Dietary Folic Acid Supplementation Research Articles

High Dietary Folic Acid Supplementation Reduced the Composition of Fatty Acids and Amino Acids in Fortified Eggs.

The study aimed to evaluate the effects of dietary folic acid (FA) on the production performance of laying hens, egg quality, and the nutritional differences between eggs fortified with FA and ordinary eggs. A total of 288 26-week-old Hy-Line Brown laying hens (initial body weights 1.65 ± 0.10 kg) with a similar weight and genetic background were used. A completely randomized design divided the birds into a control group and three treatment groups. Each group consisted of six replicates, with twelve chickens per replicate. Initially, all birds were fed a basal diet for 1 week. Subsequently, they were fed a basal diet supplemented with 0, 5, 10, or 15 mg/kg FA in a premix for a duration of 6 weeks. Supplementation of FA could significantly (p < 0.05) enhance the FA content in egg yolks, particularly when 10 mg/kg was used, as it had the most effective enrichment effect. Compared to the control group, the Glu content in the 10 and 15 mg/kg FA groups showed a significant (p < 0.05) decrease. Additionally, the contents of Asp, Ile, Tyr, Phe, Cys, and Met in the 15 mg/kg FA group were significantly (p < 0.05) lower compared to the other groups. Adding FA did not have significant effects on the levels of vitamin A and vitamin E in egg yolk, but the vitamin D content in the 5 and 10 mg/kg FA groups showed a significant (p < 0.05) increase. Furthermore, the addition of FA did not have a significant effect on the levels of Cu, Fe, Mn, Se, and Zn in egg yolk. The dietary FA did not have a significant effect on the total saturated fatty acids (SFA) and polyunsaturated fatty acid (PUFA) content in egg yolk. However, the total monounsaturated fatty acid (MUFA) content in the 5 and 10 mg/kg groups significantly (p < 0.05) increased. These changes in nutritional content might be attributed to the increased very low-density lipoprotein (VLDL) protein content. The significant decrease in solute carrier family 1 Member 1 (SLC1A1), solute carrier family 1 Member 2 (SLC1A2), and solute carrier family 1 Member 3 (SLC1A3) gene expression compared to the control group appeared to be the reason for the decrease in amino acid content in egg yolk within the dietary FA group. The findings suggest that the appropriate addition of FA can enhance the levels of MUFA and vitamin D in egg yolks, thereby improving their nutritional value. Excessive intake of FA can decrease the effectiveness of enriching FA in egg yolk and impact the enrichment of certain amino acids. The yolk of eggs produced by adding 10 mg/kg of FA to the feed contains the optimal amount of nutrients. This study informs consumers purchasing FA-fortified eggs.

Effects of Dietary Folic Acid Supplementation on Growth Performance and Immune Parameters in Weanling Piglets

In order to study the effects of dietary folic acid (FA) supplementation on growth performance and immune status in weanling piglets, a single factorial randomized block design trial was conducted with six diets supplemented with FA at 0, 0.30, 3.00, 6.00, 9.00 or 15.00 mg/kg. A total of 108 crossbred (Landrace × Yorkshire) castrated weanling piglets (at 21 d of age) were allocated by body weight into 36 feeding cages (3 piglets/cage), which were allotted randomly into six dietary groups (six cages/group). Piglets were fed ad libitum for 24 days. Blood samples were collected on the 24th day. The growth performance and immune parameters were measured. Results showed that FA supplementation increased the serum FA level of weaned piglets (p &lt; 0.01) and tended to increase the body weight (BW) at 45 d of age (p &lt; 0.1) and the average daily gain (ADG) from 29 d to 45 d of age (p &lt; 0.1). FA addition improved the feed efficiency (G/F) from 21 to 45 d of age (p &lt; 0.01) with supplementary FA levels of 0.3, 3.0, and 9.0 mg/kg compared with the control group with no FA supplementation. FA supplementation showed a trend (p &lt; 0.1) to increase the peripheral blood CD3+CD8+ lymphocyte subpopulation and a tendency (p &lt; 0.1) to decrease the CD3+CD4+/CD3+CD8+ ratio; in particular FA supplementation of 0.3 and 3.0 mg/kg showed significant differences in comparison to the non-supplemented control group. Moreover, FA addition increased the serum interferon-γ (IFN-γ) level (p &lt; 0.05) and tended to reduce the ratio of tumor necrosis factor-α to interleukin-4 (TNF-α/IL-4, p &lt; 0.1) and immunoglobulin G (IgG, p &lt; 0.1) in serum, but had no significant effect on serum IL-4, TNF-α, and nitric oxide. In conclusion, FA supplementation up to 3 mg/kg to the diet showed a tendency to improve immune function, while FA supplementation of up to 9 mg/kg improved feed efficiency, which resulted in a trend for higher growth in weaned piglets between 7 to 11 kg BW.

Effects of Dietary Folic Acid Supplementation on Sex Differences in Oriental River Prawn, Macrobrachium nipponense

To better understand the sex differences in the utilization of folic acid for male and female prawns, Macrobrachium nipponense, three experimental diets with graded folic acid contents (A: 1.22 mg/kg, B: 5.44 mg/kg, and C: 10.09 mg/kg) were provided to prawns for 8 weeks. The experimental study demonstrated that prawns fed diets containing 1.22 mg/kg showed the best values on body weight gain (BWG), specific growth rate (SGR), and individual weight for both males and females. Male prawns fed above 1.22 mg/kg of dietary folic acid significantly decreased the crude protein contents in their bodies (p &lt; 0.05), while no significant differences were observed in females among all treatments (p &gt; 0.05). The protease activity of the hepatopancreas in females was significantly (p &lt; 0.05) improved by a dietary level of 10.09 mg/kg of folic acid. However, the opposite trend was observed in males, with the highest protease activity observed at a dietary level of 1.22 mg/kg folic acid. Increasing dietary folic acid levels did not suppress early maturation but led to an increase in the fecundity of females. Furthermore, prawns fed with 10.09 mg/kg of folic acid exhibited improved tolerance against thermal stress in both males and females. Transcriptome analysis revealed that during thermal stress, the “Oxidative phosphorylation” and “Pantothenate and CoA biosynthesis” signaling pathways were significantly enriched in females, and the “Fatty acid biosynthesis” signaling pathway was significantly enriched in males. The results of this study preliminarily evaluate the differences between male and female M. nipponense in response to different dietary folic acid levels and are helpful in promoting the health and growth of aquaculture production of this species.

The Role of One-Carbon Metabolism in Healthy Brain Aging.

Aging results in more health challenges, including neurodegeneration. Healthy aging is possible through nutrition as well as other lifestyle changes. One-carbon (1C) metabolism is a key metabolic network that integrates nutritional signals with several processes in the human body. Dietary supplementation of 1C components, such as folic acid, vitamin B12, and choline are reported to have beneficial effects on normal and diseased brain function. The aim of this review is to summarize the current clinical studies investigating dietary supplementation of 1C, specifically folic acid, choline, and vitamin B12, and its effects on healthy aging. Preclinical studies using model systems have been included to discuss supplementation mechanisms of action. This article will also discuss future steps to consider for supplementation. Dietary supplementation of folic acid, vitamin B12, or choline has positive effects on normal and diseased brain function. Considerations for dietary supplementation to promote healthy aging include using precision medicine for individualized plans, avoiding over-supplementation, and combining therapies.

Prepubertal Continuous Dietary Folate Fortification Enhances the Brain Function of Adult Mice by Modulating Antioxidant Status, Inflammation, and Brain Neurotransmitter Levels.

The benefits of folic acid supplementation have been documented in several studies. However, while evidence exists regarding its benefits for growth and haematologic parameters, its possible effects on the brain have been less examined. The study aimed to examine the benefits of dietary folic acid supplementation (beginning in the prepubertal period) on neurobehaviour, oxidative stress, inflammatory parameters, and neurotransmitter levels in adult mice. Forty-eight prepubertal male mice were assigned into four groups of 12 animals each. Mice were grouped into normal control (fed standard diet) and three groups fed folic acid supplemented diet at 2.5, 5, and 10 mg/kg of feed. Animals were fed a standard diet or folic acid-supplemented diet for eight weeks during which food intake and body weight were assessed. On postnatal day 78, animals were exposed to the open-field, Y-maze, radial arm maze, elevated plus maze, bar test, and models of behavioural despair. 24 hours after the last behavioural test, animals were made to fast overnight and then sacrificed by cervical dislocation. Blood was then taken for the assessment of blood glucose, leptin, and insulin levels. Homogenates of brain tissue were prepared and used for the assessment of biochemical parameters. Results showed a concentration-dependent increase in body weight, and improved antioxidant status, memory scores, and acetylcholine levels. Also, a decrease in food intake, blood glucose, insulin, and leptin levels was observed. A reduction in open-field behaviour, anxiety-related behaviour, and proinflammatory markers, was also observed. The beneficial effect of prepubertal continuous dietary folate fortification on the brain (as the animal ages) has been shown in this study.

P27-016-23 The Impact of Dietary Folic Acid Supplementation and Hypoxia on Health Outcome Using a Fly Model System

P27-016-23 The Impact of Dietary Folic Acid Supplementation and Hypoxia on Health Outcome Using a Fly Model System

Dietary Folic Acid Supplementation Inhibits HighFat DietInduced Body Weight Gain through Gut Microbiota-Associated Branched-Chain Amino Acids and Mitochondria in Mice.

The effects of folic acid on body weight gain in obesity and gut microbiota-associated branched-chain amino acids (BCAAs) and mitochondrial function were investigated. Three- to four-wk-old male C57BL/6J conventional (CV) and germ-free (GF) mice were fed a high-fat diet (HD), folic acid-supplemented HD (FSHD) and a normal-fat diet (ND) for 25 wk. In CV mice, the HD-induced increases in body weight and plasma BCAA concentrations, downregulated expression of genes related to BCAA catabolism (Bcat2, Bckdha, or Ppm1k), mitochondrial biogenesis (Pgc-1α, Cox1, Nd1 or Nd6), fusion (Mfn1, Mfn2 or Opa1) and mitophagy (Pink1 or Park2), and upregulated expression of the fission-associated gene Drp1 in epididymal fat were reversely corrected with FSHD feeding. In contrast, the expression of these genes in the liver was the opposite under HD feeding or folic acid supplementation. In GF mice, plasma BCAA concentrations were much less affected by HD feeding and were reduced by FSHD feeding, with almost no alterations in the expression of genes associated with BCAA catabolism and mitochondrial function. Further analysis indicated a correlation between adipose and hepatic Mt C/N and plasma BCAA concentrations, and the latter had a close association with specific gut bacteria. Therefore, dietary folic acid supplementation differentially affected body weight gain, BCAA catabolism, and mitochondrial dynamics and metabolism under HD feeding between CV and GF mice, suggesting that gut bacteria-altered BCAAs and mitochondria might partially share the responsibility for the beneficial effects of dietary folic acid on obesity.

Long-term dietary folic acid supplementation attenuated aging-induced hippocampus atrophy and promoted glucose uptake in 25-month-old rats with cognitive decline

The brain has high energy demand making it sensitive to changes in energy fuel supply. Aging shrinks brain volume, decreases glucose uptake availability of the brain, and finally, causes cognitive dysfunction. Folic acid supplementation delayed cognitive decline and neurodegeneration. However, whether folic acid affects brain energy metabolism and structural changes is unclear. The study aimed to determine if long-term dietary folic acid supplementation could alleviate age-related cognitive decline by attenuating hippocampus atrophy and promoting brain glucose uptake in Sprague-Dawley (SD) rats. According to folic acid levels in diet, 3-months old male SD rats were randomly divided into four intervention groups for 22 months in equal numbers: folic acid-deficient diet (FA-D) group, folic acid-normal diet (FA-N) group, low folic acid-supplemented diet (FA-L) group, and high folic acid-supplemented diet (FA-H) group. The results showed that serum folate concentrations decreased and serum homocysteine (Hcy) concentrations increased with age, and dietary folic acid supplementation increased serum folate concentrations and decreased Hcy concentrations at 11, 18, and 22 months of intervention. Dietary folic acid supplementation attenuated aging-induced hippocampus atrophy, which was showed by higher fractional anisotropy and lower mean diffusivity in the hippocampus, increased brain 18F-Fluorodeoxyglucose (18F-FDG) uptake, then stimulated neuronal survival, and alleviated age-related cognitive decline in SD rats. In conclusion, long-term dietary folic acid supplementation alleviated age-related cognitive decline by attenuating hippocampus atrophy and promoting brain glucose uptake in SD rats.

Dietary folic acid addition reduces abdominal fat deposition mediated by alterations in gut microbiota and SCFA production in broilers

Intensive selective breeding for high growth rate and body weight cause excess abdominal fat in broilers. Gut microbiota and folic acid were reported to regulate lipid metabolism. A total of 210 one-day-old broilers were divided into the control (folic acid at 1.3mg/kg) and folic acid groups (folic acid at 13mg/kg) to illustrate the effects of folic acid on growth performance, abdominal fat deposition, and gut microbiota, and the experiment lasted 28d. Results revealed that dietary folic acid addition decreased abdominal fat percentage (P<0.05) and down-regulated genes expression related to cell proliferation and differentiation in abdominal fat including IGF1, EGF, C/EBPα, PPARγ, PLIN1, FABP4 and PCNA (P<0.05). Folic acid addition decreased caecal Firmicutes-to-Bacteroidetes ratio (P<0.01) and increased the proportions of Alistipes, Oscillospira, Ruminococcus, Clostridium, Dehalobacterium and Parabacteroides (P<0.05). Caecal acetic acid, and propionic acid contents were found to be higher under folic acid treatment (P<0.05), which were negatively related to genes expression associated with adipocyte proliferation and differentiation (P<0.05). Ruminococcus was positively correlated with caecal acetic acid content, and the same phenomenon was detected between propionic acid and Oscillospira and Ruminococcus (P<0.05). Acetic acid and Oscillospira were identified to be negatively associated with abdominal fat percentage (P<0.05). In conclusion, our data demonstrated that dietary supplementation of folic acid reduced fat deposition in broilers by inhibiting abdominal adipocyte proliferation and differentiation, which might be mediated by changes in gut microbiota and short chain fatty acid production.

Dietary folate intake and fecundability in two preconception cohorts.

To what extent is dietary folate intake and total folate intake (dietary and supplemental intakes) associated with fecundability, the per cycle probability of conception? Preconception dietary folate intake was positively associated with fecundability in a monotonic pattern. Supplemental folic acid has been associated with improved fertility, but little is known about the relation between dietary folate and fecundability. A prospective cohort study including 9559 women trying to conceive without fertility treatment and enrolled in the period 2013-2020. We used data from two internet-based prospective cohort studies of pregnancy planners from Denmark, where folic acid fortification is not performed (SnartForældre.dk (SF); n = 3755) and North America, where the food supply is fortified with folic acid (Pregnancy Study Online (PRESTO); n = 5804). Women contributed menstrual cycles at risk until they reported conception or experienced a censoring event. We used proportional probabilities regression models to compute fecundability ratios (FRs) and 95% CI, adjusting for potential confounders. Compared with a dietary folate intake ≥400 µg/day, the adjusted FRs for women in SF were 0.92 (95% CI: 0.85-0.99) for intake 250-399 µg/day, and 0.80 (95% CI: 0.68-0.94) for intake of <250 µg/day. The corresponding FRs in PRESTO were 0.95 (95% CI: 0.89-1.01) and 0.81 (95% CI: 0.65-1.00). Compared with the highest level of total folate intake (diet folate ≥400 µg/day plus folic acid supplementation), in both cohorts fecundability was lowest among women with the lowest dietary intake <250 µg/day dietary folate and no supplementation (FR: 0.76, 95% CI: 0.59-0.98 [SF] and 0.49, 95% CI: 0.31-0.77 [PRESTO]). Further, total intake dietary folate <250 µg/day plus supplementation was associated with reduced fecundability for SF participants (FR; 0.79, 95% CI: 0.65-0.98) and for PRESTO participants (FR; 0.92, 95% CI: 0.72-1.16). It is unknown whether dietary folate and folic acid intake affect fecundability on its own or if there is an interaction with other micronutrients provided in healthy diet. Thus, the observed associations may not reflect dietary folate intake alone, but overall healthy diet. Recommendations for preconception dietary folate intake and folic acid supplementation are of importance not only to prevent neural tube defects but also to enhance fecundability. The study was supported by the National Institute of Child Health and Human Development (R01-HD086742). The authors report no competing interests. N/A.

Suppression of high-fat-diet-induced obesity in mice by dietary folic acid supplementation is linked to changes in gut microbiota.

To investigate whether the effects of dietary folic acid supplementation on body weight gain are mediated by gut microbiota in obesity. Male C57 BL/6J conventional (CV) and germ-free (GF) mice both aged three to four weeks were fed a high-fat diet (HD), folic acid-deficient HD (FD-HD), folic acid-supplement HD (FS-HD) and a normal-fat diet (ND) for 25weeks. Faecal microbiota were analyzed by 16S rRNA high-throughput sequencing, and the mRNA expression of genes was determined by the real-time RT-PCR. Short-chain fatty acids (SCFAs) in faeces and plasma were measured using gas chromatography-mass spectrometry. In CV mice, HD-induced body weight gain was inhibited by FS-HD, accompanied by declined energy intake, smaller white adipocyte size, and less whitening of brown adipose tissue. Meanwhile, the HD-induced disturbance in the expression of fat and energy metabolism-associated genes (Fas, Atgl, Hsl, Ppar-α, adiponectin, resistin, Ucp2, etc.) in epididymal fat was diminished, and the dysbiosis in faecal microbiota was lessened, by FS-HD. However, in GF mice with HD feeding, dietary folic acid supplementation had almost no effect on body weight gain and the expression of fat- and energy-associated genes. Faecal or plasma SCFA concentrations in CV and GF mice were not altered by either FD-HD or FS-HD feeding. Dietary folic acid supplementation differently affected body weight gain and associated genes' expression under HD feeding between CV and GF mice, suggesting that gut bacteria might partially share the responsibility for beneficial effects of dietary folate on obesity.

Dietary folic acid supplementation improves semen quality and spermatogenesis through altering autophagy and histone methylation in the testis of aged broiler breeder roosters

The aging phenomenon often exerts a significant reduction in the reproduction performance of aged animals. The objective of this project was to investigate the effects of dietary Folic acid (FA) supplementation on the reproductive performance of aged broiler breeder roosters. A total of 16 aged ROSS 308 broiler breeder roosters (50-week-old) were randomly divided into two groups. The treatments were basal diet (CON), a basal diet supplemented with 10 mg/kg Folic acid (FAS) for four weeks. At the end of the experiment, semen quality, histopathological studies, serum concentrations of testosterone and relative mRNA and protein expressions of testes were evaluated. The results showed that dietary FA supplementation dramatically improved semen quality of aged roosters, manifested by increasing semen volume, sperm concentration, sperm motility, and sperm membrane functional integrity. Furthermore, seminiferous tubule epithelial height (SEH) and testis scores were increased by dietary supplementation with FA. Dietary FA also remarkably augmented the transcription level of spermatogenesis-related gene (CREM, PCK2, DDX4, and GDNF). No significant differences were observed in serum concentrations of testosterone between FAS and CON groups. We noted significant upregulation Beclin-1 and ATG5 protein expressions, and the ratio of LC3-Ⅱ/Ⅰ, as well as significant downregulation of p-mTOR protein expressions in testicular tissue of aged roosters with FA supplementation. In addition, dietary FA supplementation significantly increased the protein expression of H3K9me2 and reduced the protein expression of H3K27me2. In summary, dietary FA supplementation improved the testicular autophagy through the mTOR-signaling pathway, and altered histone methylation in the testis. Dietary supplementation with FA can ameliorate semen quality and spermatogenesis of aged roosters.

Effects of folic acid supplementation to basal diets of broilers on growth performance, slaughter performance, IGF2 gene expression and methylation

Folic acid (FA) is an important water-soluble vitamin and plays an important role as a cofactor and coenzyme in animal growth and development, and regulation of gene expression and methylation. A total of 270 female broiler chickens (1-day-old) were randomly allotted to three dietary treatments supplemented with 0 mg/kg (control group), 5 mg/kg, and 10 mg/kg FA in basal diets for 42 days, respectively. Each treatment had six replicate cages with 15 birds per cage. Dietary supplementation of 5 mg/kg FA significantly enhanced average body weight and average daily gain of 21-day-old broilers (P &amp;lt; 0.05), but significantly reduced subcutaneous fat thickness and widths of an intermuscular fat band of 42-day-old broilers by dietary FA treatments (P &amp;lt; 0.05). Also, a diet with 10 mg/kg FA supplementation significantly increased the relative heart weight of 42-day-old chickens (P &amp;lt; 0.05). Furthermore, dietary FA supplementation significantly improved the serum insulin-like growth factor 2 (IGF2) concentrations (P &amp;lt; 0.01) and IGF2 mRNA expression in the abdominal fat (P &amp;lt; 0.05), but no statistical differences were found in the methylation of IGF2 promoter (P &amp;gt; 0.05). The present study demonstrated that dietary FA supplementation may have positive effects on chicken growth through increased IGF2 gene expression.

Dietary Folic Acid Alters Metabolism of Multiple Vitamins in a CerS6- and Sex-Dependent Manner.

Folic acid, an oxidized synthetic pro-vitamin B9, is widely used in vitamin supplement formulations and food fortification to maintain optimal folate status in humans. Studies on folic acid (FA) efficiency in improving folate status and correcting folate deficiency pathologies are abundant, but precise knowledge of FA effects on human and animal tissues is not available. In our recent study, 10-week-old wild-type and CerS6 knockout (KO) mice were placed on FA-deficient, control, or FA over-supplemented diet for 4 weeks. Untargeted metabolomics characterization of mouse liver, brain, and testes tissues after the dietary treatment revealed profound effects of FA on the liver metabolome. Here, we present the analysis of dietary FA effects on tissue concentrations of other vitamins in mice. Despite the expectation that identical dietary supply of the vitamins (excluding FA) to each group should support similar tissue vitamins concentrations, metabolomics data demonstrate significant alterations of tissue concentrations of multiple vitamins by different levels of FA supplementation that were sex- and genotype-dependent. Moreover, we found significant differences in the liver concentration of retinol, thiamin diphosphate, pantetheine, pyridoxal, and pyridoxamine between males and females. While the liver had more changes in vitamins and vitamin derivative levels, the brain tissue and testes also showed changes linked to FA supplementation. Over-supplementation with FA had negative effects on concentrations of vitamins A, B1, B2, and B6, or their metabolites in the liver, but increased intermediates in coenzyme A (CoA) biosynthesis, as well as gamma/beta-tocopherol and phosphorylated forms of B6 in the CerS6 KO brain. Overall, our data demonstrate that dietary FA supplementation significantly affects the metabolism of other vitamins, and that these effects depend on the CerS6 status and sex of the animal. Further research is required to determine whether the observed effects are specific to FA, and the mechanisms that are involved.

Folic Acid Absorption Characteristics and Effect on Cecal Microbiota of Laying Hens.

This experiment was conducted to investigate the characteristics of folic acid (FA) absorption in laying hens and the effect of FA supplementation on cecal microbiota. A total of 432 healthy hens (30-week-old) were randomly assigned to four diets supplemented with FA: 0, 1, 6, and 24 mg/kg of feed for 8 w. Blood, duodenum, jejunum, ileum, cecum, and cecal chyme samples (six samples per treatment) were collected from the hens at the end of the feeding trial. Expression profiles of folate transport and transformation genes in intestine and cecal microbiota were detected. Results showed that serum folate level significantly increased (P < 0.01) with an increase in dietary FA supplementation, reaching a plateau at 6 mg/kg FA supplementation. The expression of FA transport and transformation genes was not affected in the cecum (P > 0.05) by dietary FA supplementation; however, it was affected in the duodenum, jejunum, and ileum and mostly showed a downward trend in treatment groups (P < 0.05). The genes affected include duodenal folate receptor (Folr) and dihydrofolate reductase (Dhfr), jejunal proton-coupled folate transporter (Pcft) and reduced folate carrier (Rfc), and ileal ATP binding cassette subfamily C member (Abcc2), Abcc3, Rfc, Folr, and Dhfr. Furthermore, according to the operational taxonomic unit classification and taxonomic position identification, the cecal microbiota population of the hens was not affected by dietary FA supplementation at the phylum, class, order, family, genus, and species levels (P > 0.05). However, the relative abundance of some microbiota was affected by dietary FA supplementation (P < 0.05). In conclusion, FA transport from the intestinal lumen into enterocytes, and then into the bloodstream, is strictly regulated, which may be associated with the regulation of the expression profiles of genes involved in FA absorption. Pathogenic bacteria decreased in the cecum, especially at 24 mg/kg supplementation, but the beneficial bacteria (Bifidobacteriaceae) decreased at this level, too. Overall, FA supplementation at 6 mg/kg, which was selected for folate-enriched egg production, did not affect the health and metabolism of laying hens negatively.

Folic acid supplementation during pregnancy modulates hepatic methyl metabolism and genes expression profile of neonatal lambs of different litter sizes.

Maternal folic acid (FA) plays an important role in the fetus development, but it is unknown the response of hepatic metabolism in the offspring from different litter sizes to maternal FA supplementation. In the present study, this was done by feeding the ewes with 0, 16 and 32 mg/(kg·DM) FA supplemented diet during pregnancy and analysing the hepatic one-carbon metabolism-related indices and gene expression in the neonatal lambs of different litter sizes (twins, TW; triplets, TR). Regardless of litter sizes, the concentrations of folate, methionine, S-adenosylmethionine and DNA methyltransferase increased significantly, but homocysteine and S-adenosylhomocysteine decreased in the liver of newborn lambs from ewes whose diet was supplemented with FA. In TW, maternal FA status has little effect on hepatic genes expression profile of newborn lambs, and no significant enriched pathway was found. However, DEG involved in cell proliferation such as CCNA2, CCNB2, CCNE2, CDK1 and BUB1 were significantly enriched when the ewes were supplemented with FA in TR groups. In addition, nucleotide synthesis-related genes such as POLD1, POLD2, MCM4 and MCM5 were enriched markedly in DNA replication and pyrimidine metabolism pathways in triplets when a higher FA ingestion [32 mg/(kg·DM)] was implemented in ewes. This finding demonstrated that the hepatic methyl metabolism in TW and TR newborn lambs was regulated by maternal FA status. The hepatic cell proliferation and nucleotide metabolism related genes in TR were more susceptible to maternal dietary FA supplementation during pregnancy.

The Role of Folate-supplementation in Depression: A Narrative Review

Background: There is a relationship between the etiology and management of clinical depression and vitamin deficiencies. Aim: To review the effect of dietary folic acid supplementation on cause, severity and treatment of depression. Methods: A narrative review of empirical and theoretical literature on the effect of folic acid supplementation on the se-verity and treatment outcomes of depression. Result: Many enzymes and neurotransmitters depend on folic acid for optimal functions. The monoamine hypothesis of depression confirms the depletion of serotonin, dopamine, and norepinephrine. The systemic level of methyl folate is dependent upon the enzyme methylenetetrahydrofolate reductase [MTHFR], which is encoded by a polymorphic gene [C677T-MTHFR], as well as being dependent on dietary folic acid intake. However, folate has procarcinogenic properties because its coenzymes are involved in de novo purine and thymine nucleotide biosynthesis. Besides, folate deficiency in normal tissues may also predispose to neoplastic transformation, while folate supplementation may suppress the development of tumors in normal tissues. Epidemiological studies revealed that low folate status is associated with depression; especially in terms of severity and the outcome of antidepressant use. Conclusion: The role of folic acid in the etiology and the management of depression cannot be overemphasized. Folate supplementation has been yielding positive results in the management of depression.

Association Between Interpregnancy Interval and Risk of Preterm Birth and Its Modification by Folate Intake: The Japan Environment and Children's Study.

Both short and long interpregnancy intervals (IPIs) have been associated with risk of preterm birth, but the evidence is limited in Asians. It is also uncertain whether the association is modified by dietary folate intake or folic acid supplementation during pregnancy. Thus, we examined associations between IPI and risk of preterm birth and effect modification of those associations by dietary intake of folate and supplementation with folic acid on the basis of a nationwide birth cohort study. Among 103,062 pregnancies registered in the Japan Environment and Children's Study, 55,203 singleton live-birth pregnancies were included in the analysis. We calculated IPI using birth date, gestational age at birth of offspring, and birth data of the latest offspring. Odds ratios (ORs) and 95% confidence intervals (CIs) of the risk of preterm birth were estimated according to IPI categories. Both <6-month and ≥120-month IPIs were associated with an increased risk of preterm birth, compared with an 18-23-month IPI. The multivariable ORs were 1.63 (95% CI, 1.30-2.04) for <6-month and 1.41 (95% CI, 1.11-1.79) for ≥120-month IPIs. These associations were confined to women with inadequate intake of dietary folate and folic acid supplementation during pregnancy. Multivariable ORs were 1.76 (95% CI, 1.35-2.29) for <6-month IPI and 1.65 (95% CI, 1.24-2.19) for ≥120-month IPI. Both <6-month and ≥120-month IPIs were associated with an increased risk of preterm birth. These higher risks were confined to women with inadequate intake of dietary folate and folic acid supplementation during pregnancy.

Effect of dietary energy density and folic acid supplementation on white striping occurrence and growth performance of broiler chickens

Broilers were allocated to eight treatments consisting of two energy levels: normal (NE) and high (HE), and four folic acid (FA) levels (2.2, 5, 10, and 15 ppm). On day 42, two male and two female chickens were euthanized per pen, and white striping (WS) evaluation was performed on the pectoralis major. Birds fed HE diets had reduced (P &lt; 0.05) feed intake and feed conversion rate than those on NE diets. With increasing FA levels, there was reduced (P &lt; 0.05) WS score and increased (P &lt; 0.05) normal breast fillet percentage in female chickens but not in the males. WS scores were higher (P &lt; 0.01) in male chickens than in the females.

Maternal Folic Acid Supplementation Differently Affects the Small Intestinal Phenotype and Gene Expression of Newborn Lambs from Differing Litter Sizes.

Simple SummaryMaternal folic acid (FA) level during gestation is a factor affecting fetal development due to the vital role of FA in nucleotide synthesis. As a key organ of lamb, the development of the small intestine during gestation in response to maternal FA is not clear. Therefore, the current study evaluated the intestinal phenotype and development-, apoptosis- and digestion-related genes expression in newborn lambs whose mothers supplemented FA during gestation. FA supplementation improved the ratio of small intestinal weight to live body weight, intestinal muscle layer thickness and the expression of IGF-I, BCL-2 and SGLT1. Meanwhile, triplets indicated poorer morphological development compared to twins, but the expression of several genes was higher in twins compared to triplets. Overall, maternal FA supplementation during gestation increased the development of offspring’s small intestinal.The purpose of this study was to investigate the effect of maternal dietary folic acid (FA) supplementation during gestation on small intestinal development of newborn lambs of different litter sizes, focusing on the intestinal morphology and development-, apoptosis- and digestion-related genes expression. One hundred and twenty Hu ewes (Ovis aries) were inseminated and randomly allotted to three groups. One group received a control diet [without FA supplementation, control (CON)] and the other two groups received control diets supplemented with different amount of FA [16 or 32 mg FA per kg dry matter (DM), i.e., F16 and F32] during pregnancy. After lambing, according to the dietary FA levels and litter size (twins, TW; triplets, TR), the neonatal lambs were divided into 6 (TW-CON, TW-F16, TW-F32, TR-CON, TR-F16, TR-F32) treatment groups. The results showed that the ratio of small intestinal weight to live body weight and the thickness of the intestinal muscle layer in the offspring was enhanced significantly with increasing maternal FA supplementation (p < 0.05). Meanwhile, the expression levels of insulin-like growth factor I (IGF-I), B-cell lymphoma-2 (BCL-2) and sodium/glucose co-transporter-1 (SGLT1) in the small intestines of the newborn lambs were increased, while the opposite was true for Bcl2-associated × (BAX) in response to FA supplementation (p < 0.05). Moreover, the small intestinal weights of twins were significantly higher than those of triplets (p < 0.01), and the expression levels of IGF-I (p < 0.05), sucrase-isomaltase (SI) (p < 0.05) and solute carrier family 2 member 5 (SLC2A5) (p < 0.01) were significantly lower than those in triplets. These findings suggest that maternal FA supplementation could improve the offspring’s small intestinal phenotype and the expression of development-, apoptosis- and digestion-related genes, so it could promote the small intestinal development of newborn lambs. Furthermore, the small intestine phenotypic development of twins was generally better than that of triplets, while the expression levels of the above genes of twins were lower than those of triplets.