Fatty acids and their metabolites (resolvins) are altered in women with gestational diabetes mellitus (GDM).

The maternal fatty acid status plays a key role in influencing pregnancy outcomes. Omega-3 fatty acids are the precursors for E-series (RvE) and D-series resolvins (RvD) and possess anti-inflammatory properties. Pregnancy complications like gestational diabetes mellitus (GDM) are associated with excess maternal inflammation. This study reports the levels of maternal fatty acids across gestation in GDM and non-GDM women, placental fatty acids, resolvins and their association with the maternal fatty acid status. Pregnant women were recruited at 11-14 (V1) weeks and followed at 18-22 (V2) and 26-28 (V3) weeks and at delivery (V4). A total of 209 women who were diagnosed as GDM and 207 non-GDM women were included in this study. Fatty acids were estimated using gas chromatography. The protein levels of resolvins (RvE1, RvE2, RvD1 and RvD2) were measured using ELISA kits. Total PUFAs, eicosapentaenoic acid (EPA), omega-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were lower, while saturated fatty acid (SFA) and alpha-linolenic acid (ALA) levels were higher in GDM women at 18-22 weeks. Placental AA was lower (p < 0.05) in women with GDM. Placental protein levels of RvE1, RvD1 and RvD2 were lower (p < 0.001 for all) in the GDM group. The maternal delta 5 desaturase index was positively associated, while erythrocyte omega-3 and omega-6 fatty acids were negatively associated with RvE2 at 11-14 weeks. Placental LA and ALA were positively associated with RvD1 and RvD2 (p < 0.05, for both), respectively. Our findings suggest that the maternal fatty acid status influences pro-resolving mediators which may lead to increased inflammation in GDM.

MicroRNAs targeting peroxisome proliferator-activated receptor (PPAR) gene are differentially expressed in low birth weight placentae.

INTRODUCTION: Peroxisome proliferator-activated receptors (PPARs) are activated by natural ligands like fatty acids and influence placental angiogenesis and pregnancy outcome. However, the underlying molecular mechanisms are not clear. This study aims to investigate the association of maternal and placental fatty acid levels with DNA methylation and microRNA regulation of PPARs in the placentae of women delivering low birth weight (LBW) babies. METHODS: This study includes 100 women delivering normal birth weight (NBW) baby and 70 women delivering LBW baby. Maternal and placental fatty acids levels were estimated by gas chromatograph. Gene promoter methylation and mRNA expression of PPARs was analyzed using Epitect Methyl-II PCR assay kit and RT-PCR respectively. Expression of miRNAs targeting PPAR mRNA were analyzed using a Qiagen miRCURY LNA PCR Array on RT-PCR. RESULTS: Placental docosahexaenoic acid (DHA) levels and placental mRNA expression of PPARα and PPARγ were lower (p < 0.05 for all) in the LBW group. Differential expression of miRNAs (upregulated miR-33a-5p and miR-22-5p; downregulated miR-301a-5p, miR-518d-5p, miR-27b-5p, miR-106a-5p, miR-21-5p, miR-548d-5p, miR-17-5p and miR-20a-5p) (p < 0.05 for all) was observed in the LBW group. Maternal and placental polyunsaturated fatty acids and total omega-3 fatty acids were positively associated while saturated fatty acids were negatively associated with expression of miRNAs (p < 0.05 for all). Placental expression of miRNAs were positively associated with birth weight (p < 0.05 for all). DISCUSSION: Our data suggests that maternal fatty acid status is associated with changes in the placental expression of miRNAs targeting PPAR gene in women delivering LBW babies.

Maternal vitamin D deficiency reduces docosahexaenoic acid, placental growth factor and peroxisome proliferator activated receptor gamma levels in the pup brain in a rat model of preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy disorder characterized with abnormal placental angiogenesis. Vitamin D and long chain polyunsaturated fatty acids (LCPUFA) play a crucial role in pregnancy and are required for normal placental and fetal growth and development. This study reports the effect of maternal vitamin D on LCPUFA levels in the mother and offspring brain fatty acid levels and angiogenic markers in a rat model of preeclampsia. METHODS: Female rats were divided into four groups from pre-pregnancy to pregnancy, viz Control; Preeclampsia (PE); Vitamin D deficient with PE (VDD-PE) and Vitamin D supplemented with PE (VDS-PE). Preeclampsia was induced by administering l-nitroarginine methyl ester (L-NAME) at the dose of 50 mg/kg body weight/day from day 14 to day 19 of gestation. Dams were sacrificed at d20 of gestation to collect dam blood, placenta and pup brain. LCPUFA levels from dam plasma, erythrocytes and placenta and its transcription factor peroxisome proliferator activated receptor gamma (PPAR-g) from placenta were estimated. Pup brain LCPUFA levels, angiogenic factors vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) and transcription factor hypoxia inducible factor (Hif-1α) and PPAR-g were also estimated. RESULTS: Maternal vitamin D status influences fatty acid levels. Placental PPAR-g levels were lower in the VDD-PE group as compared to the VDS-PE groups (p < 0.01). In the offspring brain, both PE and VDD-PE group showed lower levels of DHA (p < 0.05 for both) while saturated fatty acids (SFA) levels in the VDD-PE group were higher as compared to the control group (p < 0.05). VDD-PE group also showed lower levels of PlGF and PPAR-g (p < 0.01 and p < 0.05, respectively) in the pup brain while vitamin D supplementation demonstrated levels similar to control. CONCLUSION: This study for the first time demonstrates that maternal vitamin D status influences LCPUFA metabolism and angiogenesis in the offspring brain.

Exploring the role of LC-PUFA metabolism in pregnancy complications.

Maternal nutrition during pregnancy plays a significant role in growth and development of the placenta and influencing pregnancy outcome. Suboptimal nutritional status during early gestational period compromises the normal course of pregnancy leading to adverse maternal and fetal outcomes. Omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFA) are important for the growth and development of the placenta. Maternal fatty acids and their metabolites influence the normal course of pregnancy by regulating cell growth and development, cell signaling, regulate angiogenesis, modulate inflammatory responses and influence various structural and functional processes. Alterations in LC-PUFA and their metabolites may result in inadequate spiral artery remodeling or placental angiogenesis leading to structural and functional deficiency of the placenta which contributes to several pregnancy complications like preeclampsia, gestational diabetes mellitus, intrauterine growth restriction, and results in adverse birth outcomes. In this review, we summarize studies examining the role of fatty acids and their metabolites in pregnancy. We also discuss the possible molecular mechanisms through which LC-PUFA influences placental growth and development. Studies have demonstrated that omega-3 fatty acid supplementation lowers the incidence of preterm births, but its effect on reducing pregnancy complications are inconclusive.

Prenatal vitamin D supplementation reduces blood pressure and improves placental angiogenesis in an animal model of preeclampsia.

BACKGROUND: Preeclampsia (PE), a pregnancy complication, is characterized by abnormal placental angiogenesis. The current study examines the effect of vitamin D deficiency/supplementation on pregnancy outcome and placental angiogenesis using an animal model of PE. METHODS: Pregnant Wistar rats were divided into four groups: Control; PE; Vitamin D deficient with PE (VDD-PE) and Vitamin D supplemented with PE (VDS-PE). PE was induced by administering l-nitroarginine methyl ester (l-NAME) at the dose of 50 mg per kg body weight per day from day 14 to day 19 gestation in all the 4 groups. During the pre-pregnancy and pregnancy period, the rats from the Control and PE groups were fed a control diet, the VDD-PE group received a vitamin D deficient diet and the VDS-PE group received a vitamin D supplemented diet. Dams were sacrificed at d20 of gestation. RESULTS: l-NAME administration increased systolic as well as diastolic blood pressure in both PE and VDD-PE groups as compared to the control (p < 0.01). Vitamin D supplementation was beneficial in reducing the blood pressure. Vitamin D deficiency also lowered the placental protein levels of pro-angiogenic proteins VEGF and Flt-1 (p < 0.05 and p < 0.01, respectively), while the levels of these proteins in the VDS-PE group were similar to those in the control group. Vitamin D status did not influence the levels of PlGF and Hif1α. CONCLUSION: A low dose vitamin D supplementation given from pre-pregnancy and throughout pregnancy was beneficial in reducing the blood pressure and normalizing the placental levels of VEGF and Flt-1. This has implications for reducing the severity of preeclampsia.

Role of neurotrophins in pregnancy and offspring brain development.

Neurotrophins are a family of functionally and structurally related proteins which play a key role in the survival, development, and function of neurons in both the central and peripheral nervous systems. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) are the family members of neurotrophins. Neurotrophins play a crucial role in influencing the development of the brain and learning and memory processes. Studies demonstrate that they also play crucial role in influencing reproductive and immune systems. Neurotrophins have been shown to influence various processes in the mother, placenta, and fetus during pregnancy. Development and maturation of feto-placental unit and the fetal growth trajectories are influenced by neurotrophins. In addition to neurotrophins, neuropeptides like neuropeptide Y also play a crucial role during various processes of pregnancy and during fetal brain development. Neurotrophins have also been shown to have a cross talk with various angiogenic factors and influence placental development. Alterations in the levels of neurotrophins and neuropeptides lead to placental pathologies resulting in various pregnancy complications like preeclampsia, intrauterine growth restriction and preterm births. Studies in animals have reported low levels of maternal micronutrients like folic acid, vitamin B12 and omega-3 fatty acids influence brain neurotrophins resulting in impaired cognitive functioning in the offspring. Maternal nutrition is also known to affect the expression of neuropeptides. It is essential to understand the role of various neurotrophins across various stages of pregnancy and its relationship with neurodevelopmental outcomes in children. This will lead to early prediction of poor neurodevelopmental outcomes. The present review describes evidence describing the role of neurotrophins in determining pregnancy outcome and altered neurodevelopment in the offspring. The possible mechanism through which maternal nutrition influences neurotrophins and neuropeptides to regulate offspring brain development and function is also discussed.

Omega-3 fatty acids differentially influences embryotoxicity in subtypes of preeclampsia.

Background: Early (EOP) and late onset (LOP) preeclampsia are two subtypes of preeclampsia. This study examines the effect of maternal omega-3 fatty acids and vitamin E supplementation in a rat model of preeclampsia.Method: Pregnant Wistar rats were assigned to control; EOP; LOP; EOP+omega-3 fatty acid supplementation+vitamin E and LOP+omega-3 fatty acid supplementation+vitamin E. L-Nitroarginine methylester was used to induce preeclampsia. Blood Pressure (BP) was recorded during pregnancy and dams were dissected at d14 and d20 of gestation.Results: Animals from EOP and LOP groups demonstrated higher systolic and diastolic BP, lower weight gain, lower conceptuses size, lower conceptuses weight and fetal weight as compared to control. EOP and LOP groups showed higher percentage of fetal resorptions and embryotoxicity (deformities and hematomas).Conclusion: Supplementation reduced the diastolic BP, percentage of resorptions and embryotoxicity only in the LOP group, suggesting a need for differential supplementation regime for the two subtypes of preeclampsia.

Effect of maternal omega-3 fatty acids and vitamin E supplementation on placental apoptotic markers in rat model of early and late onset preeclampsia.

AIM: Disturbed placentation results in pregnancy complications like preeclampsia. Placental development is influenced by apoptosis during trophoblast differentiation and proliferation. Increased oxidative stress upregulates placental apoptosis. We have earlier reported increased oxidative stress, lower omega-3 fatty acids and vitamin E levels in women with preeclampsia. Current study examines effect of maternal omega-3 fatty acids and vitamin E supplementation on apoptotic markers across gestation in a rat model of preeclampsia. MAIN METHODS: Pregnant Wistar rats were randomly assigned to control; early onset preeclampsia (EOP); late onset preeclampsia (LOP); early onset preeclampsia + omega-3 fatty acid + vitamin E supplementation (EOP + O + E) and late onset preeclampsia + omega-3 fatty acid + vitamin E supplementation (LOP + O + E) groups. Animals (Control, EOP, EOP + O + E) were sacrificed at d14 and d20 of gestation while animals (LOP, LOP + O + E) were sacrificed at d20 to collect blood and placentae. Protein and mRNA levels of apoptotic markers were analyzed by ELISA and RT-PCR respectively. KEY FINDINGS: Protein levels of proapoptotic markers like Bcl-2 associated X-protein (BAX) (p < 0.05), caspase-8 and 3 (p < 0.01 for both) and malondialdehyde (p < 0.01) were higher only in the EOP group as compared to control. However, the antiapoptotic marker, B cell lymphoma 2 (Bcl-2) protein levels were lower in both the subtypes of preeclampsia (p < 0.01 for both). SIGNIFICANCE: Our findings suggest that supplementation was beneficial in reducing the caspase-8 and 3 in early onset preeclampsia but did not normalize BAX and Bcl-2 levels. This has implications for reducing placental apoptosis in preeclampsia.

Maternal omega-3 fatty acids and vitamin E improve placental angiogenesis in late-onset but not early-onset preeclampsia.

Abnormal placental vasculature is associated with preeclampsia. Preeclampsia is of two types, i.e., early- and late-onset preeclampsia (LOP), both having different etiologies. We have earlier demonstrated low levels of omega-3 fatty acids and vitamin E in women with preeclampsia. The current study examines the effect of maternal omega-3 fatty acids and vitamin E supplementation on angiogenic factors in a rat model of preeclampsia. Pregnant rats were divided into a total of five groups control, early-onset preeclampsia (EOP); LOP; EOP supplemented with omega-3 fatty acid and vitamin E and LOP supplemented with omega-3 fatty acid and vitamin E. Preeclampsia was induced by administering L-nitroarginine methylester (L-NAME) at the dose of 50 mg/kg body weight/day. The vascular endothelial growth factor gene expression and protein levels were lower (p < 0.01 for both) in animals from both EOP as well as LOP groups (p < 0.01). In the EOP group, the protein levels of VEGF receptor-1 were also lower (p < 0.01). Supplementation of omega-3 fatty acids and vitamin E to LOP improved the levels of VEGF and VEGF receptor-1 only in the LOP but not in the EOP group. In the EOP group, the gene expression of hypoxia inducible factor 1 alpha (HIF-1α) in the placenta was higher (p < 0.05) and supplementation normalized these levels. Our findings indicate that maternal supplementation of omega-3 fatty acids and vitamin E has differential effect on preeclampsia subtypes.

Maternal dairy fat diet does not influence neurotrophin levels and cognitive performance in the rat offspring at adult age.

Cognitive development may be influenced by maternal nutrition especially fats. Indian population is vegetarian and main source of fat is dairy. This study investigates the effect of dairy fat consumption during pregnancy in an animal model on fatty acids, brain neurotrophins (brain derived neurotrophic factor: BDNF; and nerve growth factor: NGF) and cognitive performance in adult offspring. Pregnant Wistar rats were assigned to control (Control C) and four treatment groups: High fat diet (HFD); High fat diet supplemented with omega-3 fatty acids (HFDO); High fat diet deficient in vitamin B12 (HFBD); High fat deficient in vitamin B12 supplemented with omega-3 fatty acids (HFBDO). Half the dams were dissected on d20 of gestation, and the brains of their pups were collected. The remaining dams delivered on d22 of gestation and were assigned to a control diet. The cognitive performance of these adult offspring was assessed at 6 mo of age. Brain fatty acids were comparable to control in the pups at birth and offspring at 6 mo of age. The protein levels of BDNF in the pup brain at birth were lower in both the HFD (p < 0.01) and HFBD (p < 0.05) groups as compared to control. The mRNA levels of TrK B were lower (p < 0.05) in the pup brain at birth in the HFD as compared to control group. In the offspring at 6 mo of age the protein levels of BDNF and NGF in all the treatment groups were similar to that of control. However, the mRNA levels of only BDNF (p < 0.01 for both) were higher in the HFBD group as compared to both control and HFD groups. The cognitive performance of the adult offspring from various dietary groups was similar to control. In conclusion, consumption of a maternal high dairy fat diet although lowered the levels of brain BDNF in the pup at birth it does not affect the cognitive health of the adult offspring.

Effect of a daily snack containing green leafy vegetables on women's fatty acid status: a randomized controlled trial in Mumbai, India.

BACKGROUND AND OBJECTIVES: There are few data on the fatty acid status of non-pregnant Indian women. Our objective was to investigate the effect of a snack containing green leafy vegetables (GLVs) on women's erythrocyte long chain polyunsaturated fatty acid status (LCPUFA). METHODS AND STUDY DESIGN: Non-pregnant women (n=222) aged 14-35 years from Mumbai slums were randomized to consume a snack containing GLVs, fruit and milk (treatment) or a control snack containing foods of low micronutrient content such as potato and onion, daily under observation. One treatment snack contained a mean (SD) of 54.1 (33.7) mg alpha-linolenic acid (ALA) and one control snack contained 4.1 (3.4) mg ALA. Blood was collected at baseline (0 weeks) and after 12 weeks of supplementation. Erythrocyte fatty acids were analyzed using gas chromatography and expressed as g/100g fatty acids. Plasma malondialdehyde, homocysteine, and erythrocyte superoxide dismutase and glutathione peroxidase were measured. The effect of the treatment on 12 week LCPUFA was assessed using ANCOVA models. RESULTS: Median (IQR) erythrocyte DHA in the treatment group increased from 1.50 (1.11, 2.03) at baseline to 1.86 (1.50, 2.43) (p<0.001) at 12 weeks, and fell in controls from 1.78 (1.37, 2.32) to 1.60 (1.32, 2.04) (p<0.001). The total n-3 fatty acids increased in the treatment group. There was no effect on malondialdehyde and antioxidant enzyme levels. Plasma homocysteine at 0 and 12 weeks was inversely associated with erythrocyte DHA at 12 weeks. CONCLUSION: Daily consumption of a snack containing GLV improved women's erythrocyte DHA levels without increasing oxidative stress.

Increased intake of vitamin B12, folate, and omega-3 fatty acids to improve cognitive performance in offspring born to rats with induced hypertension during pregnancy.

Vitamin B12, folic acid, and docosahexaenoic acid levels are reported to be altered in women with preeclampsia. This study examined the effect of the above nutrients on brain neurotrophins and on the cognitive performance in adult offspring in a pregnancy-induced hypertension rat model. Pregnant dams were assigned to control, PIH-induced, and PIH-induced supplemented with vitamin B12, folate, omega-3 fatty acids, and the combined supplementation of vitamin B12, folate, and omega-3 fatty acids groups. In the PIH group, brain-derived neurotrophic factor levels (BDNF) were lower in the offspring at birth, while the adult offspring showed lower levels of docosahexaenoic acid (DHA) in the hippocampus and BDNF (p < 0.05 for both) in the cortex as compared to in the control group. They also demonstrated higher (p < 0.05) escape latency in the Morris water maze test and performed a greater (p < 0.01 for all) number of errors in the Radial eight-arm maze test. A combined supplementation of vitamin B12, folic acid, and omega-3 fatty acids improved the levels of LCPUFA, neurotrophins, and cognition. A maternal diet consisting of high levels of folate, vitamin B12, and DHA reduced the risk for cognitive disorders in the adult offspring in an animal model of pregnancy-induced hypertension.

Maternal Micronutrients, Omega-3 Fatty Acids and Gene Expression of Angiogenic and Inflammatory Markers in Pregnancy Induced Hypertension Rats.

BACKGROUND AND AIMS: Preeclampsia is a disorder of pregnancy and is associated with inflammation and altered angiogenesis. The present study examines the effect of micronutrient and omega-3 fatty acid supplementation (individual, as well as combined) on genes involved in inflammation and angiogenesis, as well as global DNA methylation levels in a pregnancy induced hypertension (PIH) rat model. METHODS: Pregnant Wistar rats were randomly assigned to six dietary groups: control, PIH (Pregnancy induced hypertension) Induced; PIH Induced with micronutrient supplements with vitamin B12 (PIHB), folate (PIHF), omega-3 fatty acid (PIHO), and combined supplementation (PIHC) (micronutrients and omega-3 fatty acids). Half the dams were dissected on 20 d of gestation to collect placental tissue, and half were allowed to deliver normally on 22 d of gestation and were assigned to a postnatal control diet. The offspring were dissected at 3 month of age. RESULTS: PIH induction increased the mRNA levels of the pro inflammatory cytokine IL-6 (p <0.01), while lowering the placental anti inflammatory cytokine IL-10 (p <0.05) at d20 of gestation. It also increased the expression of TNF-α (p <0.05) in the liver of 3 month old offspring. The combined supplementation of folic acid, vitamin B12 and omega-3 fatty acids improved placental IL-10 levels and decreased TNF-α levels in offspring livers. CONCLUSION: Our data indicate that a combined supplementation of vitamin B12, folic acid and omega-3 fatty acid was useful for the better management of preeclampsia in an animal model.

Maternal high fat diet deficient in vitamin B12 influences long chain polyunsaturated fatty acid composition in rats.

OBJECTIVE: In India, there is a rise in non-communicable diseases due to diets deficient in vitamin B12, low in docosahexaenoic acid (DHA) and increased consumption of westernized diet. The present study aims to examine the effect of maternal high fat diet (HFD) in absence of vitamin B12 on pregnancy outcome and tissue fatty acid composition in dams. METHODS: Pregnant Wistar rats were assigned to following diets: Control (C), HFD, High fat diet supplemented with omega-3 fatty acids (HFDO), 4) High fat diet deficient in vitamin B12 (HFBD), High fat deficient in vitamin B12 supplemented with omega-3 fatty acids (HFBDO). RESULTS: There was no effect on pregnancy outcome as a consequence of different dietary treatments. The levels of DHA in HFBD group were lower (p < 0.05 for both) in placenta as compared to both control and HFD groups, which were improved by omega-3 fatty acid supplementation. CONCLUSION: This data suggests that maternal HFD (using dairy fat) did not adversely affect pregnancy outcome. However, maternal HFBD reduced levels of placental DHA. This may have implications for reduced fetal brain growth and development.

Vitamin B12 Deficiency Across Three Generations Adversely Influences Long-chain Polyunsaturated Fatty Acid Status and Cardiometabolic Markers in Rats.

BACKGROUND AND AIMS: Vitamin B12 and omega-3 fatty acid deficiency is prevalent in the vegetarian population and is associated with adverse pregnancy outcomes and cardiometabolic risk. The present study investigates the long-term effects of vitamin B12 deficiency/supplementation in the presence of omega-3 fatty acids on cardiometabolic profile and long-chain polyunsaturated fatty acid levels (LCPUFA) in the F3 generation offspring. METHODS: Three generations of rats were fed the following diets: control; vitamin B12 deficient; vitamin B12 supplemented; vitamin B12 deficient + omega-3 fatty acid supplemented; vitamin B12 + omega-3 fatty acid supplemented. Animals were sacrificed at 3 months of age. RESULTS: Vitamin B12 deficiency lowered (p <0.01 for both) plasma eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), liver DHA (p <0.05), plasma/liver omega-3 fatty acids (p <0.05 for both), increased triglycerides (p <0.05) and systolic BP (p <0.01) and lowered cholesterol levels (p <0.05) as compared to control. Vitamin B12 deficiency in the presence of omega-3 fatty acids improved plasma/liver EPA, DHA and omega-3 fatty acid profile and maintained cholesterol, triglyceride and BP levels. Vitamin B12 supplementation lowered liver DHA (p <0.05) and cholesterol (p <0.01), whereas BP was similar to control. Combined supplementation of vitamin B12 and omega-3 fatty acids improved omega-3 fatty acid profile, lowered cholesterol/triglyceride levels and maintained the BP similar to that of control. CONCLUSION: Vitamin B12 deficiency across three generations adversely affects LCPUFA and cardiometabolic profile in the adult offspring. This study provides clues for a combined supplementation of vitamin B12 and omega-3 fatty acids to reduce the risk for noncommunicable diseases.

A combined supplementation of vitamin B12 and n-3 polyunsaturated fatty acids across two generations improves nerve growth factor and vascular endothelial growth factor levels in the rat hippocampus.

Vitamin B12 and n-3 polyunsaturated fatty acid (n-3 PUFA) are known to influence cognition. This study aims to examine if these nutrients affect the protein levels and gene expression of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) in the cortex and hippocampus in the second-generation offspring at 3 mo of age. Wistar rats were fed the following diets for two generations: Control (CON), vitamin B12 deficient (VBD), vitamin B12 deficient supplemented with n-3 PUFA (VBDO), vitamin B12 supplemented (VBS), vitamin B12 supplemented with n-3 PUFA (VBSO). The VEGF and NGF gene expression and protein levels in the hippocampus were lower (P⩽0.01) in the VBD group as compared to the CON group while the VBDO group restored the VEGF and NGF gene expression (P⩽0.01). The VBS group showed similar levels of NGF and VEGF to that of the CON group. However, the VBSO group demonstrated higher (P⩽0.05) NGF gene expression and protein levels in the hippocampus and higher cortex NGF protein levels as compared to the CON group. In addition, VEGF (in hippocampus) and NGF (in cortex and hippocampus) protein levels were also higher (P⩽0.05) in the VBSO group as compared to the VBS group. Our results indicate that the combined supplementation of vitamin B12 and n-3 PUFA improves NGF and maintains VEGF levels in the brain which may improve neurovascular function.

A combined supplementation of vitamin B12 and omega-3 fatty acids across two generations improves cardiometabolic variables in rats.

Our earlier studies indicate that micronutrients (vitamin B12, folic acid) and omega-3 fatty acids especially docosahexaenoic acid (DHA) are interlinked in one carbon cycle. The present study examines the effects of a sustained vitamin B12 deficiency/supplementation in the presence of omega-3 fatty acids across two generations on the pregnancy outcome and cardiometabolic profile [blood pressure, plasma lipid profile (cholesterol and triglycerides), plasma/liver fatty acid profile and hepatic lipid metabolism] in the second generation adult Wistar rat offspring. Two generations of animals were fed the following diets: control; vitamin B12 deficient; vitamin B12 supplemented; vitamin B12 deficient diet supplemented with omega-3 fatty acids; vitamin B12 and omega-3 fatty acid supplemented diets. Male offspring were sacrificed at 3 months of age. Vitamin B12 deficiency lowered the weight gain (p < 0.01) during pregnancy, increased systolic (p < 0.05) and diastolic (p < 0.01) blood pressure, and lowered the levels of plasma/liver DHA (p < 0.05 for both) but did not affect the lipid profile. Vitamin B12 supplementation showed weight gain, blood pressure and the fatty acid profile similar to the control. However, it increased (p < 0.05) the levels of plasma triglycerides. Omega-3 fatty acid supplementation to the vitamin B12 deficient group lowered the weight gain although the levels of cardiometabolic variables were comparable to the control. Omega-3 fatty acid supplementation in the presence of vitamin B12 improved the pregnancy outcome and all cardio-metabolic variables. Our study highlights the adverse effects of sustained vitamin B12 deficiency across two generations on the pregnancy outcome, fatty acid profile and blood pressure while a combined supplementation of vitamin B12 and omega-3 fatty acids is beneficial.

Effect of vitamin B12 and omega-3 fatty acid supplementation on brain neurotrophins and cognition in rats: A multigeneration study.

Vitamin B12 and omega-3 fatty acids are important nutrients required for neuronal functioning. We have demonstrated the beneficial effects of vitamin B12 and omega-3 fatty acid supplementation on brain neurotrophins and cognition in the first and second generation offspring. However, there is a need to examine if the effects are sustained in the third generation offspring. This study reports the effects of vitamin B12 and omega-3 fatty acid supplementation across three consecutive generations on brain neurotrophins like brain derived neurotrophic factor (BDNF); nerve growth factor (NGF) and cognitive performance in the third generation male offspring. Three successive generations of Wistar rats were assigned the following groups throughout pregnancy, lactation and adulthood: i) Control, ii) vitamin B12 deficient (BD), iii) vitamin B12 deficient + omega-3 fatty acid (BDO), iv) vitamin B12 supplemented (BS) and v) vitamin B12 supplemented + omega-3 fatty acid (BSO). The BD group demonstrated lower (p < 0.01) NGF in the cortex but not BDNF levels although the cognition was impaired (p < 0.01). In contrast, in the BDO group, higher NGF levels were observed in the hippocampus and animals demonstrated improved (p < 0.01) cognitive performance. Vitamin B12 supplementation showed comparable BDNF levels in the hippocampus while their levels were lower in the cortex as compared to the control (p < 0.05). These animals showed more reference and working memory errors (p < 0.01) as compared to the control group. A combined supplementation of vitamin B12 and omega-3 fatty acid showed higher (p < 0.01) levels of DHA and NGF in the hippocampus, higher BDNF in both hippocampus and cortex and improved cognitive performance. Our findings have implications for fortification of foods with vitamin B12 and omega-3 fatty acids in improving brain development.

Maternal Fatty Acids and Their Association with Birth Outcome: A Prospective Study.

Maternal nutrition, especially LCPUFA, is an important factor in determining fetal growth and development. Our earlier cross sectional study reports lower docosahexanoic acid (DHA) levels at the time of delivery in mothers delivering low birth weight (LBW) babies. This study was undertaken to examine the role of the maternal omega-3 and omega-6 fatty acid profile across the gestation in fetal growth. This is a hospital based study where women were recruited in early gestation. Maternal blood was collected at 3 time points, i.e., T1 = 16th-20th week, T2 = 26th-30th week and T3 = at delivery. Cord blood was collected at delivery. At delivery, these women were divided into 2 groups: those delivering at term a baby weighing >2.5kg [Normal birth weight (NBW) group] and those delivering at term a baby weighing <2.5kg [LBW group]. The study reports data on 111 women recruited at T1, out of which 60 women delivered an NBW baby at term and 51 women delivered an LBW baby at term. Fatty acids were analysed using gas chromatography. At T1 of gestation, maternal erythrocyte DHA levels were positively (p<0.05) associated with baby weight. Maternal plasma and erythrocyte arachidonic acid and total erythrocyte omega-6 fatty acid levels at T2 were higher (p<0.05 for both) in the LBW group. Total erythrocyte omega-3 fatty acid levels were lower (p<0.05) while total erythrocyte omega-6 fatty acid levels were higher (p<0.05) in the LBW group at delivery. Our data demonstrates the possible role of LCPUFA in the etiology of LBW babies right from early pregnancy.

Novel insights into the effect of vitamin B12 and omega-3 fatty acids on brain function.

The prevalence of psychiatric disorders which are characterized by cognitive decline is increasing at an alarming rate and account for a significant proportion of the global disease burden. Evidences from human and animal studies indicate that neurocognitive development is influenced by various environmental factors including nutrition. It has been established that nutrition affects the brain throughout life. However, the mechanisms through which nutrition modulates mental health are still not well understood. It has been suggested that the deficiencies of both vitamin B12 and omega-3 fatty acids can have adverse effects on cognition and synaptic plasticity. Studies indicate a need for supplementation of vitamin B12 and omega-3 fatty acids to reduce the risk of cognitive decline, although the results of intervention trials using these nutrients in isolation are inconclusive. In the present article, we provide an overview of vitamin B12 and omega-3 fatty acids, the possible mechanisms and the evidences through which vitamin B12 and omega-3 fatty acids modulate mental health and cognition. Understanding the role of vitamin B12 and omega-3 fatty acids on brain functioning may provide important clues to prevent early cognitive deficits and later neurobehavioral disorders.