Publications by authors named "Michelle M Murphy"

Article Synopsis
  • Elevated levels of fasting plasma total homocysteine (tHcy) and a specific genetic variant (methylenetetrahydrofolate reductase C677T polymorphism) are linked to hypertension, but the role of the l-Arginine pathway was previously unclear.
  • A study involving 788 adults found that higher tHcy levels were positively related to two metabolites (ADMA and SDMA) and negatively associated with the l-Arginine/ADMA ratio, indicating a potential protective effect against hypertension.
  • The analysis suggested that both tHcy and ADMA play intermediary roles in how the genetic variant affects hypertension risk, highlighting the importance of the l-Arginine pathway in this relationship.
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Article Synopsis
  • * As the global population ages, health systems are increasingly burdened by treating chronic diseases instead of focusing on prevention, highlighting the need for early life research.
  • * Various studies from around the world indicate a link between maternal diet and lifestyle during pregnancy and the metabolic health of children, but more research is necessary to strengthen these findings.
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Background: Although some studies have investigated the relationships between beverage intake and reproductive health these have generated conflicting results.

Objectives: To evaluate the associations between men's beverage intake and semen quality parameters and couple outcomes of medically assisted reproduction.

Material And Methods: The relationship between preconception beverage intake and semen quality was evaluated in 896 semen samples from 343 men.

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Background: Folate and cobalamin status, although essential for pregnancy, are not routinely monitored in prenatal care.

Objectives: To investigate folate and cobalamin status and determinants throughout pregnancy, in the absence of mandatory folic acid (FA) fortification.

Methods: In a cohort study of 831 mothers recruited at <12 gestational weeks (GW), plasma folate, total homocysteine (tHcy), cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), red blood cell folate (RBCF), and the combined cobalamin status indicator (cB12) were determined at ≤12, 15, 24-27, 34 GW, labor and in the cord.

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Background: Little attention has been given to prenatal cobalamin insufficiency in settings where dietary cobalamin intake is presumed adequate, such as populations with habitual intake of foods from animal sources.

Results: However, low cobalamin status in women of fertile age has been reported in Europe, United States, and Canada. In India, where cobalamin deficiency is highly prevalent, it has been associated with an increased risk of miscarriage, intrauterine growth retardation, as well as insulin resistance and lower neurodevelopment scores in the offspring.

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Study Question: Is ultra-processed food (UPF) consumption associated with semen quality parameters?

Summary Answer: Higher UPF consumption was inversely associated with total sperm count, sperm concentration, and total motility in men of reproductive age.

What Is Known Already: The consumption of UPF, which has been rising during the last decades, has been demonstrated to be positively associated with several chronic diseases such as diabetes or cardiovascular diseases. However, the scientific evidence on its potential impact on semen quality remains notably limited.

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A functional role has been ascribed to the human dihydrofolate reductase 2 (DHFR2) gene based on the enzymatic activity of recombinant versions of the predicted translated protein. However, the in vivo function is still unclear. The high amino acid sequence identity (92%) between DHFR2 and its parental homolog, DHFR, makes analysis of the endogenous protein challenging.

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Background: Telomeres are essential for the integrity of chromosome ends during cell division and their involvement in different processes linked to aging has been established. These chromosome components are involved in spermatogenesis and seem to play an important role in fertilization and embryo development. Telomere length is shortened with each cell division.

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Background: Inadequate pregnancy cobalamin status has been associated with adverse offspring metabolic health in Indian and Nepalese studies. Studies of pregnancy cobalamin status and mid-childhood health outside of Asia are scarce.

Methods: Associations between pregnancy fasting plasma total homocysteine (tHcy), cobalamin status (plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA)) and mid-childhood metabolic score (MetSco) ((including fat mass index (zFMI), homeostatic model assessment of insulin resistance (zHOMA-IR) and dyslipidemia (zTG - zHDLc)/2) z-scores)) were investigated in a prospective study of 293 mother-child dyads.

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Introduction And Objectives: Quantification of cardiovascular risk has been based on scores such as Framingham, Framingham-REGICOR, SCORE or Life's Simple 7 (LS7). In vitro, animal, and randomized clinical studies have shown that polyphenols may provide benefits to the vascular system and reduce the inflammatory response. However, some clinical-epidemiological studies have yielded inconsistent results.

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Evidence linking fasting plasma total homocysteine (tHcy) and methylenetetrahydrofolate reductase () 677C>T genotype with hypertension is inconsistent. Differences in B vitamin status, other lifestyle factors or their consideration in analyses might explain this. We investigated these associations in the absence of mandatory fortification with folic acid and B vitamin supplement use.

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The association between elevated early pregnancy fasting plasma total homocysteine (tHcy) and miscarriage risk was investigated prospectively in participants (n = 544) from the Reus-Tarragona Birth Cohort study. Pregnancy was confirmed before 12 gestational weeks (GW) by ultrasound scan and a fasting blood sample collected. Pregnancies with complications other than miscarriages were excluded.

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Background: Periconception folic acid supplementation is widespread, but how it interacts with cobalamin status is rarely considered.

Objective: The aim of this study was to investigate whether first-trimester folate-cobalamin interactions affect pregnancy cobalamin status, hematologic variables, and pregnancy outcomes.

Design: In the longitudinal Reus-Tarragona Birth Cohort study from <12 gestational weeks throughout pregnancy, fasting plasma and red blood cell (RBC) folate, plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), total homocysteine (tHcy), hemoglobin, mean cell volume (MCV), postglucose-load serum glucose, gestational hypertension, gestational age at birth, and birth weight were recorded in 563 participants.

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Unlabelled: The effect of the betaine: homocysteine methyltransferase BHMT c.716G>A (G: guanosine; A: adenosine) single nucleotide polymorphism (SNP) on the BHMT pathway is unknown during pregnancy. We hypothesised that it impairs betaine to dimethylglycine conversion and that folate status modifies its effect.

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The central nervous system continues to develop during gestation and after birth, and folate is an essential nutrient in this process. Folate deficiency and folate receptor alpha autoantibodies (FRα-AuAb) have been associated with pregnancy-related complications and neurodevelopmental disorders. In this pilot study, we investigated the effect of exposure to FRα antibodies (Ab) during gestation (GST), the pre-weaning (PRW), and the post weaning (POW) periods on learning and behavior in adulthood in a rat model.

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Prenatal methyl donor deficiency leads to homocysteine accumulation in the brain and impaired neurodevelopment in rats. We investigated the effect of moderately elevated preconception fasting total plasma homocysteine (tHcy) on child neurodevelopment in a prospective study of 67 and 76 mother-child pairs at 4 months and 6 years of age, respectively. Fasting blood samples at 2-10 weeks preconception, from the cord (nonfasting) and the mother and child 6 years after birth, were collected.

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Periconception supplementation with folic acid is recommended until 12 gestational weeks to prevent neural tube defects. Doses of folic acid contained in supplements and timing and length of use during pregnancy vary. The effects of status in periconception and pregnancy folate, cobalamin, betaine and their interactions on one carbon metabolism (1C), as well as the global effect of 1C on foetal growth and pregnancy outcome, are reviewed.

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Background: Although combinations of biologically relevant polymorphic variants affect folate status, most studies have focused on the effects of individual polymorphisms; however, these effects may be altered by interactions between polymorphisms.

Objective: We investigated the individual and combined effects of polymorphisms that affect folate transport or metabolism on folate status.

Methods: The associations between the methylenetetrahydrofolate reductase (MTHFR) 677C > T, methionine transferase reductase (MTRR) 66A > G, MTRR 524C > T, 5,10-methylenetetrahydrofolate dehydrogenase-5,10-methylenetetrahydrofolate cyclohydrolase-10-formyltetrahydrofolate synthetase (MTHFD1) 1958G > A, MTHFD1 -105C > T, dihydrofolate reductase (DHFR) 19-bp insertion/deletion, and solute carrier family 19A, member 1 (SLC19A1) 80G > A polymorphisms and fasting plasma folate (PF), red cell folate (RCF), and plasma total homocysteine (tHcy) were tested by ANCOVA and Cox regression analysis in 781 Spanish adults.

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Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), riboflavin-dependent enzymes, participate in homocysteine metabolism. Reported effects of riboflavin status on the association between the MTHFR 677C>T polymorphism and homocysteine vary, and the effects of the MTRR 66A>G or MTRR 524C>T polymorphisms on homocysteine are unclear. We tested the hypothesis that the effects of the MTHFR 677C>T, MTRR 66A>G and MTRR 524C>T polymorphisms on fasting plasma total homocysteine (tHcy) depend on riboflavin status (erythrocyte glutathionine reductase activation coefficient, optimum: <1.

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Folate is essential for fetal development, and its deficiency during gestation causes behavioural deficits in the offspring. The present study investigated its influence during weaning on brain function in the pups of rats that were put on a folate-deficient (FD) diet on postnatal day (PND) 1. Systemic folate deficiency in pups on the FD diet (n 15) was evident from the dramatically lower hepatic folate concentrations (median 23·7, range 8·1-48·4 ng/mg protein) and higher homocysteine concentrations (median 27·7, range 14·7-45·5 pmol/mg protein), respectively, compared with those of pups on the normal diet (ND; n 9) (median 114·5, range 64·5-158·5 ng/mg protein and median 15·5, range 11·6-18·9 pmol/mg protein) on PND 23.

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Background: Folate, choline, and betaine participate in homocysteine metabolism. It is not known whether they interact during pregnancy.

Objective: The objective was to investigate how folate status affects choline, betaine, and dimethylglycine during pregnancy.

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Background: DNA methylation is an epigenetic phenomenon that can modulate gene function by up or downregulation of gene expression. Vitamin B12 and folate pathways are involved in the production of S-Adenosylmethionine, the universal methyl donor.

Findings: Brain vitamin B12 concentration and global DNA methylation was determined in transcobalamin receptor (TCblR/CD320) knock out (KO) (n = 4) and control mice (n = 4) at 20-24 weeks of age.

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The aim of this review is to evaluate the evidence for and against fasting plasma total homocysteine (tHcy) as a biomarker/risk factor of impaired reproductive function before and during pregnancy. Apart from nutritional and lifestyle factors, tHcy is also influenced by physiological factors specific to pregnancy such as hemodilution, increased glomerular filtration rate, and endocrinological changes. These lead to a considerable reduction under normal circumstances in tHcy by midpregnancy.

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Cobalamin deficiency can lead to several adverse health consequences: folate trapping in the methylation cycle and subsequent impaired DNA biosynthesis; pernicious anemia hematologically, similar to that caused by folate deficiency; elevated blood homocysteine (tHcy) (risk factor for cardiovascular disease and adverse pregnancy outcomes); and neural tube defects (NTDs). Population-wide folate status is expected to improve where folic acid fortification policies for reducing NTD occurrence are established. However, there is concern that cobalamin deficiency and its characteristic neuropathy could be masked when hematological abnormalities in risk groups such as the elderly and vegetarians are reversed through folic acid supplementation.

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