Researchers led by Tzyy-Nan Huang and Ming-Hui Lin from Academia Sinica in Taiwan report that a low-dose mixture of zinc, serine, and branch-chain amino acids can alleviate behavioral deficits in three different mouse models of autism. Published December 2nd in the open-access journal in PLOS Biology, the study shows that when combined together, these three dietary supplements promote communication between neurons in the brain and improve social behaviors.
Autism spectrum disorder (ASD) is known to result from abnormal neural development that affects how neurons are connected. At the same time, nutrition is known to be one of the environmental factors that influences ASD. Individually, zinc, serine, and branch-chain amino acids are all thought to have positive effects on neural connectivity. The authors hypothesized that a mixture of the three would be a more effective treatment than any individually and that the necessary dosages of each could be lowered. They tested their theory in three mouse models of ASD; they measured amounts of synapse-related proteins, used calcium imaging to examine neural activity in the amygdala and assessed social behavior.
The researchers found that the cocktail of supplements altered the brains of autistic mice so that the expression of proteins in the synapse resembled those of normal mice and that the abnormal hyperactivity of neurons in the amygdala was reduced after taking the cocktail. The researchers also found that social behaviors in the animals improved after they were given the cocktail. However, when each supplement was given separately, the same dosages had no effect on behavior. This was true in two additional mouse models of autism, showing that it's the synergistic effect of combining the three supplements that allows it to be effective at low doses.
Yi-Ping Hsueh summarized, "As hundreds of genes are implicated in autism, each with distinct molecular functions, a 'one gene–one therapy' approach is impractical for addressing the complexity of ASD. Our findings show that a low-dose nutrient mixture containing zinc, branched-chain amino acids (BCAAs), and serine—working synergistically to improve synaptic function and social behaviors across three ASD mouse models—offers a safer and more practical strategy for long-term, broad application, even beginning in childhood."
Tzyy-Nan Huang, one of the study's first authors, emphasized, "High doses of individual nutrient supplements such as zinc, branched-chain amino acids, and serine can improve synaptic function through different mechanisms, but low doses of any single nutrient alone are ineffective. It is exciting to see that combining these nutrients at low doses successfully restores synaptic proteomes and enhances social behaviors in three different mouse models of autism."
Ming-Hui Lin, the study's co–first author, added, "I was thrilled to observe that just seven days of treatment with the nutrient mixture significantly modulated neuronal circuit activity and connectivity in real time. These results provide strong support for the beneficial effects of low-dose nutrient supplement combinations."
In your coverage, please use this URL to provide access to the freely available paper in PLOS Biology: https://plos.io/4ol128D
Citation: Huang T-N, Lin M-H, Hsu T-T, Yu C-H, Hsueh Y-P (2025) Low-dose mixtures of dietary nutrients ameliorate behavioral deficits in multiple mouse models of autism. PLoS Biol 23(12): e3003231. https://doi.org/10.1371/journal.pbio.3003231
Author countries: Taiwan
Funding: This work was supported by grants from Academia Sinica, Taiwan (AS-IA-111-L01 to Y.-P.H.) and the National Science and Technology Council, Taiwan (NSTC 113-2326-B-001-008 and 114-2326-B-001-005 to Y.-P.H.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
