Omega-3 supplementation and outcomes of heart failure: A systematic review of clinical trials.

BACKGROUNDS: Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits. METHODS: A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials. RESULTS: The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events. CONCLUSION: Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.

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.

Association of Dietary Acid Load With Metabolic Syndrome and Its Components in Iranian Adults: A Cross-Sectional Study.

Introduction Metabolic syndrome (MetS) remains one of the leading health challenges worldwide. A combination of genetic and environmental factors has been implicated in the etiology of MetS. Diet is a changeable environmental risk factor, and dietary modifications could significantly reduce the incidence and mortality of numerous diseases, including MetS. Certain dietary factors may contribute to MetS by affecting the acid-base balance within the body. This study examined the association of dietary acid load (DAL) with MetS and its components in Iranian adults. Materials and methods This cross-sectional study was conducted in 2022 on 6356 Iranian adults aged 35-70 years. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) as two indicators of DAL were calculated based on nutrient intake data from validated food frequency questionnaires. MetS and its components were defined according to the Adult Treatment Panel III criteria. Logistic regression analysis was used to explore the associations between DAL and MetS and its components. Age, energy intake, physical activity, education, marital status, home ownership, socioeconomic status, history of obesity-related disease, and calcium supplements were included in model I. Further adjustment in model II was made for body mass index. Results Higher NEAP scores were associated with increased odds of low high-density lipoprotein cholesterol (HDL-C) in the crude model (OR: 1.26, 95% CI: 1.01-2.56, p trend = 0.06) in women, which was confirmed in the adjusted models. In model I, women in the last quintile of NEAP had 54% greater odds of having hypertriglyceridemia compared to the first quintile (OR: 1.54, 95% CI: 1.007-2.36, p trend = 0.02). This association was still significant and even stronger after further adjustment for BMI (OR: 1.55, 95% CI: 1.01-2.40, p trend = 0.01). In addition, in model I, men in the fourth quintile of NEAP had 5.68-fold greater odds of hyperglycemia compared to the first quintile (OR: 5.68, 95% CI: 1.18-27.25, p trend = 0.11). Similar results were found in the fully adjusted model (OR: 5.89, 95% CI: 1.19-28.99, p trend = 0.54). Conclusion There was no significant association between DAL and MetS. DAL was positively associated with the odds of low HDL-C and hypertriglyceridemia in women. Moreover, moderate DAL (NEAP) was associated with an increased odds of hyperglycemia in men.

The association between dietary insulin index and load with mental health.

BACKGROUND: Depression, anxiety, and stress are common mental problems. The aim of this cross-sectional study was to investigate the association between two indexes that measure postprandial insulin response to different food, dietary insulin index (DII) and insulin load (DIL), with psychological disorders. METHOD: Participants (n = 10,000) aged 20-69 were randomly selected from 200 clusters in Yazd from the recruitment phase of the Yazd Health Study. The dietary intake of participants was collected by a reliable and validated food frequency questionnaire (FFQ) consisting of 178 food items. DII and DIL were calculated from the FFQ data using previously published reference values. To assess psychological disorders an Iranian validated short version of a self-reported questionnaire (Depression Anxiety Stress Scales 21 [DASS21]) was used. RESULTS: No significant association was observed between DIL and DII with odds of depression or anxiety using crude or adjusted models. However, individuals in the highest quartiles of DIL had the lowest odds of stress (OR: 0.69; 95% CI 0.48-1.01, P-trend = 0.047). This association remained significant after adjustment for potential confounders in model II including marital status, smoking, education, job status, salt intake, and multi-vitamin supplement use (OR: 0.38; 95% CI 0.16-0.91, P-trend = 0.039) and the third and final model which is further adjusted for BMI (OR: 0.39; 95% CI 0.16-0.91, P-trend = 0.041). CONCLUSION: Overall, consumption of foods with higher DII as well as DIL were associated with lower stress scores; however, no significant relationship was observed between DII or DIL with respective depression or anxiety scores.

Evaluation of the recovery after heart surgery following preoperative supplementation with a combination of beta-hydroxy-beta-methylbutyrate, L-arginine, and L-glutamine: a double-blind randomized placebo-controlled clinical trial.

BACKGROUND: The preoperative period is a good time to improve nutrition status, compensate for nutrient deficiencies, and optimize immune function in patients' underlying surgery. In some medical conditions, supplementation with a combination of L-glutamine (Gln), ß-hydroxy-ß-methylbutyrate (HMB), and L-arginine (Arg) had promising effects on improving recovery. The present study aimed to evaluate the effect of supplementation with Gln/Arg/HMB in patients undergoing heart surgery. METHODS: This randomized clinical trial was conducted on 70 patients undergoing cardiac surgery. Participants were requested to consume 2 sachets of a combination of 7 g L-arginine, 7 g L-glutamine, and 1.5 g daily HMB or placebo 30 days before operation. At the baseline and end of the study, left ventricular ejection fraction and the serum levels of troponin, creatine phosphokinase (CPK), CPK-MB, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin were measured. Also, the Sequential Organ Failure Assessment (SOFA) score, time of stay in hospital and intensive care unit (ICU), and postoperative complications were recorded after surgery. RESULTS: In total, 60 preoperative patients (30 in each group) with a mean age of 53.13 ± 14.35 years completed the study (attrition rate = 85.7%). Subjects in the Gln/Arg/HMB group had lower serum levels of CPK-MB (median [IQR] = 49 [39.75] vs. 83 [64.55]; P = 0.011), troponin (median [IQR] = 2.13 [1.89] vs. 4.34 [1.99]; P < 0.001), bilirubin (median [IQR] = 0.50 [0.20] vs. 0.40 [0.22]; P < 0.001), and SOFA score (median [IQR] = 2 [2] vs. 5 [2]; P < 0.001) at end of the study compared to the placebo. Also, the time of stay in the hospital (median [IQR] = 5 [1] vs. 6 [3]; P < 0.001) and ICU (median [IQR] = 2.50 [1.00] vs. 3.50 [1.50]; P = 0.002) was lower in the Gln/Arg/HMB group. CONCLUSION: The present study showed that perioperative supplementation with a combination of Gln, Arg, and HMB enhances the recovery, reduces myocardial injury, and decreases the time of hospital and ICU stay in cardiac surgery patients. These results need to be confirmed in a larger trial. TRIAL REGISTRATION: IRCT.ir IRCT20120913010826N31. Registered on 13 October 2020.

The effects of preoperative supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine on inflammatory and hematological markers of patients with heart surgery: a randomized controlled trial.

BACKGROUND: Cardiac surgery is associated with a widespread inflammatory response, by an additional release of free radicals. Due to the importance of these patient's nutritional status, the present study was designed to evaluate the effectiveness of supplementation with a combination of glutamine, ß-hydroxy-ß-methylbutyrate (HMB) and arginine in patients undergoing to the heart surgery. METHODS: The experiment was performed in 1 month (30 days) before cardiac surgery. patients were asked to take 2 sachets of Heallagen® (a combination of 7 g L-arginine, 7 g L-glutamine, and 1.5 g daily HMB) or placebo with identical appearance and taste (maltodextrin) with 120 cc of water. Clinical and biochemical factors were evaluated in the baseline and end of the study. RESULTS: Totally, 60 preoperative patients (30 interventions and 30 placeboes) with a mean age of 53.13 ± 14.35 years participated in the study. Subjects in Heallagen® group had a lower serum levels of interleukin-6 (P = 0.023), erythrocyte sedimentation rate (P < 0.01), high sensitivity C-reactive protein (P < 0.01), and lymphocyte number (P = 0.007) compared to the placebo, at end of the study. CONCLUSION: In the patients undergoing heart surgery, Heallagen® significantly improved some of the inflammatory factors and hematological parameters. These results need to be confirmed in a larger trial. TRIAL REGISTRATION: The protocol of the study was registered in the IRCT.ir with registration no. IRCT20120913010826N31 at 13/10/2020.

Common Polymorphisms in Genes Related to Vitamin D Metabolism Affect the Response of Cognitive Abilities to Vitamin D Supplementation.

It is possible that vitamin D acts as a neurosteroid and that vitamin D deficiency may have an adverse impact on brain function and cognitive function. There are a few reports that have demonstrated an association between polymorphisms of genes involved in vitamin D metabolism and neurodegenerative disease. We aimed to evaluate the relationship between common, functional vitamin D-associated gene variants and cognitive abilities and to investigate the effect size of this polymorphism on cognitive capabilities associated with high-dose vitamin D supplementation. A total of 319 healthy adolescents received a high dose of vitamin D (50,000 IU)/week for 9 weeks. A questionnaire was used to assess cognitive abilities at baseline and after treatment. The genotypes of the CYP2R1-rs10766197 and GC-rs4588 variants were determined using TaqMan genotyping techniques. At baseline, total cognitive ability scores were higher in the AA group who were homozygous for the uncommon allele, compared with the other (AG and GG) genotypes of the CYP2R1-rs10766197 polymorphism (104.9 ± 27.8 vs. 79.1 ± 38.8 vs. 73.1 ± 25.6; p < 0.001, respectively). During the supplementation period, cognitive ability scores increased in individuals with the AG and GG genotypes, while individuals with a AA genotype did not show significant change in total score after intervention (p = 0.17). For GC SNP (rs4588), no major differences at baseline and trial-net change of cognitive tasks score were observed between the genotypes under three genetic models (pSNP = 0.67). Vitamin D supplements have trait-dependent effects on cognitive performance that suggests a causal role for vitamin D in cognitive performance. The rs10766197 variant, near the CYP2R1 gene locus, significantly modified the efficacy of high-dose vitamin D3 supplementation for its effects on improving cognitive abilities indicate that some subjects might require a higher dose to benefit from in terms of cognitive performance.

What is the best solution to manage vitamin D deficiency?

Nowadays, vitamin D deficiency is the most common nutritional deficiency worldwide. In addition to the skeletal effects, it is now recognized that vitamin D deficiency is associated with higher morbidity and mortality. Currently, optimizing serum concentration of 25-hydroxy vitamin D with targeted strategies is becoming one the most interesting topics of public health nutrition. It is not possible for everyone to obtain sufficient serum concentrations of vitamin D by effective solar ultraviolet B exposure or usual dietary intake. Nutritional supplements and fortified foods as an available and cost-effective way to provide the recommended amount of vitamin D. Although, vitamin D supplementation is considered a good and simple short-term solution for vitamin D deficiency treatment; however, it seems that at a population level, food fortification, using staple foods, is the best method to increase vitamin D consumption and long-term treatment of vitamin D deficiency. © 2019 IUBMB Life, 71(9):1190-1191, 2019.

High dose vitamin D supplementation is associated with an improvement in serum markers of liver function.

Limited studies have examined the effects of vitamin D on liver enzymes in patients with liver disease but none has explored its effects in the healthy subjects. The aim of present study was to evaluate the effects of a high dose vitamin D supplementation on measures of liver function. A total of 988 adolescent girls were recruited; all were assessed for liver function tests (LFTs) including alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (ϒGT), alkaline phosphatase (ALP), total bilirubin, direct bilirubin, albumin, and total protein before and after supplementation with 50,000 IU cholecalciferol perls. Significant reductions were observed for AST, ALT, direct bilirubin, total bilirubin, LDH, and ϒGT at the end of supplementation, only in the group with abnormal reference value. Serum levels of total protein and albumin were higher at the end of follow up in the group with abnormal value. No significant change was obtained for LFTs in the group with normal value. Our findings suggest that vitamin D supplementation may improve markers of liver function in adolescents with abnormal LFTs. More randomized controlled trial with longer follow-up time will be required. © 2019 BioFactors, 45(3):335-342, 2019.

Associations of vitamin D binding protein variants with the vitamin D-induced increase in serum 25-hydroxyvitamin D.

BACKGROUND: Vitamin D deficiency is a global problem that may be improved by vitamin D supplementation; however, the individual's response to the intervention varies. We aimed to investigate possible genetic factors that may modify the impact of environmental exposure on vitamin D status. The candidate gene variant we investigated was the Gc gene-rs4588 polymorphism at the vitamin D receptor (DBP) locus. METHODS: A total of 619 healthy adolescent Iranian girls received 50000 IU of vitamin D3 weekly for 9 weeks. Serum 25(OH) D concentrations, metabolic profiles and dietary intake were measured at baseline and after 9 weeks of supplementation. The genotypes of the DBP variant (rs4588) were analyzed using the TaqMan genotyping assay. RESULTS: Our results revealed that the rs4588 polymorphism might be associated with serum 25-hydroxy vitamin D both at baseline (p value = 0.03) and after intervention (p value = 0.008). It seemed that the outcome of the intervention was gene-related so that the subjects with common AA genotype were a better responder to vitamin D supplementation (Changes (%) 469.5 (427.1) in AA carriers vs. 335.8 (530) in GG holders), and carriers of the less common GG genotype experienced a rise in fasting blood glucose after 9 weeks (Changes (%) 0 (1.5)). Our findings also showed that the statistical interaction between this variant and supplementation was statistically significant (intervention effect p-value<0.001 and p-value SNP effect = 0.03). The regression model also revealed that after adjusted for potential confounders, likelihood of affecting serum 25(OH)D in individuals who were homozygous for the uncommon allele G was less than those homozygous for the more common AA genotype (OR = 4.407 (1.82-8.89); p = 0.001). CONCLUSION: Serum vitamin 25(OH) D following vitamin 25(OH) D3 supplementation appears to be modified by genetic background. The Gc genetic variant, rs4588 encoding the vitamin D receptor seems to influence the response to vitamin D supplementation.

A variant in CYP2R1 predicts circulating vitamin D levels after supplementation with high-dose of vitamin D in healthy adolescent girls.

AIM: The determinants of serum vitamin D seems to be the environmental factors (dietary and supplementary intake and exposure to ultraviolet light) and genetic factors. We aimed to study the relationship between a vitamin D-associated genetic polymorphism and serum 25(OH)D concentrations in healthy adolescent girls in Iran, and its effects on a high-dose supplement of vitamin D. MATERIAL AND METHOD: A total of 616 healthy adolescent girls with mean age 15 received 50,000 IU of vitamin D3 weekly over 9 weeks. Serum vitamin D levels and other metabolic factors were measured at baseline and after the intervention. The genotyping of the CYP2R1 variant (rs10741657) was performed by TaqMan genotyping assays. RESULTS: Regardless of the genetic background, at baseline, 87% of adolescent girls were vitamin D deficient (serum 25(OH)D level < 50 nmol/l). High-dose supplementation with VitD reduced the proportion of girls who were deficient substantially to about 24%. The genetic analysis revealed that although at baseline there was not a gene-vitamin D association ( p trend = 0.1), the response to supplementation appeared to be modulated by this variant ( p trend < 0.001). However, other anthropometric and biochemical measures were not affected by this intervention, over this short period. Serum 25(OH)D was increased in all participants although the carriers of the minor A allele seemed to be better responders so that the percentages of the change serum vitamin D in the holder of AA and AG genotypes were 539.4 ± 443.1 and 443.7 ± 384.6, respectively, compared with those with common GG genotype (363.3 ± 354.0). Our regression analysis revealed that the probability of an increase in serum 25(OH)D in a participant with AA genotype was 2.5-fold greater than those with a GG genotype (OR = 2.5 (1.4-4.4); p value = 0.002). CONCLUSION: Based on our findings, it appears that the rs10741657 variant of the CYP2R1 gene modulates the response to high-dose of vitamin D supplementation.

High Dose Vitamin D Supplementation Is Associated With a Reduction in Depression Score Among Adolescent Girls: A Nine-Week Follow-Up Study.

Although vitamin D deficiency is known to be a risk factor for some psychological disorders, there have been few studies on the effects of vitamin D supplementation on their symptoms. Depression and aggression are common mental disorders and are associated with disability and disease burden. We aimed to evaluate the effectiveness of high-dose vitamin D supplementation on depression and aggression scores in adolescent girls. Nine hundred forty adolescent girls received vitamin D3 at a dose of 50,000 IU/week for 9 weeks. Anthropometric parameters and blood pressure were measured using standard protocols at the baseline and at the end of the study. Depression score was evaluated using the Beck Depression Inventory-II and aggression was evaluated using the Buss-Perry Aggression Questionnaire at baseline and at the end of the study. Comparison among the four categories of depression score (normal, mild, moderate, and severe) revealed no significant differences in demographic and anthropometric parameters at baseline. After 9 weeks of vitamin D supplementation, there was a significant reduction on mild, moderate, and severe depression score. However, vitamin D supplementation had no significant effect on aggression score. Our results suggest that supplementation with vitamin D may improve depressive symptoms among adolescent girls, as assessed by questionnaire, but not aggression score. Formal, larger, randomized controlled studies are required to confirm this effect on cases with different degrees of depression.

Nutrients intake, and serum calcium and phosphorus levels: An evidence-based study.

INTRODUCTION: Dietary calcium and phosphorus appear to be important determinants of dyslipidemia and hypertension. We have investigated (1) the prevalence of hypocalcemia and hypophosphatemia in an Iranian population, and (2) the association between nutrient's intake and serum levels of calcium and phosphorus. METHODS: A total of 908 individuals were enrolled using a stratified-cluster sampling method from the Mashhad stroke and heart atherosclerosis disorder (MASHHAD) study. Dietplan6 software was used for 24-hour recalls and food frequency questionnaire to investigate macro- and micronutrient intakes of our population, followed by univariate analysis for evaluation of the association of dairy consumption with serum calcium and phosphorus. RESULTS: We observed that the mean dietary Ca intake was 862.4 mg/d (672.7-1052) for men and 864.2 mg/d (604.5-1123) for women in our population, which is lower than the dietary reference intake for Ca. Moreover, a significant relationship was detected between serum calcium level and dietary intakes of saturated fatty acids, copper, iodine, sucrose, potato, and juices. Of note, we observed a negative association between copper intake, and serum Ca (P˂.01). Also, a significant association was found between serum phosphorus levels and dietary intakes of chicken meat and fresh fruits. Interestingly, we observed an inverse relationship between tea and Ca/P ratio (eg, -r=.098; P=.02). CONCLUSION: We found that the dietary intake of Ca was not sufficient in our population and was associated with the dietary intake of some macro- and micronutrient, supporting further investigation on clinical impact of this condition on calcium/phosphorus deficiency related diseases.