Thiamin pyrophosphate is a co-factor for the multi-subunit enzyme, branched chain a-ketoacid dehydrogenase (BCKD) and is an adjunct to be considered in the treatment regime for MSUD.  Because it is a water-soluble vitamin, reported thiamin dosages have varied from 10-1000 mg/day and have been given for extended periods of time in both the newborn period and later without any reported toxic side-effects. Patients with MSUD for whom supplemental thiamin has increased dietary branched chain amino acid (BCAA) tolerance (or decreased plasma BCAA on a constant dietary intake), appear to be only those with some residual BCKD activity, especially those with E2 mutations. Patients should be continued on a BCAA restricted diet during the assessment of the thiamin response, as well as during long-term supplementation. Studies have reported a thiamin response is apparent within one month.