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The strongest human clinical evidence is for topical use, including the Leyden 2002 photoaging trial and a 2023 NEEL gel topical study reporting an average 28% increase in skin collagen density at 3 months

However, significant risks and limitations must be considered

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VPA is used to treat psychiatric disorders and as such there is an association with accidental or deliberate overdose, the incidence of which is increasing [135, 136]

Figure 9 3.8 Proposed substrate recognition and enzyme mechanism of MSA-DH The potential substrate binding site of MSA-DH was explored by superimposing the three-dimensional structure of human succinic semialdehyde dehydrogenase in complex with its substrate (PDB ID: 2W8Q) (Supplementary Figure S1)

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