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MTHFR and Folate Transport Systems The MTHFR gene (methylenetetrahydrofolate reductase) plays a key role in the conversion of dietary folate into its biologically active form, L-methylfolate (5-MTHF)

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But only the R-isomer (R-ALA) is naturally produced in the body and actively participates in mitochondrial energy metabolism.12 Some studies suggest that R-ALA may be more bioavailable than standard racemic ALA though the clinical significance of this difference is still under investigation.17 In addition, anecdotal reports and small studies indicate that R-ALA may be easier on digestion, with fewer gastrointestinal side effects than standard racemic ALA, especially at higher doses.18 However, R-ALA is chemically unstable on its own