How we wish to be cited:
Sandström H, Norberg B. Folate fortification masks cobalamin deficiency [evaluation]. Rondel 2003; 14. URL: http://www.rondellen.net

Folate fortification masks cobalamin deficiency

Scientific source
I. Johnson MA, Hawthorne NA, Brackett WR, Fischer JG, Gunter EW, Allen RH, Stabler SP. Hyperhomocysteinemia and vitamin B-12 deficiency in elderly using Title IIIc nutrition services. Am J Clin Nutr. 2003 Jan;77(1):211-20.

Reviewers
Herbert Sandström, general practitioner and lecturer, Department of Family Medicine, University of Umeå, and Bo Norberg, The Rondel

E-mail: herbert.sandstrom@fammed.umu.se

Summary
A high prevalence of cobalamin deficiency was found in elderly persons living on a diet fortified by folate. Cobalamin deficiency was associated with deteriorated cognition. Cognition was improved by oral high-dose cobalamin therapy. The results support previous fear of folate masking of cobalamin deficiency in progress.

Background
In 1998, cereals were fortified with folate in the USA in order to reduce the prevalence of neural tube defects in newborn infants. There was also a hope that folate fortification would reduce the incidence of thrombo-embolic vascular events in the population. The homocysteine levels have decreased in the population after folate fortification. The incidence of neural tube defects also appears to have been reduced.

Folate masking of cobalamin deficiency
Since folate and cobalamin are joined by a series connection in the metabolism (methionine cycle) of the human cell ( cf 1,2), many experts feared that folate fortification would mask a cobalamin deficiency in progress. The legendary Victor Herbert (3) was for example an outspoken representative of this view. The present study (I) verified a high prevalence of cobalamin deficiency in elderly persons on folate fortification. It also verified the efficacy of treating B12 deficiency with oral high-dose cobalamin. Otherwise, interpretation of the results should be cautious; selection biases and high dropout rates weaken the values of the study.

Role of spoke-in-the-wheel
An interesting observation is that the present study (I) actualizes the interplay between micronutrients in deficiency states. Folate fortification preserved a normal hemoglobin value and a normal erythrocyte size in most participants. However, cobalamin deficiency was reflected by elevated homocysteine levels. On the other hand, a cobalamin deficiency with anemia could not be treated successfully in the presence of an iron deficiency. The findings correlate closely with clinical experience from 1950 and forward, that the treatment of an "isolated deficiency" may unmask other incipient deficiencies (cf 4). Thus, one or two incipient deficiencies may act as spoke in the wheel in any deficiency treatment.

Conclusion
In folate-fortified elderly persons on nutrition programs, cobalamin deficiency was prevalent and associated with poor cognition, anemia, and hyperhomocysteinemia.

Herbert Sandström Bo Norberg

References

  1. Hultdin J. High homocysteine levels in elderly [editorial]! Rondel 2003; 14. URL: http://www.rondellen.net/publisher14_eng.htm
  2. Lökk J. Monocarbon metabolism – between conception and death [debate]. Rondel 2003; 14. URL: http://www.rondellen.net/debate14_eng.htm
  3. Halsted CH. In memoriam - Victor Herbert 1927-2002. Am J Clin Nutr 2003; 77:759-9.
  4. Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood 1998; 92:1191-8

Published March 26, 2003