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The observed threshold effect at 358.7 pg/mL (OR = 1.04 per 10 pg/mL, 95% CI: 1.00–1.08, P = 0.03) suggests a plateau in B12 benefit beyond this level, likely due to saturation of methionine synthase activity—a mechanism consistent with non-linear enzymatic dose-response relationships, where additional B12 may not enhance methylation capacity [21]

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Shinaman is a leading research physician in California, contributing significantly to the pain medicine field with publications focusing on novel opioid medications and the innovative use of radiofrequency technology