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Table 2 Animal models studies that evaluated the effect of FA on CLP formation

From: Effect of folic acid on animal models, cell cultures, and human oral clefts: a literature review

Author, year of publication

Sample

FA dose/time of treatment

Conclusion

Authors’ judgment

Paros and Beck, 1999 [27]

Pregnant mice:

19 experimental

9 controls

12 mg/24 h, during gestation days 8, 5–9, 5

FA administered continuously during the critical period ofdevelopment, reduces CLP frequency.

This study shows the associationbetween folates and theprevention of CLP.

Bienengraber et al. 2001 [24]

Pregnant rats:

11 experimental

3 controls

9.06 μM from day 14–17 post-conception,depending on the assigned group

Percentage of complete CP was significantly lower in theFA group (4 %) compared to the percentage observed inthe non-folate group (53 %).

Indicates a protective effect ofFA against CP.

Burgoon et al. 2002 [7]

Female mice:

21 experimental

39 controls

0.09–4.53 μM/kg diet, 4 weeks before mating

80% of the mice fed with FA-deficient diet had CP,compared with 37% of those that consumed a diet with4.53 μM/kg.

Shows evidence of the protectiveeffect of FA against CP.

Reynolds et al. 2003 [8]

Female mice:

30–36 experimental

10–12 control

9.06–6.79 μM/kg of body weight, on gestationday 8–11 depending on the assigned group

FA decreases the incidence of CP to 6.3%, while Metreduces the incidence to 5.7%; the FA + Met group didnot present CP.

FA prevents the formation of CP.

Yao et al. 2011 [25]

Female adult miceexplanted palates:

32 experimental

8 control

100 μM for 72 h

FA allows the development and fusion of the palateinhibited by retinoic acid.

FA inhibits CP formation inducedby retinoic acid.

Scheller et al. 2013 [28]

150 female mice

Experimental group:761 fetuses

No FA applied. FA concentration wasdetermined in the blood and amniotic fluidof the dams

The reduced availability of certain subgroups of vitamin B(B1, B5, and FA) in the amniotic fluid and serum wasrelated to an increase in the appearance of clefts inA/WySn mice.

This finding confirms that FA isessential in preventing clefts.

Kriangkrai et al. 2017 [26]

Rat explanted embryos

100 μM for 18 h

FA decreases the teratogenic effects of 13-cis-retinoic acidin tissues of the middle facial process.

Pretreatment with FA exhibitsbeneficial effects on CLPprevention.

  1. FA folic acid, CLP cleft lip palate, CL cleft lip, HCY homocysteine, Met methionine