Special Issue "The Health Aspects of Dietary Choline"

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (15 September 2018).

Special Issue Editor

Prof. Dr. Rima Obeid
E-Mail Website
Guest Editor
Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, Building 57, D-66424, Homburg, Germany
Interests: one-carbon metabolism; folate; B-vitamins; choline; methylation; epigenetics; maternal nutrition; cancer nutrition; nutrition epidemiology; public health nutrition; nutritional biomarkers
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Special Issue Information

Dear Colleagues,

The journal Nutrients is planning a Special Issue on “The Health Aspects of Dietary Choline”. I kindly invite you and your co-workers to be part of this Special Issue by publishing your original results or a review article on the topic.

Choline is an essential nutrient for lipid metabolism, synthesis of acetylcholine, and as a source of methyl groups. Choline deficiency causes liver dysfunction and perturbations in lipid metabolism and transfer. The requirements for choline nutrients may depend on the intake of other cluster-related nutrients, such as betaine and folate. The recommendations for choline and betaine intakes and the actual intakes of these two nutrients have not been worked out in many countries. Foods contain several forms of choline, but the differential importance for health is not well established. Choline nutrient has recently gained additional interest because of its potential role in foetal programming, cognitive function at early and late ages, type 2 diabetes, and cancer.

Recent studies also suggested possible negative effects of choline on health, through interaction with gut microbiome that produces trimethylamine that in turn is absorbed and metabolized in the liver or in muscles by flavin-dependent monoaminooxydase (FMO3) to Trimethylamine-N-oxide (TMAO). TMAO is mainly excreted via the kidney. Elevated TMAO shows significant associations with vascular diseases. Consumption of foods that contain large amounts of choline or TMAO (e.g., fish) has not been shown to be associated with atherosclerosis. Most of the associations between TMAO and disease outcome could be explained by renal dysfunction. 

This Special Issue will be published in the journal Nutrients and intends to address the different aspects relating choline to health and disease conditions. The aim is to communicate the newest results in the field (both original articles and review articles are accepted) to scientist working in the field. We encourage all authors to discuss the impact of their results on future studies, and to specify gaps in knowledge that would be necessary to solve in the following steps.

I welcome your proposed publication title with 3-6 explanatory sentences (max. 150 words) until 20th January 2018. The final deadline for submitting the articles is 15 July 2018. All articles will be peer reviewed and articles received before the deadline will be immediately processed. Please take note of the deadline.

It would be a great pleasure to have you as part of this Special Issue.

Prof. Dr. Rima Obeid
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Choline concentration
  • TMAO
  • Nutrient-Nutrient interaction
  • Randomized controlled trials
  • Risk
  • Prevention
  • Gut microbiome
  • Choline intake

Published Papers (6 papers)

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Research

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Open AccessArticle
Maternal Choline and Betaine Supplementation Modifies the Placental Response to Hyperglycemia in Mice and Human Trophoblasts
Nutrients 2018, 10(10), 1507; https://doi.org/10.3390/nu10101507 - 15 Oct 2018
Cited by 3
Abstract
Gestational diabetes mellitus (GDM) is characterized by excessive placental fat and glucose transport, resulting in fetal overgrowth. Earlier we demonstrated that maternal choline supplementation normalizes fetal growth in GDM mice at mid-gestation. In this study, we further assess how choline and its oxidation [...] Read more.
Gestational diabetes mellitus (GDM) is characterized by excessive placental fat and glucose transport, resulting in fetal overgrowth. Earlier we demonstrated that maternal choline supplementation normalizes fetal growth in GDM mice at mid-gestation. In this study, we further assess how choline and its oxidation product betaine influence determinants of placental nutrient transport in GDM mice and human trophoblasts. C57BL/6J mice were fed a high-fat (HF) diet 4 weeks prior to and during pregnancy to induce GDM or fed a control normal fat (NF) diet. The HF mice also received 25 mM choline, 85 mM betaine, or control drinking water. We observed that GDM mice had an expanded placental junctional zone with an increased area of glycogen cells, while the thickness of the placental labyrinth zone was decreased at E17.5 compared to NF control mice (p < 0.05). Choline and betaine supplementation alleviated these morphological changes in GDM placentas. In parallel, both choline and betaine supplementation significantly reduced glucose accretion (p < 0.05) in in vitro assays where the human choriocarcinoma BeWo cells were cultured in high (35.5 mM) or normal (5.5 mM) glucose conditions. Expression of angiogenic genes was minimally altered by choline or betaine supplementation in either model. In conclusion, both choline and betaine modified some but not all determinants of placental transport in response to hyperglycemia in mouse and in vitro human cell line models. Full article
(This article belongs to the Special Issue The Health Aspects of Dietary Choline)
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Open AccessArticle
Glucose and Fat Tolerance Tests Induce Differential Responses in Plasma Choline Metabolites in Healthy Subjects
Nutrients 2018, 10(9), 1209; https://doi.org/10.3390/nu10091209 - 01 Sep 2018
Cited by 1
Abstract
Plasma choline shows associations with plasma glucose and lipids. We studied changes of choline metabolites after oral glucose tolerance test (OGTT) and fat tolerance test (OFTT). Eighteen healthy subjects (mean age 54.3 years; BMI 26.8 kg/m2) underwent 2 tests. First, OFTT [...] Read more.
Plasma choline shows associations with plasma glucose and lipids. We studied changes of choline metabolites after oral glucose tolerance test (OGTT) and fat tolerance test (OFTT). Eighteen healthy subjects (mean age 54.3 years; BMI 26.8 kg/m2) underwent 2 tests. First, OFTT (80 g fat) was applied and blood was collected at baseline and 4 h after OFTT. Seven days later, 75 g glucose was applied and blood was collected at baseline and 2 h after OGTT. Plasma concentrations of choline, betaine, trimethylamine N-oxide (TMAO), dimethylglycine, S-adenosylmethionine (SAM), lipids and glucose were measured. After OFTT, plasma choline declined (10.6 to 9.2 µmol/L; p = 0.004), betaine declined (33.4 to 31.7 µmol/L; p = 0.003), TMAO slightly increased (4.1 to 5.6 µmol/L; p = 0.105), glucose declined (5.39 to 4.98 mmol/L; p < 0.001), and triglycerides increased (1.27 to 2.53 mmol/L; p < 0.001). After OGTT, plasma choline increased (10.1 to 11.1 µmol/L; p < 0.001), TMAO declined (4.0 to 3.5 µmol/L; p = 0.029), dimethylglycine declined (2.0 to 1.7 µmol/L; p = 0.005), SAM declined (103 to 96 nmol/L; p = 0.041), but betaine, glucose, and SAM were unchanged. In conclusion, OFTT lowered plasma betaine and choline and caused heterogeneous changes in plasma TMAO. OGTT reduced the flow of methyl groups and plasma TMAO. Full article
(This article belongs to the Special Issue The Health Aspects of Dietary Choline)
Open AccessArticle
Choline Supplementation Prevents a Hallmark Disturbance of Kwashiorkor in Weanling Mice Fed a Maize Vegetable Diet: Hepatic Steatosis of Undernutrition
Nutrients 2018, 10(5), 653; https://doi.org/10.3390/nu10050653 - 22 May 2018
Cited by 2
Abstract
Hepatic steatosis is a hallmark feature of kwashiorkor malnutrition. However, the pathogenesis of hepatic steatosis in kwashiorkor is uncertain. Our objective was to develop a mouse model of childhood undernutrition in order to test the hypothesis that feeding a maize vegetable diet (MVD), [...] Read more.
Hepatic steatosis is a hallmark feature of kwashiorkor malnutrition. However, the pathogenesis of hepatic steatosis in kwashiorkor is uncertain. Our objective was to develop a mouse model of childhood undernutrition in order to test the hypothesis that feeding a maize vegetable diet (MVD), like that consumed by children at risk for kwashiorkor, will cause hepatic steatosis which is prevented by supplementation with choline. A MVD was developed with locally sourced organic ingredients, and fed to weanling mice (n = 9) for 6 or 13 days. An additional group of mice (n = 4) were fed a choline supplemented MVD. Weight, body composition, and liver changes were compared to control mice (n = 10) at the beginning and end of the study. The MVD resulted in reduced weight gain and hepatic steatosis. Choline supplementation prevented hepatic steatosis and was associated with increased hepatic concentrations of the methyl donor betaine. Our findings show that (1) feeding a MVD to weanling mice rapidly induces hepatic steatosis, which is a hallmark disturbance of kwashiorkor; and that (2) hepatic steatosis associated with feeding a MVD is prevented by choline supplementation. These findings support the concept that insufficient choline intake may contribute to the pathogenesis of hepatic steatosis in kwashiorkor. Full article
(This article belongs to the Special Issue The Health Aspects of Dietary Choline)
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Open AccessFeature PaperArticle
Maternal Choline Supplementation during Normal Murine Pregnancy Alters the Placental Epigenome: Results of an Exploratory Study
Nutrients 2018, 10(4), 417; https://doi.org/10.3390/nu10040417 - 28 Mar 2018
Cited by 6
Abstract
The placental epigenome regulates processes that affect placental and fetal development, and could be mediating some of the reported effects of maternal choline supplementation (MCS) on placental vascular development and nutrient delivery. As an extension of work previously conducted in pregnant mice, the [...] Read more.
The placental epigenome regulates processes that affect placental and fetal development, and could be mediating some of the reported effects of maternal choline supplementation (MCS) on placental vascular development and nutrient delivery. As an extension of work previously conducted in pregnant mice, the current study sought to explore the effects of MCS on various epigenetic markers in the placenta. RNA and DNA were extracted from placentas collected on embryonic day 15.5 from pregnant mice fed a 1X or 4X choline diet, and were subjected to genome-wide sequencing procedures or mass-spectrometry-based assays to examine placental imprinted gene expression, DNA methylation patterns, and microRNA (miRNA) abundance. MCS yielded a higher (fold change = 1.63–2.25) expression of four imprinted genes (Ampd3, Tfpi2, Gatm and Aqp1) in the female placentas and a lower (fold change = 0.46–0.62) expression of three imprinted genes (Dcn, Qpct and Tnfrsf23) in the male placentas (false discovery rate (FDR) ≤ 0.05 for both sexes). Methylation in the promoter regions of these genes and global placental DNA methylation were also affected (p ≤ 0.05). Additionally, a lower (fold change = 0.3; Punadjusted = 2.05 × 10−4; FDR = 0.13) abundance of miR-2137 and a higher (fold change = 1.25–3.92; p < 0.05) expression of its target genes were detected in the 4X choline placentas. These data demonstrate that the placental epigenome is responsive to maternal choline intake during murine pregnancy and likely mediates some of the previously described choline-induced effects on placental and fetal outcomes. Full article
(This article belongs to the Special Issue The Health Aspects of Dietary Choline)
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Review

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Open AccessReview
Dietary Choline Intake: Current State of Knowledge Across the Life Cycle
Nutrients 2018, 10(10), 1513; https://doi.org/10.3390/nu10101513 - 16 Oct 2018
Cited by 11
Abstract
Choline, an essential dietary nutrient for humans, is required for the synthesis of the neurotransmitter, acetylcholine, the methyl group donor, betaine, and phospholipids; and therefore, choline is involved in a broad range of critical physiological functions across all stages of the life cycle. [...] Read more.
Choline, an essential dietary nutrient for humans, is required for the synthesis of the neurotransmitter, acetylcholine, the methyl group donor, betaine, and phospholipids; and therefore, choline is involved in a broad range of critical physiological functions across all stages of the life cycle. The current dietary recommendations for choline have been established as Adequate Intakes (AIs) for total choline; however, dietary choline is present in multiple different forms that are both water-soluble (e.g., free choline, phosphocholine, and glycerophosphocholine) and lipid-soluble (e.g., phosphatidylcholine and sphingomyelin). Interestingly, the different dietary choline forms consumed during infancy differ from those in adulthood. This can be explained by the primary food source, where the majority of choline present in human milk is in the water-soluble form, versus lipid-soluble forms for foods consumed later on. This review summarizes the current knowledge on dietary recommendations and assessment methods, and dietary choline intake from food sources across the life cycle. Full article
(This article belongs to the Special Issue The Health Aspects of Dietary Choline)
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Open AccessReview
Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target
Nutrients 2018, 10(10), 1398; https://doi.org/10.3390/nu10101398 - 01 Oct 2018
Cited by 24
Abstract
Trimethylamine N-oxide (TMAO) is a molecule generated from choline, betaine, and carnitine via gut microbial metabolism. The plasma level of TMAO is determined by several factors including diet, gut microbial flora, drug administration and liver flavin monooxygenase activity. In humans, recent clinical studies [...] Read more.
Trimethylamine N-oxide (TMAO) is a molecule generated from choline, betaine, and carnitine via gut microbial metabolism. The plasma level of TMAO is determined by several factors including diet, gut microbial flora, drug administration and liver flavin monooxygenase activity. In humans, recent clinical studies evidence a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events. A direct correlation between increased TMAO levels and neurological disorders has been also hypothesized. Several therapeutic strategies are being explored to reduce TMAO levels, including use of oral broad spectrum antibiotics, promoting the growth of bacteria that use TMAO as substrate and the development of target-specific molecules. Despite the accumulating evidence, it is questioned whether TMAO is the mediator of a bystander in the disease process. Thus, it is important to undertake studies to establish the role of TMAO in human health and disease. In this article, we reviewed dietary sources and metabolic pathways of TMAO, as well as screened the studies suggesting possible involvement of TMAO in the etiology of cardiovascular and neurological disorders, underlying the importance of TMAO mediating inflammatory processes. Finally, the potential utility of TMAO as therapeutic target is also analyzed. Full article
(This article belongs to the Special Issue The Health Aspects of Dietary Choline)
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