Amanda J MacFarlane's research while affiliated with Ocean Nutrition Canada and other places

Publications (99)

Article
Background: Achieving optimal folate status during early gestation reduces risk of neural tube defects (NTD). While inadequate folate intake remains a concern, it is becoming increasingly common for individuals to consume higher than recommended doses of folic acid (FA) with minimal additional benefit. Objective: Here, we sought to investigate t...
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Persistent organic pollutants (POPs) are ubiquitous in the environment, which is of concern since they are broadly toxic for wildlife and human health. It is generally accepted that maternal prenatal folic acid supplementation (FA) may beneficially impact offspring development, but it has been recently shown that the father's exposures also influen...
Article
National health and nutrition monitoring is an important federal effort in the U.S. and Canada, and the basis for many of their nutrition and health policies. Understanding of child exposures through human milk (HM) remains out of reach due to lack of current and representative data on its composition and intake volume. This paper provides an overv...
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Gestational arsenic exposure adversely impacts child health. Folate-mediated 1-carbon metabolism facilitates urinary excretion of arsenic and may prevent arsenic-related adverse health outcomes. We investigated the potential for maternal folate status to modify associations between gestational arsenic exposure and child health. We used data from 36...
Preprint
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Background The persistent organochlorine dichlorodiphenyltrichloroethane (DDT) is banned world-wide due to its negative health effects and persistence in the environment. It is exceptionally used as an insecticide for malaria control. Exposure occurs in regions where DDT is applied, as well as in the arctic where it’s endocrine disrupting metabolit...
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Transparent reporting of nutrition research promotes rigor, reproducibility and relevance to human nutrition. We performed a scoping review of recent articles reporting dietary folate interventions in mice as a case study to determine the reporting frequency of generic study design items (i.e. sex, strain and age) and nutrition-specific items (i.e....
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Fetal and child development are shaped by early life exposures, including maternal health states, nutrition and educational and home environments. We aimed to determine if suboptimal pre-pregnancy maternal body mass index (BMI; underweight, overweight, obese) would associate with poorer cognitive outcomes in children, and whether early life nutriti...
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Folate and choline are interconnected metabolically. The MTHFD1 R653Q SNP is a risk factor for birth defects and there are concerns that choline deficiency may interact with this SNP and exacerbate health risks. 80–90% of women do not meet the Adequate Intake (AI) for choline. The objective of this study was to assess the effects of choline deficie...
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Background Dietary exposure assessments are a critical issue in evaluating human nutrition studies; however, nutrition-specific criteria are not consistently included in existing bias assessment tools. Objective Our objective was to develop a set of Risk of Bias (RoB) tools that integrated nutrition-specific criteria into validated generic assessm...
Article
Two questions regarding the scientific literature have become grist for public discussion: 1) what place should P values have in reporting the results of studies? 2) How should the perceived difficulty in replicating the results reported in published studies be addressed? We consider these questions to be 2 sides of the same coin; failing to addres...
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Given the challenges with nutrition research, the Canadian Nutrition Society and Intertek Health Sciences Inc held an expert consultation in late 2019 to discuss the development and implementation of best practices for clinical trials on whole foods. Key challenges in the design, interpretation, and reporting of clinical efficacy studies on whole f...
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Background: Periconceptional folic acid (FA) supplementation is recommended to prevent neural tube defects; however, the extent to which recommendations are met through dietary sources and supplements is not clear. Objectives: Our objective was to evaluate the dietary and supplemental intakes of FA in a Canadian pregnancy cohort and to determine...
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Exposure to persistent organic pollutants (POPs) is associated with insulin resistance while folic acid (FA) may offer a protective effect. However, the paternal contribution to metabolic phenotypes in offspring is not well known yet. Hence, we investigated whether maternal exposure to POPs affects glucose homeostasis and whether maternal FA supple...
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Background While cancer is common, its incidence varies widely by tissue. These differences are attributable to variable risk factors, such as environmental exposure, genetic inheritance, and lifetime number of stem cell divisions in a tissue. Folate deficiency is generally associated with increased risk for colorectal cancer (CRC) and acute lympho...
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Background: Periconceptional folic acid (FA) supplementation is recommended to prevent the occurrence of neural tube defects. Currently, most over-the-counter FA supplements in Canada and the United States contain 1 mg FA and some women are prescribed 5 mg FA/d. High-dose FA is hypothesized to impair 1-carbon metabolism. We aimed to determine fola...
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Given the focus on developing Dietary Reference Intakes (DRIs) based on chronic disease risk reduction and recent research for omega-3 long chain PUFA since the last DRI review, the Canadian Nutrition Society convened a panel of stakeholders for a 1-day workshop in late 2019. Attendees discussed the new NASEM guidelines for establishing DRI values...
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BACKGROUND: The etiology of autism spectrum disorder is poorly understood. Few studies have investigated the link between endocrine-disrupting chemicals and autistic traits. We examined the relationship between gestational phthalates and autistic traits in 3-to 4-y-old Canadian children. We also investigated potential effect modification by sex and...
Article
Folate, an essential nutrient found naturally in foods in a reduced form, is present in dietary supplements and fortified foods in an oxidized synthetic form (folic acid). There is widespread agreement that maintaining adequate folate status is critical to prevent diseases due to folate inadequacy (e.g., anemia, birth defects, and cancer). However,...
Preprint
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Cancer incidence varies by tissue due to differences in environmental risk factor exposure, gene variant inheritance, and lifetime number of stem cell divisions in a tissue. Folate deficiency is associated with increased risk for colorectal cancer (CRC) and acute lymphocytic leukemia. Conversely, high folic acid (FA) intake has been associated with...
Article
It is well established that maternal age is associated with a rapid decline in the production of healthy and high-quality oocytes resulting in reduced fertility in women older than 35 years of age. In particular, chromosome segregation errors during meiotic divisions are increasingly common and lead to the production of oocytes with an incorrect nu...
Article
Objectives To develop and validate a set of 3 quality assessment instruments (QAls) for evaluating the quality of nutrition studies, for each of the commonly used study designs: (1) randomized controlled trials (RCTs), (2) prospective cohort, and (3) case-control studies. Methods The QAI development and validation process included 8 steps: 1) iden...
Article
Objective Observational studies have linked elevated homocysteine to vascular conditions. Folate intake has been associated with lower homocysteine concentration, although randomised controlled trials of folic acid supplementation to decrease the incidence of vascular conditions have been inconclusive. We investigated determinants of maternal homoc...
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Background: The etiology of autism spectrum disorder is poorly understood. Few studies have investigated the link between endocrine-disrupting chemicals and autistic traits. We examined the relationship between gestational phthalates and autistic traits in 3- to 4-y-old Canadian children. We also investigated potential effect modification by sex a...
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Persistent organic pollutants (POPs) can induce epigenetic changes in the paternal germline. Here, we report that folic acid (FA) supplementation mitigates sperm miRNA profiles transgenerationally following in utero paternal exposure to POPs in a rat model. Pregnant founder dams were exposed to an environmentally relevant POPs mixture (or corn oil)...
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The paternal environment is thought to influence sperm quality and future progeny may also be impacted. We hypothesized that prenatal exposure to environmentally-relevant contaminants impairs male reproduction, altering embryo gene expression over multiple generations. Folic acid (FA) can improve sperm quality and pregnancy outcomes, thus we furthe...
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Prenatal exposure to persistent organic pollutants (POPs) has been associated with the development of metabolic syndrome-related diseases in offspring. According to epidemiological studies, father’s transmission of environmental effects in addition to mother’s can influence offspring health. Moreover, maternal prenatal dietary folic acid (FA) may b...
Preprint
Maternal malnutrition and micronutrient deficiencies can alter fetal development. However, the mechanisms underlying these relationships are poorly understood. A systems-approach was used to investigate the effects of malnutrition on maternal gut microbes and folate/inositol transport in the maternal/fetal gut and placenta. Female mice were fed a c...
Article
Background: Maternal nutrition and genetics are determinants of breast-milk nutrient composition and, as such, are determinants of the nutritional exposure of breastfed infants. Objectives: The aim of this study was to determine whether common maternal single nucleotide polymorphisms (SNPs) in folate-dependent enzymes are associated with breast-...
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Background: Homocysteine is an intermediate metabolite implicated in the risk of placenta-mediated complications, including preeclampsia, placental abruption, fetal growth restriction, and pregnancy loss. Large cohort and case-control studies have reported inconsistent associations between homocysteine and these complications. The purpose of this...
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The governments of the United States and Canada have jointly undertaken the development of the Dietary Reference Intakes (DRIs) since the mid-1990s. The Federal DRI committees from each country work collaboratively to identify DRI needs, prioritize nutrient reviews, advance work to resolve methodological issues that is necessary for new reviews, an...
Article
Background Despite a substantial prevention of neural tube defects with mandatory folic acid (FA) fortification, a significant number of cases still exist in Alberta, Canada, particularly spina bifida (SB). The purpose of this study was to review cases with SB to provide a possible explanation as to why SB is still prevalent in Alberta. Methods Ca...
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The Government of Canada and the Society of Obstetricians and Gynaecologists of Canada both recommend a daily multivitamin supplement containing 400 µg folic acid (FA) for the primary prevention of neural tube defects among low-risk women from before conception and throughout lactation. Prenatal supplements marketed and prescribed in Canada typical...
Article
Folate deficiency causes megaloblastic anemia and neural tube defects, and is also associated with some cancers. In vitro, folate deficiency increases mutation frequency and genome instability, as well as exacerbates the mutagenic potential of known environmental mutagens. Conversely, it remains unclear whether or not elevated folic acid (FA) intak...
Article
Study question: Do paternal exposures to folic acid deficient (FD), and/or folic acid supplemented (FS) diets, throughout germ cell development adversely affect male germ cells and consequently offspring health outcomes? Summary answer: Male mice exposed over their lifetimes to both FD and FS diets showed decreased sperm counts and altered impri...
Article
Folates are B-vitamins that play an important role in brain function. Dietary and genetic deficiencies in folate metabolism result in elevated levels of homocysteine which have been linked to increased risk of developing a stroke. Reducing levels of homocysteine before or after a stroke through B-vitamin supplementation has been a focus of many cli...
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Background: Folate requirements increase during pregnancy and lactation. It is recommended that women who could become pregnant, are pregnant, or are lactating consume a folic acid (FA)–containing supplement. Objectives: We sought to determine breast-milk total folate and unmetabolized folic acid (UMFA) contents and their relation with FA-supplemen...
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Dietary Reference Intakes (DRIs) are used in Canada and the United States in planning and assessing diets of apparently healthy individuals and population groups. The approaches used to establish DRIs on the basis of classical nutrient deficiencies and/or toxicities have worked well. However, it has proved to be more challenging to base DRI values...
Article
The common R653Q variant (∼20% homozygosity in Caucasians) in the synthetase domain of the folate-metabolizing enzyme MTHFD1 reduces purine synthesis. Although this variant does not appear to affect risk for colorectal cancer, we questioned whether it would affect growth of colorectal tumors. We induced tumor formation in a mouse model for MTHFD1-s...
Article
Objective To examine the association between BMI and folate concentrations in serum and red blood cells (RBC) in pregnant women. Design A cross-sectional comparison of folate concentrations in serum and RBC sampled simultaneously from the same individual. Setting The Ottawa Hospital and Kingston General Hospital, Ontario, Canada. Subjects Pregna...
Article
Introduction: The combined intake of folic acid (FA) from prenatal multivitamin supplements and fortified foods can result in FA intake values that exceed the tolerable upper intake level (UL). It is unclear what impact FA intake above the UL may have on the feto-placental unit. Our objective was to determine the effects of increasing concentratio...
Article
Background: Mandatory folic acid fortification of white-wheat flour and selected other grain products has reduced the prevalence of neural tube defects in Canada; however, the fortification of whole-wheat flour is not permitted. Objective: The objective of this study was to model the impact of adding folic acid to whole-wheat flour on the folate...
Article
Objective: Prenatal folic acid supplementation or maternal folate sufficiency may protect the offspring from obesity and insulin resistance. This study aims to summarize the findings of association between prenatal folic acid supplementation/maternal folate sufficiency and obesity/insulin resistance in the offspring. Methods: Twelve databases we...
Article
Objective: To provide updated information on the pre- and post-conception use of oral folic acid with or without a multivitamin/micronutrient supplement for the prevention of neural tube defects and other congenital anomalies. This will help physicians, midwives, nurses, and other health care workers to assist in the education of women about the p...
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Dietary folate is a major source of methyl groups required for DNA methylation, an epigenetic modification that is actively maintained and remodelled during spermatogenesis. While high dose folic acid supplementation (up to ten times the daily recommended dose) has been shown to improve sperm parameters in infertile men, the effects of supplementat...
Article
Folate is an essential B vitamin required for de novo purine and thymidylate synthesis, and for the remethylation of homocysteine to form methionine. Folate deficiency has been associated with placenta-related pregnancy complications, as have SNP in genes of the folate-dependent enzymes, methionine synthase (MTR) and methylenetetrahydrofolate dehyd...
Article
Immunoregulatory and regenerative processes are activated in the pancreas during development of type 1 diabetes (T1D) but are insufficient to prevent the disease. We hypothesized that induction of cytoprotective heme oxygenase-1 (HO-1) by cobalt protophoryrin (CoPP) would prevent T1D by promoting anti-inflammatory and pro-repair processes. Diabetes...
Article
Folate is an essential B vitamin required for the de novo synthesis of purines, thymidylate and methionine. Folate deficiency can lead to mutations and genome instability, and has been shown to exacerbate the genotoxic potential of environmental toxins. We hypothesized that a folic acid (FA) deficient diet would induce genotoxicity in mice as measu...
Article
Rèsumé Objectif Offrir des renseignements à jour sur l’utilisation pré et postconceptionnelle d’acide folique par voie orale, avec ou sans supplément de multivitamines / micronutriments, aux fins de la prévention des anomalies du tube neural et d’autres anomalies congénitales. Ces renseignements aideront les médecins, les sages-femmes, les infirmi...
Article
Genetic variation can cause variable responses to environmental stimuli. A number of single-nucleotide polymorphisms (SNPs) have been associated with B vitamin status or chronic diseases related to vitamin B-12 and folate metabolism. Our objective was to identify associations between common SNPs in genes related to folate and vitamin B-12 metabolis...
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By virtue of its role in nucleotide synthesis, as well as the provision of methyl groups for vital methylation reactions, one-carbon metabolism plays a crucial role in growth and development. Formate, a critical, though neglected, component of one-carbon metabolism, occurs extracellularly and may provide insights into cellular events. We examined f...
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It is now established that the mitochondrial production of formate is a major process in the endogenous generation of folate-linked one-carbon groups. We have developed an in vivo approach, involving the constant infusion of 13C-formate, until isotopic steady state is attained, to measure the rate of endogenous formate production in rats fed on eit...
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Objective: Mandatory folic acid fortification was implemented in Canada in 1998 to reduce the risk of neural tube defects (NTD). Our objective was to assess the relationship between socio-demographic factors and folate status in non-supplement-consuming Canadian women of childbearing age. Methods: Data on demographic factors, lifestyle factors,...
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By combining the sciences of nutrition, bioinformatics, genomics, population genetics, and epidemiology, nutrigenomics is improving our understanding of how diet and nutrient intake can interact with or modify gene expression and disease risk. In this review, we explore various approaches to examine gene-nutrient interactions and the modifying role...
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Over-the-counter vitamin supplements on the Canadian market are permitted to contain a daily vitamin B-12 dose of up to 1000 μg. Our objective was to determine the association between total daily vitamin B-12 supplement dose and markers of vitamin B-12 status in Canadians. Blood collected from a nationally representative sample aged 6-79 y (n = ∼56...
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Folate metabolism affects DNA synthesis, methylation, mutation rates, genomic stability, and gene expression, which are altered in colon cancer. Serine hydroxymethyltransferase 1 (SHMT1) regulates thymidylate (dTMP) biosynthesis and uracil accumulation in DNA, and as such affects genome stability. Previously, we showed that decreased SHMT1 expressi...
Chapter
Type 1 diabetes (T1D) results from the immune-mediated destruction of insulin-secreting β-cells that reside in the pancreatic Islets of Langerhans. Genetic susceptibility is necessary but not sufficient for the development of autoimmune diabetes, indicating a key role for risk modification by environmental factors. Epigenetic mechanisms could media...
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The 7S globulins are plant seed storage proteins that have been associated with the development of a number of human diseases, including peanut allergy. Immune reactivity to the wheat seed storage protein globulin-3 (Glo-3) has been associated with the development of the autoimmune disease type 1 diabetes in diabetes-prone rats and mice, as well as...