As a statement made by one of the leaders in vitamin B12 field more than 10 years ago, Carmel’s idea of “cobalamin deficiency should not be diagnosed unless megaloblastic changes are found’ is still followed by many physicians and health authorities when accepting B12 deficiency diagnosis. But as time goes by, evidence and clinical cases showed that B12 deficiency symptoms can be seen even when B12 level in blood is within the reference range, as 200 – 900 pg/mL in the United States, and 135-650 pmol/L in Australia. In clinical practice, signs and symptoms of B12 deficiency start when plasma B12 levels are ‘normal’, and long historical studies showed that neurological symptoms of deficiency occur in patients without sign of anaemia. As a matter of fact, Japan raised its B12 reference range to 500 – 1300 Pmol in 1980s.
These phenomena raise some questions to us: Is the current reference range or normal lower limit of B12 set too low? What level should be set as the lower limit of B12 reference range?