Essential Nutrients-Cognition:  Research Article

Essential Nutrients Menu

Cognitive Function and Low Cobalamine

CITATION:  Louwman, M.W.J., van Dusseldorp, M., et al.  (2000)  Signs of Impaired Cognitive Function in Adolescents with Marginal Cobalamin Status.  Am J Clin Nutr; 72:762-9.


Background: Lack of cobalamin may lead to neurologic disorders, which have been reported in strict vegetarians. 

Objective: The objective of this study was to investigate whether cognitive functioning is affected in adolescents (aged 10–16 y) with marginal cobalamin status as a result of being fed a macrobiotic diet up to an average age of 6 y.

Design: Data on dietary intake, psychological test performance, and biochemical variables of cobalamin status were collected from 48 adolescents who consumed macrobiotic (vegan type) diets up to the age of 6 y, subsequently followed by lactovegetarian or omnivorous diets, and from 24 subjects (aged 10–18 y) who were fed omnivorous diets from birth onward. Thirty-one subjects from the previously macrobiotic group were cobalamin deficient according to their plasma methylmalonic acid concentrations. Seventeen previously macrobiotic subjects and all control subjects had normal cobalamin status.

Results: The control subjects performed better on most psychological tests than did macrobiotic subjects with low or normal cobalamin status. A significant relation between test score and cobalamin deficiency (P = 0.01) was observed for a test measuring fluid intelligence (correlation coefficient: –0.28; 95% CI: –0.48, –0.08). This effect became more pronounced (P = 0.003) within the subgroup of macrobiotic subjects (correlation coefficient: –0.38; 95% CI: –0.62, –0.14).
Conclusion: Our data suggest that cobalamin deficiency, in the absence of hematologic signs, may lead to impaired cognitive performance in adolescents.


1. Dagnelie PC, van Staveren WA, Vergote FJ, Dingjan PG, van den Berg
H, Hautvast JG. Increased risk of vitamin B-12 and iron deficiency in infants on macrobiotic diets. Am J Clin Nutr 1989;50:818–24.

2. Dagnelie PC, van Staveren WA. Macrobiotic nutrition and child health: results of a population-based, mixed-longitudinal cohort study in The Netherlands. Am J Clin Nutr 1994;59(suppl):1187S–96S.

3. Ashkenazi S, Weitz R, Varsano I, Mimouni M. Vitamin B12 deficiency due to a strictly vegetarian diet in adolescence. Clin Pediatr (Phila) 1987;26:662–3.

4. Bar-Sella P, Rakover Y, Ratner D. Vitamin B12 and folate levels in long-term vegans. Isr J Med Sci 1990;26:309–12.

5. Graham SM, Arvela OM, Wise GA. Long-term neurologic consequences of nutritional vitamin B12 deficiency in infants. J Pediatr 1992;121:710–4.

6. Prakken AB, Veenhuizen L, Bruin MC, Waelkens JJ, Van Dijken PJ.
Vitamine B12-deficientie bij 2 kinderen door afwijkende voedingsgewoonte.
(Vitamin B-12 deficiency due to abnormal eating habits.) Ned Tijdschr Geneeskd 1994;138:474–6 (in Dutch).

7. Sadowitz PD, Livingston A, Cavanaugh RM. Developmental regression as an early manifestation of vitamin B12 deficiency. Clin Pediatr (Phila) 1986;25:369–71.

8. Stollhoff K, Schulte FJ. Vitamin B12 and brain development. Eur J Pediatr 1987;146:201–5.

9. Dagnelie PC, Van Staveren WA, Vergote FJ, et al. Nutritional status of infants aged 4 to 18 months on macrobiotic diets and matched omnivorous control infants: a population-based mixed- longitudinal study. II. Growth and psychomotor development. Eur J Clin Nutr 1989;43:325–38.

10. Van Dusseldorp M, Arts IC, Bergsma JS, De Jong N, Dagnelie PC,
Van Staveren WA. Catch-up growth in children fed a macrobiotic diet in early childhood. J Nutr 1996;126:2977–83.

11. Van Dusseldorp M, Schneede J, Refsum H, et al. Risk of persistent
cobalamin deficiency in adolescents fed a macrobiotic diet in early life. Am J Clin Nutr 1999;69:664–71.

12. Parsons TJ, Van Dusseldorp M, Van der Vliet M, Van de Werken K,
Schaafsma G, Van Staveren WA. Reduced bone mass in Dutch adolescents
fed a macrobiotic diet in early life. J Bone Miner Res 1997;12:1486–94.

13. Benhayoun S, Adjalla C, Nicolas JP, Gueant JL, Lambert D. Method for the direct specific measurement of vitamin B12 bound to transcobalamin II in plasma. Acta Haematol 1993;89:195–9.

14. Schneede J, Ueland PM. Application of capillary electrophoresis with laser-induced fluorescence detection for routine determination of methylmalonic acid in human serum. Anal Chem 1995;67:812–9.

15. Fiskerstrand T, Refsum H, Kvalheim G, Ueland PM. Homocysteine and other thiols in plasma and urine: automated determination and sample stability. Clin Chem 1993;39:263–71.

16. Lozoff B, Jimenez E, Wolf AW. Long-term developmental outcome of infants with iron deficiency. N Engl J Med 1991;325:687–94.

17. Walter T, De Andraca I, Chadud P, Perales CG. Iron deficiency anemia:
adverse effects on infant psychomotor development. Pediatrics 1989;84:7–17.

18. Pollitt E, Hathirat P, Kotchabhakdi NJ, Missell L, Valyasevi A. Iron deficiency and educational achievement in Thailand. Am J Clin Nutr 1989;50:687–96.

19. Bruner AB, Joffe A, Duggan AK, Casella JF, Brandt J. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls. Lancet 1996;348:992–6.

20. Huebers HA, Beguin Y, Pootrakul P, Einspahr D, Finch CA. Intact transferrin receptors in human plasma and their relation to erythropoiesis. Blood 1990;75:102–7.

21. Raven JC. Manual for the Raven’s progressive matrices and vocabulary
scales. London: Lewis, 1979.

22. Van Haassen PP, De Bruin EEJ, Pijl YJ, et al. Nederlandstalige uitgave.
WISC-R. (Wechsler Intelligence Scale for Children—Revised). Lisse, Netherlands: Swets & Zeitlinger, 1986 (in Dutch).

23. Stinissen J, Willemsen PJ, Coetsier P, Hulsman WLL. WAIS. Nederlandstalige bewerking. (WAIS. Translated and adapted for the
Dutch language.) Lisse: Swets & Zeitlinger, 1970 (in Dutch).

24. Rey A. L’examen clinique en psychologie. (Clinical and psychological
examinations.) 2nd ed. Paris: Presses Universitaires de France, 1964 (in French).

25. Bleichrodt N. Intelligentiemeting bij kinderen. (Tests of intelligence in children.) Lisse: Swets & Zeitlinger, 1987 (in Dutch).

26. Benton AL, Hamsher K. Multilingual aphasia examination manual revised. Iowa City, IA: University of Iowa, 1978.

27. Bleichrodt N. Intelligentie-meting ten behoeve van het onderwijs in Indonesie. (Tests of intelligence for educational purposes in Indonesia.) Amsterdam: Frisch, 1989 (in Dutch).

28. Helms-Lorenz M, van de Vijver FJR. Cognitive assessment in education
in a multicultural society. Eur J Psych Assess 1995;11:158–69.

29. NEVO table. (Dutch food and nutrition table.) Zeist: Stichting NEVO, Voorlichtingsbureau voor de Voeding, 1995 (in Dutch).

30. Brandts HAM, Hulshof KFAM. De ontwikkeling van een voedingsmiddelen
tabel met foliumzuur gehalten, rapportnr V98-089. (Development of a food-composition table including data on folic acid, report no. 98-089.) Zeist, Netherlands: TNO, 1995 (in Dutch).

31. Van der Heijden L, Brouwer C, Roosemalen K, Van Dusseldorp M,
Van Staveren WA. Vitamine B12 waarden in voedingsmiddelen. Een
inventarisering op basis van literatuur. (Vitamin B-12 values of foods. An inventory based on literature research.) Wageningen, Netherlands: Division of Human Nutrition and Epidemiology Wageningen Agricultural University, 1997 (in Dutch).

32. Dagnelie PC, Van Staveren WA, Verschuren SA, Hautvast JG. Nutritional
status of infants aged 4 to 18 months on macrobiotic diets and matched omnivorous control infants: a population-based mixedlongitudinal study. I. Weaning pattern, energy and nutrient intake. Eur J Clin Nutr 1989;43:311–23.

33. Schneede J, Dagnelie PC, Van Staveren WA, Vollset SE, Refsum H,
Ueland PM. Methylmalonic acid and homocysteine in plasma as
indicators of functional cobalamin deficiency in infants on macrobiotic
diets. Pediatr Res 1994;36:194–201.

34. Herens MC, Dagnelie PC, Kleber RJ, Mol MCJ, Van Staveren WA.
Nutrition and mental development of 4–5-year old children on macrobiotic
diets. J Hum Nutr Diet 1992;5:1–9.

35. Healton EB, Savage DG, Brust JC, Garrett TJ, Lindenbaum J. Neurologic
aspects of cobalamin deficiency. Medicine (Baltimore) 1991;70:229–45.

36. Meadows ME, Kaplan RF, Bromfield EB. Cognitive recovery with
vitamin B12 therapy: a longitudinal neuropsychological assessment.
Neurology 1994;44:1764–5.

37. Doyle JJ, Langevin AM, Zipursky A. Nutritional vitamin B12 deficiency
in infancy: three case reports and a review of the literature. Pediatr Hematol Oncol 1989;6:161–72.

38. Oski FA, Honig AS, Helu B, Howanitz P. Effect of iron therapy on behavior performance in nonanemic, iron-deficient infants. Pediatrics 1983;71:877–80.

39. Lozoff B, Brittenham GM, Wolf AW, et al. Iron deficiency anemia and iron therapy effects on infant developmental test performance. Pediatrics 1987;79:981–95.

40. Walter T. Effects of iron-deficiency anaemia on cognitive skills in infancy and childhood. Baillieres Clin Haematol 1994;7:815–27.