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Unlike the other common amino acids, rotation about the C-N bond in proline is not possible due to the structural constraint of the five-membered ring

People with MTHFS variants cannot do this efficientlyfolinic acid builds up instead of being metabolized. In a landmark 2018 study, treating MTHFS-deficient patients with folinic acid caused it to accumulate 30-fold and actually worsened their cerebral folate deficiency

The results obtained demonstrated that the use of ALA (600 mg/day) as an additional therapy to doxorubicin and paclitaxel induces a significant improvement in the peripheral sensory neuropathy grading (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) and in the FACT/GOG-Ntx-12 (12-item neurotoxicity questionnaire) total score

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