How we wish to be cited:
Norberg B. Oral high-dose cyanocobalamin - a contagious concept [editorial]. Rondel 2001; 8. URL: http://www.rondellen.net

Oral high-dose cyanocobalamin – a contagious concept

It is reasonable to assume that the oral versus parenteral B12 discussion will flare shortly. The Kuzminski study (1) summarised and confirmed previous experience with oral high-dose cyanocobalamin in the treatment of vitamin B12 deficiency. The results were later subject to constructive criticism in The Lancet (2,3). It seems likely that preparations of oral high-dose cyanocobalamin are about to be registered worldwide.

For historical reasons, the experience with oral high-dose cyanocobalamin is extensive in Sweden (1-4). Such preparations were introduced about 1965 and gradually gained the confidence of the doctors (Table 1). The injections topped 1998 with 56,700 patient years and decreased to 53,354 patient years in 2000.

Table 1 Percentage of patients on oral high-dose cyanocobalamin in Sweden 1981-2000. Patient years (PY) with parenteral B12 are based on sale statistics and the assumption that each patient was treated with 1 mg each month as an average dose. Correspondingly, the average oral dose of B12 was assumed to be 1 mg daily.

Year Oral B12 PY(i.m.) PY(oral)
1981a 25%    
1988?b 40%    
1990c 62% 25,465 41,852
1998c 67% 56,700 119,935
2000c 73% 53,354 145,700

aBorch K, Liedberg G. Scand J Gastroenterol 1984; 19:154-60.
bBerlin R. Written communication, Nov 1989 (Cited by Lederle FA, JAMA 1991; 265:94-5).
cSwedish Pharmaceutical Data (Läkemedelsstatistik AB, Stockholm, Sweden).

It should be emphasised that the slanting from injections to tablets was a spontaneous change of prescription habits; the choice was financially neutral for the patient, the producer, and the prescriber.

The success for oral high-dose cyanocobalamin now provides an obstacle for further clinical trials in Sweden. Most patients are discovered in an early stage of deficiency and promptly treated with cobalamin. Thus, it is difficult to recruit a sufficient number of patients to a prospective trial.

Most workers with personal experience of oral high-dose cyanocobalamin believe that the oral regimen is efficient for neurological and neuropsychological signs and symptoms of B12 deficiency (1,5). Indeed, the oral regimen has the official indication for such deficiency states in Sweden. The matter is, however, not settled on a global level. It is desirable that this aspect is attended in the design of future registration trials for oral high-dose cyanocobalamin.

Two holy bulls were lain, or at least shaken, by new Danish reports:

  1. Increased levels of plasma methylmalonic acid (MMA) did not predict manifestations of B12 deficiency (6).
  2. Parenteral cyanocobalamin treatment normalised plasma levels of MMA and homocysteine but bore small clinical benefit (7).

In future trials, it is desirable to test oral high-dose cyanocobalamin instead of injections. The B12 therapy should be supported by oral high-dose folic acid, since combined deficiency states are common (cf. 1,8). This quest is suitable for Swedish general practitioners, the B12-folate competence of who is documented (9).

Bo Norberg

References

  1. Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood 1998; 92:1191-8.
  2. Elia M. Oral or parenteral therapy for B12 deficiency. Lancet 1998; 352:1721-2.
  3. Freeman AG, Nyholm ES, Snowden JA, Chan-Lam D, Thomas SE, Ng J-P. Oral or parenteral therapy for vitamin B12 deficiency. Lancet 1999; 353:410-1.
  4. Norberg B. Vitamin B12 – spectrum of views. Rondel 2000; 3:Editorial (www.rondellen.net, April-June 2000)
  5. Nilsson K, Gustafson L, Hultberg B. Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. Int J Geriatr Psychiatry 2001; 16:609-14.
  6. Hvas A-M. Ellegaard J, Nexö E. Increased plasma methylmalonic acid level does not predict clinical manifestations of vitamin B12 deficiency. Arch Intern Med 2001;161:1534-41.
  7. Hvas A-M. Ellegaard J, Nexö E. Vitamin B12 treatment normalizes metabolic markers but has limited clinical effect: A randomized placebo-controlled study. Clin Chem 2001; 47(8):1396-1404.
  8. Hoffbrand AV, Weir DG. The history of folic acid. Brit J Haematol 2001; 113:579-89.
  9. 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.

Published September 7, 2001