FA Supplementation Research Articles

Periconceptional folic acid supplementation and sex difference in prevention of neural tube defects and their subtypes in China: results from a large prospective cohort study.

BackgroundFolic acid (FA) supplementation is known to prevent neural tube defects (NTDs). We examined whether this preventive effect differs by the sex of the infant.MethodsData were gathered from a large population-based cohort study in China that evaluated the effects of FA supplementation on NTDs. All births at 20 complete gestational weeks, including live births, stillbirths, and pregnancy terminations, and all NTDs, regardless of gestational age, were recorded. In a northern China province, a total of 30,801 singleton live births to women whose use of FA supplements during the first trimester was known at the time were included in the study. The birth prevalence of NTDs was classified by sex, subtype, and maternal FA supplementation. Male to female rate ratios [RR] and their 95% confidence intervals [CI] were calculated.ResultsA total of 106 NTDs cases were recorded. The overall prevalence of NTDs was 2.5‰ among males and 4.4‰ among females; NTDs were less prevalent among males than among females (RR, 0.58; 95% CI, 0.54–0.63). There was a higher prevalence of anencephaly (RR, 0.34; 95% CI, 0.27–0.43) and spina bifida (RR, 0.73; 95% CI, 0.63–0.84) among females. However, FA supplementation led to significantly greater decreases in the rates of anencephaly (4.8‰) and total NTDs (7.6‰) in females than in males (1.6‰ and 2.8‰, respectively).ConclusionsFA supplementation successfully reduces the prevalence of NTDs in both male and female infants, although we found a significantly greater decrease in anencephaly and total NTDs in females than in males. How the protective effects of FA supplementation affect the sexes differently needs to be studied further.

Role of folic acid deficiency as a possible risk factor for erectile dysfunction

Background: erectile dysfunction (ED) is the persistent inability to attain or maintain an erection. ED affects millions of men worldwide. The pathophysiology of ED includes vasculogenic, neurogenic, hormonal, anatomical, drug-induced and psychogenic causes. Endothelial dysfunction (EDys) is an important pathophysiologic factor underlying vasculogenic erectile dysfunction. The pathogenesis of both EDys and ED are linked through decreased expression and activation of endothelial nitric oxide synthase (NOS) which is responsible for formation of Nitric Oxide (NO). NO is a relaxing factor which plays a major role in activation and maintenance of the erection process. Aim of the work: this study aimed to detect the possible relationship between serum folic acid and erectile dysfunction by measuring serum FA concentration in patients with erectile dysfunction and comparing them with the healthy controls. Methodology: our study has been carried out on 90 individuals who were categorized into two groups. Group 1: 60 married males complained of ED. Group 2: 30 married potent males as a control.All participants were subjected to : personal history, past history of medical diseases and operations, sexual history, general examination, genital examination and evaluation of erectile function according to the International Index of Erectile Function (IIEF-5) Questionnaire). Fasting serum samples were collected from all participants and assayed for serum total testosterone, serum prolactin, serum cholesterol, serum triglycerides (TG), HbA1c and serum folic acid.Results: results of the current study showed a significant relation between folic acid and ED. FA level was declined as ED severity increased. It is thought that ED severity was related to HHcy which was related to the severity of FA deficiency.Conclusion: a significant association between serum FA level and ED severity was detected in the current study. Serum FA level decreased as the severity of ED increased. These results suggest that FA deficiency might reflect the severity of ED. Recommendations: serum folic acid assessment as a part of the routine investigations for patients complaining with erectile dysfunction. Additional experimental and clinical studies are needed to determine whether FA supplementation may be beneficial for patients having ED.

Role of folic acid deficiency as a possible risk factor for erectile dysfunction

Background: erectile dysfunction (ED) is the persistent inability to attain or maintain an erection. ED affects millions of men worldwide. The pathophysiology of ED includes vasculogenic, neurogenic, hormonal, anatomical, drug-induced and psychogenic causes. Endothelial dysfunction (EDys) is an important pathophysiologic factor underlying vasculogenic erectile dysfunction. The pathogenesis of both EDys and ED are linked through decreased expression and activation of endothelial nitric oxide synthase (NOS) which is responsible for formation of Nitric Oxide (NO). NO is a relaxing factor which plays a major role in activation and maintenance of the erection process. Aim of the work: this study aimed to detect the possible relationship between serum folic acid and erectile dysfunction by measuring serum FA concentration in patients with erectile dysfunction and comparing them with the healthy controls. Methodology: our study has been carried out on 90 individuals who were categorized into two groups. Group 1: 60 married males complained of ED. Group 2: 30 married potent males as a control.All participants were subjected to : personal history, past history of medical diseases and operations, sexual history, general examination, genital examination and evaluation of erectile function according to the International Index of Erectile Function (IIEF-5) Questionnaire). Fasting serum samples were collected from all participants and assayed for serum total testosterone, serum prolactin, serum cholesterol, serum triglycerides (TG), HbA1c and serum folic acid.Results: results of the current study showed a significant relation between folic acid and ED. FA level was declined as ED severity increased. It is thought that ED severity was related to HHcy which was related to the severity of FA deficiency.Conclusion: a significant association between serum FA level and ED severity was detected in the current study. Serum FA level decreased as the severity of ED increased. These results suggest that FA deficiency might reflect the severity of ED. Recommendations: serum folic acid assessment as a part of the routine investigations for patients complaining with erectile dysfunction. Additional experimental and clinical studies are needed to determine whether FA supplementation may be beneficial for patients having ED.

The Gut-Brain Axis in Alzheimer's Disease and Omega-3. A Critical Overview of Clinical Trials.

Despite intensive study, neurodegenerative diseases remain insufficiently understood, precluding rational design of therapeutic interventions that can reverse or even arrest the progressive loss of neurological function. In the last decade, several theories investigating the causes of neurodegenerative diseases have been formulated and a condition or risk factor that can contribute is described by the gut-brain axis hypothesis: stress, unbalanced diet, and drugs impact altering microbiota composition which contributes to dysbiosis. An altered gut microbiota may lead to a dysbiotic condition and to a subsequent increase in intestinal permeability, causing the so-called leaky-gut syndrome. Herein, in this review we report recent findings in clinical trials on the risk factor of the gut-brain axis in Alzheimer’s disease and on the effect of omega-3 supplementation, in shifting gut microbiota balance towards an eubiosis status. Despite this promising effect, evidences reported in selected randomized clinical trials on the effect of omega-3 fatty acid on cognitive decline in Alzheimer’s disease are few. Only Mild Cognitive Impairment, a prodromal state that could precede the progress to Alzheimer’s disease could be affected by omega-3 FA supplementation. We report some of the critical issues which emerged from these studies. Randomized controlled trials in well-selected AD patients considering the critical points underlined in this review are warranted.

442 Effect of Fetal Programming and Finishing FA Supplementation on Hypothalamus mRNA Concentration.

Maternal nutrition produces metabolic and endocrine changes that may cause fetal programming effects. The objective of this study was to evaluate the effect of feeding an enriched diet with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to ewes during late gestation and its effect to their offspring on the hypothalamus gene expression of hormones, metabolites and neurotransmitter receptors in finishing lambs. Lambs born from ewes fed during the last 50 days of gestation, either with a diet containing 0.39 % Ca salts of a palmitic fatty acid distillate (PFAD) or Ca salts enriched with EPA and DHA (PUFA) were used in this study. At lambing all ewes and lambs were penned together and fed the same pasture until weaning. After weaning the lambs were blocked by BW and divided in a 2x2 factorial into 2 finishing diet containing 1.5% of PFAD or PUFA. The 2 factors were the ewe diet and the finishing diet. On d 43, 14 female hypothalamuses were obtained and 18 metabolic genes were analyzed. There was a significant mother/treatment interaction in melanocortin receptor (MCR) 3 and cholecystokinin receptor (CCK-R) mRNA (P<0.01), and a tendency in cortisol receptor (Cor-R; P=0.06) and cocaine and amphetamine regulated protein (CART; P=0.08) mRNA; animals which had the same treatment as their mothers showed lower concentration than those with different treatment from their mother. Lambs born from PUFA ewes had lower concentration of MCR-4 mRNA showing a tendency (P=0.09) than PFDA. Agouti related peptides (AGRP) mRNA concentration was lower in lambs fed with PUFA (P=0.06) (Table 1) than PFDA. None of the other genes analyzed (insulin receptor, NPY and its receptors and POMC) had significant differences (P>0.1). Fatty acids change the expression of neuropeptides and their receptors and hormones receptors mRNA in the hypothalamus. Animals fed finishing diets with fatty acids that were opposite of the fatty acids in their dam’s diet during late gestation showed higher levels of mRNA than those with the same fatty acids in their diet. Table 1. Hypothalamic mRNA concentration in lambs fed with PUFA or PFAD and born from ewes with the similar FA supplementation. Table 1. Hypothalamic mRNA concentration in lambs fed with PUFA or PFAD and born from ewes with the similar FA supplementation.

The validation & verification of an LC/MS method for the determination of total docosahexaenoic acid concentrations in canine blood serum

Docosahexaenoic acid (DHA), is an omega 3 fatty acid (n-3 FA) that has been shown to play a role in canine growth and physiological integrity and improvements in skin and coat condition. However, potential adverse effects of n-3 FA specifically, impaired cellular immunity has been observed in dogs fed diets with elevated levels of n-3 FA. As such, a safe upper limit (SUL) for total n-3 FAs (DHA and EPA) in dogs has been established. Considering this SUL, sensitive methods detecting DHA in blood serum as a biomarker when conducting n-3 FA supplementation trials involving dogs are required. In this study, an LC-ESI-MS/MS method of DHA detection in dog serum was validated and verified. Recovery of DHA was optimized and parallelism tests were conducted with spiked samples demonstrating that the serum matrix did not interfere with quantitation. The stability of DHA in serum was also investigated, with −80 °C considered suitable when storing samples for up to six months. The method was linear over a calibration range of 1–500 μg/mL and precision and accuracy were found to meet the requirements for validation. This method was verified in an alternative laboratory using a different analytical system and operator, with the results meeting the criteria for verification.

The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney disease

BackgroundNeutrophils release leukotriene (LT)B4 and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB5 and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB4. ObjectiveThis study evaluated the independent and combined effects of n-3 FA and CoQ supplementation on neutrophil leukotrienes, the pro-inflammatory eicosanoid 5-hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD. DesignIn a double-blind, placebo-controlled intervention of factorial design, 85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were measured at baseline and after 8 weeks. ResultsSeventy four patients completed the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB5 (P < 0.0001) and the SPM 18-hydroxyeicosapentaenoic acid (18-HEPE), resolvin E1 (RvE1), resolvin E2 (RvE2) and resolvin E3 (RvE3) that derive from EPA, as well as 17-hydroxydocosahexaenoic acid (17-HDHA) and resolvin D5 (RvD5) that derive from DHA (all P < 0.01). Neutrophil LTB4 and its metabolites, and 5-HETE were not significantly altered by n-3 FA or CoQ. Plasma MPO was significantly reduced with n-3 FA alone (P = 0.013) but not when given in combination with CoQ. Conclusionn-3 FA supplementation in patients with CKD leads to increased neutrophil release of LTB5 and several SPM, as well as a reduction in plasma MPO that may have important implications for limiting chronic inflammation.

The Correlation between Infants’ Congenital Heart Defects and Maternal Folic Acid Supplementation

Background: Congenital heart defects (CHDs) are significant drivers of mortality and morbidity in children, folic acid supplementation for the pregnant month during or before delivery is said to influence risk reduction of congenital heart defects (CHDs). However, there are controversial claims and the hypothesis is concluded from limited epidemiologic studies. Aim of the Study: Conduct a systematic review and meta-analysis of published studies to reliably evaluate the correlation between Folic acid or multivitamins containing FA supplementation taken during pregnancy and the risk of CHDs. Methods: A systematic review and meta-analysis was conducted. PUBMED and EMBASE were searched to identify prospective cohort and case-control studies that had reported on the association between 1960 and 2017.Studies conducted in primarily high-risk populations (Case control and cohort studies) while participants in randomized controlled trials were excluded. Results: The search yielded 10 studies published between 2000 and 2013 enrolling 13126 female participants. These studies included only one cohort study, and nine case-control studies. The overall results of this meta-analysis provide evidence that maternal folate supplementation is associated with a significantly decreased risk of CHDs (RR = 0.69, 95% CI: 0.54–0.84). Statistically significant heterogeneity was detected (Q = 79.43, P < 0.001, I2 = 70.2%). Conclusion: FA supplementation during pregnancy significantly decreases the risk of CHDs in newborns.

Folic acid prevents cardiac dysfunction and reduces myocardial fibrosis in a mouse model of high-fat diet-induced obesity

BackgroundFolic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia. We hypothesized that FA supplementation prevents cardiac fibrosis and cardiac dysfunction induced by obesity.MethodsSix-week-old C57BL6/J mice were fed a high-fat diet (HFD), normal diet (ND), or an HFD supplemented with folic acid (FAD) for 14 weeks. Cardiac function was measured using a transthoracic echocardiographic exam. Phenotypic analysis included measurements of body and heart weight, blood glucose and tissue homocysteine (Hcy) content, and heart oxidative stress status.ResultsHFD consumption elevated fasting blood glucose levels and caused obesity and heart enlargement. FA supplementation in HFD-fed mice resulted in reduced fasting blood glucose, heart weight, and heart tissue Hcy content. We also observed a significant cardiac systolic dysfunction when mice were subjected to HFD feeding as indicated by a reduction in the left ventricular ejection fraction and fractional shortening. However, FAD treatment improved cardiac function. FA supplementation protected against cardiac fibrosis induced by HFD. In addition, HFD increased malondialdehyde concentration of the heart tissue and reduced the levels of antioxidant enzyme, glutathione, and catalase. HFD consumption induced myocardial oxidant stress with amelioration by FA treatment.ConclusionFA supplementation significantly lowers blood glucose levels and heart tissue Hcy content and reverses cardiac dysfunction induced by HFD in mice. These functional improvements of the heart may be mediated by the alleviation of oxidative stress and myocardial fibrosis.

The association between omega-3 fatty acid biomarkers and inflammatory arthritis in an anti-citrullinated protein antibody positive population.

Higher circulating omega-3 fatty acids (n-3 FAs) are associated with a lower prevalence of anti-CCP antibodies and RF in subjects without RA. We examined whether, in anti-CCP+ subjects, n-3 FAs also play a role in development of inflammatory arthritis (IA). At Colorado-based health fairs from 2008 to 2014, participants without a previous diagnosis of RA who were anti-CCP3+ (n = 47) were recruited into a follow-up study; symptom assessments and joint examinations were conducted every 6 months for the determination of IA. We measured n-3 FAs as a percentage of total lipids in red blood cell membranes (n-3 FA%) at each visit. We detected IA in 10 anti-CCP3+ subjects (21%) at the baseline visit. Increased total n-3 FA% in red blood cell membranes [odds ratio (OR) = 0.09, 95% CI: 0.01, 0.76], specifically docosapentaenoic acid (OR = 0.16, 95% CI: 0.03, 0.83) and docosahexaenoic acid (OR = 0.23, 95% CI: 0.06, 0.86), was associated with a lower odds of IA at the baseline visit, adjusting for n-3 FA supplement use, current smoking, RF+, elevated CRP+ and shared epitope. We followed 35 of the anti-CCP3+ subjects who were IA negative at baseline and detected 14 incident IA cases over an average of 2.56 years of follow-up. In a time-varying survival analysis, increasing docosapentaenoic acid significantly decreased risk of incident IA (hazard ratio = 0.52, 95% CI: 0.27, 0.98), adjusting for age at baseline, n-3 FA supplement use, RF+, CRP+ and shared epitope. n-3 FAs may potentially lower the risk of transition from anti-CCP positivity to IA, an observation that warrants further investigation.

Supplementation of docosahexaenoic acid (DHA) / Eicosapentaenoic acid (EPA) in a ratio of 1/1.3 during the last trimester of pregnancy results in EPA accumulation in cord blood

Omega-3 fatty acids (n-3 FA), specifically DHA, are associated with fetal growth and development. We aimed to determine the levels of DHA and EPA in cord serum after n-3 FA supplementation during the last trimester of pregnancy. Among 55 women, 23 were administered daily one capsule of n-3 FA supplement, involving DHA/EPA in a ratio of 1/1.3. Twenty nine women were enrolled as control group. Blood samples were collected at 22–24 weeks of gestation and at delivery. Fatty acids were analyzed with the method of GC-MS. Cord DHA level increased and EPA level decreased in both groups between the days of 22–24 and delivery. However, decrease in cord EPA level was significant in control group (p < 0.001) but not in supplement group (p > 0.05). Supplementation of DHA/EPA in a ratio of 1/1.3 during the last trimester of pregnancy caused higher cord EPA level compared to control group indicating an accumulation in umbilical cord.

Distinctions in gene-specific changes in DNA methylation in response to folic acid supplementation between women with normal weight and obesity

Obesity and maternal folate deficiency are associated with increased risk for neural tube defects (NTDs). Limited knowledge exists on the impact of folate status or obesity on DNA methylation of genes related to NTD risk and folate metabolism. Women (18-35y) with normal weight (NW; BMI 18.5-24.9kg/m2; n=12) and obesity (OB; BMI >30kg/m2; n=6) were provided FA (800μg/d) for 8-weeks. Serum folate concentration and changes in DNA methylation across 2098 CpG sites in 91 genes related to NTD risk and folate metabolism were examined. Serum folate concentration increased in both groups following FA supplementation, but OB maintained a relative lower concentration (NW; 38.36±2.50-71.41±3.02nmol/L and OB; 27.12±3.09-56.85±3.90nmol/L). Methylation of 56 and 99 CpG sites changed in response to supplementation in NW and OB, respectively, and majority of these sites decreased in methylation in both groups. Only 4 CpG sites responded to supplementation in both groups. Gene ontology analysis revealed a response to supplementation in 61 biological processes (BPs) from the selected genes. Five of the 61 BPs were identified only in NW, including neural tube closure, while 13 of the 61 BPs were enriched only in OB, including folate metabolism, vitamin B12 metabolism and methylation related processes. Changes in DNA methylation in genes related to NTD risk and folate metabolism in response to FA supplementation were different in NW and OB. Increased NTD risk and abnormal folate metabolism in obesity may be due to a distinctive epigenetic response to folate status in these genes.

Provision of folic acid for reducing arsenic toxicity in arsenic-exposed children and adults

Provision of folic acid for reducing arsenic toxicity in arsenic-exposed children and adults

The Use of Omega-3 Fatty Acids to Improve Insulin Sensitivity in Pregnancy: A Pilot Study of Safety and Tolerability [6Q

INTRODUCTION: Omega-3 fatty acid (n3 FA) consumption is associated with improved insulin sensitivity in some diabetic populations, but can cause adverse effects at high doses. The objective was to evaluate the tolerability of high-dose n3 FA supplementation in obstetric patients with diet-controlled gestational diabetes (GDM). METHODS: Women with diet-controlled GDM between 24 and 30 weeks of gestation were randomized in a prospective, double-blind fashion to receive either 2200 mg daily of commercial fish oil (1300 mg eicosapentaenoic acid (EPA) + 900 mg docosahexaenoic acid (DHA)) or an identical placebo for a minimum of 6 weeks. Pre-and post-treatment evaluations were calculated using the homeostatic model assessment of insulin resistance (HOMA-IR) and measures of safety and tolerability. RESULTS: In this pilot study, 14 GDM patients were randomized to treatment with fish oil (N=7) or placebo (N=7). Of these, 35.7% (3 in the treatment group, 2 in the placebo group) did not complete the treatment course due to intolerance. No clinically significant adverse effects, obstetric or neonatal complications were noted. Two patients in each group required initiation of medical therapy for glucose control subsequent to enrollment. While the pilot study was not adequately powered to detect a difference in objective measures of glucose control between the groups, no significant differences in fasting glucose, fasting insulin, or HOMA-IR levels were noted. CONCLUSION: High dose omega-3 fatty acid supplementation appears to be safe in pregnancy, but some patients have bothersome side effects that may limit compliance. The use of omega-3 fatty acids to mitigate insulin resistance in gestational diabetes warrants further investigation.

Epigenetic changes in blood leukocytes following an omega-3 fatty acid supplementation

BackgroundOmega-3 polyunsaturated fatty acids (n-3 FAs) have several beneficial effects on cardiovascular (CV) disease risk factors. These effects on CV risk profile may be mediated by several factors, including epigenetic modifications. Our objective is to investigate, using genome-wide DNA methylation analyses, methylation changes following an n-3 FA supplementation in overweight and obese subjects and to identify specific biological pathways potentially altered by the supplementation.ResultsBlood leukocytes genome-wide DNA methylation profiles of 36 overweight and obese subjects before and after a 6-week supplementation with 3 g of n-3 FAs were compared using GenomeStudio software. After supplementation, 308 CpG sites, assigned to 231 genes, were differentially methylated (FDR-corrected Diffscore ≥│13│~ P ≤ 0.05). Using Ingenuity Pathway Analysis system, a total of 55 pathways were significantly overrepresented following supplementation. Among these pathways, 16 were related to inflammatory and immune response, lipid metabolism, type 2 diabetes, and cardiovascular signaling. Changes in methylation levels of CpG sites within AKT3, ATF1, HDAC4, and IGFBP5 were correlated with changes in plasma triglyceride and glucose levels as well as with changes in the ratio of total cholesterol/HDL-cholesterol following the supplementation.ConclusionsThese data provide key differences in blood leukocytes DNA methylation profiles of subjects following an n-3 FA supplementation, which brings new, potential insights on metabolic pathways underlying the effects of n-3 FAs on CV health.

N-3 Fatty Acid Supplementation During 4 Weeks of Training Leads to Improved Anaerobic Endurance Capacity, but not Maximal Strength, Speed, or Power in Soccer Players.

Omega-3 fatty acid (n-3 FA) supplementation could promote adaptation to soccer-specific training. We examined the impact of a 4-week period of n-3 FA supplementation during training on adaptations in 1RM knee extensor strength, 20-m sprint speed, vertical jump power, and anaerobic endurance capacity (Yo-Yo test) in competitive soccer players. Twenty six soccer players were randomly assigned to one of two groups: n-3 FA supplementation (n-3 FA; n = 13) or placebo (n = 13). Both groups performed two experimental trial days. Assessments of physical function and respiratory function were conducted pre (PRE) and post (POST) supplementation. Training session intensity, competitive games and nutritional intake were monitored during the 4-week period. No differences were observed in respiratory measurements (FEV1, FVC) between groups. No main effect of treatment was observed for 1RM knee extensor strength, explosive leg power, or 20 m sprint performance, but strength improved as a result of the training period in both groups (p < .05). Yo-Yo test distance improved with training in the n-3 FA group only (p < .01). The mean difference (95% CI) in Yo-Yo test distance completed from PRE to POST was 203 (66-340) m for n-3 FA, and 62 (-94-217) m for placebo, with a moderate effect size (Cohen's d of 0.52). We conclude that 4 weeks of n-3 FA supplementation does not improve strength, power or speed assessments in competitive soccer players. However, the increase in anaerobic endurance capacity evident only in the n-3 FA treatment group suggests an interaction that requires further study.

Rationale and Design of PEMVITASTART—An Open-label Randomized Trial Comparing Simultaneous Versus Standard Initiation of Vitamin B12 and Folate Supplementation in Nonsquamous, Non–Small-cell Lung Cancer Patients Undergoing First-line Pemetrexed-based Chemotherapy

Pemetrexed is the preferred chemotherapeutic drug for nonsquamous, non–small-cell lung cancer patients whenever the predictive molecular biomarkers for targeted therapy have either not been assessed or are absent. As per manufacturers' instructions, supplementation with folic acid (FA; folate) at a dose of 350 to 1000 μg daily should be started seven days before the first dose of pemetrexed-based chemotherapy and continued during therapy and for 21 days after therapy cessation. Vitamin B12 injections (1000 μg intramuscularly) should also be started one week before the first dose of chemotherapy. However, the evidence for delaying chemotherapy by one week for the purpose of providing vitamin B12 and FA supplementation is not robust. Observational and prospective single-arm studies have not shown any increased toxicity if pemetrexed was started earlier than the recommended duration of supplementation. In a resource-constrained setting, the standard (conventional) approach would lead to one additional visit and a 1-week chemotherapy delay, both of which could be inconvenient for patients. Hence, an open-label, randomized trial (PEMVITASTART [Vitamin Supplementation in NSCLC Patients on Pemetrexed Based Chemotherapy]; ClinicalTrials.gov identifier, NCT02679443) is being undertaken to evaluate whether any differences exist in pemetrexed-related hematologic toxicity among patients who receive delayed initiation of chemotherapy (after 5-7 days of vitamin B12 and FA supplementation [delayed arm]) compared with those for whom vitamin B12 and FA supplementation is started simultaneously (within 24 hours) of chemotherapy initiation (immediate arm). The present report describes the rationale and detailed design of the PEMVITASART trial.

Omega-3 Fatty Acids and Maternal and Child Health: An Updated Systematic Review.

To update a prior systematic review on the effects of omega-3 fatty acids (n-3 FA) on maternal and child health and to assess the evidence for their effects on, and associations with, additional outcomes. MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Centre for Agriculture and Biosciences (CAB) Abstracts from 2000 to August 2015; eligible studies from the original report; and relevant systematic reviews. We included randomized controlled trials (RCTs) of any defined dose of n-3 FA (or combination) compared to placebo, any other n-3 FA, or alternative dose with an outcome of interest conducted in pregnant or breastfeeding women or neonates (preterm or term). We also included prospective observational studies that analyzed the association between baseline n-3 FA intake or biomarker level and followup outcomes. Postnatal interventions began within a week of birth for term infants and within a week of beginning enteral or oral feeding for preterm infants. Standard methods were used for data abstraction and analysis, according to the Evidence-based Practice Center Methods Guide. We identified 4,275 potentially relevant titles from our searches, of which 95 RCTs and 48 observational studies met the inclusion criteria. Risk of bias was a concern with both RCTs and observational studies. Outcomes for which evidence was sufficient to draw a conclusion are summarized here with the Strength of Evidence (SoE). (Outcomes for which the evidence was insufficient to draw a conclusion are summarized in Appendix G of the report.). Most studies in this report examined the effects of fish oil (or other combinations of DHA and EPA) supplements on pregnant or breastfeeding women or the effects of infant formula fortified with DHA plus AA. As with the original report, with the exception of small increases in birth weight and length of gestation,n-3 FA supplementation or fortification has no consistent evidence of effects on peripartum maternal or infant health outcomes. No effects of n-3 FA were seen on gestational hypertension, peripartum depression, or postnatal growth. Apparent effects of n-3 FA supplementation were inconsistent across assessment methods and followup times for outcomes related to infant visual acuity, cognitive development and prevention of allergy and asthma. Future RCTs need to assess standardized preparations of n-3 and n-6 FA, using a select group of clinically important outcomes, on populations with baseline n-3 FA intakes typical of those of most western populations.

Omega-3 Fatty Acids and Cardiovascular Disease: An Updated Systematic Review.

The effect and association of omega-3 fatty acids (n-3 FA) intake and biomarker levels with cardiovascular (CV) clinical and intermediate outcomes remains controversial. We update prior Evidence Reports of n-3 FA and clinical and intermediate CV disease (CVD) outcomes. Evaluate the effect of n-3 FA on clinical and selected intermediate CV outcomes and the association of n-3 FA intake and biomarkers with CV outcomes. The n-3 FA under review include eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), stearidonic acid (SDA), and alphalinolenic acid (ALA). MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CAB Abstracts from 2000 or 2002 to June 8, 2015, and eligible studies from the original reports and relevant existing systematic reviews. We included randomized controlled trials (RCTs) of any n-3 FA intake compared to no, lower, or other n-3 FA intake with an outcome of interest conducted in healthy adults, those at risk for CVD, or those with CVD. We also included prospective observational studies of the association between baseline n-3 FA intake or biomarker level and followup outcomes. We required 1 year or more of followup for clinical outcomes and 4 weeks for intermediate outcomes (blood pressure [BP] and lipids). From 11,440 citations (from electronic literature searches and existing systematic reviews), 829 abstracts met basic eligibility criteria; 61 RCTs and 37 longitudinal observational studies (in 147 articles) were included. Most RCTs and observational studies had few risk-of-bias concerns. The 61 RCTs mostly compared marine oil supplements with placebo on CVD outcomes in populations at risk for CVD or with CVD, while the 37 observational studies mostly examined associations between various individual n-3 FA and long-term CVD events in generally healthy populations. Compared with the prior report on n-3 FA and CVD, there is more robust RCT evidence on ALA and on clinical CV outcomes; also, by design there are newly added data on associations between n-3 FA biomarkers and CV outcomes. However, conclusions regarding the effect of n-3 FA intake on CV outcomes or associations with outcomes remain substantially unchanged. Marine oils statistically significantly raise HDL-c and LDL-c by similar amounts (≤2 mg/dL), while lowering Tg in a dose-dependent manner, particularly in individuals with elevated Tg; they have no significant effect on BP. ALA has no significant effect on intermediate outcomes. Limited data were available from RCTs on the effect of n-3 FA on clinical CVD outcomes. Observational studies suggest that higher marine oil intake (including from dietary fish) is associated with lower risk of several CVD outcomes. No clear differences in effects or associations were evident based on population, demographic features, or cointerventions. Future RCTs would be needed to establish adequate evidence of the effect of n-3 FA on CVD outcomes or to clarify differential effects in different groups of people. However, future trials are unlikely to alter conclusions about the effects of n-3 FA supplementation on intermediate cardiovascular outcomes (BP, LDL-c, HDL-c, or Tg).

Omega-3 fatty acids are associated with a lower prevalence of autoantibodies in shared epitope-positive subjects at risk for rheumatoid arthritis

ObjectivesPreviously, we found that omega-3 fatty acids (n-3 FAs) were inversely associated with anti-cyclic citrullinated peptide (anti-CCP) positivity in participants at risk for future rheumatoid arthritis (RA). We investigated whether...