Turn of tide for oral vitamin B12 treatment

The recent report in Blood[1] on the efficiency of oral B12 for haematological and neurological symptoms in B12-deficient patients sounded much like the trumpet blast that shattered the walls of Jericho. A leading group of neurologists expanded a classical neurological concept of parenteral vitamin B12 treatment only and included a classical haematological concept of oral vitamin B12 treatment as an equally efficient alternative in the therapeutic arsenal. The acknowledgement was supported by a controlled study of oral vs. parenteral B12 treatment. Several investigators provided evidence in the 1950s and 1960s that oral B12 is absorbed by an alternative pathway not dependent on intrinsic factor or intact distal ileum [1]. Approximately 1% of an oral dose in the range 200–2000 µg a day was absorbed by the alternative pathway. Haematological response, neurological response, patient compliance and long-term results were reported to be excellent in the following clinical trials on patients with B12-deficiency disorders. The individual patient served as their own control. Improvement was documented by rectification of blood variables and disappearance of neurological signs. Only one group of medical pedagogues achieved implementation of the concept of oral vitamin B12 treatment into clinical practice: Ragnar Berlin and his co-workers [2–4]. Their success was based on a comparatively large patient group and meticulous long-term follow-up. Oral vitamin B12, 1000 µg daily, became an alternative first-line treatment for B12 deficiency from 1964 in Sweden. The Swedish turn of tide for oral B12 treatment occurred around 1970, when a majority of internists, haematologists and family physicians/general practitioners were convinced by the long-term results of the Berlin group [2]. Treatment by the oral route has stood the test of time. About 80% of vitamin B12 costs in Sweden are now accounted for by oral preparations [cf. 5]. These observations, however, received only sparse international attention [1, 6–9]. It is a token of time that the same group of scientists, who launched the metabolites methylmalonic acid (MMA) and homocysteine as markers for cellular deficiency of vitamin B12 a decade ago, now verified the efficiency of oral B12 treatment even for neurone lesions [1]. A modern controversial concept is that the metabolites react early when a deficiency state is emerging [10, 11]. A deficiency state is distinguished by elevated metabolites, anaemia, neurological and mental signs. The deficiency signs mentioned may appear isolated or in combinations. The development of metabolites as diagnostic tools has made vitamin B12 deficiency a common disease, especially in elderly people of postindustrial societies [11, 12]. It was estimated that approximately 20% of people above 69 years of age have known or unknown vitamin B12 deficiency [13]. The state of the metabolite homocysteine as a risk marker for thromboembolic vascular disease is even more controversial than the correct diagnosis and handling of vitamin B12 deficiency [14, 15]. Associated problems are the role of vitamin B12 in pregnancy disorders, in neural tube defects in new-born infants and in folate monotherapy. It is reasonable to assume that the scientific discussion on these subjects has stimulated knowledge and competence in primary healthcare and promoted a shift of patients with B12-associated problems from hospital specialists to primary healthcare [5, 12]. Parenteral B12 therapy was considered a burden for primary health care in England already 15 years ago [9, 16]. The Kuzminski study [1] opens for new consensus and a possibility to shift most B12-deficient patients from parenteral supplementation to oral supplementation. Nevertheless, it should be emphasized that group results cannot be translated to every individual. In the past, some patients by experience fared better with oral B12 than with parenteral B12 despite the current paradigm. The past experience also suggests that some patients cannot be managed by oral regimens. Finally, the Kuzminski study [1] highlighted the association between vitamin B12 deficiency and folate deficiency in clinical practice. Every fifth patient recruited into their study had to be excluded because of concomitant lack of folate, masked before B12 therapy. The observation, in perfect agreement with past experience, has bearings on the clinical management of such patients. Received 19 February 1999; accepted 15 March 1999.