The Lipotropic Effect of Folic Acid on Rats Receiving Various Purified Diets

Kelley, Barbara; Totter, John R.; Day, Paul L.

doi:10.1016/s0021-9258(18)56196-2

Cited by 14 publications

(2 citation statements)

References 8 publications

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“…Moreover, dietary folate restriction in pre-menopausal women reduced plasma phosphatidylcholine levels, which increased after folate treatment [24]. Hepatic steatosis occurred with chronic folate insufficiency associated with greater utilization of betaine for homocysteine remethylation [25], whereas folate had a lipotropic effect in animal models of fatty liver [26]. Similar to dietary folate deficiency, disruption of the gene that codes for methylenetetrahydrofolate reductase (MTHFR) may influence choline metabolism as indicated by lower hepatic concentrations of phosphocholine, glycerophosphocholine, and betaine [27].…”

Section: Folate and Choline Interdependent Metabolismmentioning

confidence: 99%

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

Chen,

Schwartz,

Cho

2023

Lifestyle Genomics

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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.

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Section: Folate and Choline Interdependent Metabolismmentioning

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

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“…Results from an animal study indicated that folate supplements in doses of 5 mg/kg were associated with a reduction in the liver lipid content. [ 16 ] Furthermore, based on the evidence from another animal study, folate deficiency might have destructive impacts on the antioxidant defense system. [ 17 ]…”

Section: Introductionmentioning

confidence: 99%

Effects of folic acid supplementation on liver enzymes, lipid profile, and insulin resistance in patients with non-alcoholic fatty liver disease: A randomized controlled trial

Sharifi¹,

Molaqanbari²,

Zarringol³

et al. 2023

Adv Biomed Res

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Background: Previous evidence revealed an association between folate deficiency and non-alcoholic fatty liver disease (NAFLD). This study is the first one investigating the effects of folic acid on hepatic steatosis grade, liver enzymes, insulin resistance, and lipid profile in NAFLD cases. Materials and Methods: Sixty-six participants with NAFLD were allocated randomly to take either a placebo or one oral tablet of folic acid (1 mg) on a daily basis within eight weeks. Serum folate, homocysteine, glucose, aminotransferases, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and lipids were assessed. Ultrasonography was used for assessing the liver steatosis grade. Results: The serum alanine transaminase, grade of hepatic steatosis, and aspartate transaminase significantly were decreased within both study groups; however, the between-group comparison was not statistically significant. Of note, the decrease in ALT was more pronounced in folic acid compared with the placebo group (-5.45 ± 7.45 vs. -2.19 ± 8.6 IU/L). The serum homocysteine was decreased after receiving folic acid compared to the placebo (-0.58 ± 3.41 vs. +0.4 ± 3.56 μmol/L; adjusted P = 0.054). Other outcomes did not significantly change. Conclusion: Supplementation with folic acid (1 mg/d) for eight weeks among cases with NAFLD did not change significantly the serum levels of liver enzymes, the hepatic steatosis grade, insulin resistance and lipid profile. However, it was able to prevent the increase in homocysteine in comparison with the placebo. Conducting further research is suggested with the longer duration and different doses of folic acid, adjusted to the genotypes of methylenetetrahydrofolate reductase polymorphism, among NAFLD patients.

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Novel insights on interactions between folate and lipid metabolism

et al. 2013

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Folate is an essential B vitamin required for the maintenance of AdoMet-dependent methylation. The liver is responsible for many methylation reactions that are used for post-translational modification of proteins, methylation of DNA, and the synthesis of hormones, creatine, carnitine, and phosphatidylcholine. Conditions where methylation capacity is compromised, including folate deficiency, are associated with impaired phosphatidylcholine synthesis resulting in non-alcoholic fatty liver disease and steatohepatitis. In addition, folate intake and folate status have been associated with changes in the expression of genes involved in lipid metabolism, obesity, and metabolic syndrome. In this review, we provide insight on the relationship between folate and lipid metabolism, and an outlook for the future of lipid-related folate research. © 2013 BioFactors, 40(3):277–283, 2014

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The Lipotropic Effect of Folic Acid on Rats Receiving Various Purified Diets

Cited by 14 publications

References 8 publications

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

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

Effects of folic acid supplementation on liver enzymes, lipid profile, and insulin resistance in patients with non-alcoholic fatty liver disease: A randomized controlled trial

Novel insights on interactions between folate and lipid metabolism

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