Clinical evaluation

In Sweden, it was hard for the clinicians to accept that homocysteine replaces cobalamin and folate in the first laboratory screening of a suspected case of malnutrition or malabsorption (Fig); most general practitioners rejected such a statement 1996 and 1998. Nevertheless, present opinion appears to sway towards the conclusion that homocysteine is the screning test of choice, when deficiency of cobalamin or folate is suspected. The paradigm shift has been subject to an intense discussion for about 15 years (cf 1-7). Now the standard text-book of clinical chemistry recommends homocysteine as screening test, a suggestion which was met with enthusiasm by the referee of ALLMÄNMEDICIN, the official journal of family medicine in Sweden.

The virtues of homocysteine in deficiency diagnosis of cobalamin and folate are evident from a glance at its key position in a chart of the methionine cycle. A lack of coenzyme (methylcobalamin) will dam up the levels of homocysteine. A lack of substrate (5-methyltetrahydrofolate) will dam up homocysteine levels; and so will a combined deficiency of both cobalamin and folate.Thus, homocysteine provides a sensitive marker for early stages of deficiency of cobalamin, folate, or both.

The limitation of homocysteine as deficiency marker is a lack of specificity. Inborn errors of metabolism, impaired renal function (nephrosclerosis), impaired liver function, and several drugs dam up homocysteine levels in the presence of cobalamin and folate in physiological concentrations.

In elderly citizens, general practitioners often find it convenient to give test treatment with both cobalamin and folate and observe the effect on the clinical symptoms, which brought the patient to the doctor (cf 1). Mild symptoms, often neuropsychiatric, are expected to vanish within 1-12 weeks. It should be emphasized that the use of test treatment requires a close follow-up.

It is reasonable to assume that the intense Swedish debate on cobalamin deficiency and folate deficiency provides a mutual dialogue between "senders" and "receivers", a two-way communication (cf 2). The details of this communication are subject to further research.

Mats Nilsson
County Council of Västerbotten
SE-901 89 Umeå, Sweden
mats.nilsson@vll.se

1. Björkegren K. Focus on folate. [editorial]. Rondel 2004; 18. URL: http://www.rondellen.net/publisher18_eng.htm
2. Nilsson M. Cobalamin communication – receivers and senders [editorial]. Rondel 2003; 15. URL: http://www.rondellen.net/publisher15_eng.htm
3. Nilsson M. Error of the art [debate]. Rondel 2002; 11. URL: http://www.rondellen.net/debate11_eng.htm
4. Lökk J, Nilsson M, Norberg B, Rudolphi O, Sandström H, Westman G. Controversies around vitamin B12 in Sweden. Attitudes and values behind clinical decision-making in primary health care 1996. Hematology 1997; 2:341-50
5. Lökk J, Nilsson M, Norberg B, Hultdin J, Sandström H, Westman G. Shifts in B12 opinions in primary health care of Sweden. Scand J Public Health 2001; 29:122-8
6. Lökk J, Nilsson M, Norberg B, Hultdin J, Sandström H, Westman G. Vitamin B12 in primary health care and geriatrics – attitudes, knowledge and competence. Internat J Geriatr Psychiatry 2001; 16:987-92
7. Nilsson M, Lökk J, Norberg B, Hultdin J, Sandström H, Westman G. Sex differences in cobalamin (vitamin B12) opinions of Swedish physicians. Nord J Psychiatry 2002; 56:299-303

Published March 29, 2004