Systematic review of adverse health outcomes associated with high serum or red blood cell folate concentrations

Colapinto, Cynthia K; O'Connor, Deborah L; Sampson, Margaret; Williams, Brock A; Tremblay, Mark S.

doi:10.1093/pubmed/fdv087

Cited by 19 publications

(16 citation statements)

References 89 publications

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“…Given the protective role of RBC folate for NTDs and other folate-sensitive defects ( 21 ), it is justifiable to maintain an optimal level of ∼400 ng/mL for women with baseline RBC levels less than this value. However, for those with a RBC folate level of >400 ng/mL, attention should be paid to the potential increased risk of GDM as well as other health outcomes ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Association of Maternal Folate and Vitamin B12 in Early Pregnancy With Gestational Diabetes Mellitus: A Prospective Cohort Study

et al. 2020

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To investigate the association of folate and vitamin B 12 in early pregnancy with gestational diabetes mellitus (GDM) risk. RESEARCH DESIGN AND METHODSThe data of this study were from a subcohort within the Shanghai Preconception Cohort Study. We included pregnancies with red blood cell (RBC) folate and vitamin B 12 measurements at recruitment (between 9 and 13 gestational weeks) and those with three samples available for glucose measurements under an oral glucose tolerance test. GDM was diagnosed between 24 and 28 weeks' gestation. Odds ratio (OR) and 95% CI of having GDM was used to quantify the association. RESULTSA total of 1,058 pregnant women were included, and GDM occurred in 180 (17.01%). RBC folate and vitamin B 12 were significantly higher in pregnancies with GDM than those without GDM (P values were 0.045 and 0.002, respectively) and positively correlated with 1-h and 2-h serum glucose. Daily folic acid supplementation in early pregnancy increases the risk of GDM; OR (95% CI) was 1.73 (1.19-2.53) (P 5 0.004). Compared with RBC folate <400 ng/mL, pregnancies with RBC folate ‡600 ng/mL were associated with ∼1.60-fold higher odds of GDM; the adjusted OR (95% CI) was 1.58 (1.03-2.41) (P 5 0.033). A significant trend of risk effect on GDM risk across categories of RBC folate was observed (P trend 5 0.021). Vitamin B 12 was significantly associated with GDM risk (OR 1.14 per 100 pg/mL; P 5 0.002). No significant association of serum folate and percentile ratio of RBC folate/vitamin B 12 with GDM was observed. CONCLUSIONSHigher maternal RBC folate and vitamin B 12 levels in early pregnancy are significantly associated with GDM risk, while the balance of folate/vitamin B 12 is not significantly associated with GDM.As one of the most common pregnancy complications, gestational diabetes mellitus (GDM) affects ;17% of pregnancies worldwide (1). In China, ;2.9 million pregnant women suffer from this disorder (2). GDM has long-term adverse outcomes in both mothers and offspring (3). Despite its serious complications, the diagnosis of GDM is

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Section: Discussionmentioning

confidence: 99%

Association of Maternal Folate and Vitamin B12 in Early Pregnancy With Gestational Diabetes Mellitus: A Prospective Cohort Study

et al. 2020

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“…Moreover, 70•2 % of the children presented with consumption above the RDA value for this vitamin (27) . Despite the known beneficial effects of high acid folic intake in reducing the risk of neural tube defects and other congenital anomalies, and (less conclusively) reducing the risk of CVD and cancer (28) , an increasing amount of evidence has raised concerns regarding the adverse effects of high folate concentrations on one's health, especially in individuals with marginal or deficient vitamin B 12 status (13) .…”

Section: Discussionmentioning

confidence: 99%

Serum folate and vitamin B12 status in young Brazilian children

Silva

Fawzi

Cardoso

2019

Public Health Nutr.

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ObjectiveTo assess the nutritional status of folate and vitamin B12 with anaemia in young children.DesignA cross-sectional study was conducted at the primary health-care centres of four Brazilian cities. Folate and vitamin B12 were assessed by fluoroimmunoassay. Multilevel Poisson regression models were used to explore the association of folate and vitamin B12 status in relation to anaemia in young children.SettingBrazil.ParticipantsChildren (n 460) aged 11 to 15 months.ResultsThe median (interquartile range) of serum folate was 39·7 (28·8–55·3) nmol/l and only four children presented with folate deficiency (<10 nmol/l). Surprisingly, 30·9 % of children presented with serum folate concentrations above the upper limit of detectable values by the commercial kit used for analysis. The frequency of vitamin B12 deficiency (<148 pmol/l) was 15 % and it was inversely associated with the highest tertile of serum folate concentrations (P<0·001). Having high serum folate concentration (≥50·1 nmol/l) and vitamin B12≥148 pmol/l was associated with lower frequency of anaemia in these children (prevalence ratio=0·53; 95% CI 0·30, 0·92).ConclusionsHigh frequency of elevated serum concentration of folate was found among young Brazilian children and 15 % of them had vitamin B12 deficiency. The combination of high serum folate and normal vitamin B12 status was associated with a lower frequency of anaemia in these children. Improvements in the current strategies to promote healthy food-based complementary feeding along with prevention and control of micronutrient deficiencies are recommended to improve children’s health.

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“…28 Thus, folate deficiency is associated with many complications, and a priori, increasing the intake of folate to correct this deficiency will be beneficial to human health. 29 However, there is evidence that the indiscriminate increase in folate intake in the population can also cause various undesirable complications, especially in populations that are not folate deficient or have diseases whose progression can be affected by folate levels, such as some types of cancer. 14,30 Malaria Disease…”

Section: Folate Biochemistrymentioning

confidence: 99%

Malaria in the Era of Food Fortification With Folic Acid

Nzila

Okombo

Hyde³

2016

Food Nutr Bull

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Food fortified with folic acid has been available for consumption in North America for over a decade. This strategy has led to an increase in folate levels in the general population and, more importantly, a significant decrease in the incidence of neural tube defects. However, this increase in folate intake has been associated with a greater risk of cancer disease. Many African countries are now embracing this concept; however, because folate promotes malaria parasite division, as it does in cancer cells, there is a possibility of malaria exacerbation if folate intake is increased. A precedent for such a concern is the now compelling evidence showing that an increase in iron intake can lead to a higher malaria risk; as a result, mass administration of iron in malaria-endemic areas is not recommended. In this article, we review work on the effect of folate on malaria parasites. Although this topic has received little research attention, the available data suggest that the increase in folate concentration could be associated with an increase in malaria infection. Thus, the introduction of food fortification with folic acid in malaria-endemic areas should be attended by precautionary programs to monitor the risk of malaria.

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Systematic review of adverse health outcomes associated with high serum or red blood cell folate concentrations

Cited by 19 publications

References 89 publications

Association of Maternal Folate and Vitamin B12 in Early Pregnancy With Gestational Diabetes Mellitus: A Prospective Cohort Study

Association of Maternal Folate and Vitamin B12 in Early Pregnancy With Gestational Diabetes Mellitus: A Prospective Cohort Study

Serum folate and vitamin B12 status in young Brazilian children

Malaria in the Era of Food Fortification With Folic Acid

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