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Patients should be reviewed 812 weeks after commencing treatment to assess: Symptomatic improvement, particularly resolution of fatigue and neurological symptoms Haematological response (normalisation of haemoglobin and mean cell volume) Reticulocyte count typically rises within one week, indicating bone marrow response Repeat serum B12 testing is generally not useful after starting parenteral therapy, as levels remain elevated for months

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Fasting in the context of CR is required for the benefits on insulin sensitivity, frailty, cognition, and lifespan in wild-type mice 12,54 , and indeed fasting alone without reduction of calories is sufficient for many of the molecular effects of CR as well as extending lifespan in wild-type mice 12,55