Going back for seconds? You are what you eat- A tale of too much Vitamin B12

Vitamin B12 (“B12”) helps with nerve function, red blood cell production, and cellular metabolism. There has been plenty of research done to learn about the effects of having low B12, but very little research has been done to know what happens if you have too much B12. Some exploration on high B12 shows that high serum B12 at 2x the average normal level is related to solid tumors and poor tumor prognosis. It is speculated that a potential outcome of high B12 levels can cause cognitive dysfunction as there is one peer reviewed paper demonstrating a link between high B12 consumption during pregnancy and increased autism rates in offspring. Therefore, we sought to determine if high B12 exposure affects gene expression in a human neuronal cell line. Our lab’s data from Summer 2023 demonstrated that 4 microRNAs from a panel of 95 were significantly upregulated, and theoretically, their targets would be downregulated since microRNAs target other genes’ mRNA molecules for degradation. After performing gene ontology, we noted over 40 genes that are targets of the microRNAs are related to ubiquitination, which is a process for degrading old or misfolded proteins to prevent disease. If ubiquitination is decreased, old and misfolded proteins can lead to disease. We studied expression of ubiquitination-related genes through a qPCR panel after growing SH-SY5Y cells and treating them with control medium or 2x B12 medium using cobamamide as the B12 supplementation. Cobamamide is the form found in fortified grains and drinks. We found that 2 genes, RNF148 and UBE2D2, were significantly downregulated. Six genes were nearly significant with 0.05< p< 0.1, and 31 genes had a fold change that was >3 fold or < 0.5 fold. We currently are validating our findings with individual Taqman assays to determine which genes are significantly altered with 2x B12 treatment.