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According to the NIH Office of Dietary Supplements, functional B12 deficiency is most commonly seen in patients with one or more of the following: Age over 50 stomach acid production declines with age, and stomach acid is required to free B12 from food PPI or H2 blocker use reflux medications suppress the acid needed for B12 absorption Metformin use, which interferes with B12 absorption directly Vegan or vegetarian diets B12 is found almost exclusively in animal products Gut conditions including celiac, IBS, SIBO, and Crohns MTHFR mutations that affect how B12 is metabolized once absorbed Heavy alcohol use The symptoms of low B12 are easy to dismiss: fatigue, brain fog, low mood, tingling in the hands or feet, weakness, and shortness of breath on mild exertion

the secondary C3-amine derivative intermediate e.g., compound 9) may then be methylated to obtain the desired cation (e.g., compound 1f)

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