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To mitigate these risks, comprehensive in vitro and in vivo studies evaluating the immunogenic potential of peptide compounds should be conducted before initiating clinical trials

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A 2025 meta-analysis of 16 studies involving 6,098 participants found no statistically significant difference between intramuscular, oral, and sublingual B12 supplementation routes (p=0.270)

The definition and our understanding of the condition has evolved significantly since Biermers original description