How we wish to be cited:
Björkegren K. Focus on folate. [editorial]. Rondel 2004; 18. URL: http://www.rondellen.net

Focus on folate
The classical picture of severe deficiency of cobalamin and/or folate is inhibition of cell division in prophase (1); the result is few big cells, macrocytes or megalocytes. The deficiency affects all tissues with dividing cells, producing anemia, infertility and thin vulnerable mucous membranes (1,2). In non-dividing cells, polyneuropaty due to defective maintenance of myelin sheaths is widely recognized (3). In a modern post-industrial society, deficiency states of cobalamin and folate are mainly a concern of primary health care; even preclinical deficiencies may produce infertility, miscarriages, and lesions of the fetus. However, elderly people provide the main part of deficiency patients (4). Since folate treatment may mask cobalamin deficiency, it is suggested that folate monotherapy is abandoned; every patient treated with folate should also be treated with cobalamin. Likewise, cobalamin deficiency should always be treated with both cobalamin and folate.
Figure
The giant nucleus (2x46 chromosomes) of a neutrophil leukocyte released from the bone marrow in the G2 stage of cell division is prone to hypersegmentation, a classical feature in cobalamin/folate deficiency.

For about 50 years, it has been considered an error of the art to medicate with folate alone, without cover up with cobalamin (5). Conversely, it is becoming increasingly evident, that it is an error of the art to medicate with cobalamin without simultaneous folate therapy; out of 38 patients with apparent monodeficiency of cobalamin, the therapeutic effect of vitamin B12 alone was blocked by an incipient folate deficiency in five patients (6). Likewise, cobalamin monotherapy normalized methylmalonic acid in 87% of elderly patients with suspected deficiency but only 21% of associated homocysteine values; addition of oral folic acid normalized all homocysteine values (4,7).

If cobalamin/folate deficiency is allowed to progress, the deficiency states become crippling and life threatening, as suggested by the name of the index disease, pernicious anemia. In contrast, the cost of treatment of deficiency in early stages amounts to less than one cigarette per day (8). It is reasonable to assume that most residents will be able to bear this burden themselves, without subvention from the society. In contrast, it is up to society to secure, that the information from the health care system is adequate and balanced. Furthermore, the vitamin preparations on the market should be monitored for adequate bioavailability for both healthy persons and those with e.g. achylia due to atrophic gastritis.

Karin Björkegren

References

  1. Nilsson-Ehle H. The macrocyte secrets [evaluation]. Rondel 2001; 8. URL: http://www.rondellen.net/evaluation08_eng.htm
  2. Gräsbeck R. R. Infertility –folate, cobalamin and other micronutrients [evaluation]. Rondel 2002; 10. URL: http://www.rondellen.net/evaluation10_eng.htm
  3. Norberg B. Painful sensory neuropathy [editorial]. Rondel 2003; 16. URL: http://www.rondellen.net/publisher16_eng.htm
  4. Björkegren K. Studies on vitamin B12 and folate deficiency markers in the elderly. A population-based study (dissertation). Uppsala University, Uppsala, Sweden, 2003 (http://publications.uu.se/uu/fulltext/nbn_se_uu_diva-3364.pdf)
  5. Nilsson M. Error of the art [debate]. Rondel 2002; 11. URL: http://www.rondellen.net/debate11_eng.htm
  6. Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood 1998; 92:1191-8
  7. Nilsson-Ehle H. Skutskär and the world – deficiency of vitamin B12 and folate in the elderly [evaluation]. Rondel 2003; 16. URL: http://www.rondellen.net/evaluation16_eng.htm
  8. Lökk J. Homocysteine lowering – from skunk to rose [debate]? Rondel 2003; 17. URL: http://www.rondellen.net/debate17_eng.htm

Published January 20, 2004