Effect of epigenetics on vitamin D levels: a systematic review until December 2020.

BACKGROUND: The association between epigenetic modification of the genes involved in the vitamin D metabolic pathway and vitamin D metabolites' status has been elucidated incompletely. This study aims to review the studies on the mentioned association and create a brighter view of this topic. METHODS: A systematic literature search was conducted in Medline database (PubMed), Scopus, and Web of Science up to the end of November 2020. Original articles which reported the effect of epigenetic alteration-methylation level or its changes-of genes involved in vitamin D regulation on the vitamin D metabolites serum level or its changes were included. The National Institutes of Health (NIH) checklist was used to assess the quality of included articles. RESULTS: Among 2566 records, nine reports were included in the systematic review according to the inclusion and exclusion criteria. Studies discussed the contribution of methylation status of members of the cytochrome P450 family (CYP2R1, CYP27B1, CYP24A1), and Vitamin D Receptor (VDR) genes to vitamin D level variance. CYP2R1 methylation status could regulate the contributing factors affecting the vitamin D serum level and predict response to vitamin D supplementation. Studies revealed that impaired methylation of CYP24A1 occurs in response to an increase in serum level of 25-hydroxyvitamin D (25(OH)D). It is reported that the association between methylation levels of CYP2R1, CYP24A1, and VDR genes and 25(OH)D level is not affected by the methyl-donors bioavailability. CONCLUSIONS: The epigenetic modification of the vitamin D-related genes could explain the vitamin D levels variation among populations. Large-scale clinical trials in various ethnicities are suggested to find the effect of epigenetics on vitamin D response variation. REGISTRATION: The systematic review protocol was registered on PROSPERO (registration number: CRD42022306327).

The association between vitamin C dietary intake and its serum levels with anthropometric indices: A systematic review and meta-analysis.

BACKGROUND: studies showed inflammatory background of overweight and obesity. Prevalence of weight disorders has dramatically increased over the past few decades. Vitamin C is an antioxidant and may be associated with weight disorders. This study aims to systematically review the relationship between dietary and serum vitamin C levels with anthropometric indices. METHODS: A systematic search was conducted in Medline database (PubMed), Scopus, Embase, Web of Science, Cochrane library and Google Scholar up to the end of August 2021. All observational studies that assessed the relationship between dietary or circulating vitamin C levels and body mass index (BMI) and waist circumference (WC) on adults were included. The quality of included studies was assessed using the National Institute of Health quality assessment tool. RESULTS: Among 11,689 studies, 47 and 37 articles were included in the systematic review and meta-analysis, respectively. There was an inverse significant correlation between WC and serum vitamin C levels (r = -0.28, 95% CI: -0.35,-0.21, I2 = 14.2%) and between BMI and serum vitamin C levels (r = -0.17, 95% CI: -0.25, -0.09, I2 = 72.8%). Higher vitamin C consumption was significantly associated with lower BMI. There were no significant differences in serum vitamin C levels between normal-weight and overweight subjects, but serum vitamin C levels were significantly higher in obese subjects in comparison with normal-weight subjects. CONCLUSION: Results showed that both dietary and serum vitamin C levels were inversely associated with BMI and WC. More well-designed clinical trials are needed to assess the effect of vitamin C supplementation in prevention and treatment of obesity.

Effects of shrimp oil on cardio-metabolic risk factors in children and adolescents.

Background: Antioxidants have beneficial effects on health. Shrimp oil has Astaxanthin and omega 3 that act as powerful antioxidants and might have anti-inflammatory effects on cardiovascular diseases. This study aims to investigate the effects of shrimp oil supplementation on cardio-metabolic risk factors in overweight and obese children and adolescents. Methods: This randomized, triple-blind, placebo-controlled clinical trial was conducted on 64 overweight and obese participants with 10-18 years of age. They were randomly assigned to receive either 500 mg shrimp oil or identical placebo that contained medium-chain triglycerides once per day for eight weeks. Dietary intake was obtained using food record questionnaire for three days at baseline and at the end of the study. Fasting blood samples were obtained at baseline and after eight weeks of intervention. Results: Overall, 53 participants completed the study; 30 subjects received shrimp oil and 23 subjects received placebo. There were no significant effects of shrimp oil on total cholesterol, triglyceride, HDL-C, LDL-C and blood pressure compared with the placebo group (p>0.05). Shrimp oil had no significant effects on body mass index, waist circumference and hip circumference compared with the placebo group (p>0.05). Conclusions: Supplementation with shrimp oil had no significant effects on improving the anthropometric measures and cardio-metabolic risk factors. Future clinical trials are needed to investigate the beneficial effects of higher doses of shrimp oil on cardio-metabolic risk factors in the pediatric age groups.

Growth Hormone Response to L-Arginine Alone and Combined with Different Doses of Growth Hormone-Releasing Hormone: A Systematic Review and Meta-Analysis.

Background: Arginine (ARG) can modulate growth hormone (GH) release by suppressing its endogenous inhibitory regulator, somatostatin. ARG also induces the release of the GH-releasing hormone (GHRH). This study aims to review the effects of L-arginine supplementation alone and combined with GHRH in different doses on GH secretion. Methods: In this systematic review and meta-analysis, an electronic literature search was conducted on Medline database (PubMed), Scopus, and Web of Science databases. All eligible studies were randomized clinical trials that reported the effects of ARG supplementation alone or with GHRH on GH levels. Mean difference (MD) and 95% confidence intervals (CI) were computed as the effect size. Results: Meta-analyses showed significant effects of ARG alone on GH release (MD = 10.07, 95% CI: 7.87, 12.28). Moreover, the response of GH was greater with ARG in combination with GHRH (MD = 24.96, 95% CI: 17.51, 32.42). There was no significant difference between the patients and healthy individuals and between oral and injection use of ARG. The systematic review revealed the important role of ARG in combination with other amino acids on GH secretion in patients with GH deficiency. Conclusion: This study revealed that in GH-deficient individuals, high doses of ARG supplementation in combination with GHRH and/or other amino acids might have potential therapeutic effects on increasing GH concentrations. These findings propose that ARG supplementation can be considered as a potential stimulator in management of GH deficiency.

Association of selenium, zinc and copper concentrations during pregnancy with birth weight: A systematic review and meta-analysis.

BACKGROUND: Normal fetal growth is associated with maternal nutrition. Trace elements play important roles in fetus growth. This review aims to provide a summary of the literature evaluating the relation between selenium, zinc and copper levels during pregnancy with birth weight. METHOD: A systematic literature search was conducted in Medline database (PubMed), Scopus, Web of science and Google scholar up to September 2020. Fifty observational studies were included in the final analyses. The desired pooled effect size was considered as standardized mean differences with 95 % CI or correlation. Cochran's Q statistic was used to test the heterogeneity between the included studies (I2). RESULT: A significant differences were found between pooled standardized mean differences (SMD) of umbilical cord blood copper levels in small-for-gestational age birth weight (SGA) and appropriate-for-gestational age birth weight (AGA) (SMD: 0.34 µg/L, 95 % CI: 0.13 to 0.56). There was a significant pooled correlation between umbilical cord blood selenium concentrations and birth weight (r: 0.08, 95 % CI: 0.01 to 0.16). A significant pooled correlation was found between umbilical cord blood zinc concentrations and birth weight (r: 0.09, 95 % CI: 0.04 to 0.15), with significant heterogeneity (I2 % = 0.63). There was significant positive association between maternal blood zinc concentrations and birth weight. CONCLUSION: Findings showed the association of trace elements including selenium, zinc and copper during pregnancy with birth weight. There was significant correlation between umbilical cord and maternal blood selenium and zinc levels with birth weight. The umbilical cord blood copper levels in SGA birth weight was higher than copper levels in AGA birth weight.

Effect of l-carnitine supplementation on children and adolescents with nonalcoholic fatty liver disease (NAFLD): a randomized, triple-blind, placebo-controlled clinical trial.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in the pediatric population at global level. Present study aims to assess the effect of l-carnitine supplementation on the NAFLD in children and adolescents. METHODS: This randomized, triple-blind, placebo-controlled clinical trial was conducted in 2018-2019. Study was carried out in NAFLD participants (5-15 years). They were randomly assigned to receive either 50 mg/kg/day l-carnitine twice a day or identical placebo per day for three months. Liver enzymes and liver ultrasonography were assessed before and after the intervention. Both groups received similar consultation for lifestyle changes. RESULTS: Overall, 55 participants completed the study, 30 patients in the l-carnitine group and 25 patients in placebo group. Mean changes of anthropometric measurements did not have significant differences between groups (p>0.05). No significant differences in the mean changes of aspartate aminotransferase (AST) (p=0.82) and alanine aminotransferase (ALT) (p=0.76) levels were documented between two groups. Based on within-group analysis, there were significant changes in AST and ALT levels before and after the intervention in both groups. The sonographic grades of fatty liver were not significantly different between two groups before (p=0.94) and after intervention (p=0.93). CONCLUSIONS: In the present clinical trial, L-carnitine did not have significant effect on improving biochemical and sonographic markers of NAFLD in children and adolescents. Future studies are necessary to evaluate the applicability and efficacy of long-term l-carnitine supplementation to treatment of NAFLD in pediatric population. TRIAL REGISTRATION: IRCT20170628034786N2.

Association of serum 25-hydroxyvitamin D concentration with anthropometric measures in children and adolescents: the CASPIAN-V study.

BACKGROUND: Serum 25-hydroxyvitamin D (25(OH)D) concentrations reflect vitamin D status, with deficiency implicated as an underlying factor for many adverse health effects. This study aims to analyze the association between vitamin D status and different anthropometric measures in a large pediatric population. METHODS: This nationwide cross-sectional study was conducted in 2019 in blood samples obtained from school students of 30 provinces in Iran. Participants were 2596 children and adolescents aged 7-18 years. Weight, height, waist circumference (WC), hip circumference (HC), neck circumference (NC), and wrist circumference (WrC) were measured. Body mass index (BMI) and waist-to-height ratio (W/HtR) were calculated. Serum 25(OH)D concentrations were measured using chemiluminescent immunoassay. RESULTS: Participants consisted of 55% boys, 71.3% urban inhabitants, with a mean (SD) age of 12.1 (3.0) years. Overall, vitamin D deficiency was documented in 10.6% of participants, insufficiency in 60.4%, and sufficiency in 29% of the population studied. The mean of BMI and WC was higher in the vitamin D deficient than in the vitamin D sufficient group (19.31 kg/m2 and 69.24 cm vs. 18.34 kg/m2 and 65.73 cm, respectively, P < 0.01). Multivariate linear regression models revealed a significant association of vitamin D insufficiency with WC and W/HtR (P < 0.05). Likewise, in the multivariate regression models, vitamin D deficiency was associated with BMI, WC, and W/HtR (P < 0.05). CONCLUSION: Our findings on the inverse association between vitamin D status and some anthropometric measures underscore the importance of providing vitamin D by fortification and supplementation programs of vitamin D for the pediatric population. LEVEL OF EVIDENCE: V.

Herbal formulation "turmeric extract, black pepper, and ginger" versus Naproxen for chronic knee osteoarthritis: A randomized, double-blind, controlled clinical trial.

Osteoarthritis is the most common articular disease that can lead to chronic pain and severe disability. Curcumin-an effective ingredient in turmeric with anti inflammatory property-plays an important role in protecting the joints against destructive factors. Gingerols and piperine, are the effective ingredients of ginger and black pepper, which may potentially enhance and sustain the effect of curcumin in this direction. To determine the effect of cosupplementation with turmeric extract, black pepper, and ginger on prostaglandin E2 (PGE2 ) in patients with chronic knee osteoarthritis, compared with Naproxen. Sixty patients with two different levels of knee osteoarthritis (Grade 2 and 3) were studied. Individuals were randomly assigned to receive daily turmeric extract, ginger, and black pepper together or Naproxen capsule for 4 weeks. PGE2 was evaluated by ELISA method. 24-hr recall was also assessed. All of participants completed the study. PGE2 decreased significantly in both groups (p < .001), but there was no significant differences between groups. The results of this study indicated that intake of the selected herbs twice a day for 4 weeks may improve the PGE2 levels in patients with chronic knee osteoarthritis similar to Naproxen drug.

Effect of Vitamin D and Magnesium Supplementation on Behavior Problems in Children with Attention-Deficit Hyperactivity Disorder.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by the three main symptom domains including inattention, hyperactivity, and impulsivity. Recent findings suggested that nutrients might play an important role in the pathology of ADHD. The present study aimed to examine the effects of Vitamin D and magnesium supplementation on behavior problems in children with ADHD. METHODS: This double-blind, randomized controlled clinical trial study was conducted on 66 children with ADHD in Clinic of Noor and Ali Asghar Hospital in Isfahan, Iran, in 2016. Children were randomly allocated to receive both Vitamin D (50,000 IU/week) and magnesium (6 mg/kg/day) supplements (n = 33) or placebos (n = 33) for 8 weeks. Conners' Parent Rating Scale was used to evaluate children's behavior at baseline and at the end of the study. RESULTS: After 8 weeks of Vitamin D consumption as well as magnesium, the serum levels of 25-hydroxy-Vitamin D3 and magnesium increased significantly in the intervention group compared with placebo group. Supplementation with Vitamin D and magnesium caused a significant decrease in conduct problems, social problems, and anxiety/shy scores; but it had no significant effect on psychosomatic problems score. CONCLUSIONS: Vitamin D and magnesium supplementation in children with ADHD was effective on conduct problems, social problems, and anxiety/shy scores compared with placebo intake, but it did not affect psychosomatic problem scores, significantly.

Serum Zinc Level and Eating Behaviors in Children Receiving Zinc Supplements without Physician Prescription.

BACKGROUND: The aim of the study was to compare the serum zinc level and eating behaviors in 2-8-year-old children with and without arbitrarily zinc supplementation. MATERIALS AND METHODS: This case-control study was conducted from December 2015 to December 2017 in Isfahan, Iran. The case group consisted of seventy children, aged 2-8 years, who have received zinc supplement without physician prescription; the controls were an equal number of age-matched children who did not receive any supplement. The serum zinc level was measured, and eating behaviors were identified using Children's Eating Behavior Questionnaire (CEBQ). RESULTS: There was no significant difference in serum zinc level between two groups (P = 0.18). Some differences in CEBQ subscales were identified between the groups studied. In the control group, the subscale of enjoyment of food was higher than the case group (P < 0.001). In the case group, the subscales of food fussiness and satiety responsiveness were higher than controls (P < 0.001). CONCLUSION: In this study, serum zinc levels were not significantly different between the two groups, and arbitrarily zinc supplementation does not play an important role in improving anorexia subscales.

Association of Omega-3 Fatty Acid and Epileptic Seizure in Epileptic Patients: A Systematic Review.

The evidence on the association between omega-3 consumption and epileptic seizure is inconsistent. Therefore, we have conducted this systematic review to clarify the possible relationship. Original articles were searched in electronic databases (PubMed, Scopus, Google Scholar, Cochrane, and Ovid) and by reviewing the reference lists of retrieved articles. The main evaluated outcome was the epileptic seizures. We included the English language studies that reported the original data on the effect of omega-3 on epileptic human patients. We included the nine articles with 230 patients in the present systematic review. The mean ± standard deviation age of them was about 31.01 ± 14.99 years. The average of study duration was 22 ± 15.27 weeks. Omega-3 fatty acid supplements were defined as the sum of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (1100 mg/d); as the sum of EPA, DHA, and alpha-linolenic acid (5 g/d); and as the sum of EPA alone (565 mg/d) in different studies. Among the nine studies, four studies reported a significant positive association between omega-3 fatty acids and epileptic seizures. However, power and quality of these studies are low, and we cannot consider the beneficial effect of omega-3 on seizures. In addition, five studies did not reveal any significant effect. Majority of the included studies did not show a significant association between omega-3 and epileptic seizure in epileptic patients, but further studies are necessary. It is controversial whether omega-3 fatty acids can produce positive effects on epileptic patients or not.

Association of conjugated linoleic acid consumption and liver enzymes in human studies: A systematic review and meta-analysis of randomized controlled clinical trials.

OBJECTIVE: The aim of this study was to systematically review the association of conjugated linoleic acid (CLA) consumption in two forms of foods enriched or supplemented with CLA on serum liver enzymes in human studies. METHODS: We searched PubMed, Google Scholar, Cochrane Library, ScienceDirect, ProQuest, and Ovid up to January 2015. Studies that examined the effect of CLA supplementation or foods enriched with CLA on liver enzymes concentrations among healthy adults were included. The mean difference and SD of changes in serum liver enzymes between the intervention and control groups were used as effect size for the meta-analysis. RESULTS: The analysis demonstrated that CLA supplementation led to slight and nonsignificant decreases in alkaline phosphatase (ALP) levels (mean difference [MD] -0.216; 95% confidence interval [CI], -0.60 to 0.17; P = 0.28). CLA intake can nonsignificantly increase alanine transaminase (ALT) levels (MD = 0.107 U/L; 95% CI, -0.29 to 0.244; P = 0.124) and can significantly increase aspartate aminotransferase (AST) levels (MD = 0.171 U/L; 95% CI, 0.034-0.307; P = 0.01). Subgroup analysis based on CLA source showed that CLA supplementation or foods enriched with CLA did not significantly alter ALT levels. Subgroup analysis showed that CLA supplementation led to significant increases in AST levels (MD = 0.224 U/L; 95% CI, 0.071-0.376; P = 0.004). However, foods enriched with CLA did not have any significant effects on AST levels. CONCLUSION: CLA supplementation was associated with a significantly increased circulating AST without any significant effect on ALP and ALT levels. Prospective studies are necessary to assess the clinical outcomes of the association between CLA and liver enzyme concentrations.

Association of foods enriched in conjugated linoleic acid (CLA) and CLA supplements with lipid profile in human studies: a systematic review and meta-analysis.

OBJECTIVE: The present study aimed to review the association of conjugated linoleic acid (CLA) consumption in two forms, foods enriched in CLA and CLA supplements, with serum lipid profile in human studies. DESIGN: Systematic review and meta-analysis. SETTING: Search process was conducted in PubMed, Cochrane Library, Google Scholar, Scopus and Science Direct. Clinical trials that investigated the association of CLA intakes either in the form of supplements or enriched foods with lipid profile in healthy adults were included. All outcomes were recorded as continuous variables, and the effect size was measured by analysis of the mean and standard deviation before and after the intervention for case and control groups. SUBJECTS: Healthy adult population. RESULTS: CLA supplementation was associated with a significant decrease in LDL cholesterol (mean difference = -0.218; 95% CI -0.358, -0.077; P = 0.002), a non-significant decrease in HDL cholesterol (mean difference = -0.051; 95% CI -0.188, 0.086; P = 0.468), a non-significant increase in total cholesterol (mean difference = 0.009; 95% CI -0.128, 0.146; P = 0.896) and a non-significant decrease in TAG (mean difference = -0.065; 95% CI -0.20, 0.07; P = 0.344). Foods enriched with CLA were associated with significantly decreased LDL cholesterol (mean difference = -0.231; 95% CI -0.438, -0.024; P = 0.028), non-significantly increased HDL-C (mean difference = 0.075; 95% CI -0.121, 0.270; P=0.455), non-significantly decreased total cholesterol (mean difference = -0.158; 95% CI -0.349, 0.042; P = 0.124) and non-significantly decreased TAG (mean difference = -0.078; 95% CI -0.274, 0.117; P = 0.433). CONCLUSIONS: According to our analysis, consumption of foods enriched with CLA or CLA supplements has favourable effects on LDL cholesterol levels.