Folic acid oversupplementation during pregnancy disorders lipid metabolism in male offspring via regulating arginase 1-associated NOS3-AMPKα pathway

Liu, Zhipeng; Zhang, Yuntao; Liu, Zengjiao; Tian, Zhen; Pei, Xinyi; Liu, Liyan; Liu, Ying

doi:10.1016/j.clnu.2021.11.004

Cited by 12 publications

(4 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Table 1 presents the maternal and pregnancy data for 604 SCOPE and 711 STOP women with an uncomplicated pregnancy. Compared to SCOPE, STOP women were older (Median (IQ): 23 y [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ] vs. 25 y [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ], p < 0.0001), had a higher SEI (Median (IQ): 24 [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ] vs. 29 [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ], p...…”

Section: Resultsmentioning

confidence: 99%

“…Findings from animal models suggest that high maternal FA intake leads to dysregulation of maternal and/or foetal one-carbon metabolism (1Cm) and lipid metabolism as well as increased insulin resistance and glucose intolerance, but the proposed mechanisms are lacking [ 42 , 43 , 44 , 45 , 46 ]. Although rising, the incidence of Type 2 diabetes in Australia is not on the same trajectory as GDM; hence, given their shared aetiology, it is likely that FA acts at least partially via the placenta, a transient organ unique to pregnancy that is an essential regulator of maternal insulin resistance and glucose transport to the foetus [ 47 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Elevated Maternal Folate Status and Changes in Maternal Prolactin, Placental Lactogen and Placental Growth Hormone Following Folic Acid Food Fortification: Evidence from Two Prospective Pregnancy Cohorts

et al. 2023

View full text Add to dashboard Cite

Folic acid (FA) food fortification in Australia has resulted in a higher-than-expected intake of FA during pregnancy. High FA intake is associated with increased insulin resistance and gestational diabetes. We aimed to establish whether maternal one-carbon metabolism and hormones that regulate glucose homeostasis change in healthy pregnancies post-FA food fortification. Circulating folate, B12, homocysteine, prolactin (PRL), human placental lactogen (hPL) and placental growth hormone (GH2) were measured in early pregnancy maternal blood in women with uncomplicated pregnancies prior to (SCOPE: N = 604) and post (STOP: N = 711)-FA food fortification. FA food fortification resulted in 63% higher maternal folate. STOP women had lower hPL (33%) and GH2 (43%) after 10 weeks of gestation, but they had higher PRL (29%) and hPL (28%) after 16 weeks. FA supplementation during pregnancy increased maternal folate and reduced homocysteine but only in the SCOPE group, and it was associated with 54% higher PRL in SCOPE but 28% lower PRL in STOP. FA food fortification increased maternal folate status, but supplements no longer had an effect, thereby calling into question their utility. An altered secretion of hormones that regulate glucose homeostasis in pregnancy could place women post-fortification at an increased risk of insulin resistance and gestational diabetes, particularly for older women and those with obesity.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevated Maternal Folate Status and Changes in Maternal Prolactin, Placental Lactogen and Placental Growth Hormone Following Folic Acid Food Fortification: Evidence from Two Prospective Pregnancy Cohorts

et al. 2023

View full text Add to dashboard Cite

show abstract

“…On the other hand, a number of publications explored the adverse effects of excessive FA supplementation during pregnancy. According to a review article, excessive FA supplementation may have a negative effect on neurodevelopmental outcomes and may affect the lipid metabolism of offspring [ 27 , 28 ]. It was also found that excessive FA supplementation was not linked to improved brain development in the offspring.…”

Section: Discussionmentioning

confidence: 99%

Level of Knowledge and Awareness of Female Undergraduate Students and Determinants of Knowledge of Folic Acid and Supplementation

et al. 2022

View full text Add to dashboard Cite

Background and Objectives: Folic acid (FA) is a necessary ingredient for numerous bodily activities including pregnancy. Because of this, women should have knowledge and awareness of the health benefits of FA supplementation. Thus, we aimed to investigate the level of knowledge on the importance of FA and determine associated factors for knowledge among female college students at King Saud University in Riyadh, Saudi Arabia. Material and Methods: We conducted a cross-sectional study using a questionnaire between January 2020 and February 2021 among female college students aged 17 to 26 years old. The questionnaire adapted with permission from Alnaami et al. included questions on the demographic profile of the participants as well as questions related to their knowledge and awareness of FA, FA supplementation, the importance of supplementation and their sources of knowledge of FA. Results: A total of 437 female undergraduate students participated in the study, 285 (65.2%) of whom were from the non-health colleges and 152 (34.8%) from the health colleges. The majority of participants were between ages 17 and 21 years old (n = 361, 82.6%). Half of the respondents were in their 3rd and 4th year of study (n = 122, 50.8%), 138 respondents (31.6%) were married, and 111 of these married women (80.4%) had children. There were 266 respondents (61.0%) who had heard and had knowledge of FA, 241 (55.3%) knew of FA timing of intake, 243 (55.7%) of FA duration of intake and 362 (83.0%) knew of the diseases prevented by FA supplementation. Linear regression analysis showed that being in the health college (B = 1.464, t = 11.37, p < 0.001, 95% CI = 1.211, 1.717) and a higher educational year level (B = 0.139, t = 2.442, p = 0.015, 95% CI = 0.027, 0.251) were the significant predictors of knowledge of FA. Conclusions: Knowledge of FA and FA supplementation was low at 61% considering that our study population were college students. Being enrolled in a health college and in a higher educational year level were significant positive correlates of higher knowledge of FA and FA supplementation. Despite this, there exists a gap of information regarding FA and FA supplementation particularly among single women and college educated women in the early years of their college life as well as those in non-health colleges.

show abstract

“…Other doses at ×2.5, ×5, and ×20 also produced greater body weight as well as various indicators of glucose and lipid dysfunctions in male and female offspring in adulthood [40–42], suggesting wide-ranging metabolic consequences across high amounts of folic acid.…”

Section: Programming By Folatementioning

confidence: 99%

Folate and Choline: Does It Take Two to Tango in Early Programming of Disease?

Chen,

Schwartz,

Cho

2023

Lifestyle Genomics

View full text Add to dashboard Cite

Background: The early life period marks a critical time during which the health trajectory of offspring can be shaped by external influences including maternal nutrition. Folate and choline are water-soluble micronutrients important for fetal development and involved in one-carbon metabolism. Intakes above and below the recommendations commonly occur for both of these nutrients including over-consumption of synthetic folic acid due to widespread vitamin supplement uses and discretionary fortification practices, whereas choline is under-consumed by a majority of the populations including pregnant women. Despite these intake patterns, long-term impact on offspring health is largely unknown. Moreover, limited attention has been on the combined effects of folate and choline despite being metabolically interrelated as methyl nutrients. This review summarizes evidence from animal models and human studies investigating the role of inadequate or supplemental maternal intakes of folic acid, choline and combined effects of folic acid and choline as modulators of health and disease in offspring. With the recent rise in the prevalence of obesity and metabolic diseases, our primary measures of interest were metabolic outcomes. Summary: Studies examining the role of maternal folate and/or choline in metabolic phenotypes of offspring have mostly been conducted in animal models with a limited number of reports that consider folate and choline together. Interdependent relationship between folate and choline has been demonstrated in studies where a deficiency in one leads to metabolic aberrations in another. Both deficient and excess maternal intakes of folic acid (in varying doses) have been shown to increase risk of obesity and characteristics of the metabolic syndrome in offspring but these findings were restricted to animal studies. Potential metabolic benefits of choline have been suggested in the presence of obesogenic environment but human data were sparse. An imbalanced intake of high folic acid and inadequate choline in the gestational diet created adverse consequences consistent with the obesogenic phenotypes whereas narrowing this imbalance with high choline blocked these effects. Mechanisms by which maternal folate and/or choline influence offspring outcomes may involve epigenetic modification of gene expression with DNA methylation that can be altered globally and gene-specifically. However, the effects of epigenetic programming were inconsistent, as compensatory changes in metabolic products may occur and other contributors including the gut microbiota may provide additional insights into the mechanisms. Key Messages: Folate and/or choline can impact offspring long-term health, with metabolic consequences that may arise from imbalances between folic acid and choline intakes. However, there is a paucity of mechanistic understanding as various contributors influence programming effects including those beyond epigenetics. As folate and choline are metabolically interrelated, future studies need to consider both nutrients to better elucidate metabolic programming of health and disease.

show abstract

Folic acid oversupplementation during pregnancy disorders lipid metabolism in male offspring via regulating arginase 1-associated NOS3-AMPKα pathway

Cited by 12 publications

References 36 publications

Elevated Maternal Folate Status and Changes in Maternal Prolactin, Placental Lactogen and Placental Growth Hormone Following Folic Acid Food Fortification: Evidence from Two Prospective Pregnancy Cohorts

Elevated Maternal Folate Status and Changes in Maternal Prolactin, Placental Lactogen and Placental Growth Hormone Following Folic Acid Food Fortification: Evidence from Two Prospective Pregnancy Cohorts

Level of Knowledge and Awareness of Female Undergraduate Students and Determinants of Knowledge of Folic Acid and Supplementation

Folate and Choline: Does It Take Two to Tango in Early Programming of Disease?

Contact Info

Product

Resources

About