Choline metabolome response to prenatal choline supplementation across pregnancy: A randomized controlled trial

Taesuwan, Siraphat; McDougall, Melissa; Malysheva, Olga; Bender, Erica; Nevins, Julie; Devapatla, Srisatish; Vidavalur, Ramesh; Caudill, Marie A.; Klatt, Kevin C

doi:10.1096/fj.202101401rr

Cited by 16 publications

(16 citation statements)

References 43 publications

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“…Ischemic and non-ischemic cortical brain tissue from offspring was measured for acetylcholine, betaine, choline, glycerophosphocholine, methionine, phosphocholine, phosphatidylcholine, and sphingomyelin levels using the LC-MS method as previously reported (26, 27).…”

Section: Methodsmentioning

confidence: 99%

Maternal dietary deficiencies in folates or choline during pregnancy and lactation worsen stroke outcome in 3-month-old male and female mouse offspring

Clementson

Hurley

Coonrod

et al. 2022

Preprint

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Maternal one-carbon (1C) metabolism plays an important role in early life programming. There is a well-established connection between the fetal environment and the health status of the offspring. However, there is a knowledge gap on how maternal nutrition impacts stroke outcome in offspring. The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcome in 3-month-old offspring. Adult female mice were fed a folic acid deficient diet (FADD), choline deficient diet (ChDD), or control diet (CD) prior to pregnancy. They were continued on diets during pregnancy and lactation. Male and female offspring were weaned onto a CD and at 2 months of age were subject to ischemic stroke within the sensorimotor cortex via photothrombosis damage. At 3-months-of-age, motor function was measured in offspring and tissue was collected for analysis. Mothers maintained on either a FADD or ChDD had reduced levels of S-adenosylmethionine in liver and S-adenosylhomocysteine in plasma. After ischemic stroke, motor function was impaired in 3-month-old offspring from deficient mothers compared to CD animals. In brain tissue, there was no difference in ischemic damage volume. When protein levels were assessed in brain tissue, there were lower levels of neurodegeneration in males compared to females and betaine levels were reduced in offspring from ChDD mothers. Our results demonstrate that a deficient maternal diet during critical timepoints in neurodevelopment results in worse stroke outcomes. This study emphasizes the importance of maternal diet and the impact it can have on offspring health.

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Section: Methodsmentioning

confidence: 99%

Maternal dietary deficiencies in folates or choline during pregnancy and lactation worsen stroke outcome in 3-month-old male and female mouse offspring

Clementson

Hurley

Coonrod

et al. 2022

Preprint

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“…While we compared 2 doses of supplemental choline, informed by previously observed cognitive benefits ( 14 ), we did not have a third intermediate group to assess the dose–response relation between choline supplementation and DHA outcomes. Additionally, while our isotopic enrichment data support a clear role for the PEMT pathway metabolites in improving DHA status, there are notable nuances to the interpretation of the labeled choline metabolome in the context of an intervention that alters endogenous pool sizes across pregnancy, a physiological state that violates steady state assumptions, which we have detailed elsewhere ( 27 ).…”

Section: Discussionmentioning

confidence: 60%

“…Participant adherence to the study protocol was >99%, based on the number of returned juice containers (containing the choline supplement) and the number of returned DHA capsules. Further, mean concentrations of plasma free choline, which have been shown to be responsive to choline supplementation during pregnancy ( 10 ), were significantly higher in this cohort in the choline intervention (vs. control) group, with between-group differences detected at visit 2, visit 3, and delivery ( 27 ).…”

Section: Resultsmentioning

confidence: 79%

Prenatal choline supplementation improves biomarkers of maternal docosahexaenoic acid (DHA) status among pregnant participants consuming supplemental DHA: a randomized controlled trial

Klatt

McDougall

Malysheva

et al. 2022

The American Journal of Clinical Nutrition

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Background Dietary methyl donors (e.g., choline) support the activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, which generates phosphatidylcholine (PC) molecules enriched in docosahexaenoic acid (DHA) that are exported from the liver and made available to extrahepatic tissues. Objective This study investigated the effect of prenatal choline supplementation on biomarkers of DHA status among pregnant participants consuming supplemental DHA. Design Pregnant participants (N=30) were randomized to supplemental choline intakes of 550 mg/d (500 mg/d d0-choline + 50 mg/d deuterium labeled-choline [d9-choline]; intervention) or 25 mg/d (25 mg/d d9-choline; control) from gestational week (GW) 12-16 until delivery. All participants received a daily 200-mg DHA supplement and consumed self-selected diets. Fasting blood samples were obtained at baseline, GW 20-24, and GW 28-32; maternal/cord blood was obtained at Delivery. Mixed effects linear models were used to assess the impact of prenatal choline supplementation on maternal and newborn DHA status. Results Choline supplementation (550 vs 25 mg/d) did not achieve a statistically significant intervention-x-time interaction for RBC PC-DHA (P=0.11); a significant interaction was observed for plasma PC-DHA and RBC total DHA, with choline supplementation yielding higher levels (+32-38% and +8-11%, respectively) at GW28-32 (P<0.05) and Delivery (P<0.005). A main effect of choline supplementation on plasma total DHA was also observed (P=0.018); its interaction with time was not significant (P=0.068). Compared with controls, the intervention group exhibited higher (P=0.007); main effect) plasma enrichment of d3-PC (d3-PC/total PC). Moreover, the ratio of d3-PC:d9-PC was higher (+50-67%, P<0.001) in the choline intervention arm (vs control) at GW 20-24, GW 28-32 and Delivery. Conclusions Prenatal choline supplementation improves hepatic DHA export and biomarkers of DHA status by bolstering methyl group supply for PEMT activity among pregnant participants consuming supplemental DHA Clinical Trial Registry: Synergy BetweenCholine and DHA; NCT03194659 (www.clinicaltrials.gov)

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“…During pregnancy and lactation, the mother transmits choline to offspring through the placenta and breast milk 24 . Many studies have found that choline supplementation during the embryonic period can not only improve the cognitive ability of the adult brain, but also advance the cognitive development of the brain 25,26 . Specifically, Moreno et al found that prenatal choline supplementation could accelerate the development of long‐term memory in offspring rats 27 .…”

Section: Introductionmentioning

confidence: 99%

“…24 Many studies have found that choline supplementation during the embryonic period can not only improve the cognitive ability of the adult brain, but also advance the cognitive development of the brain. 25,26 Specifically, Moreno et al found that prenatal choline supplementation could accelerate the development of long-term memory in offspring rats. 27 Moreover, Johns et al reported that choline supplementation alleviated chemotherapeutic-induced spatial memory deficits.…”

Section: Introductionmentioning

confidence: 99%

Choline alleviated perinatal fluoride exposure‐induced learning and memory impairment through α4β2 nAChRs and α7 nAChRs in offspring mice

Zhao

Wang

2022

Environmental Toxicology

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Fluoride pollution is widely present in the living environment. As a critical period of brain development, the perinatal period is extremely vulnerable to fluoride. Studies have found that choline can protect the brain's memory and enhance the ability to focus. However, the effect of choline on perinatal fluoride-induced nerve damage remains unclear. Therefore, 32 Kunming newly conceived female mice and their offspring mice were randomly divided into control, NaF, LC + NaF, and HC + NaF groups, and the HE staining, Y-maze test, RT-PCR, western blotting, immunohistochemistry, etc. were used in this study. The results showed that fluoride decreased the brain organ coefficients and brain protein content (p < 0.05, p < 0.01), and caused histomorphological damage in the hippocampus and cortex, which suggested that fluoride affected the development of the brain and damaged the brain. Moreover, the results of the Y-maze test showed that fluoride increased the number of learning days, error reaction time, and total reaction time, and decreased the AchE activity in the brain (p < 0.05, p < 0.01), which indicated that fluoride reduced the learning and memory ability of the mice. Besides, the results showed that fluoride decreased the mRNA and protein expression levels of α4β2 nAChRs and α7 nAChRs in the hippocampus and cortex (p < 0.05, p < 0.01). However, perinatal choline supplementation reversed the aforementioned fluoride-induced changes. In short, these results demonstrated that choline alleviated perinatal fluoride-induced learning and memory impairment, which will provide a rationale for the mitigation and prevention of fluoride-induced brain damage.

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Choline metabolome response to prenatal choline supplementation across pregnancy: A randomized controlled trial

Cited by 16 publications

References 43 publications

Maternal dietary deficiencies in folates or choline during pregnancy and lactation worsen stroke outcome in 3-month-old male and female mouse offspring

Maternal dietary deficiencies in folates or choline during pregnancy and lactation worsen stroke outcome in 3-month-old male and female mouse offspring

Prenatal choline supplementation improves biomarkers of maternal docosahexaenoic acid (DHA) status among pregnant participants consuming supplemental DHA: a randomized controlled trial

Choline alleviated perinatal fluoride exposure‐induced learning and memory impairment through α4β2 nAChRs and α7 nAChRs in offspring mice

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