Daily Folic Acid Supplementation Research Articles

Low-dose daily folic acid (400 μg) supplementation does not affect regulation of folate transporters found present throughout the terminal ileum and colon of humans: a randomized clinical trial

BackgroundFolic acid supplementation during the periconceptional period reduces the risk of neural tube defects in infants, but concern over chronic folic acid exposure remains. An improved understanding of folate absorption may clarify potential risks. Folate transporters have been characterized in the small intestine, but less so in the colon of healthy, free-living humans. The impact of folic acid fortification or supplementation on regulation of these transporters along the intestinal tract is unknown. ObjectiveThe objective was to characterize expression of folate transporters/receptor (FT/R) and folate hydrolase, glutamate carboxypeptidase II (GCPII), from the terminal ileum and throughout the colon of adults and assess the impact of supplemental folic acid. MethodsIn this 16-wk open-labeled randomized clinical trial, adults consumed a low folic acid-containing diet, a folate-free multivitamin, and either a 400 μg folic acid supplement or no folic acid supplement. Dietary intakes and blood were assessed at baseline, 8 wk, and 16 wk (time of colonoscopy). Messenger RNA (mRNA) expression and protein expression of FT/R and GCPII were assessed in the terminal ileum, cecum, and ascending and descending colon. ResultsAmong 24 randomly assigned subjects, no differences in dietary folate intake or blood folate were observed at baseline. Mean ± SD red blood cell folate at 16 wk was 1765 ± 426 and 911 ± 242 nmol/L in the 400 and 0 μg folic acid group, respectively (P < 0.0001). Reduced folate carrier, proton-coupled folate transporter, and folate-receptor alpha expression were detected in the terminal ileum and colon, as were efflux transporters of breast cancer resistance protein and multidrug resistance protein-3. Other than a higher mRNA expression of FR-alpha and GCPII in the 400 μg supplement group in the ascending colon, no treatment differences were observed (P < 0.02). ConclusionsFolate transporters are present throughout the terminal ileum and colon; there is little evidence that a low dose of folic acid supplementation affects colonic absorption.This trial was registered at clinicaltrials.gov as NCT03421483.

Folic acid supplementation in women of childbearing age with epilepsy: No association with type or number of antiepileptic drugs.

For over two decades, a daily folic acid (FA) supplementation has been recommended for women of childbearing age with epilepsy. This recommendation is based on evidence that FA administration before conception and during pregnancy can decrease the risk of fetal malformations in the general population, improve cognitive development, and reduce the risk of autistic traits in children exposed in utero to antiepileptic drugs (AEDs). The aim of this study was to evaluate FA supplementation rate in nonpregnant women of childbearing age with epilepsy and its relation to AED type and number. We retrospectively reviewed the computerized database and the medical records of all the women who had a first visit to our outpatient epilepsy clinic (Shamir-Assaf Harofeh Medical Center, Zerifin, Israel) during a 10-year period (2012-2021). Only 61 (22%) of 282 nonpregnant women of childbearing age with epilepsy treated with AEDs received FA supplementation. Ninety-two (33%) of the women were treated with AED polytherapy, and 41 (15%) received valproic acid in monotherapy or polytherapy. FA supplementation rate was higher in women aged ≤40 versus >40 (25% vs. 8.5%) (p = .004). No correlation was found between FA supplementation and AED type or number. FA supplementation rate was low and was unaffected by AED treatment. Patient and physician-targeted interventions should be implemented to increase FA prescription and patient adherence.

Periconceptional intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further reduce the risk of neural tube defects in offspring: a United States population–based case-control study of women meeting the folic acid recommendations

BackgroundNeural tube defects (NTDs) still occur among some women who consume 400 μg of folic acid for prevention. It has been hypothesized that intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further protect against NTDs. ObjectivesTo investigate whether intakes of vitamin B6, vitamin B12, choline, betaine, methionine, thiamine, riboflavin, and zinc, individually or in combination, were associated with NTD risk reduction in offspring of women meeting the folic acid recommendations. MethodsData were from the National Birth Defects Prevention Study (United States population–based, case-control). We restricted deliveries between 1999 and 2011 with daily periconceptional folic acid supplementation or estimated dietary folate equivalents ≥400 μg. NTD cases were live births, stillbirths, or terminations affected by spina bifida, anencephaly, or encephalocele (n = 1227). Controls were live births without a major birth defect (n = 7095). We categorized intake of each micronutrient as higher or lower based on a combination of diet (estimated from a food frequency questionnaire) and periconceptional vitamin supplementation. We estimated NTD associations for higher compared with lower intake of each micronutrient, individually and in combination, expressed as odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age, race/ethnicity, education, and study center. ResultsNTD associations with each micronutrient were weak to modest. Greater NTD reductions were observed with concurrent higher-amount intakes of multiple micronutrients. For instance, NTD odds were ∼50% lower among participants with ≥4 micronutrients with higher-amount intakes than among participants with ≤1 micronutrient with higher-amount intake (adjusted OR: 0.53; 95% CI: 0.33, 0.86). The strongest reduction occurred with concurrent higher-amount intakes of vitamin B6, vitamin B12, choline, betaine, and methionine (adjusted OR: 0.26; 95% CI: 0.09, 0.77) compared with ≤1 micronutrient with higher-amount intake. ConclusionsOur findings support that NTD prevention, in the context of folic acid fortification, could be augmented with intakes of methyl donors and other micronutrients involved in folate metabolism.

Daily Folic Acid and/or Vitamin B12 Supplementation Between 6 and 30 Months of Age and Cardiometabolic Risk Markers After 6–7 Years: A Follow-Up of a Randomized Controlled Trial

BackgroundDeficiencies of vitamin B12 and folate are associated with elevated concentrations of metabolic markers related to CVDs. ObjectivesWe investigated the effect of supplementation of vitamin B12 with or without folic acid for 6 mo in early childhood on cardiometabolic risk markers after 6–7 y. MethodsThis is a follow-up study of a 2 × 2 factorial, double-blind, randomized controlled trial of vitamin B12 and/or folic acid supplementation in 6–30-mo-old children. The supplement contained 1.8 μg of vitamin B12, 150 μg of folic acid, or both, constituting >1 AI or recommended daily allowances for a period of 6 mo. Enrolled children were contacted again after 6 y (September 2016–November 2017), and plasma concentrations of tHcy, leptin, high molecular weight adiponectin, and total adiponectin were measured (N = 791). ResultsAt baseline, 32% of children had a deficiency of either vitamin B12 (<200 pmol/L) or folate (<7.5 nmol/L). Combined supplementation of vitamin B12 and folic acid resulted in 1.19 μmol/L (95% CI: 0.09; 2.30 μmol/L) lower tHcy concentration 6 y later compared to placebo. We also found that vitamin B12 supplementation was associated with a lower leptin–adiponectin ratio in subgroups based on their nutritional status. ConclusionsSupplementation with vitamin B12 and folic acid in early childhood was associated with a decrease in plasma tHcy concentrations after 6 y. The results of our study provide some evidence of persistent beneficial metabolic effects of vitamin B12 and folic acid supplementation in impoverished populations.The original trial was registered at www.clinicaltrials.gov as NCT00717730, and the follow-up study at www.ctri.nic.in as CTRI/2016/11/007494.

Effect of Iron and Folic Acid supplementation among nutritionally anemic women of reproductive age in rural Maharashtra: Acommunity-based intervention study

Background: In the context of the limited effectiveness of daily iron supplementation in national programs, intermittent iron supplementation is currently under debate as a possible alternative. Objective: To study the outcome of twice weekly iron supplementation compared to daily supplementation. Methods: A community-based interventional study was carried out in 283 women of the 15-49 years age group who were not pregnant and not lactating at the initiation of the study. For intervention purpose, women with mild and moderate anemia were taken. In two schedules, an interventional drug (100 mg elemental iron with 0.5 mg folic acid) was given for three months. In the daily schedule, one tablet every day; and in the weekly schedule, two tablets once a week on a fixed day were given. Result: Out of 283 anemic participants, 141 received daily while 142 received weekly iron and folic acid supplementation. Post intervention, the weekly iron supplementation group revealed that, proportion of anemia cases reduced to the tune of 32.4% and the mean increase in hemoglobin level was 1.42 gm/dl (SD ± 0.77). In contrast, in patients who had a daily supplementation regimen, the mean increase in hemoglobin level was 1.78 gm/dl (SD ± 0.83). Conclusion: Result of present study shows that, effect of daily Iron and Folic Acid (IFA) supplementation to raise hemoglobin level was higher as compared to weekly IFA supplementation. But weekly supplementation when considered separately also had significant effect to raise the hemoglobin level. It is observed that, there is no statistically significant difference in the rise of hemoglobin in both the groups, signifying weekly iron therapy as effective role as daily iron therapy in reducing anemia

Dietary Advice to Support Glycaemic Control and Weight Management in Women with Type 1 Diabetes during Pregnancy and Breastfeeding.

In women with type 1 diabetes, the risk of adverse pregnancy outcomes, including congenital anomalies, preeclampsia, preterm delivery, foetal overgrowth and perinatal death is 2-4-fold increased compared to the background population. This review provides the present evidence supporting recommendations for the diet during pregnancy and breastfeeding in women with type 1 diabetes. The amount of carbohydrate consumed in a meal is the main dietary factor affecting the postprandial glucose response. Excessive gestational weight gain is emerging as another important risk factor for foetal overgrowth. Dietary advice to promote optimized glycaemic control and appropriate gestational weight gain is therefore important for normal foetal growth and pregnancy outcome. Dietary management should include advice to secure sufficient intake of micro- and macronutrients with a focus on limiting postprandial glucose excursions, preventing hypoglycaemia and promoting appropriate gestational weight gain and weight loss after delivery. Irrespective of pre-pregnancy BMI, a total daily intake of a minimum of 175 g of carbohydrate, mainly from low-glycaemic-index sources such as bread, whole grain, fruits, rice, potatoes, dairy products and pasta, is recommended during pregnancy. These food items are often available at a lower cost than ultra-processed foods, so this dietary advice is likely to be feasible also in women with low socioeconomic status. Individual counselling aiming at consistent timing of three main meals and 2-4 snacks daily, with focus on carbohydrate amount with pragmatic carbohydrate counting, is probably of value to prevent both hypoglycaemia and hyperglycaemia. The recommended gestational weight gain is dependent on maternal pre-pregnancy BMI and is lower when BMI is above 25 kg/m2. Daily folic acid supplementation should be initiated before conception and taken during the first 12 gestational weeks to minimize the risk of foetal malformations. Women with type 1 diabetes are encouraged to breastfeed. A total daily intake of a minimum of 210 g of carbohydrate is recommended in the breastfeeding period for all women irrespective of pre-pregnancy BMI to maintain acceptable glycaemic control while avoiding ketoacidosis and hypoglycaemia. During breastfeeding insulin requirements are reported approximately 20% lower than before pregnancy. Women should be encouraged to avoid weight retention after pregnancy in order to reduce the risk of overweight and obesity later in life. In conclusion, pregnant women with type 1 diabetes are recommended to follow the general dietary recommendations for pregnant and breastfeeding women with special emphasis on using carbohydrate counting to secure sufficient intake of carbohydrates and to avoid excessive gestational weight gain and weight retention after pregnancy.

Effectiveness of public health education on the uptake of iron and folic acid supplements among pregnant women: a stepped wedge cluster randomised trial

IntroductionIron deficiency is the most prevalent micronutrient deficiency in pregnancy globally responsible for nearly 120 000 maternal deaths per year and a fifth of maternal mortality. Over 46% of pregnant...

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

Stopping Folic Acid Supplementation in Hydroxyurea Treated Children with Sickle Cell Disease

Daily folic acid supplementation for all children with sickle cell disorders is a widely used preventative measure in UK practice. However, a Cochrane review in 2016 concluded there is little evidence for this practice (CD011130). The only randomised clinical trial of folate supplementation in children, conducted in 1983, showed no evidence of benefit. (Rabb et al. ,1983).More convincing evidence as to the benefits of hydroxyurea and penicillin exists. However, adherence to these effective therapies can be a problem. We hypothesised that stopping folic acid could be clinically useful as this would reduce treatment burden on patients and allow them to focus on adherence to more effective medicines.We reviewed the medical records of children receiving hydroxyurea for sickle cell disorders managed in our treatment centre. Children were selected for withdrawal from folic acid supplementation based on an absence of uncontrolled haemolysis; reticulocytes <200 x109/L and bilirubin <80µmol/L, and an absence of low serum folate or low red cell folate. Clinical and laboratory monitoring was performed every 4 weeks to establish whether any benefit or adverse effect could be identified. This included monitoring Hb, HbF, MCV, neutrophils, platelets, reticulocytes, serum folate and red cell folate levels.We withdrew folic acid supplementation from 30 children with sickle cell disorders (mean age 9.5 years (range 2-18)) and monitored clinical and laboratory parameters. At the time of this review, mean follow up time was 11.5 months (range 7-14).Baseline investigations showed that serum folate levels in 14 children were so high in comparison to normal reference ranges that they were unquantifiable by standard laboratory analysis at our centre. The mean serum folate level in the other 16 children was 39.5 nmol/L (reference range 3.4-38.5 nmol/L). Similarly, red cell folate levels in 5 children were above maximum quantifiable levels. The mean red cell folate level in the other 25 children was 1445 nmol/L (reference range 272-1948 nmol/L).On withdrawal of folic acid supplementation, all patients' serum folate and red cell folate levels returned to within the normal range. At the end of this observation period, mean serum folate level was 20.9 nmol/L and mean red cell folate level was 617.2 nmol/L, with no patients developing low serum folate or low red cell folate levels. No patients developed megaloblastic changes or any other clinical need to restart supplementation. Folic acid levels began to reduce immediately on withdrawal of supplementation and in most cases reached a plateau by 6 months. However, plateauing levels were not recorded in all patients and this is likely attributable to the shorter follow up time for some patients.All patients were managed as per our standard protocol of escalating hydroxyurea therapy to maximum tolerated dose. An increase in mean dose from 27.0 mg/kg/day to 30.3 mg/kg/day (p=0.0003) was recorded during the observation period. Other statistically significant changes in haematological parameters were: increased HbF (25.8% to 29.7%, p=0.0002 and increased MCV (91.2 to 94.7, p=0.026). No significant differences were recorded in haemoglobin, neutrophils, platelets or reticulocytes (statistical analysis was performed by paired T-test).Stopping folic acid supplementation has caused no observable adverse effects either clinically or in laboratory haematological parameters. The significant increases in HbF and MCV observed here can be explained by the significant increase in hydroxyurea dose during the observation period and are not likely to be an effect of stopping folic acid.Stopping folic acid is a minor change in patient management however, patients generally don't like taking medicines and stopping a medicine that is not required was seen as an improvement in quality of life. At the end of our observation period, laboratory parameters had improved and there was no evidence of any adverse effect of stopping folic acid supplementation in children with sickle cell disease.Dixit et al., 2016. Cochrane Review, CD011130Rabb et al., 1983. British Journal of Haematology 54(4):589-94 DisclosuresNo relevant conflicts of interest to declare.

Folic acid ameliorates neonatal isolation-induced autistic like behaviors in rats: epigenetic modifications of BDNF and GFAP promotors.

The current study investigated the role of epigenetic dysregulation of brain derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) genes and oxidative stress as possible mechanisms of autistic-like behaviors in neonatal isolation model in rats and the impact of folic acid administration on these parameters. Forty Wistar albino pups were used as follows: control, folic acid administered, isolated, and isolated folic acid treated groups. Isolated pups were separated from their mothers for 90 min daily from postnatal day (PND) 1 to 11. Pups (isolated or control) received either the vehicle or folic acid (4 mg/kg/day) orally from PND 1 to 29. Behavioral tests were done from PND 30 to 35. Oxidative stress markers and antioxidant defense in the frontal cortex homogenate were determined. DNA methylation of BDNF and GFAP genes was determined by qPCR. Histopathological examination was carried out. Neonatal isolation produced autistic-like behaviors that were associated with BDNF and GFAP hypomethylation, increased oxidative stress, increased inflammatory cell infiltration, and structural changes in the frontal cortex. Folic acid administration concurrently with isolation reduced neonatal isolation-induced autistic-like behaviors, decreased oxidative stress, regained BDNF and GFAP gene methylation, and ameliorated structural changes in the frontal cortices of isolated folic acid treated rats. Novelty: Neonatal isolation induces "autistic-like" behavior and these behaviors are reversed by folic acid supplementation. Neonatal isolation induces DNA hypomethylation of BDNF and GFAP, increased oxidative stress markers, and neuroinflammation. All of these changes were reversed by daily folic acid supplementation.

Daily Versus Weekly Iron and Folic Acid Supplementation Regimen- A Randomized Parallel Open Label Trial among Reproductive Age Group Women in an Urban Poor Locality of Bengaluru

Introduction:The global prevalence of anaemia in non-pregnant women is 30.2% and in India it is 56.2%.At least half the burden of anaemia is associated with iron deficiency. Women of reproductive age are at higher risk of developing iron deficiency because of losses during menstruation. Though Daily supplementation with iron and folic acid for a period of 3 months has been the standard as an approach for the prevention and treatment of iron deficiency anaemia among women of reproductive age, there has been limited success with the daily regimen in public health programmes, Intermittent use of oral iron supplements has been proposed as an effective alternative. Objectives: To compare the effectiveness of weekly and daily oral iron and folic acid therapy in improving the Hemoglobin levels among the reproductive age group women, adverse effects and compliance to both the regimens. Method:This was a comparative Randomized parallel open label trial conducted in an urban poor locality of Bengaluru conducted between January 2014 and January 2016. All the women in the reproductive age group (15-45 years) with mild to moderate anemia were included in the study. Sample size of 106 subjects was randomly allocated into the 2 groups (53 into weekly regimen and 53 into daily regimen). The subjects were supplemented with IFA tablets for 3 months according to their regimen. Results:Mean increase in Haemoglobin (Hb) in the daily group (1.92±1.1 g/dl) was significantly (P=&lt;0.01) more when compared to that in the weekly group (0.91±0.82 g/dl). Incidence of all the Adverse Drug Reactions (ADRs) were more in the daily group compared to weekly group. However, the difference was only significant for abdominal pain and metallic taste (P=&lt;0.01 and 0.02 respectively). The proportion of subjects reporting at least one ADR was also significantly more (P=&lt;0.01) in the daily group compared to the weekly group. Compliance for weekly regimen (97.12%) was found to be significantly better(P=&lt;0.01) when compared to that of the daily regimen (94.07%). Conclusions: Daily regimen was more effective in raising the hemoglobin levels when compared to weekly regimen. Incidence of abdominal pain and metallic taste were significantly more in the daily group compared to weekly group. Compliance for weekly regimen was significantly better when compared to that of the daily regimen.

Association of Maternal Folate and Vitamin B12 in Early Pregnancy With Gestational Diabetes Mellitus: A Prospective Cohort Study.

OBJECTIVETo investigate the association of folate and vitamin B12 in early pregnancy with gestational diabetes mellitus (GDM) risk.RESEARCH DESIGN AND METHODSThe data of this study were from a subcohort within the Shanghai Preconception Cohort Study. We included pregnancies with red blood cell (RBC) folate and vitamin B12 measurements at recruitment (between 9 and 13 gestational weeks) and those with three samples available for glucose measurements under an oral glucose tolerance test. GDM was diagnosed between 24 and 28 weeks’ gestation. Odds ratio (OR) and 95% CI of having GDM was used to quantify the association.RESULTSA total of 1,058 pregnant women were included, and GDM occurred in 180 (17.01%). RBC folate and vitamin B12 were significantly higher in pregnancies with GDM than those without GDM (P values were 0.045 and 0.002, respectively) and positively correlated with 1-h and 2-h serum glucose. Daily folic acid supplementation in early pregnancy increases the risk of GDM; OR (95% CI) was 1.73 (1.19–2.53) (P = 0.004). Compared with RBC folate <400 ng/mL, pregnancies with RBC folate ≥600 ng/mL were associated with ∼1.60-fold higher odds of GDM; the adjusted OR (95% CI) was 1.58 (1.03–2.41) (P = 0.033). A significant trend of risk effect on GDM risk across categories of RBC folate was observed (Ptrend = 0.021). Vitamin B12 was significantly associated with GDM risk (OR 1.14 per 100 pg/mL; P = 0.002). No significant association of serum folate and percentile ratio of RBC folate/vitamin B12 with GDM was observed.CONCLUSIONSHigher maternal RBC folate and vitamin B12 levels in early pregnancy are significantly associated with GDM risk, while the balance of folate/vitamin B12 is not significantly associated with GDM.

Usefulness of daily folic acid supplementation during methotrexate treatment of Japanese patients with rheumatoid arthritis

Objectives We investigated the effect of daily folic acid supplementation on methotrexate (MTX) toxicity and efficacy in Japanese patients with rheumatoid arthritis (RA). Methods We followed 19 patients treated with MTX who switched from taking weekly 5 mg folic acid supplementation (weekly regimen) to 1.25 mg daily (daily regimen). White blood cell (WBC) and platelet (PLT) counts, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were collected for 24 weeks following the change. Results We observed no significant changes in WBC or PLT counts. AST and ALT levels, which had exceeded the upper limits of their normal ranges at the beginning of the study, were improved significantly at weeks 4 and 8, no subsequent deterioration in liver function was found. Further, no significant changes in ESR and CRP levels were observed. Conclusion Our data indicate that supplementing 1.25 mg of folic acid daily rather than 5 mg weekly reduces toxicity caused by MTX without affecting its efficacy.

Lower rates of neural tube defects in Israel following folic acid supplementation policy

Neural tube defects (NTDs) are common and disabling congenital malformations that remain a public health challenge despite prevention efforts. In 2000, The Israeli Ministry of Health published recommendations on daily folic acid (FA) supplementation for women of reproductive age and established a national NTD registry. This study aims to evaluate the long-term impact of the FA supplementation policy on NTD rates in Israel and the need for further intervention.In this descriptive report, we present the rate of NTD-affected pregnancies recorded in the registry between 2000 and 2012, their subtype (anencephaly, spina bifida or other), outcome (live birth, stillbirth or pregnancy termination), ethnic group (Jewish, Bedouin and non-Bedouin Muslim) and years of maternal education.The final analysis included 2374 NTD cases reported between 2000 and 2012, compared with 1,668,073 live births. During this period NTD rates decreased from 20.3 to 11.2 cases per 10,000 live births, a 45% reduction. Reductions were seen in rates of spina bifida, anencephaly and encephalocele. NTD rates decreased in all pregnancy outcomes and in all ethnic groups, though rates among Bedouins remain high. Women with higher levels of education tended to have lower NTD rates, and were more prone to choose termination of an affected pregnancy.Following the institution of FA supplementation in Israel, a substantial reduction was seen in NTD rates. Nonetheless, Israeli NTD rates remain higher than in other developed countries. FA interventions should continue to be vigorously implemented, especially in vulnerable populations. The global success of mandatory fortification of grain strongly advocates its consideration in Israel.

Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment

Importance Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale trial has examined the efficacy of this therapy for improving semen quality or live birth. Objective To determine the effect of daily folic acid and zinc supplementation on semen quality and live birth. Design, Setting, and Participants The Folic Acid and Zinc Supplementation Trial was a multicenter randomized clinical trial. Couples (n = 2370; men aged ≥18 years and women aged 18-45 years) planning infertility treatment were enrolled at 4 US reproductive endocrinology and infertility care study centers between June 2013 and December 2017. The last 6-month study visit for semen collection occurred during August 2018, with chart abstraction of live birth and pregnancy information completed during April 2019. Interventions Men were block randomized by study center and planned infertility treatment (in vitro fertilization, other treatment at a study site, and other treatment at an outside clinic) to receive either 5 mg of folic acid and 30 mg of elemental zinc (n = 1185) or placebo (n = 1185) daily for 6 months. Main Outcomes and Measures The co–primary outcomes were live birth (resulting from pregnancies occurring within 9 months of randomization) and semen quality parameters (sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count) at 6 months after randomization. Results Among 2370 men who were randomized (mean age, 33 years), 1773 (75%) attended the final 6-month study visit. Live birth outcomes were available for all couples, and 1629 men (69%) had semen available for analysis at 6 months after randomization. Live birth was not significantly different between treatment groups (404 [34%] in the folic acid and zinc group and 416 [35%] in the placebo group; risk difference, −0.9% [95% CI, −4.7% to 2.8%]). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) were not significantly different between treatment groups at 6 months after randomization. A statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group and 27.2% in the placebo group; mean difference, 2.4% [95% CI, 0.5% to 4.4%]). Gastrointestinal symptoms were more common with folic acid and zinc supplementation compared with placebo (abdominal discomfort or pain: 66 [6%] vs 40 [3%], respectively; nausea: 50 [4%] vs 24 [2%]; and vomiting: 32 [3%] vs 17 [1%]). Conclusions and Relevance Among a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples’ live birth rates. These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility. Trial Registration ClinicalTrials.gov Identifier:NCT01857310

Successful Treatment of Isotretinoin Induced Musculoskeletal Pain by Vitamin B12 and Folic Acid.

BACKGROUND:Daily supplementation with vitamin B12 and folate, which are the cofactors of the enzymatic reactions involved in Hcy metabolism, can lower plasma levels of Hcy and prevent osteoporosis induced by retinoidCASE PRESENTATION:We reported six patients with nodulocystic acne who reported musculoskeletal pain after taking isotretinoin which successfully treated with daily supplementation of folic acid and B12.CONCLUSION:We suggest our colleagues consider these supplements when a patient suffers from musculoskeletal pain following starting isotretinoin and continue the treatment as well. In the end, the authors concluded that robust trials with more patients are needed to establish the efficacy of Vit B12 and folic acid in the treatment of isotretinoin induced musculoskeletal pain.

Periconceptional folic acid and risk for neural tube defects among higher risk pregnancies

Women with a previous neural tube defect (NTD)-affected pregnancy are recommended to consume 4,000 μg daily folic acid (FA) for prevention (10 times the general-population recommendation). Protection from doses between 400 and 4,000 μg for this and other higher risk groups is unclear. In the case-control Slone Birth Defects Study (1988-2015), we examined the associations between periconceptional FA doses and NTDs among four higher risk groups: NTD family history, periconceptional antiepileptic drug exposure (AED), pregestational diabetes, and prepregnancy obesity. Mothers completed standardized interviews about pregnancy events and exposures. FA categorizations were based on (a) supplements only and (b) supplements and diet ("total folate"). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) (adjusted for age and study center) using logistic regression. Cases and controls included: 45 and 119 with family history, 25 and 108 with AED exposure, 12 and 63 with pregestational diabetes, 111 and 1,243 with obesity. Daily FA supplementation was associated with lower NTD risk compared to no supplementation (adjusted ORs were 0.33 [95% CI 0.13, 0.76] for family history, 0.31 [0.09, 0.95] for AED exposure, 0.25 [0.04, 1.05] for pregestational diabetes, 0.65 [0.40, 1.04] for obesity). Though estimates were imprecise, as total folate increased stronger point estimates were observed, notably among family history. No mothers with a prior NTD-affected pregnancy supplemented with 4,000 μg. Our findings reinforce that all women of childbearing potential should consume at least 400 μg FA/day to protect against NTDs. Higher risk groups may benefit from higher doses.

Effect of routine iron-folic acid supplementation among rural pregnant women living in low- and high-groundwater-iron areas in Bangladesh.

The present study investigated the risks and benefits of routine Fe-folic acid (IFA) supplementation in pregnant women living in low- and high-groundwater-Fe areas in Bangladesh. A case-controlled prospective longitudinal study design was used to compare the effect of daily Fe (60mg) and folic acid (400 μg) supplementation for 3·5 months. A rural community in Bangladesh. Pregnant women living in low-groundwater-Fe areas (n 260) and high-groundwater-Fe areas (n 262). Mean Hb and serum ferritin concentrations at baseline were significantly higher in pregnant women in the high-groundwater-Fe areas. After supplementation, the mean change in Hb concentration in the women in the low-groundwater-Fe areas (0·10 g/dl) was higher than that in the pregnant women in the high-groundwater-Fe areas (-0·08 g/dl; P = 0·052). No significant changes in the prevalence of anaemia or Fe deficiency (ID) in either group were observed after IFA supplementation; however, the prevalence of Fe-deficiency anaemia (IDA) decreased significantly in the women in the low-groundwater-Fe areas. The risk of anaemia, ID and IDA after supplementation did not differ significantly between the groups. None of the participants had Fe overload. However, a significant proportion of the women in the high- and low-groundwater-Fe areas remained anaemic and Fe-deficient after supplementation. IFA supplementation significantly increased the Hb concentration in pregnant women living in the low-groundwater-Fe areas. Routine supplementation with 60 mg Fe and 400 μg folic acid does not pose any significant risk of haemoconcentration or Fe overload. Further research to identify other nutritional and non-nutritional contributors to anaemia is warranted to prevent and treat anaemia.

Preconception care needs among female patients of childbearing age in an urban community pharmacy setting

ObjectivesTo perform a needs assessment with the use of evidence-based core indicators developed by the Preconception Health and Heath Care (PCHHC) Initiative Clinical Workgroup and Centers for Disease Control and Prevention (CDC) to describe the preconception care needs among female patients of a community pharmacy. MethodsWomen of childbearing age received a paper survey in either English or Spanish containing questions about patient demographics, health status, and pregnancy considerations. On completion of the survey, patient medication history data were retrospectively gathered from the medication profile and vaccination status on select vaccines was determined using the Michigan vaccination reporting system. ResultsNinety-nine surveys were completed. The median age was 30 years (range 18-44). Of survey participants, 77.8% indicated that they were sexually active, 70.7% had an abnormal body mass index, 78.8% were missing documentation of one or more recommended vaccinations, 66.7% were not taking any form of daily folic acid supplementation, and 49.5% were using at least 1 medication with potential teratogenic effects. ConclusionA preconception health needs assessment conducted in a community pharmacy with female patients of childbearing age found multiple opportunities for intervention such as improving daily folic acid supplementation and ensuring appropriate management of medications with potential teratogenic effects. Each of the preconception care needs assessed can be addressed through services provided by community pharmacists.

RANDOMISED DOUBLE-BLIND PLACEBO-CONTROLLED STUDY OF FOLIC ACID ADJUNCT FOR 8 WEEKS IN HYPERHOMOCYSTEINAEMIC HYPERTENSIVE PATIENTS IN ZARIA, NIGERIA

Objectives: This study was aimed at determining the effect of folic acid adjunct therapy on homocysteine (HCY) and blood pressure (BP) levels in hypertensive subjects.&#x0D; Method: The study was a double blind placebo-controlled trial on 100 hypertensive patients randomised into 50 folate and 50 placebo groups, where the folate group had 5 mg folic acid daily for 8 weeks. Fasting plasma homocysteine, folate and blood pressure levels were determined at baseline, at 4 and at 8 weeks. The Mixed Model Repeated Measures analysis of variance was applied for data analysis.&#x0D; Results: Hyperhomocysteinaemia was found at baseline in the folate (21.3 ± 5.7 µmol/L) and placebo (21.6 ± 4.9 µmol/L) groups which did not differ statistically (p &gt; 0.05). Folic acid adjunct therapy, reduced homocysteine levels at 4 weeks by 2.0 µmol/L (9.2 %, p &lt; 0.05) and at 8 weeks by 1.2 µmol/L (5.6 %, p &lt; 0.05), with no significant (p &gt; 0.05) systolic and diastolic blood pressure lowering effect. High base-line folate levels were found in both folate (113.8 ± 51.2 ng/ml) and placebo groups (109.5 ± 51.4 ng/ml) with no statistically significant difference (p &gt; 0.05).&#x0D; Conclusion: Short-term daily folic acid supplementation over 8 weeks had a significant homocysteine reduction effect with no significant reduction in systolic and diastolic blood pressures of hypertensive subjects in Zaria, Nigeria. Hyperhomocysteinaemia could not be accounted for by suboptimal folate levels.&#x0D; Keywords: Hypertension, Homocysteine, Blood pressure, Folate, Placebo, Nigeria.