Submit to Nutrients Review for Nutrients Propose a Special Issue

Journal Browser

► Journal Browser

Dietary Choline

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

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

Deadline for manuscript submissions: closed (15 June 2017) | Viewed by 116835

Share This Special Issue

Special Issue Editor

Prof. Dr. Steven Zeisel

E-Mail Website
Guest Editor

MD, Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USA
Interests: choline; essential nutrient; nutrient metabolism; brain development

Special Issue Information

Dear Colleagues,

The purpose of this Special Issue, “Dietary Choline” is two-fold: 1) to address the evidence about dietary intake of choline compared to the recommended daily intake of this nutrient and the genetic differences that modify the requirements for this nutrient; and 2) to focus on the role of dietary choline in human health, including effects on brain and the cardiovascular system as well as effects of choline on epigenetic marks important for normal development.

Prof. Dr. med. Steven Zeise
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 submissions that pass pre-check are 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 semimonthly 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 2900 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
microbiome
cardiovascular disease
brain
diet intake

Published Papers (13 papers)

Download All Papers

Research

Jump to: Review

2692 KiB

Open AccessArticle

Choline and Choline alphoscerate Do Not Modulate Inflammatory Processes in the Rat Brain

by Seyed Khosrow Tayebati, Ilenia Martinelli, Michele Moruzzi, Francesco Amenta and Daniele Tomassoni

Nutrients 2017, 9(10), 1084; https://doi.org/10.3390/nu9101084 - 29 Sep 2017

Cited by 12 | Viewed by 5054

Abstract

Choline is involved in relevant neurochemical processes. In particular, it is the precursor and metabolite of acetylcholine (ACh). Choline is an essential component of different membrane phospholipids that are involved in intraneuronal signal transduction. On the other hand, cholinergic precursors are involved in ACh release and carry out a neuroprotective effect based on an anti-inflammatory action. Based on these findings, the present study was designed to evaluate the effects of choline and choline precursor (Choline alphoscerate, GPC) in the modulation of inflammatory processes in the rat brain. Male Wistar rats were intraperitoneally treated with 87 mg of choline chloride/kg/day (65 mg/kg/day of choline), and at choline-equivalent doses of GPC (150 mg/kg/day) and vehicle for two weeks. The brains were dissected and used for immunochemical and immunohistochemical analysis. Inflammatory cytokines (Interleukin-1β, IL-1β; Interleukin-6 , IL-6 and Tumor Necrosis Factor-α, TNF-α) and endothelial adhesion molecules (Intercellular Adhesion Molecule, ICAM-1 and Vascular cell Adhesion Molecule, VCAM-1) were studied in the frontal cortex, hippocampus, and cerebellum. The results clearly demonstrated that treatment with choline or GPC did not affect the expression of the inflammatory markers in the different cerebral areas evaluated. Therefore, choline and GPC did not stimulate the inflammatory processes that we assessed in this study. Full article

(This article belongs to the Special Issue Dietary Choline)

► Show Figures

Figure 1

884 KiB

Open AccessArticle

Choline and Working Memory Training Improve Cognitive Deficits Caused by Prenatal Exposure to Ethanol

by Jaylyn Waddell and Sandra M. Mooney

Nutrients 2017, 9(10), 1080; https://doi.org/10.3390/nu9101080 - 29 Sep 2017

Cited by 31 | Viewed by 4907

Abstract

Prenatal ethanol exposure is associated with deficits in executive function such as working memory, reversal learning and attentional set shifting in humans and animals. These behaviors are dependent on normal structure and function in cholinergic brain regions. Supplementation with choline can improve many behaviors in rodent models of fetal alcohol spectrum disorders and also improves working memory function in normal rats. We tested the hypothesis that supplementation with choline in the postnatal period will improve working memory during adolescence in normal and ethanol-exposed animals, and that working memory engagement during adolescence will transfer to other cognitive domains and have lasting effects on executive function in adulthood. Male and female offspring of rats fed an ethanol-containing liquid diet (ET; 3% v/v) or control dams given a non-ethanol liquid diet (CT) were injected with choline (Cho; 100 mg/kg) or saline (Sal) once per day from postnatal day (P) 16–P30. Animals were trained/tested on a working memory test in adolescence and then underwent attentional set shifting and reversal learning in young adulthood. In adolescence, ET rats required more training to reach criterion than CT-Sal. Choline improved working memory performance for both CT and ET animals. In young adulthood, ET animals also performed poorly on the set shifting and reversal tasks. Deficits were more robust in ET male rats than female ET rats, but Cho improved performance in both sexes. ET male rats given a combination of Cho and working memory training in adolescence required significantly fewer trials to achieve criterion than any other ET group, suggesting that early interventions can cause a persistent improvement. Full article

(This article belongs to the Special Issue Dietary Choline)

► Show Figures

Figure 1

1379 KiB

Open AccessArticle

Choline Supplementation Normalizes Fetal Adiposity and Reduces Lipogenic Gene Expression in a Mouse Model of Maternal Obesity

by Chauntelle Jack-Roberts, Yaelle Joselit, Khatia Nanobashvili, Rachel Bretter, Olga V. Malysheva, Marie A. Caudill, Anjana Saxena, Kathleen Axen, Ahmed Gomaa and Xinyin Jiang

Nutrients 2017, 9(8), 899; https://doi.org/10.3390/nu9080899 - 18 Aug 2017

Cited by 27 | Viewed by 5771

Abstract

Maternal obesity increases fetal adiposity which may adversely affect metabolic health of the offspring. Choline regulates lipid metabolism and thus may influence adiposity. This study investigates the effect of maternal choline supplementation on fetal adiposity in a mouse model of maternal obesity. C57BL/6J mice were fed either a high-fat (HF) diet or a control (NF) diet and received either 25 mM choline supplemented (CS) or control untreated (CO) drinking water for 6 weeks before timed-mating and throughout gestation. At embryonic day 17.5, HF feeding led to higher (p < 0.05) percent total body fat in fetuses from the HFCO group, while the choline supplemented HFCS group did not show significant difference versus the NFCO group. Similarly, HF feeding led to higher (p < 0.05) hepatic triglyceride accumulation in the HFCO but not the HFCS fetuses. mRNA levels of lipogenic genes such as Acc1, Fads1, and Elovl5, as well as the transcription factor Srebp1c that favors lipogenesis were downregulated (p < 0.05) by maternal choline supplementation in the HFCS group, which may serve as a mechanism to reduce fat accumulation in the fetal liver during maternal HF feeding. In summary, maternal choline supplementation improves indices of fetal adiposity in obese dams at late gestation. Full article

(This article belongs to the Special Issue Dietary Choline)

► Show Figures

Figure 1

240 KiB

Open AccessArticle

Choline Intake and Its Food Sources in the Diet of Romanian Kindergarten Children

by Cristian Reinhard Prelicz and Lucia Maria Lotrean

Nutrients 2017, 9(8), 896; https://doi.org/10.3390/nu9080896 - 18 Aug 2017

Cited by 7 | Viewed by 4688

Abstract

The objective of this study is to assess the usual intake and food sources of choline in a group of Romanian kindergarten children. A cross-sectional study was performed among 71 children aged 4–6 years from four kindergartens from Cluj-Napoca, Romania. Dietary intake data were collected by means of three-day food records. The mean (SD) daily intake of choline was 215 (32) mg/day, 22.5% of the participants fulfilling the adequate intake (AI) for children 4–6 years of age of 250 mg of choline per day. The main food sources were meat (mainly poultry), eggs, grains, cereals, and baked products (mainly bread), and dairy products (mainly milk). The results of the logistic regression analyses show that an appropriate consumption of choline/day was statistically significantly associated with the consumption of at least one egg per three days (OR = 7.5, p < 0.05), a minimum of two portions of milk or dairy products per day (500 mL milk or yoghurt, or 60 g of cheese/day) (OR = 4.4, p < 0.05), and at least one portion of meat/day (90 g/day) (OR = 14.4, p < 0.05). The results underline the need for future surveys in this field, as well as actions to encourage an appropriate diet for children, including an appropriate content of choline. Full article

(This article belongs to the Special Issue Dietary Choline)

228 KiB

Open AccessArticle

Usual Choline Intakes Are Associated with Egg and Protein Food Consumption in the United States

by Taylor C. Wallace and Victor L. Fulgoni

Nutrients 2017, 9(8), 839; https://doi.org/10.3390/nu9080839 - 05 Aug 2017

Cited by 61 | Viewed by 19952

Abstract

Choline is an essential nutrient with critical roles in several biological processes including neuronal development, cell signaling, nerve impulse transmission, and lipid transport and metabolism. The National Cancer Institute method was used to assess usual intakes of choline from foods according to data for participants enrolled in the National Health and Nutrition Examination Survey 2009–2014 datasets and pregnant women in the 2005–2014 datasets. Suboptimal intakes of choline are present across many gender and life-stage subpopulations, as well as pregnant women in the U.S. Only 8.03 ± 0.56% of adults and 8.51 ± 2.89% pregnant women meet the AI for choline. Children 2–3 years were the most likely to meet their gender and life-stage specific AI, followed by children 4–8 years. Adults 19+ years who consume eggs were more likely to meet their gender and life-stage AI as compared to non-consumers (57.3 ± 1.45% and 2.43 ± 0.28%). Consumers of eggs had almost double the usual intake of choline as compared to non-consumers (525 ± 5.17 mg/d and 294 ± 1.98; p < 0.0001). Protein food (meat, poultry and seafood) consumption also increased usual choline intakes compared to non-consumers (345 ± 2.21 mg/day and 235 ± 8.81; p < 0.0001) to a lesser degree, but did not result in substantial increases in the percent of individuals meeting the AI. No subpopulation exceeded the UL for choline. This research illustrates that it is extremely difficult to achieve the AI for choline without consuming eggs or taking a dietary supplement. Full article

(This article belongs to the Special Issue Dietary Choline)

1157 KiB

Open AccessArticle

Maternal Choline Supplementation Alters Fetal Growth Patterns in a Mouse Model of Placental Insufficiency

by Julia H. King, Sze Ting (Cecilia) Kwan, Jian Yan, Kevin C. Klatt, Xinyin Jiang, Mark S. Roberson and Marie A. Caudill

Nutrients 2017, 9(7), 765; https://doi.org/10.3390/nu9070765 - 18 Jul 2017

Cited by 23 | Viewed by 5168

Abstract

Impairments in placental development can adversely affect pregnancy outcomes. The bioactive nutrient choline may mitigate some of these impairments, as suggested by data in humans, animals, and human trophoblasts. Herein, we investigated the effects of maternal choline supplementation (MCS) on parameters of fetal growth in a Dlx3+/− (distal-less homeobox 3) mouse model of placental insufficiency. Dlx3+/− female mice were assigned to 1X (control), 2X, or 4X choline intake levels during gestation. Dams were sacrificed at embryonic days E10.5, 12.5, 15.5, and 18.5. At E10.5, placental weight, embryo weight, and placental efficiency were higher in 4X versus 1X choline. Higher concentrations of hepatic and placental betaine were detected in 4X versus 1X choline, and placental betaine was positively associated with embryo weight. Placental mRNA expression of Igf1 was downregulated by 4X (versus 1X) choline at E10.5. No differences in fetal growth parameters were detected at E12.5 and 15.5, whereas a small but significant reduction in fetal weight was detected at E18.5 in 4X versus 1X choline. MCS improved fetal growth during early pregnancy in the Dlx3+/− mice with the compensatory downregulation of Igf1 to slow growth as gestation progressed. Placental betaine may be responsible for the growth-promoting effects of choline. Full article

(This article belongs to the Special Issue Dietary Choline)

► Show Figures

Figure 1

1031 KiB

Open AccessArticle

Feeding a Mixture of Choline Forms during Lactation Improves Offspring Growth and Maternal Lymphocyte Response to Ex Vivo Immune Challenges

by Erin D. Lewis, Caroline Richard, Susan Goruk, Emily Wadge, Jonathan M. Curtis, René L. Jacobs and Catherine J. Field

Nutrients 2017, 9(7), 713; https://doi.org/10.3390/nu9070713 - 07 Jul 2017

Cited by 8 | Viewed by 4151

Abstract

Study objectives were to examine the impact of feeding a mixture of choline forms, or a diet high in glycerophosphocholine (GPC) on maternal immune function and offspring growth during lactation. Lactating Sprague-Dawley rat dams (n = 6/diet) were randomized to one of three diets, providing 1 g/kg total choline: Control (100% free choline (FC)), Mixed Choline (MC; 50% phosphatidylcholine (PC), 25% FC, 25% GPC), or High GPC (HGPC; 75% GPC, 12.5% PC, 12.5% FC). At 3 weeks, cell phenotypes and cytokine production with Concanavalin A (ConA)-or lipopolysaccharide (LPS)-stimulated splenocytes and mesenteric lymphocytes were measured. Feeding MC or HGPC diets improved pups’ growth compared to Control (+22% body weight, p < 0.05). In spleen, MC-and HGPC-fed dams had higher proportions of cytotoxic (CD8+) T cells expressing CD27, CD71 and CD127, total B cells (CD45RA+) and dendritic cells (OX6+OX62+), and produced less IL-6 and IFN-γ after ConA than Control-fed dams (p < 0.05). MC and HGPC LPS-stimulated splenocytes produced less IL-1β and IL-6 than Control. ConA-stimulated mesenteric lymphocytes from MC and HGPC dams produced more IL-2 and IFN-γ than Control (p < 0.05). In summary, feeding a mixture of choline forms during lactation improved offspring growth and resulted in a more efficient maternal immune response following mitogenic immune challenge. Full article

(This article belongs to the Special Issue Dietary Choline)

► Show Figures

Figure 1

936 KiB

Open AccessArticle

Feeding a Mixture of Choline Forms to Lactating Dams Improves the Development of the Immune System in Sprague-Dawley Rat Offspring

by Caroline Richard, Erin D. Lewis, Susan Goruk, Emily Wadge, Jonathan M. Curtis, René L. Jacobs and Catherine J. Field

Nutrients 2017, 9(6), 567; https://doi.org/10.3390/nu9060567 - 02 Jun 2017

Cited by 10 | Viewed by 4796

Abstract

Dietary choline is essential during lactation, but few studies have examined the implications of feeding a mixture of choline forms on immune function. This study investigates the impact of feeding lactating dams different mixtures of choline forms, similar to those in human diets, on the development and later immune function of suckled offspring. Sprague-Dawley lactating dams (n = 6/diet) were randomized to consume one of three diets, containing 1 g/kg choline: Control (100% free choline (FC)), Mixed Choline (MC: 50% phosphatidylcholine (PC), 25% FC, 25% glycerophosphocholine (GPC)), or High GPC (HGPC: 75% GPC, 12.5% PC, 12.5% FC). At weaning, female pups (n = 2/dam) were fed the Control diet until 10 weeks. At 3 weeks, MC and HGPC pups were heavier and their splenocytes had a higher proportion of helper T cells expressing CD25 and CD28 and produced less interferon gamma (IFN-γ) and tumor-necrosis factor-α (TNF-α) after Concanavalin A stimulation vs. Control pups (p < 0.05). At 10 weeks, MC and HGPC offspring had a lower proportion of macrophages and dendritic cells and produced less interleukin (IL)-1β but more IL-10 after lipopolysaccharide stimulation vs. Control pups (p < 0.05). In summary, feeding mixed choline diets during lactation improved T cell phenotype/function at the end of suckling and programmed a less inflammatory response later in life. Full article

(This article belongs to the Special Issue Dietary Choline)

► Show Figures

Figure 1

585 KiB

Open AccessArticle

Relationships among Different Water-Soluble Choline Compounds Differ between Human Preterm and Donor Milk

by Sara Moukarzel, Lynda Soberanes, Roger A. Dyer, Susan Albersheim, Rajavel Elango and Sheila M. Innis

Nutrients 2017, 9(4), 369; https://doi.org/10.3390/nu9040369 - 07 Apr 2017

Cited by 16 | Viewed by 4238

Abstract

Choline is essential for infant development. Human milk choline is predominately present in three water-soluble choline (WSC) forms: free choline (FC), phosphocholine (PhosC), and glycerophosphocholine (GPC). It is unclear whether mother’s own preterm milk and pooled donor milk differ in WSC composition and whether WSC compounds are interrelated. Mother’s own preterm milk (n = 75) and donor milk (n = 30) samples from the neonatal intensive care unit, BC Women’s Hospital were analyzed for WSC composition using liquid chromatography tandem mass spectrometry (LC-MS/MS). Associations between different WSC compounds were determined using Pearson’s correlations, followed by Fischer r-to-z transformation. Total WSC concentration and concentrations of FC, PhosC, and GPC did not significantly differ between mother’s own milk and donor milk. FC was negatively associated with PhosC and GPC in mother’s own milk (r = −0.27, p = 0.02; r = −0.34, p = 0.003, respectively), but not in donor milk (r = 0.26, p = 0.181 r = 0.37, p = 0.062, respectively). The difference in these associations between the two milk groups were statistically significant (p = 0.03 for the association between PhosC and FC; and p = 0.003 for the association between FC and GPC). PhosC and GPC were positively associated in mother’s own milk (r = 0.32, p = 0.036) but not donor milk (r = 0.36, p = 0.062), although the difference in correlation was not statistically significant. The metabolic and clinical implications of these associations on the preterm infant need to be further elucidated. Full article

(This article belongs to the Special Issue Dietary Choline)

► Show Figures

Figure 1

Review

Jump to: Research

834 KiB

Open AccessReview

Common Genetic Variants Alter Metabolism and Influence Dietary Choline Requirements

by Ariel B. Ganz, Kevin C. Klatt and Marie A. Caudill

Nutrients 2017, 9(8), 837; https://doi.org/10.3390/nu9080837 - 04 Aug 2017

Cited by 33 | Viewed by 12132

Abstract

Nutrient needs, including those of the essential nutrient choline, are a population wide distribution. Adequate Intake (AI) recommendations for dietary choline (put forth by the National Academies of Medicine to aid individuals and groups in dietary assessment and planning) are grouped to account for the recognized unique needs associated with age, biological sex, and reproductive status (i.e., pregnancy or lactation). Established and emerging evidence supports the notion that common genetic variants are additional factors that substantially influence nutrient requirements. This review summarizes the genetic factors that influence choline requirements and metabolism in conditions of nutrient deprivation, as well as conditions of nutrient adequacy, across biological sexes and reproductive states. Overall, consistent and strong associative evidence demonstrates that common genetic variants in choline and folate pathway enzymes impact the metabolic handling of choline and the risk of nutrient inadequacy across varied dietary contexts. The studies characterized in this review also highlight the substantial promise of incorporating common genetic variants into choline intake recommendations to more precisely target the unique nutrient needs of these subgroups within the broader population. Additional studies are warranted to facilitate the translation of this evidence to nutrigenetics-based dietary approaches. Full article

(This article belongs to the Special Issue Dietary Choline)

► Show Figures

Figure 1

910 KiB

Open AccessReview

Neuroprotective Actions of Dietary Choline

by Jan Krzysztof Blusztajn, Barbara E. Slack and Tiffany J. Mellott

Nutrients 2017, 9(8), 815; https://doi.org/10.3390/nu9080815 - 28 Jul 2017

Cited by 155 | Viewed by 24287

Abstract

Choline is an essential nutrient for humans. It is a precursor of membrane phospholipids (e.g., phosphatidylcholine (PC)), the neurotransmitter acetylcholine, and via betaine, the methyl group donor S-adenosylmethionine. High choline intake during gestation and early postnatal development in rat and mouse models improves cognitive function in adulthood, prevents age-related memory decline, and protects the brain from the neuropathological changes associated with Alzheimer’s disease (AD), and neurological damage associated with epilepsy, fetal alcohol syndrome, and inherited conditions such as Down and Rett syndromes. These effects of choline are correlated with modifications in histone and DNA methylation in brain, and with alterations in the expression of genes that encode proteins important for learning and memory processing, suggesting a possible epigenomic mechanism of action. Dietary choline intake in the adult may also influence cognitive function via an effect on PC containing eicosapentaenoic and docosahexaenoic acids; polyunsaturated species of PC whose levels are reduced in brains from AD patients, and is associated with higher memory performance, and resistance to cognitive decline. Full article

(This article belongs to the Special Issue Dietary Choline)

► Show Figures

Figure 1

626 KiB

Open AccessReview

Dietary Choline and Betaine and Risk of CVD: A Systematic Review and Meta-Analysis of Prospective Studies

by Katie A. Meyer and Jonathan W. Shea

Nutrients 2017, 9(7), 711; https://doi.org/10.3390/nu9070711 - 07 Jul 2017

Cited by 72 | Viewed by 8902

Abstract

Studies implicate choline and betaine metabolite trimethylamine N-oxide (TMAO) in cardiovascular disease (CVD). We conducted a systematic review and random-effects meta-analysis to quantify a summary estimated effect of dietary choline and betaine on hard CVD outcomes (incidence and mortality). Eligible studies were prospective studies in adults with comprehensive diet assessment and follow-up for hard CVD endpoints. We identified six studies that met our criteria, comprising 18,076 incident CVD events, 5343 CVD deaths, and 184,010 total participants. In random effects meta-analysis, incident CVD was not associated with choline (relative risk (RR): 1.00; 95% CI: 0.98, 1.02) or betaine (RR: 0.99; 95% CI: 0.98, 1.01) intake. Results did not vary by study outcome (incident coronary heart disease, stroke, total CVD) and there was no evidence for heterogeneity among studies. Only two studies provided data on phosphatidylcholine and CVD mortality. Random effects meta-analysis did not support an association between choline and CVD mortality (RR: 1.09, 95% CI: 0.89, 1.35), but one study supported a positive association and there was significant heterogeneity (I² = 84%, p-value < 0.001). Our findings do not support an association between dietary choline/betaine with incident CVD, but call for further research into choline and CVD mortality. Full article

(This article belongs to the Special Issue Dietary Choline)

► Show Figures

Figure 1

223 KiB

Open AccessReview

Choline, Other Methyl-Donors and Epigenetics

by Steven Zeisel

Nutrients 2017, 9(5), 445; https://doi.org/10.3390/nu9050445 - 29 Apr 2017

Cited by 146 | Viewed by 11444

Abstract

Choline dietary intake varies such that many people do not achieve adequate intakes. Diet intake of choline can modulate methylation because, via betaine homocysteine methyltransferase (BHMT), this nutrient (and its metabolite, betaine) regulate the concentrations of S-adenosylhomocysteine and S-adenosylmethionine. Some of the epigenetic mechanisms that modify gene expression without modifying the genetic code depend on the methylation of DNA or of histones; and diet availability of choline and other methyl-group donors influences both of these methylations. Examples of methyl-donor mediated epigenetic effects include the changes in coat color and body weight in offspring when pregnant agouti mice are fed high choline, high methyl diets; the changes in tail kinking in offspring when pregnant Axin(Fu) mice are fed high choline, high methyl diets; the changes in Cdkn3 methylation and altered brain development that occurs in offspring when pregnant rodents are fed low choline diets. When choline metabolism is disrupted by deleting the gene Bhmt, DNA methylation is affected (especially in a region of chromosome 13), expression of specific genes is suppressed, and liver cancers develop. Better understanding of how nutrients such as choline and methyl-donors influence epigenetic programs has importance for our understanding of not only developmental abnormalities but also for understanding the origins of chronic diseases. Full article

(This article belongs to the Special Issue Dietary Choline)

Journal Menu

Journal Browser

Dietary Choline

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (13 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI