Maternal methyl donor supplementation regulates the effects of cafeteria diet on behavioral changes and nutritional status in male offspring.
Methyl-donor supplements during pregnancy restored mouse social interaction lost to cafeteria diet but also raised anxiety.
01Research in Context
What this study did
Scientists fed pregnant mice an all-you-can-eat cafeteria diet. Half the moms also got methyl-donor powder—folic acid, B12, choline, betaine.
After birth, the team watched the male pups play, sniff, and explore. They scored social time, anxiety signs, and body weight.
What they found
Cafeteria babies stayed away from new mice—like social withdrawal. Methyl donors brought their play back to normal.
But the same pups froze more in open spaces and buried more marbles—clear anxiety spikes.
So the supplement fixed social skills yet created new worry behaviors.
How this fits with other research
Whitehouse et al. (2014) saw the same social boost in humans. Moms who took prenatal vitamins during month 5 had preschoolers with fewer autistic-like traits. K et al. now prove cause and effect in animals.
Li et al. (2025) repeated the rescue with a different tool. They gave sodium benzoate to moms with immune-triggered pregnancies and also saw normal mouse play. Two different supplements, same social win.
Mao et al. (2026) looks like the opposite: more lead and cadmium meant worse social scores in autistic preschoolers. The clash fades when you see they studied kids who already have ASD, while K et al. started with healthy-bound mice. Different starting points, different stories.
Why it matters
You now have mouse proof that methyl donors can undo junk-food damage to social circuits. Share this with OB-GYN partners—stress prenatal vitamins, especially when mom’s diet drifts toward fast food. Track both social and anxiety gains after birth; fixing one may wake the other.
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02At a glance
03Original abstract
<h4>Background</h4>Nutritional status and maternal feeding during the perinatal and postnatal periods can program the offspring to develop long-term health alterations. Epidemiologic studies have demonstrated an association between maternal obesity and intellectual disability/cognitive deficits like autism spectrum disorders (ASDs) in offspring. Experimental findings have consistently been indicating that maternal supplementation with methyl donors, attenuated the social alterations and repetitive behavior in offspring.<h4>Objective</h4>This study aims to analyze the effect of maternal cafeteria diet and methyl donor-supplemented diets on social, anxiety-like, and repetitive behavior in male offspring, besides evaluating weight gain and food intake in both dams and male offspring.<h4>Design</h4>C57BL/6 female mice were randomized into four dietary formulas: control Chow (CT), cafeteria (CAF), control + methyl donor (CT+M), and cafeteria + methyl donor (CAF+M) during the pre-gestational, gestational, and lactation period. Behavioral phenotyping in the offspring was performed by 2-month-old using Three-Chamber Test, Open Field Test, and Marble Burying Test.<h4>Results</h4>We found that offspring prenatally exposed to CAF diet displayed less social interaction index when compared with subjects exposed to Chow diet (CT group). Notably, offspring exposed to CAF+M diet recovered social interaction when compared to the CAF group.<h4>Discussion</h4>These findings suggest that maternal CAF diet is efficient in promoting reduced social interaction in murine models. In our study, we hypothesized that a maternal methyl donor supplementation could improve the behavioral alterations expected in maternal CAF diet offspring.<h4>Conclusions</h4>The CAF diet also contributed to a social deficit and anxiety-like behavior in the offspring. On the other hand, a maternal methyl donor-supplemented CAF diet normalized the social interaction in the offspring although it led to an increase in anxiety-like behaviors. These findings suggest that a methyl donor supplementation could protect against aberrant social behavior probably targeting key genes related to neurotransmitter pathways.
, 2023 · doi:10.29219/fnr.v67.9828