assessment of the turmeric/curcumin product used in most studies as well as potential sources of bias, results should be interpreted with caution.

Association of Genotypes of ANGPTL3 with Vitamin D and Calcium Concentration in Cardiovascular Disease.

One of the leading causes of mortality worldwide is cardiovascular disease, which is influenced by some variables, including calcium and vitamin D. This study aimed to assess the relationship between Angiopoietin-Like 3 (ANGPTL3) gene polymorphisms with vitamin D and calcium levels in cardiovascular disease (CVD) patients. In this research, 1002 people participated. Participants' anthropometric parameters, and FBG, calcium, and vitamin D were assessed. Blood samples were used to extract DNA. Taqman®-based polymerase chain reaction (PCR) was used to conduct genetic analysis for the rs10789117 and rs17458195. Statistical analysis was applied to determine differences across subgroups and the relationship between polymorphisms and disease. Age, body mass index (BMI), fasting Blood Sugar (FBG), phenylalanine ammonia-lyase (PAL), and smoking history were significantly correlated with CVD. Vitamin D was statistically associated with rs10789117 and rs17458195 in non-CVD individuals. In the moderate group, individuals with the C allele in rs10789117 showed a tenfold increase in vitamin D deficiency compared to those with the A allele. However, in rs11207997, individuals with the T allele had 5 to 6 times higher vitamin D deficiency than those with the C allele in all groups. This research demonstrates the relationship between some ANGPTL3 gene polymorphisms and complement levels in CVD patients. It may be concluded that individuals carrying these variants would likely benefit from using vitamin D and calcium supplements to avoid CVD.

Curcumin's effect on serum zinc, copper and magnesium levels in obese individuals.

Objective: The obesity prevalence is growing worldwide. There is strong evidence indicating that a disturbance of zinc, copper and magnesium concentrations is associated with the development of obesity and its related diseases. Our aim was to determine the effect of curcumin supplementation on serum zinc, magnesium and copper in obese individuals. Materials and Methods: In this randomized crossover trial study, thirty obese patients with an age range of 18 to 65 years were randomized to treatment with curcumin 1 g/day or placebo for 30 days. There was then a two-week wash-out period, after which, subjects crossed to the alternate regimen. Serum levels of zinc, copper and magnesium were determined at baseline and at the end of the study. Results: The study groups were similar to each other in base line characteristics. We did not observe significant impacts (p>0.05) of curcumin on Cu, Zn, Mg serum concentrations. Conclusion: Curcumin administration at a dose of 1 g/day for 30 days did not affect serum Cu, Zn, Mg levels in obese subjects.

Effect of curcumin on inflammatory biomarkers and iron profile in patients with premenstrual syndrome and dysmenorrhea: A randomized controlled trial.

Premenstrual syndrome (PMS) and primary dysmenorrhea are common gynecological problems and inflammation may have a role in their etiology. Curcumin is a polyphenolic natural product for which there is increasing evidence of anti-inflammatory and iron chelation effects. This study assessed the effects of curcumin on inflammatory biomarkers and iron profile in young women with PMS and dysmenorrhea. A sample of 76 patients was included in this triple-blind, placebo-controlled clinical trial. Participants were randomly allocated to curcumin (n = 38) and control groups (n = 38). Each participant received one capsule (500 mg of curcuminoid+ piperine, or placebo) daily, from 7 days before until 3 days after menstruation for three consecutive menstrual cycles. Serum iron, ferritin, total iron-binding capacity (TIBC) and high-sensitivity C-reactive protein (hsCRP), as well as white blood cell, lymphocyte, neutrophil, platelet counts, mean platelet volume (MPV) and red blood cell distribution width (RDW), were quantified. Neutrophil: lymphocyte ratio (NLR), platelet: lymphocyte ratio (PLR), and RDW: platelet ratio (RPR) were also calculated. Curcumin significantly decreased the median (interquartile range) serum levels of hsCRP [from 0.30 mg/L (0.0-1.10) to 0.20 mg/L (0.0-1.3); p = 0.041] compared with placebo, but did not show any difference for neutrophil, RDW, MPV, NLR, PLR and RPR values (p > 0.05). The treatment schedule was well-tolerated, and none of markers of iron metabolism statistically changed after the intervention in the curcumin group (p > 0.05). Curcumin supplementation may have positive effects on serum hsCRP, a marker of inflammation, with no any changes on iron homeostasis in healthy women with PMS and dysmenorrhea.

Low phytic acid pea supplementation as an approach to combating iron deficiency in female runners: A randomized control trial.

Background: Iron deficiency (ID) is the most prevalent micronutrient deficiency in the world and the leading cause of anemia globally. Female athletes are at a disproportionate risk for ID due to blood loss through menstruation and decreased iron absorption secondary to exercise. Field peas are a rich source of iron but, similar to iron from other plant-based sources, the iron has limited bioavailability due to high levels of phytic acid, an inherent compound that binds to cations, creating a salt (phytate), which limits absorption during digestion. Aim: The purpose of our research was to investigate the effect of a field pea variety bred to have low levels of phytic acid on plasma ferritin, exercise performance, and body composition in female runners. Methods: Twenty-eight female runners (age:34.6 ± 9.7 years; weight: 65.1 ± 8.1 kg; VO2max: 50.7 ± 8.9 ml/kg/min) underwent measures of ferritin, exercise performance, and body composition before and after being randomly assigned to consume a powder derived from regular peas, low phytic acid peas, or a non-pea control (maltodextrin), plus vitamin C for 8 weeks. Results: The regular pea and low phytic acid pea groups had a 14.4% and 5.1% increase in plasma ferritin, respectively, while the maltodextrin group had a decrease of 2.2%; however, the difference in changes between groups was not statistically significant. No differences between groups were evident in any of the other measures. Conclusion: Larger doses or longer duration of pea supplementation may be necessary to induce meaningful changes in iron status. This trial was registered at ClinicalTrials.gov (NCT04872140).

A 2-yr Randomized Controlled Trial on Creatine Supplementation during Exercise for Postmenopausal Bone Health.

PURPOSE: Our purpose was to examine the effects of 2 yr of creatine monohydrate supplementation and exercise on bone health in postmenopausal women. METHODS: Two hundred and thirty-seven postmenopausal women (mean age, 59 yr) were randomized to receive creatine (0.14 g·kg -1 ·d -1 ) or placebo during a resistance training (3 d·wk -1 ) and walking (6 d·wk -1 ) program for 2 yr. Our primary outcome was the femoral neck bone mineral density (BMD), with lumbar spine BMD and proximal femur geometric properties as the secondary outcomes. RESULTS: Compared with placebo, creatine supplementation had no effect on BMD of the femoral neck (creatine: 0.725 ± 0.110 to 0.712 ± 0.100 g·cm -2 ; placebo: 0.721 ± 0.102 to 0.706 ± 0.097 g·cm -2 ), total hip (creatine: 0.879 ± 0.118 to 0.872 ± 0.114 g·cm -2 ; placebo: 0.881 ± 0.111 to 0.873 ± 0.109 g·cm -2 ), or lumbar spine (creatine: 0.932 ± 0.133 to 0.925 ± 0.131 g·cm -2 ; placebo: 0.923 ± 0.145 to 0.915 ± 0.143 g·cm -2 ). Creatine significantly maintained section modulus (1.35 ± 0.29 to 1.34 ± 0.26 vs 1.34 ± 0.25 to 1.28 ± 0.23 cm 3 (placebo), P = 0.0011), predictive of bone bending strength, and buckling ratio (10.8 ± 2.6 to 11.1 ± 2.2 vs 11.0 ± 2.6 to 11.6 ± 2.7 (placebo), P = 0.011), predictive of reduced cortical bending under compressive loads, at the narrow part of the femoral neck. Creatine reduced walking time over 80 m (48.6 ± 5.6 to 47.1 ± 5.4 vs 48.3 ± 4.5 to 48.2 ± 4.9 s (placebo), P = 0.0008) but had no effect on muscular strength (i.e., one-repetition maximum) during bench press (32.1 ± 12.7 to 42.6 ± 14.1 vs 30.6 ± 10.9 to 41.4 ± 14 kg (placebo)) and hack squat (57.6 ± 21.6 to 84.4 ± 28.1 vs 56.6 ± 24.0 to 82.7 ± 25.0 kg (placebo)). In the subanalysis of valid completers, creatine increased lean tissue mass compared with placebo (40.8 ± 5.7 to 43.1 ± 5.9 vs 40.4 ± 5.3 to 42.0 ± 5.2 kg (placebo), P = 0.046). CONCLUSIONS: Two years of creatine supplementation and exercise in postmenopausal women had no effect on BMD; yet, it improved some bone geometric properties at the proximal femur.

Efficacy of Curcumin on Cognitive Function Scores in Women with Premenstrual Syndrome and Dysmenorrhea: A Triple-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To assess the efficacy of a curcumin supplementation on cognitive abilities in women suffering from premenstrual syndrome (PMS) and dysmenorrhea. METHODS: A randomized, triple-blind, placebo-controlled trial was conducted from December 2019 to March 2020. A total of 124 women who had both PMS and dysmenorrhea were enrolled, and were equally and randomly assigned to the curcumin group or placebo group, 62 cases in each. Each subject received either a capsule containing 500 mg of curcuminoid, or a placebo daily, for 10 days (7 days before and until 3 days after the onset of menstrual bleeding) over 3 menstrual cycles. The cognitive abilities questionnaire was used to measures cognitive functions in 7 specific areas. Adverse reactions were monitored during and after the trial in both groups. RESULTS: Administration of curcumin was associated with a significant increase in memory score (P=0.002), inhibitory control and selective attention (P=0.020), and total cognitive ability task (P=0.024). In addition, significant increments were found in scores of memory (3.5±3.1 vs. 0.4±3.8 in the curcumin and placebo groups, respectively; P=0.035), inhibitory control and selective attention (3.0±3.7 vs. 0.4±3.7; P=0.027) and total cognitive abilities (8.3±12.3 vs. 2.2±12.4; P=0.025) in the curcumin group versus placebo groups. Curcumin was safe and well-tolerable in current clinical trial. CONCLUSION: Curcumin has a beneficial efficacy on cognitive function scores in women with PMS and dysmenorrhea, with improvements in memory, inhibitory control and selective attention. (Registration No. IRCT20191112045424N1, available at: https://www.irct.ir ).

Therapeutic effect of turmeric on radiodermatitis: A systematic review.

Radiodermatitis (RD) occurs in 95% of cancer patients undergoing radiation therapy. At present, there is no effective treatment for the management of this complication of radiotherapy. Turmeric (Curcuma longa) is a polyphenolic and biologically active natural compound with various pharmacological functions. The aim of this systematic review was to determine the efficacy of curcumin supplementation for reducing RD severity. This review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A comprehensive literature search was conducted in Cochrane library, PubMed, Scopus, Web of Science, and MEDLINE databases. A total of seven studies comprising 473 cases and 552 controls were included in this review. Four studies demonstrated that curcumin supplementation had a beneficial effect on RD intensity. These data provide evidence for the potential clinical use of curcumin in supportive cancer care. Further large prospective and well-designed trials are warranted to exactly determine the "real effective extract, supplemental form and dose of curcumin" for RD prevention and treatment of patients receiving radiotherapy.

The national health program for vitamin D supplementation in a developing country.

BACKGROUND: Previous studies have reported a high frequency of vitamin D deficiency (VDD) among different age groups in Iran. AIMS: In this study, the current coverage, status of vitamin D supplement taking, and program efficacy have been evaluated by the Office of Nutrition Department Society in Iran since 2014. METHODS: This study was conducted in collaboration with the International UNESCO center for Health-Related Basic Sciences and Human Nutrition and the Office of Nutrition Department Society. Sixty three medical universities were included in the current study to calculate the availability, accessibility and acceptability coverages. Furthermore, 3 medical universities including Mashhad (MUMS), Qom (QUMS) and Zahedan (ZAUMS) University of Medical Sciences were selected based on the results of the National Integrated Micronutrient Survey 2012 (NIMS-II study), in order to assess the status of vitamin D supplement intake in all age ranges. RESULTS: Quantitative analysis showed that availability coverage was 74.96% and 77.56% and accessibility was 80.70% and 83.26% in elderly and middle-aged subjects, respectively in 2018. The acceptability was approximately 43.7% and 43.9% among elderly and middle-aged participants, respectively. The availability and acceptability coverage was 80.99% and 85.0% among students in high schools. The mean vitamin D supplement uptake frequency was 27.0% (n = 387); 20.7% and 29.2% in rural and urban area, respectively (P = 0.001). The results showed that there was no significant difference in serum vitamin D levels between urban (20.41 ± 6.43 ng/ml) and rural areas, (P = 0.887). There was no significant difference in the serum vitamin D concentrations between men and women (P = 0.461). CONCLUSIONS: The frequency of taking vitamin D supplements was 27.0% in Iran in 2018. The frequency of taking of vitamin D supplements among vitamin D deficient group (serum vitamin D levels <19.99 ng/ml) was 43.6%. Lack of knowledge was the most important reason for not taking vitamin D supplement. Moreover, the serum vitamin D levels have increased in subjects aged 18-30 years old after the implementation of the vitamin D supplementary program.

Therapeutic Potential of Herbal Medicine against Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder associated with obesity, diabetes mellitus, dyslipidemia, and cardiovascular disease. A "multiple hit" model has been a widely accepted explanation for the disease's complicated pathogenesis. Despite advances in our knowledge of the processes underlying NAFLD, no conventional pharmaceutical therapy exists. The only currently approved option is to make lifestyle modifications, such as dietary and physical activity changes. The use of medicinal plants in the treatment of NAFLD has recently gained interest. Thus, we review the current knowledge about these agents based on clinical and preclinical studies. Moreover, the association between NAFLD and colorectal cancer (CRC), one of the most common and lethal malignancies, has recently emerged as a new study area. We overview the shared dysregulated pathways and the potential therapeutic effect of herbal medicines for CRC prevention in patients with NAFLD.

Efficacy of Curcumin on Cognitive Function Scores in Women with Premenstrual Syndrome and Dysmenorrhea: A Triple-Blind, Placebo-Controlled Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To assess the efficacy of a curcumin supplementation on cognitive abilities in women suffering from premenstrual syndrome (PMS) and dysmenorrhea.@*METHODS@#A randomized, triple-blind, placebo-controlled trial was conducted from December 2019 to March 2020. A total of 124 women who had both PMS and dysmenorrhea were enrolled, and were equally and randomly assigned to the curcumin group or placebo group, 62 cases in each. Each subject received either a capsule containing 500 mg of curcuminoid, or a placebo daily, for 10 days (7 days before and until 3 days after the onset of menstrual bleeding) over 3 menstrual cycles. The cognitive abilities questionnaire was used to measures cognitive functions in 7 specific areas. Adverse reactions were monitored during and after the trial in both groups.@*RESULTS@#Administration of curcumin was associated with a significant increase in memory score (P=0.002), inhibitory control and selective attention (P=0.020), and total cognitive ability task (P=0.024). In addition, significant increments were found in scores of memory (3.5±3.1 vs. 0.4±3.8 in the curcumin and placebo groups, respectively; P=0.035), inhibitory control and selective attention (3.0±3.7 vs. 0.4±3.7; P=0.027) and total cognitive abilities (8.3±12.3 vs. 2.2±12.4; P=0.025) in the curcumin group versus placebo groups. Curcumin was safe and well-tolerable in current clinical trial.@*CONCLUSION@#Curcumin has a beneficial efficacy on cognitive function scores in women with PMS and dysmenorrhea, with improvements in memory, inhibitory control and selective attention. (Registration No. IRCT20191112045424N1, available at: https://www.irct.ir ).

Plasmodium falciparum Sexual Commitment Rate Variation among Clinical Isolates and Diverse Laboratory-Adapted Lines.

Asexual blood-stage malaria parasites must produce sexual progeny to infect mosquitoes. It is important to understand the scope and causes of intraspecific variation in sexual commitment rates, particularly for the major human parasite P. falciparum. First, two alternative assay methods of measuring sexual commitment were compared to test a genetically modified P. falciparum line with elevated commitment rates inducible by overexpression of GDV1. The methods yielded correlated measurements with higher sensitivity and precision being achieved by one employing detection of the early gametocyte differentiation marker Pfs16. Thus, this was used to survey a diverse range of parasite lines and test each in multiple biological replicate assays in a serum-free medium supplemented with Albumax. There were differences among six recent clinical isolates from Ghana in their mean rates of sexual commitment per cycle, ranging from 3.3% to 12.2%. Among 13 diverse long-term laboratory-adapted lines, mean sexual commitment rates for most ranged from 4.7% to 13.4%, a few had lower rates with means from 0.3 to 1.6%, and one with a nonfunctional ap2-g gene always showed zero commitment. Among a subset of lines tested for the effects of exogenous choline to suppress commitment, there were significant differences. As expected, there was no effect in a line that had lost the gdv1 gene and that had generally low commitment, whereas the others showed quantitatively variable but significant responses to choline, suggesting potential trait variation. The results indicated the value of performing multiple replicate assays for understanding the variation of this key reproductive trait that likely affects transmission. IMPORTANCE Only sexual-stage malaria parasites are transmitted from human blood to mosquitoes. Thus, it is vital to understand variations in sexual commitment rates because these may be modifiable or susceptible to blocking. Two different methods of commitment rate measurement were first compared, demonstrating higher sensitivity and precision by the detection of an early differentiation marker, which was subsequently used to survey diverse lines. Clinical isolates from Ghana showed significant variation in mean per-cycle commitment rates and variation among biological replicates. Laboratory-adapted lines of diverse origins had a wider range with most being within the range observed for the clinical isolates, while a minority consistently had lower or zero rates. There was quantitative variation in the effects when adding choline to suppress commitment, indicating differing responsiveness of parasites to this environmental modification. Performing multiple assay replicates and comparisons of diverse isolates was important to understand this trait and its potential effects on transmission.

Effects of curcumin-piperine supplementation on systemic immunity in young women with premenstrual syndrome and dysmenorrhea: A randomized clinical trial.

INTRODUCTION: Premenstrual syndrome (PMS) and primary dysmenorrhea (PD) are common gynecological complications and there is evidence that inflammation may be an important factor in their etiology. There is a relationship between PMS and PD with susceptibility to allergic disorders. We aimed to assess the effect of curcumin co-administered with piperine on serum IL-10, IL-12 and IgE levels in patients with PD and PMS. MATERIALS AND METHODS: A sample of 80 patients were recruited to this triple-blind, placebo-controlled clinical trial. Participants were randomly allocated to curcumin (n = 40) and control groups (n = 40). Each participant received one capsule (500 mg of curcuminoid plus piperine, or placebo) daily, from 7 days before until 3 days after menstruation for three consecutive menstrual cycles. RESULTS: Serum IgE, IL-10 and IL-12 levels were quantified by using an ELISA kit. No significant differences were found between the two groups at baseline, including: age, BMI, and dietary intakes (P > 0.05). Curcumin + piperine treatment was associated with a significant reduction in the mean serum levels of IgE [from 223.6 ± 258.7 IU/mL to 161.3 ± 240.7; P = 0.001]; but there were no significant changes in the placebo group (P = 0.12). Serum concentrations of IL-10 and IL-12 before and after the trial period did not differ significantly between the two groups (P > 0.05). CONCLUSION: Curcumin plus piperine might be have positive effect on serum IgE levels with no significant changes on serum IL-10 and IL-12 in healthy young women with PMS and PD. Studies with higher doses and longer durations of treatment with curcumin are required to confirm these findings.

The Pharmacologically Active Alkaloid Cryptolepine Activates a Type 1 Interferon Response That Is Independent of MAVS and STING Pathways.

Type 1 interferons (IFN-1) are pleiotropic cytokines with well-established anticancer and antiviral properties, particularly in mucosal tissues. Hence, natural IFN-1-inducing treatments are highly sought after in the clinic. Here, we report for the first time that cryptolepine, a pharmacoactive alkaloid in the medicinal plant Cryptolepis sanguinolenta, is a potent IFN-1 pathway inducer. Cryptolepine increased the transcript levels of JAK1, TYK2, STAT1, STAT2, IRF9, and OAS3, as well as increased the accumulation of STAT1 and OAS3 proteins, similar to recombinant human IFN-α. Cryptolepine effects were observed in multiple cell types including a model of human macrophages. This response was maintained in MAVS and STING-deficient cell lines, suggesting that cryptolepine effects are not mediated by nucleic acids released upon nuclear or organelle damage. In agreement, cryptolepine did not affect cell viability in concentrations that triggered potent IFN-1 activation. In addition, we observed no differences in the presence of a pharmacological inhibitor of TBK1, a pleiotropic kinase that is a converging point for Toll-like receptors (TLRs) and nucleic acid sensors. Together, our results demonstrate that cryptolepine is a strong inducer of IFN-1 response and suggest that cryptolepine-based medications such as C. sanguinolenta extract could be potentially tested in resource-limited regions of the world for the management of chronic viral infections as well as cancers.

Review on the Therapeutic Potential of Curcumin and its Derivatives on Glioma Biology.

Gliomas are common and aggressive brain tumors that carry a poor prognosis. The current multimodal therapeutic option for glioma includes surgery subsequently temozolomide chemotherapy and/or radiation; but gliomas are often associated with multidrug resistance, intensive adverse events, and tumor relapse. Thus, novel interventions that can enhance successful chemo-prevention and overcome therapeutic resistance are urgently needed. Phytochemicals have several biological properties with multi-target sites and relatively limited degrees of toxicity. Curcumin is a natural polyphenolic compound with several anti-tumor effects which potentially inhibit tumor growth, development, proliferation, invasion, dissemination, and angiogenesis in different human malignancies. Experimental model studies have demonstrated that curcumin attenuates glioma cell viability by G2/M cell cycle arrest, apoptosis, induction of autophagy, gene expression alteration, and disruption of multi-molecular pathways. Moreover, curcumin has been reported to re-sensitize cancer to chemotherapeutics as well as augment the effect of radiotherapy on glioma cells. In this review, we have provided an update on the in vitro and in vivo effects of curcumin-based therapy on gliomas. We have also discussed the use of curcumin in combination therapies, its effectiveness on drug-resistant cells, and new formulations of curcumin in the treatment of gliomas.

Molecular Targets of Curcumin and Its Therapeutic Potential for Ovarian Cancer.

Ovarian cancer is the fifth most common gynecological cancer in women globally. Conventional chemotherapy is the first therapeutic approach in the treatment of ovarian cancer, but its success is limited by severe side effects, transient response, and the high prevalence of relapse. Curcumin is a natural product found in the rhizome extract of Curcuma longa and has been extensively used over the last decades for its unique biological and medicinal properties, which include: having antioxidant, analgesic, anti-inflammation, and anti-tumor activities. Curcumin exerts its anticancer properties against ovarian cancer via multiple mechanisms: interfering with cellular interactions necessary for metastasis and recurrence of OC cells, increasing pro-apoptotic proteins as well as inducing or suppressing generation of different molecules such as cytokines, transcription factors, enzymes, protein kinases, and growth factors. Moreover, curcumin down-regulates various signaling pathways such as PI3K/Akt, Wnt/ß-catenin, JAK/STAT3, and MEK/ERK1/2 axes, which at least in part have a role in inhibiting further tumor proliferation, growth, and angiogenesis. In this review, we overview the potential of incorporating curcumin into the treatment of ovarian cancer. In particular, we summarize the preclinical evidence supporting its use in combination with current chemotherapeutic regimens as well as new analogues and formulations under investigation.

Benefits of a plant-based diet and considerations for the athlete.

Individuals may opt to follow a plant-based diet for a variety of reasons, such as religious practices, health benefits or concerns for animal or environmental welfare. Such diets offer a broad spectrum of health benefits including aiding in the prevention and management of chronic diseases. In addition to health benefits, a plant-based diet may provide performance-enhancing effects for various types of exercise due to high carbohydrate levels and the high concentration of antioxidants and phytochemicals found in a plant-based diet. However, some plant-based foods also contain anti-nutrional factors, such as phytate and tannins, which decrease the bioavailability of key nutrients, such as iron, zinc, and protein. Thus, plant-based diets must be carefully planned to ensure adequate intake and absorption of energy and all essential nutrients. The current narrative review summarizes the current state of the research concerning the implications of a plant-based diet for health and exercise performance. It also outlines strategies to enhance the bioavailability of nutrients, sources of hard-to-get nutrients, and sport supplements that could interest plant-based athletes.

The effects of L-carnitine supplementation on inflammatory factors, oxidative stress, and clinical outcomes in patients with sepsis admitted to the intensive care unit (ICU): study protocol for a double blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Sepsis is a common cause for admission to the intensive care unit (ICU), and its incidence has been increasing. It is associated with a significant increase in serum inflammatory biomarkers such as C-reactive protein (CRP) and cytokines such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF). Sepsis is also associated with pathophysiological changes that include fluid accumulation in the lungs, eventually leading to acute respiratory distress syndrome (ARDS), tissue edema, hypotension, and acute kidney injury (AKI). Conventional therapies include antibiotics, but these may have important adverse effects, so novel therapeutic approaches are required. In animal studies, L-carnitine improves antioxidant status, and in some clinical trials, it has been shown to reduce inflammation. It has also been shown to improve respiratory distress and help maintain coenzyme A homeostasis, metabolic flexibility, promoting the normal function of the tricarboxylic acid (TCA) cycle, and oxidation of fatty acids by peroxisomes. We aim to determine the effects of very high doses of L-carnitine on inflammatory factors, oxidative stress, and clinical outcomes of patients with sepsis in ICU. METHOD AND DESIGN: In this double-blind, randomized controlled clinical trial, we will use block randomization of 60 patients with sepsis, aged between 20 and 65 years from Al-Zahra Hospital, Isfahan, Iran. The intervention group (n = 30) will receive three capsules of L-carnitine (each capsule contains 1000 mg L-carnitine; totally 3000 mg/day) for 7 days, and a control group (n = 30) will receive a placebo with the same dose and for the same duration in addition to usual care. At baseline, scores for clinical and nutritional status (Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), and NUTRIC Score) will be assessed. At beginning and end point of the study, inflammatory markers (CRP, erythrocyte sedimentation rate (ESR)), oxidative stress status (total oxidative stress (TOS), total antioxidant capacity (TAC)), and clinical variables will be evaluated also. The mortality rate will be assessed within 28 days of the beginning of the intervention. DISCUSSION: Because of the anti-inflammatory and antioxidant properties of L-carnitine, it is possible that using a high dose of 3000 mg daily of this nutritional supplement may reduce inflammation and oxidative stress and improve subsequent mortality of critically ill patients with sepsis. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20201129049534N1 . Registered on 2 May 2021.

Effects of curcumin supplementation on vitamin D levels in women with premenstrual syndrome and dysmenorrhea: a randomized controlled study.

BACKGROUND: Vitamin D has an established role in female reproduction. There is also evidence for an association between vitamin D levels and menstrual problems such as premenstrual syndrome (PMS) and dysmenorrhea. Curcumin, is a bioactive polyphenol constituent of turmeric, that can potentially interact with vitamin D receptors and its molecular targets. This study evaluated the effects of curcumin on vitamin D levels in young women with PMS and dysmenorrhea. METHODS: In this randomized, triple-blind, placebo-controlled trial, women with PMS and dysmenorrhea were divided randomly into experimental and control groups to receive one capsule (500 mg of curcuminoid+ 5 mg piperine, or placebo) daily, from approximately 7 days before until 3 days after menstruation for three consecutive menstrual cycles. Serum vitamin D levels, renal function, and liver enzymes were also measured before and after intervention. RESULTS: A total of 76 subjects (38 in each group) were recruited into the trial. Curcumin significantly increased the median (IQR) serum levels of vitamin D [from 12.8 ng/ml (7.0-24.6) to 16.2 ng/ml (6.4-28.8); P = 0.045], compared with placebo [from 18.6 ng/ml (2.2-26.8) to 21.3 ng/ml (5.2-27.1); P = 0.17]. Serum levels of aspartate aminotransferase and direct bilirubin were reduced by the end of trial in the curcumin group (p < 0.05), but did not change significantly in the control group (p > 0.05). Finally, no significant differences in levels of fasting blood glucose were detected between curcumin and placebo groups. CONCLUSION: Curcumin supplementation in women with PMS and dysmenorrhea led to a significant improvement of vitamin D, liver function enzyme test, but did not affect blood glucose. TRIAL REGISTRATION: The trial was registered on Iranian Registry of Clinical Trials registry (Trial ID: IRCT20191112045424N1 on 23 January 2020; available at https://www.irct.ir ).

The impact of the COVID-19 pandemic on the diet, training habits and fitness of Masters cyclists.

Background: The number of Masters-level athletes (≥ 35 years of age) taking part in cycling has increased in the past years which may have beneficial effects on their health. The restrictions brought on by the COVID-19 pandemic has the potential to negatively impact the diet, training and fitness of these individuals due to restrictions in place to slow the spread of the virus. Aim: To investigate how the COVID-19 pandemic impacted the diet, training and fitness of Masters-level cyclists. Methods: 32 Masters cyclists (12 males, 20 females; mean age 47 ± 10 years) completed two incremental exercise tests one month apart during the pandemic to assess sport-specific fitness. Participants also completed online questionnaires to report their sedentary behavior and dietary intake before and during the pandemic, and their training volume and intensity for a specified week in February (before the pandemic) and each of March, April and May (during the pandemic). Results: No differences were seen in fitness (p = 0.6), training volume (p = 0.24) or intensity (p = 0.79) and sedentary behavior (p = 0.14) during the pandemic. Energy intake was unchanged (p = 1.0) during the pandemic, but participants consumed lower amounts of key nutrients such as fiber, vitamin A, omega-3 fatty acids and potassium (p < 0.05) while consuming more alcohol (p = 0.008) and vitamin C (p = 0.03). Conclusions: Our data shows that the COVID-19 pandemic has undesirable effects on nutrient and alcohol intake of Masters cyclists without impacting their training regimes, which may have adverse effects on their overall health and fitness in the long term.