Background Folic acid (FA), as a synthetic form of folate, has been widely used for dietary supplementation in pregnant women. The preventive effect of FA supplementation on the occurrence and recurrence of fetal neural tube defects (NTD) has been confirmed. Incidence of congenital heart diseases (CHD), however, has been parallelly increasing worldwide. The present study aimed to evaluate whether FA supplementation is associated with a decreased risk of CHD. Methods We searched the literature using PubMed, Web of Science and Google Scholar, for the peer-reviewed studies which reported CHD and FA and followed with a meta-analysis. The study-specific relative risks were used as summary statistics for the association between maternal FA supplementation and CHD risk. Cochran's Q and I2 statistics were used to test for the heterogeneity. Results Maternal FA supplementation was found to be associated with a decreased risk of CHD (OR = 0.82, 95% CI: 0.72–0.94). However, the heterogeneity of the association was high (P < 0.001, I2 = 92.7%). FA supplementation within 1 month before and after pregnancy correlated positively with CHD (OR 1.10, 95%CI 0.99–1.23), and high-dose FA intake is positively associated with atrial septal defect (OR 1.23, 95%CI 0.64–2.34). Pregnant women with irrational FA use may be at increased risk for CHD. Conclusions Data from the present study indicate that the heterogeneity of the association between maternal FA supplementation and CHD is high and suggest that the real relationship between maternal FA supplementation and CHD may need to be further investigated with well-designed clinical studies and biological experiments.

Folate is a vitamin beneficial for humans that plays an important role in metabolism, but it cannot be well supplemented by food; it is necessary to supplement it in other ways. Based on this consideration, a novel crystal form C of 6S-5-methyltetrahydrofolate calcium salt (MTHF CAC) was obtained. To explore the difference between MTHF CAC and the crystal form Ⅰ of 6S-5-methyltetrahydrofolate calcium salt (MTHF CA) as well as an amorphous product of 6S-5-methyltetrahydrofolate glucosamine salt (MTHF GA), their stability and pharmacokinetic behaviours were compared. The results of high-performance liquid chromatography coupled with ultraviolet detection analysis indicated that MTHF CAC showed a better stability than MTHF CA and MTHF GA. After oral administration of MTHF CAC, MTHF CA, and MTHF GA to male rats, the MTHF concentrations were analysed using a validated liquid chromatography–tandem mass spectrometry, and the pharmacokinetic parameters were compared. The mean residence times (0–t) of MTHF CAC, MTHF CA, and MTHF GA were 3.7 ± 1.9 h, 1.0 ± 0.2 h (p < 0.01), and 1.5 ± 0.3 h (p < 0.05), respectively. The relative bioavailability of MTHF CAC was calculated to be 351% and 218% compared with MTHF CA and MTHF GA, respectively, which suggests that MTHF CAC can be better absorbed and utilized for a longer period of time.

Qu‐feng‐sheng‐shi Granules (QFSSG), a common prescription for the treatment of chronic inflammation and allergic rhinitis, is widely used in the clinic as a traditional Chinese medicine. Chemical analysis and quality control studies of this formulation are relatively limited compared with pharmacological studies. In this study, a high‐performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry (HPLC–ESI–Q/TOF–MSn) was used to identify the components in this prescription. Next, to quantify six major compounds, an HPLC–UV method was developed and validated. The results showed that 53 compounds were identified based on the MSn data, retention time and previous reports, including 17 coumarins, 14 lignans, 10 chromones, nine phenylethanoid glycosides and three other compounds, were identified or tentatively assigned. Contents of six major bioactive compounds (4′‐O‐β‐glucopyranosyl‐5‐O‐methylvisamminol, Prim‐O‐glucosylcimifugin, forsythin, magnolin, imperatorin, isoimperatorin) could be determined by HPLC simultaneously. In addition, the potential anti‐inflammatory activity of six major compounds was determined too, and we found that four compounds (4′‐O‐β‐glucopyranosyl‐5‐O‐methylvisamminol, Prim‐O‐glucosylcimifugin, forsythin, imperatorin) have a potent nitric oxide inhibitory effect. In conclusion, this work provided comprehensive information on the quality control of QFSSG and evaluated the potential biological activity of the main components in QFSSG, which can contribute to understanding and using it more scientifically.

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Folic acid (FA) is a synthetic and highly stable version of folate, while 6S-5-methyltetrahydrofolate is the predominant form of dietary folate in circulation and is used as a crystalline form of calcium salt (MTHF-Ca). The current study aims to evaluate the toxicity and safety of FA and MTHF-Ca on embryonic development, with a focus on cardiovascular defects. We began to analyze the toxicity of FA and MTHF-Ca in zebrafish from four to seventy-two hours postfertilization and assessed the efficacy of FA and MTHF-Ca in a zebrafish angiogenesis model. We then analyzed the differently expressed genes in in vitro fertilized murine blastocysts cultured with FA and MTHF-Ca. By using gene-expression profiling, we identified a novel gene in mice that encodes an essential eukaryotic translation initiation factor (Eif1ad7). We further applied the morpholino-mediated gene-knockdown approach to explore whether the FA inhibition of this gene (eif1axb in zebrafish) caused cardiac development disorders, which we confirmed with qRT-PCR. We found that FA, but not MTHF-Ca, could inhibit angiogenesis in zebrafish and result in abnormal cardiovascular development, leading to embryonic death owing to the downregulation of eif1axb. MTHF-Ca, however, had no such cardiotoxicity, unlike FA. The current study thereby provides experimental evidence that FA, rather than MTHF-Ca, has cardiovascular toxicity in early embryonic development and suggests that excessive supplementation of FA in perinatal women may be related to the potential risk of cardiovascular disorders, such as congenital heart disease.