Do we need to reconsider the desirable blood level of vitamin B12?

“The proscription that cobalamin deficiency should not be diagnosed unless megaloblastic changes are found is akin to requiring jaundice to diagnose liver disease.” [1]. This statement by Carmel, one of the leaders in the vitamin B12 field, was made more than 10 years ago and yet many physicians and health authorities still insist on haematological changes before accepting a diagnosis of vitamin B12 (cobalamin) deficiency. It is not unusual that health authorities refuse prescriptions for vitamin B12 in patients with clinical signs of neuropathy because the patients have no haematological signs and their plasma vitamin B12 levels are reported as ‘normal’. This situation is disconcerting in view of the long history of studies showing that neurological signs of deficiency may occur in patients who do not show anaemia [2]. Even in patients with clinical pernicious anaemia, up to 28% do not have anaemia and up to 33% have normal mean corpuscular volume [1]. How, then do we define which patients with clinical signs or symptoms should be treated and what is the desirable plasma vitamin B12 level below which treatment is required?