Effects of vitamin D supplementation on liver fibrogenic factors, vitamin D receptor and liver fibrogenic microRNAs in metabolic dysfunction-associated steatotic liver disease (MASLD) patients: an exploratory randomized clinical trial.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global metabolic problem which can lead to irreversible liver fibrosis. It has been shown that vitamin D and its receptors contribute to fibrogenic pathways in the liver. However, the effect of vitamin D supplementation on liver fibrosis related factors have not been examined. This double blinded placebo controlled clinical trial was designed to investigate the effects on vitamin D supplementation on serum levels of VDR, fibrogenic factors and fibrogenic MicroRNAs in MASLD patients. METHODS: Forty six MASLD patients after block matching for sex and BMI were randomly assigned to receive 4000 IU/d vitamin D or placebo for 12 weeks. Weight, height and waist circumference were measured. Serum fibrogenic microRNAs, laminin, collagen type IV, hyaluronic acid, vitamin D, VDR, PTH, blood fasting glucose, serum fasting insulin, lipid profile, ALT and AST were determined at the baseline and at the end of the trial. Insulin resistance and insulin sensitivity were calculated using the HOMA-IR and QUICKI equation. RESULTS: Supplementation with vitamin D for 12 weeks led to the significant increases in serum 25(OH) vitamin D, VDR and HDL-C compared to placebo (P < 0.001, P = 0.008 and P < 0.001). There were significant decreases in ALT, AST, FBS and LDL-C levels in the vitamin D group as compared to the placebo (P < 0.05). Laminin and hyaluronic acid concentrations were significantly decreased in the vitamin D group as compared to the placebo group, by -10.6 and - 28.7 ng/mL, respectively. Supplementation with vitamin D for 12 weeks resulted in a significant lower MiR-21 and MiR-122 gene expressions compared to the placebo group (P = 0.01 and P < 0.001, respectively). DISCUSSION: As the first randomized controlled trial on the effect of vitamin D supplementation on serum levels of VDR, fibrogenic factors and fibrogenic MicroRNAs in MASLD patients, we found a significant reduction in some liver fibrogenic factors, in liver transaminases and corresponding changes in some fibrosis-related MiRs and some metabolic factors. Further clinical trials with larger sample sizes and direct measures of liver fibrosis are needed to confirm these findings. TRIAL REGISTRATION NUMBER: (available at: http://www.irct.ir , identifier: IRCT201405251485N13), Registration date: 14-03-2017.

Nutrient patterns in relation to insulin resistance and endothelial dysfunction in Iranian women.

Prior studies have mainly focused on the association of one specific nutrient with insulin resistance (IR) and endothelial dysfunction and limited studies have assessed the association with different nutrient patterns (NPs). We examined the association between various NPs and IR and endothelial dysfunction among Iranian women. This cross-sectional study was carried out on a sample of 368 female nurses. A 106-items food frequency questionnaire (FFQ) was applied for dietary assessments. Using factor analysis, the relationships between NPs and markers of insulin resistance (HOMA-IR, HOMA-ß, and QUICKY), and endothelial dysfunction (E-selectin, sICAM-1, and sVCAM-1) were assessed. Mean age and body mass index of participants were respectively 35.21 years and 24.04 kg/m2. Three major NPs were identified. NP1, named as "dairy, fruits, and vegetables" had high values of potassium, folate, vitamins A and C, magnesium, and beta carotene. No significant association was observed between this NP and insulin resistance or endothelial dysfunction indices. The second NP was full of chromium, selenium, copper, vitamin B6, monounsaturated fatty acid (MUFA), thiamin, vitamin D, and iron. Adherence to NP2 (named "legumes, nuts, and protein foods") was associated with lower values of insulin (6.8 ± 1.1 versus 8.4 ± 1.1, P = 0.01), homeostasis model assessment-Insulin resistance (HOMA-IR) (1.3 ± 0.2 versus 1.7 ± 0.2, P = 0.02), and vascular adhesion molecule 1 (VCAM-1) (444.2 ± 27.9 versus 475.8 ± 28.4, P = 0.03). However, adherence to the third NP, rich in saturated fatty acid (SFA), cholesterol, sodium, zinc, vitamin E, and B12, described as "animal fat and meat + vitamin E", was associated with higher amounts of homeostasis model assessment-ß (HOMA-ß) (531.3 ± 176.2 versus 48.7 ± 179.8, P = 0.03). In conclusion, following the NP2, correlated with higher intakes of chromium, selenium, copper, vitamin B6, MUFA and thiamin was associated with lower values of insulin, HOMA-IR, and sVCAM-1. Adherence to NP3, rich in SFA, cholesterol, vitamin E, vitamin B12, and zinc was associated with higher levels of HOMA-ß.

The Effect of Mediterranean Diet on Body Composition, Inflammatory Factors, and Nutritional Status in Patients with Cachexia Induced by Colorectal Cancer: A Randomized Clinical Trial.

BACKGROUND: Along with high calorie and high protein diet, a new comprehensive dietary approach is needed to control cachexia caused by cancer and its related outcomes. This study was done to evaluate the effect of a Mediterranean diet on body composition, nutritional status, and inflammatory markers among cancer cachexia patients. METHODS: In this randomized clinical trial, 46 patients with colorectal cancer-induced cachexia were included. After randomization, 23 patients were allocated to the intervention group (Mediterranean diet) and 23 to the control group (nutritional counseling for weight gain and prevention of weight loss in cancer patients). The primary outcome including muscle health, nutritional status, and inflammatory markers along with secondary outcomes such as quality of life, and serum proteins were evaluated at the start and the eighth week of the study. Statistical analysis was performed according to the intention-to-treat concept. To compare changes in dependent variables between the 2 groups, analysis of covariance (ANCOVA) was performed. RESULTS: After adjustment for the baseline values, age, sex, and supplements use, in the Mediterranean diet group mean of weight (P < .001), lean body mass (P = .001), fat mass (P = .002), and muscle strength (P < .001) were significantly increased compared to the control group. Regarding inflammatory markers, the mean serum level of tumor necrosis factor-alpha (TNF-α) (P < .001), high sensitive-C-reactive protein (hs-CRP) (P = .01) and Interleukin 6 (IL-6) (P < .001) were significantly improved in the Mediterranean diet group. Moreover, in the Mediterranean diet group, the score for global health status (P = .02) and physical performance score (P < .001) were significantly increased. CONCLUSION: It appears that the implementation of the Mediterranean diet might be a strategy to improve nutritional status, quality of life, inflammatory markers, and body composition in patients with colorectal cancer cachexia. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (www.irct.ir); ID: IRCT20211027052884N1.

The impact of a blend of Pistacia atlantica seed and canola oil compared with a blend of corn-canola oil with synthetic antioxidant and corn-canola oil without synthetic antioxidant on oxidative stress markers in patients with metabolic syndrome: protocol for a triple-blind, randomized, three-way cross-over clinical trial.

BACKGROUND: Metabolic syndrome (MetS) is regarded as a complex metabolic disorder. Recently, the role of dietary antioxidants in the underlying pathogenesis and complications of MetS has come into focus. Pistacia atlantica oil is known as a high antioxidant oil which might improve the antioxidant status of dietary oils and also oxidative stress markers. On the other hand, tert-Butylhydroquinone (TBHQ) is an approved food-grade synthetic antioxidant that acts both as an inducer and inhibitor of carcinogenesis. The current trial will explore the possible effect of a blend of Pistacia atlantica seed-canola oils, corn-canola oils with TBHQ, and corn-canola oil without TBHQ on oxidative stress markers in patients with MetS. METHODS: We will conduct a single-center, triple-blind, three-way randomized cross-over clinical trial (RCT) among 72 patients with MetS. After a 1-month run-in period, eligible participants will consume the intervention oils as their regularly consumed oils in a random order. Each intervention period will last 8 weeks separated by 4-week washout periods. Anthropometric indices, body composition, physical activity, blood pressure, and 24-h dietary food recall measurements will be assessed at the beginning and the end of each intervention period. The primary outcome will be oxidative stress markers including serum total antioxidant capacity, total oxidant status, malondialdehyde, nitric oxide, and the enzyme activity of myeloperoxidase, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. The secondary outcomes will be changes in MetS components including blood pressure, fasting blood glucose, triglyceride, high-density lipoprotein cholesterol, and anthropometric measurements. DISCUSSION: Pistacia atlantica seed oil is high in antioxidants. An intervention with this oil could offer an option for oxidative stress prevention among patients with metabolic syndrome. The present clinical trial will be the first one assessing the impact of Pistacia atlantica oil on human oxidative stress markers. TRIAL REGISTRATION: Iranian Registry of Clinical trials IRCT20130223012571N8 . Registered on 4 March 2022.

Double burden of malnutrition in Afghanistan: Secondary analysis of a national survey.

BACKGROUND: Reports about the magnitude of co-existence of under- and over-nutrition is limited in Afghanistan. This study aimed to assess the prevalence of double burden of malnutrition (DBM) at individual and household level in Afghanistan. METHODS: This study was done based on the Afghanistan National Nutrition Survey 2013, which included a representative sample of 126,890 individuals (including more than 18,000 households) throughout Afghanistan. Intra-individual DBM was defined as the co-existence of "overweight/obese" and "stunting or micronutrient deficiencies" (including anemia, vitamin A deficiency, vitamin D deficiency and iodine deficiency). At the household level, DBM was considered as having at least one household member as overweight/obese and at least one another member of that household as undernourished (stunted, wasted, underweight or any micronutrient deficiency). SPSS and Stata software were used in the current analysis. Cross-tabulations was used to estimate the prevalence and its 95% confidence interval(CI). This study was ethically approved at Tehran University of Medical sciences. RESULTS: The overall prevalence of intra-individual DBM was 12.5% (95% CI: 12.1; 12.9). Among the whole study participants at individual level of DBM, 11.7% (11.3; 12.1) of individuals had overweight along with stunting simultaneously and 20.5% (18.8; 22.4) had overweight and micronutrient deficiencies at the same time at individual level. The household level of DBM was found among 28.6% (95% CI: 27.9; 29.4) of households; such that 27.3% (26.6; 28.1) of households had at least one member with overweight and another member with stunting or wasting or underweight. Co-existence of overweight and micronutrient deficiencies at the same household was seen in 38.3% (35.5; 41.2). CONCLUSION: This study demonstrated a high prevalence of DBM at individual and household level in Afghanistan. Therefore, developing appropriate national macro-policies and strategies and designing appropriate programs such as public awareness programs, subsidization, food assistance programs, food fortification and dietary supplementation should be implemented by the ministry of public health, inter- related organs and international health agencies to reduce the burden of this problem in this country.

Effects of omega-3 supplementation on serum albumin, pre-albumin and the CRP/albumin ratio in hospitalized patients: a systematic review and meta-analysis.

CONTEXT: Low serum albumin and pre-albumin concentrations are associated with edema, infection, thrombosis, heart failure, and mortality. OBJECTIVE: This comprehensive systematic review and meta-analysis of clinical trials was conducted to summarize the available findings on the impact of omega-3 supplementation on albumin, pre-albumin, and the C-reactive protein/albumin ratio in hospitalized patients. DATA SOURCES: PubMed, Web of Science, Scopus, and Google Scholar databases were searched from January 1990 to October 2021. DATA EXTRACTION: Extracted data from 50 randomized controlled trials (RCTs) with a total number of 3196 participants were analyzed using the random-effects model. The dose-dependent effect was also evaluated. DATA ANALYSIS: Oral omega-3 supplementation significantly increased serum albumin concentrations in patients with cancer (weighted mean difference [WMD]: 0.19; 95% CI: 0.05, 0.33, P= 0.006), patients on dialysis (WMD: 0.14; 95% CI: 0.01, 0.28, P= 0.042), and those with hypoalbuminemia (WMD: 0.38; 95% CI: 0.03, 0.72, P = 0.033); however, there was no significant effect among patients with gastrointestinal or hepatologic diseases. Moreover, each 1000 mg/day increase in oral omega-3 supplementation resulted in elevated serum albumin levels in cancer patients (WMD: 0.15; 95% CI: 0.07, 0.24, P < 0.001). In addition, a favorable effect of oral omega-3 supplementation on pre-albumin levels was observed among patients with cancer (WMD: 33.87; 95% CI: 12.34, 55.39, P = 0.002). A similar significant effect of parenteral omega-3 supplementation on pre-albumin concentrations was seen among those with gastrointestinal and hepatologic diseases as well (WMD: 23.30; 95% CI: 13.58, 33.03, P < 0.001). No significant effect of oral omega-3 supplementation on the CRP/albumin ratio was found. CONCLUSIONS: Overall, omega-3 fatty acids supplementation resulted in a favorable change in serum albumin and pre-albumin concentrations in hospitalized patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021285704.

Coffee consumption and caffeine intake in relation to risk of fractures: a systematic review and dose-response meta-analysis of observational studies.

BACKGROUND: Conflicting reports are available about the association of coffee or caffeine intake and risk of fracture. We performed the current updated systematic review and dose-response meta-analysis of coffee consumption and caffeine intake and risk of fracture to quantify this association. MATERIALS AND METHODS: PubMed/Medline, ISI Web of Science, and Scopus, Cochrane database were searched up to July 2021. Random-effects model or fixed-effects model was used to pool the study-specific effect sizes (ESs) and 95% confidence intervals (CIs). Dose-response relationship was examined using linear and non-linear dose-response analyses. The certainty of evidence was assessed using NutriGrade tool. RESULTS: Out of 22 eligible studies included in the meta-analysis, 15 had cohort and 7 had case-control design. We found no significant association between coffee consumption and risk of fracture, either based on pooling cohort (RR: 0.99; 95% CI: 0.88, 1.12; I2 = 71.4%, Pheterogeneity < 0.01) or case-control studies (OR: 1.13; 95% CI: 0.87, 1.46; I2 = 49.0%, Pheterogeneity=0.08). In the subgroup analysis of cohort studies, we observed that higher coffee intake was inversely associated with risk of fracture in men (RR: 0.85; 95% CI: 0.76 to 0.94). In addition, a positive association was seen between coffee consumption and risk of fracture in studies with less than 12 years of follow-up (RR: 1.14; 95% CI: 1.02 to 1.27). With regard to caffeine intake, a statistically significant positive association was seen with risk of fracture (RR: 1.15; 95% CI, 1.08 to 1.23; I2=26.6%, n = 8). In the dose-response analysis, we found that each additional 100 mg caffeine intake was marginally associated with 2% greater risk of fracture (RR: 1.02; 95% CI: 1 to 1.05; I2= 70.3%, n = 6). CONCLUSION: High coffee consumption was protectively associated with risk of fracture in men, while caffeine intake was positive associated with risk.

Probiotics as a New Regulator for Bone Health: A Systematic Review and Meta-Analysis.

Despite the proposed role of the gut microbiota-bone axis, findings on the association between probiotic consumption and bone health are conflicting. This systematic review aimed to assess the effect of probiotic consumption on bone health parameters. A systematic literature search of relevant reports published in PubMed/Medline, Web of Science, SCOPUS, EMBASE, and Google scholar before December 2020 was conducted. All clinical trials or experimental studies, which examined the relationship between probiotic consumption and bone health parameters, were included. No limitation was applied during the search. After screening articles based on inclusion criteria, 44 studies remained. In clinical trials, probiotic consumption affects bone health parameters such as serum calcium levels (3.82; 95% CI: 1.05, 6.59 mmol/l), urinary calcium levels (4.85; 95% CI: 1.16, 8.53 mmol/l), and parathyroid hormone (PTH) levels (-5.53; 95% CI: -9.83, -0.86 ng/l). In most studies, Lactobacillus species such as L. helveticus, L. reuteri, and L. casei were consumed and women aged 50 years or older were assessed. Spinal and total hip bone mineral density (BMD) was not affected significantly by probiotic consumption. In 37 animal experiments, probiotic or symbiotic feeding mostly had effects on bone health parameters. Some strains of Bifidobacterium and Lactobacillus including L. reuteri, L. casei, L. paracasei, L. bulgaricus, and L. acidophilus have indicated beneficial effects on bone health parameters. In conclusion, this systematic review and meta-analysis indicate that probiotic supplementation might improve bone health. Further studies are needed to decide on the best probiotic species and appropriate dosages.

The effects of vitamin D supplementation on inflammatory biomarkers in patients with abnormal glucose homeostasis: A systematic review and meta-analysis of randomized controlled trials.

FINDINGS: on the level of inflammatory cytokines following vitamin D supplementation among individuals with abnormal glucose homeostasis (AGH) are controversial. Therefore, the present study was conducted on AGH patients to assess the impact of vitamin D on inflammatory cytokines such as CRP, TNF-α and IL-6. A systematic search up to September 2020 was performed through PubMed and Scopus databases. All clinical studies which evaluated the effect of oral vitamin D supplementation on inflammation in patients with AGH were included. The random-effects model was applied to obtain pooled results. For dose-response analysis, we used a fractional polynomial model. Overall, 38 studies, with 46 effect sizes, were included in this study. Combining effect sizes, we found that vitamin D considerably decrease serum concentrations of CRP (weight mean difference (WMD): - 0.67 mg/l; 95%CI: - 0.92, - 0.43; P < 0.001), IL-6 (WMD: -1.93 pg/mL; 95%CI: -2.80, -1.07; P < 0.001) and TNF-α (WMD: -0.81 pg/mL; 95%CI: -1.59, -0.03; P = 0.04). In the dose-response analysis, we failed to find any correlation between dosage of supplements and inflammatory biomarkers concentrations. Summarizing earlier studies, we demonstrated that circulating concentrations of inflammatory cytokines such as CRP, TNF-α, and IL-6 might be decreased following vitamin D supplementation among individuals with AGH.

Total, Dietary, and Supplemental Magnesium Intakes and Risk of All-Cause, Cardiovascular, and Cancer Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

A meta-analysis of prospective studies was conducted to examine the association of total, supplemental, and dietary magnesium intakes with risk of all-cause, cancer, and cardiovascular disease (CVD) mortality and identify the dose-response relations involved in these association. We performed a systematic search of PubMed, Scopus, Google Scholar, and ISI Web of Knowledge up to April 2020. Prospective cohort studies that reported risk estimates for the association between total, supplemental, and dietary magnesium intakes and risk of mortality were included. Random effects models were used. Nineteen publication with a total of 1,168,756 participants were included in the current meta-analysis. In total, 52,378 deaths from all causes, 23,478 from CVD, and 11,408 from cancer were identified during the follow-up period of 3.5 to 32 years. Dietary magnesium intake was associated with a lower risk of all-cause [pooled effect size (ES): 0.87; 95% CI: 0.79, 0.97; P = 0.009; I2 = 70.7%; P < 0.001] and cancer mortality (pooled ES: 0.80; 95% CI: 0.67, 0.97; P = 0.023; I2 = 55.7%; P = 0.027), but not with CVD mortality (pooled ES: 0.93; 95% CI: 0.82, 1.07; P = 0.313; I2 = 72.3%; P < 0.001). For supplemental and total magnesium intakes, we did not find any significant associations with risks of all-cause, CVD, and cancer mortality. However, linear dose-response meta-analysis indicated that each additional intake of 100 mg/d of dietary magnesium was associated with a 6% and 5% reduced risk of all-cause and cancer mortality, respectively. In conclusion, higher intake of dietary magnesium was associated with a reduced risk of all-cause and cancer mortality, but not CVD mortality. Supplemental and total magnesium intakes were not associated with the risk of all-cause, CVD, and cancer mortality. These findings indicate that consumption of magnesium from dietary sources may be beneficial in reducing all-cause and cancer mortality and thus have practical importance for public health.

The state of child nutrition in Ethiopia: an umbrella review of systematic review and meta-analysis reports.

BACKGROUND: Malnutrition remains to be a major public health problem in developing countries, particularly among children under-5 years of age children who are more vulnerable to both macro and micro-nutrient deficiencies. Various systematic review and meta-analysis (SRM) studies were done on nutritional statuses of children in Ethiopia, but no summary of the findings was done on the topic. Thus, this umbrella review was done to summarize the evidence from SRM studies on the magnitude and determinants of malnutrition and poor feeding practices among under-5 children in Ethiopia. METHODS: PubMed, Embase, Scopus, Web of Sciences, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and Google Scholar were searched for SRM studies on magnitude and risk factors of malnutrition and child feeding practice indicators in Ethiopia. The methodological quality of the included studies was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. The estimates of the included SRM studies on the prevalence and determinants of stunting, wasting, underweight, and poor child feeding practices were pooled and summarized with random-effects meta-analysis models. RESULT: We included nine SRM studies, containing a total of 214,458 under-5 children from 255 observation studies. The summary estimates of prevalence of stunting, underweight, and wasting were 42% (95%CI = 37-46%), 33% (95%CI = 27-39%), and 15% (95%CI = 12-19%), respectively. The proportion of children who met the recommendations for timely initiation of breastfeeding, exclusive breastfeeding during the first 6 months, and timely initiation of complementary feeding were 65, 60, and 62%, respectively. The proportion of children who met the recommendations for dietary diversity and meal frequency were 20, and 56%, respectively. Only 10% of children fulfilled the minimum criteria of acceptable diet. There was a strong relationship between poor feeding practices and the state of malnutrition, and both conditions were related to various health, socio-economic, and environmental factors. CONCLUSION: Child malnutrition and poor feeding practices are highly prevalent and of significant public health concern in Ethiopia. Only a few children are getting proper complementary feeding. Multi-sectoral efforts are needed to improve children's feeding practices and reduce the high burden of malnutrition in the country.