Clinical evaluation

How we wish to be cited:
Lökk J. Neuropathy as the first sign of vitamin B12 deficiency [evaluation]. Rondel 2004; 20. URL: http://www.rondellen.net

The Norwegian physician Erik Magnus performed one of the most conclusive studies in the history of polyneuropahy due to cobalamin deficiency (1). He worked with pernicious anemia in experimental relapse. He demonstrated that about one third of the patients relapsed with neurological symptoms. Another finding was that each patient tended to relapse with the same type of symptoms as at the start of the disease; those who had fallen ill with neuropathy relapsed with neuropathy.

The ethical basis of the Magnus investigation was that the Berlin group of Sweden had demonstrated that oral cyanocobalamin, 1 mg daily, was a safe and reliable treatment for all types of cobalamin deficiency (2). The observations of Magnus are at variance with the concept that neurological lesions due to vitamin B12 deficiency can be treated only by injections. Furthermore, the observations of Magnus suggest that polyneuropathy from vitamin B12 deficiency not readily becomes permanent (cf 3). This interpretation is supported by the effects of oral cobalamin, 1 mg daily, and oral folic acid, 5 mg daily, on the cognitive functions of demented patients with deficiency suggested by elevated plasma homocysteine, more than 20 micromoles/L (4).

The observation of Magnus that about one third of patients start with neuropsychiatric signs of B12 deficiency has been verified by other workers (5) and is now generally accepted. "An important subgroup of patients present with neurological effects of B12 deficiency, without any macrocytosis or megaloblastic changes. Neurological manifestations include peripheral neuropathy, optic atrophy, subacute combined degeneration of the cord, and mental abnormalities such as irritability, somnolence, and dementia" (6).

It is still obscure why some patients present with neurological disorders, other with hematological disorders or lesions of mucous membranes (1,7) or infertility (8). Now it is suggested that such individual reactions may be due to genetic polymorphisms of transcobalamin (9, 10). Such hypotheses are to be verified or falsified. From a principal point of view, there are also possibilities for genetic variations in other receptors of cobalamin in the human body (8). From a practical point of view, Rosenberg and co-workers emphasized that there is still insufficient evidence for any effect of cobalamin and folate on dementia (11). Nevertheless, deficiency of folate and cobalamin can by experience cause states easily mistaken for dementia or depression. Finally, a demented patient with established deficiency has the same right to have vitamin therapy as other citizens.

1. Magnus EM. Cobalamin and unsaturated transcobalamin values in pernicious anaemia; Relation to treatment. Scand J Haematol 1986; 36; 457-65
2. Berlin H, Berlin R, Brante G. Oral treatment of pernicious anemia with high doses of vitamin B12 without intrinsic factor. Acta Med Scand 1968; 184:247-58
3. Norberg B. Cobalamin and folate for better and worse [editorial]. Rondel 2004; 20. URL: http://www.rondellen.net/publisher20_eng.htm
4. Nilsson K, Gustafson L, Hultberg B. Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. Internat J Geriatr Psyk 2001; 16:609-14
5. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988; 318:1720-8
6. Norberg B. Medicine – concentrated and structured [evaluation]. Rondel 2004; 19. URL: http://www.rondellen.net/evaluation19_eng.htm
7. Björkegren K. Studies on vitamin B12 and folate deficiency markers in elderly: A population-based study. Dissertation, Uppsala 2003
8. Gräsbeck R. R. Infertility –folate, cobalamin, and other micronutrients [evaluation] Rondel 2002; 10. URL: http://www.rondellen.net/evaluation10_eng.htm
9. Zetterberg H, Nexö E, Regland B, Minthon L, Boson R, Palmér M, Rymo L, Blennow K. The transcobalamin (TC) codon 259 genetic polymerism influences holo-TC concentration in cerebrospinal fluid in patients with alzheimer`s disease. Clin Chem 2003; 49:1195-8
10. McCaddon A, Blennow K, Hudson P, Hughes A, Barber J, Gray R, Davies G, Williams JH, Doguid J, Lloyd A, Tandy S, Everall M, McCaddon A, Ellis D, Palmer M, Bogdanovic N, Gottfries C-G, Zetterberg H, Rymo L, Regland B . Transcobalamin polymorphism and serum holo-transcobalamin in Alzheimers´s disease. Dement Geriatr Cogn disord 2004; 17: 2215-21
11. Rosenberg P, Hernborg A, Håkansson J, Skoglund I, Svartholm R, Söderström U, Wahlström L. B vitamins and dementia – lack of evidence in Cochrane analysis [debate]. Rondel 2004; 19. URL: http://www.rondellen.net/debate19_eng.htm

Published november 15, 2004