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This is by design, and reflects the necessity of RCTs to assess clinical impact for a specific therapeutic and indication

Side effects are generally mild, including nausea, vomiting, and gastrointestinal discomfort, but these diminish over time as the body adjusts to treatment

Soberg S, Sandholt CH, Jespersen NZ, Toft U, Madsen AL, von Holstein-Rathlou S, Grevengoed TJ, Christensen KB, Bredie WLP, Potthoff MJ, Solomon TPJ, Scheele C, Linneberg A, Jorgensen T, Pedersen O, Hansen T, Gillum MP, Grarup N

Howe S, Zphel D, Subbaraman H, Unger C, Held J, Engleitner T, et al

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Effects are likely mediated via circumventricular organs (brain regions lacking a complete blood-brain barrier) and vagal afferent pathways, with limited direct penetration