Home Medizin Die Auswirkungen einer hohen mütterlichen Folsäureaufnahme auf die Gesundheitsergebnisse der Nachkommen

Die Auswirkungen einer hohen mütterlichen Folsäureaufnahme auf die Gesundheitsergebnisse der Nachkommen

von NFI Redaktion

A recent overview article in Nutrients summarized what is known about the effects of excessive folic acid (FA) supplementation by mothers on children.


Study: Risk of excessive maternal folic acid supplementation in offspring. Image Credit: luchschenF/Shutterstock.com









Study: Risk of excessive maternal folic acid supplementation in offspring. Image Credit: luchschenF/Shutterstock.com

The conclusion was that while folate is a crucial nutrient, higher than necessary FA intake by the mother may have negative effects on their offspring.

Folate is an Essential Nutrient

Water-soluble vitamin B9 or folic acid is needed for the formation of red blood cells (RBC) and to promote healthy cell growth and function. Doctors consider it essential during pregnancy and breastfeeding to promote fetal and placental growth, enlarge the uterus, reduce the risk of brain and spinal cord birth defects in the child, and improve cardiovascular and reproductive health in other ways.

Folate naturally occurs in some foods such as beans, peas, green leafy vegetables, and nuts. However, synthesized FA in fortified foods and supplements is widespread. After consumption, it facilitates the transfer of methyl groups between molecules, aiding in nucleotide synthesis and amino acid metabolism. It is particularly involved in the methionine donor-metabolism.

Adequate FA supplementation has been linked to higher birth and placental weights and a reduced risk of children being small for gestational age and low birth weight. It also reduces the likelihood of neural tube defects (NTDs).

Continued supplementation in the second and third trimesters has shown sustained benefits for the neurocognitive development of children up to 11 years old. These include emotional intelligence, word sequence, semantic processing, verbal-executive and motor function, attention, communication, and social skills.

A folic acid deficiency in mothers has been associated with numerous adverse consequences, including increased blood pressure and obesity in children. However, the availability of fortified foods and supplements has significantly increased serum, erythrocyte, and total folate levels, and recent studies have highlighted the potential negative consequences of excessive supplementation.

FA Supplementation and ASD

In addition to the benefits for neurological development, maternal folic acid intake has been associated with the occurrence of Autism Spectrum Disorders (ASD). A study in Norway found that taking FA from four weeks before conception and continuing for 12 weeks provides protection against ASD.

However, a recent study in the United States revealed a „U-shaped“ relationship between ASD risk and the frequency of maternal multivitamin supplementation. This suggests that the risk of ASD is highest at very low and very high supplementation levels.

Further analysis suggests that the presence of unmetabolized folic acid (UMFA) in umbilical cord blood may be positively associated with ASD risk, especially in black children. However, more research is needed to shed light on these mechanisms.

Insights from Mouse Models

While well-designed mouse models can provide valuable information on the effects of high FA supplementation that cannot be ethically explored through human experiments, the timing and duration of supplementation, concentration of FA, method of FA administration, and the potential for different effects depending on the offspring’s gender must be considered.

Researchers used microarrays, Western blot, RNA sequencing (RNA-seq), and Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) to analyze the effects of FA.

Results from some studies indicate that mice exposed to moderate FA levels showed more gene alterations. In terms of gender-specific differences, some genes were more affected in female mice, while others were stronger in male mice, leading to different effects on the placenta, embryonic brain, and early postnatal brain. There were also indications that FA could impair brain development early in life but lead to lasting behavioral changes into adulthood.

While maternal FA deficiency is associated with NTDs, excessive supplementation has been linked to reduced placental and embryonic weights, smaller hippocampal areas, and increased weight gain in male but not female offspring. Observed effects on neurological development included impaired short-term memory, hyperactivity-like and repetitive behaviors, and increased anxiety in mouse pups.

Results varied across different studies, but there is clear evidence that excessive maternal FA intake can have long-term consequences on physical and behavioral outcomes. It may also be involved in glucose metabolism and reproductive disorders, although there is no evidence of transgenerational inheritance effects.

Conclusions

Concerns about maternal folate deficiency are widespread, but FA supplements and enriched foods are now common, and excessive intake can have far-reaching effects on the central nervous system.

While there is increasing evidence of detrimental effects alongside benefits, there is a need to translate insights from mouse models into human studies and investigate gender-specific effects. Additionally, focus should be placed on new forms of FA supplementation that can mitigate the potential harms of currently available supplements.

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