The Dihydrofolate Reductase 19 bp Polymorphism Is Not Associated with Biomarkers of Folate Status in Healthy Young Adults, Irrespective of Folic Acid Intake

Ozaki, Mari; Molloy, Anne M.; Mills, James L.; Fan, Ruzong; Wang, Yifan; Gibney, Eileen R.; Shane, Barry; Brody, Lawrence C.; Parle‐McDermott, Anne

doi:10.3945/jn.115.216101

Cited by 7 publications

(4 citation statements)

References 32 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Nevertheless, this does not mean that it is inappropriate to take folic acid. There is evidence that folic acid could be absorbed and utilized by humans within a tolerable upper intake level (1000 µg/day), and DHFR has sufficient capacity in humans to efficiently metabolize normal doses of folic acid [ 42 , 43 , 44 , 45 ]. Furthermore, folic acid is more readily available than folinic acid in China.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial

et al. 2016

View full text Add to dashboard Cite

Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial

et al. 2016

View full text Add to dashboard Cite

show abstract

“…We also demonstrated for the first time that DHFR 19-bp polymorphism (rs70991108) is associated with ALT and HSI in overweight and obese subjects. Our previous results [20] and those of others [38, 39] indicate that DHFR 19-bp polymorphism does not affect folate status; however, neither we nor the other authors examined these associations in overweight and obese subjects separately, which might change the results.…”

Section: Discussionmentioning

confidence: 65%

Comparison of Associations between One-Carbon Metabolism, Lipid Metabolism, and Fatty Liver Markers in Normal-Weight and Overweight People Aged 20–40 Years

et al. 2021

View full text Add to dashboard Cite

The aim of the present study was to compare biomarkers of one-carbon metabolism (OCM), lipid metabolism, and fatty liver in people with normal and increased body weight. The study was performed on 421 participants, aged 20–40 years, enrolled in Poznan, Poland, in 2016–2018. Choline and betaine intakes were assessed. DNA samples were genotyped for polymorphisms of phosphatidylethanolamine N-methyltransferase (PEMT; rs7946 and rs12325817), methylene tetrahydrofolate reductase (MTHFR; rs180113), methylenetetrahydrofolate dehydrogenase (MTHFD1; rs2236225), and dihydrofolate reductase (DHFR; rs70991108). To assess the associations between blood metabolites (choline, betaine, folate, L-carnitine, o-acetyl-L-carnitine, and trimethylamine N-oxide]), circulating lipids, and fatty liver indices, multiple logistic regression analyses were performed. Overweight/obese participants had 5.8% higher choline (p < 0.05) and 10% higher L-carnitine (p < 0.001) levels than normal-weight subjects. Serum folate and betaine levels were associated with lower total cholesterol (p < 0.001 and p < 0.05), low-density lipoprotein (LDL) cholesterol (p < 0.001 and p < 0.05, respectively), triacylglycerols (p < 0.01 and p < 0.001), and triglyceride glucose index (p < 0.001 and p < 0.01, respectively), though only in overweight/obese people. The PEMT rs12325817 CC genotype was associated with higher levels of high-density lipoprotein (HDL) cholesterol (p < 0.01) in overweight/obese people. The associations between OCM markers, fatty liver indices, and blood lipids differ in subjects with normal and excessive body weight.

show abstract

“…A 19-base pair deletion polymorphism in DHFR (del/del genotype) has also been found to be associated with increased plasma UFA concentrations and decreased plasma/red blood cell folate compared with the wild type (WT)/del and WT/ WT genotypes in some studies (Bortolus et al, 2020;Kalmbach et al, 2008), and a potential functional effect from this polymorphism on folate status/function has been proposed (Kalmbach et al, 2008). In contrast, other studies failed to detect any association between the del/del genotype and folate biomarkers (Gellekink et al, 2007;Ozaki et al, 2015;Stanisławska-Sachadyn et al, 2008).…”

Section: Geneticsmentioning

confidence: 99%

Scientific opinion on the tolerable upper intake level for folate

Turck,

Bohn,

Castenmiller

et al. 2023

EFS2

View full text Add to dashboard Cite

Following a request from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for folic acid/folate. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of folate (including folic acid and the other authorised forms, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts), namely risk of cobalamin-dependent neuropathy, cognitive decline among people with low cobalamin status, and colorectal cancer and prostate cancer. The evidence is insufficient to conclude on a positive and causal relationship between the dietary intake of folate and impaired cognitive function, risk of colorectal and prostate cancer. The risk of progression of neurological symptoms in cobalamin-deficient patients is considered as the critical effect to establish an UL for folic acid. No new evidence has been published that could improve the characterisation of the dose-response between folic acid intake and resolution of megaloblastic anaemia in cobalamin-deficient individuals. The ULs for folic acid previously established by the Scientific Committee on Food are retained for all population groups, i.e. 1000 μg/day for adults, including pregnant and lactating women, 200 μg/day for children aged 1-3 years, 300 μg/day for 4-6 years, 400 μg/day for 7-10 years, 600 μg/day for 11-14 years and 800 μg/ day for 15-17 years. A UL of 200 μg/day is established for infants aged 4-11 months. The ULs apply to the combined intake of folic acid, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts, under their authorised conditions of use.It is unlikely that the ULs for supplemental folate are exceeded in European populations, except for regular users of food supplements containing high doses of folic acid/5-methyltetrahydrofolic acid salts. K E Y W O R D S folate, folic acid, 5-methyltetrahydrofolic acid salt, tolerable upper intake level 2 of 119 |

show abstract

The Dihydrofolate Reductase 19 bp Polymorphism Is Not Associated with Biomarkers of Folate Status in Healthy Young Adults, Irrespective of Folic Acid Intake

Abstract: In this cohort of healthy young individuals, the DHFR 19 bp deletion allele did not significantly affect circulating folate status, irrespective of folic acid intake. Our data rule out a strong functional effect from this polymorphism on blood folate concentrations.

Cited by 7 publications

References 32 publications

Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial

Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial

Comparison of Associations between One-Carbon Metabolism, Lipid Metabolism, and Fatty Liver Markers in Normal-Weight and Overweight People Aged 20–40 Years

Scientific opinion on the tolerable upper intake level for folate

Contact Info

Product

Resources

About