Nutrient Supplementation

NSUP: Vitamin B12 (2008)

• Assessment
  What is the evidence regarding the effect of oral vitamin B12 supplementation and/or fortification on serum cobalamin levels in deficient older adults?

  • Conclusion

    13 studies (eight RCTs, one non-randomized trial, three cohort studies, one cross-sectional study) found a dose-response effect in the administration of oral cobalamin to cobalamin-deficient older adults. Two of these studies used multi-vitamin mineral supplements containing six mcg vitamin B₁₂ and the remaining studies used oral cobalamin ranging from 2.5mcg to 2,000mcg per day. Research endpoints were measured using serum cobalamin or serum methylmalonic acid (MMA) levels. Four studies compared oral B₁₂ supplementation to intramuscular injection and concluded that oral supplementation was as effective as intramuscular supplementation. All of the studies used doses of vitamin B₁₂ greater than the current US RDA of 2.4mcg per day for older adults. Further research is needed to define serum cobalamin deficiency and to determine appropriate levels of oral cobalamin supplementation in deficient older adults.

  • Grade: II
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: Oral Vitamin B12 Supplementation and/or Fortification on Serum Cobalamin Levels in Deficient Older Adults
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      • Andres E, Affenberger S, Vinzio S, Kurtz J-E, Noel E, Kaltenbach G, Maloisel F, Schlienger J-L, Blickle, J-F. Food-cobalamin malabsorption in elderly patients: Clinical manifestations and treatment. Am J Med. 2005 Oct; 118 (10): 1,154-1,159.
      • Andrès E, Affenberger S, Zimmer J, Vinzio S, Grosu D, Pistol G, Maloisel F, Weitten T, Kaltenbach G, Blicklé JF. Current hematological findings in cobalamin deficiency. A study of 201 consecutive patients with documented cobalamin deficiency. Clin Lab Haematol. 2006 Feb; 28 (1): 50-56.
      • Andrès E, Kurtz JE, Perrin AE, Maloisel F, Demangeat C, Goichot B, Schlienger JL.Oral cobalamin therapy for the treatment of patients with food-cobalamin malabsorption. 1: Am J Med. 2001 Aug; 111 (2): 126-129. PMID 11498066.
      • Andres E, Kaltenbach G, Noel E, Noblet-Dick M, Perrin A-E, Vogel T, Schlienger J-L, Berthel M, Blickle JF. Efficacy of short-term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food-cobalamin malabsorption: A study of 30 patients. Clin. Lab. Haematol. 2003 Jun; 25 (3) : 161-166.
      • Blacher J, Czernichow S, Raphael M, Roussel C, Chadefaux-Vekemans B, Morineau G, Giraudier S, Tibi A, Henry O, Vayssiere M, Oudjhani M, Nadai S, Vincent J-P, Bodak A, Di Menza C, Menard J, Zittoun J, Ducimetiere P. Very Low Oral Doses of Vitamin B-12 Increase Serum Concentrations in Elderly Subjects with Food-Bound Vitamin B-12 Malabsorption. The Journal of Nutrition. 2007 Feb; 137 (2): 373-378. 
      • Bolaman Z, Kadikoylu G, Yukselen V, Yavasoglu I, Barutca S, Senturk T. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study. Clin Ther. 2003 Dec; 25 (12): 3,124-3,134.
      • Bor MV, Lydeking-Olsen E, Møller J, Nexø E. A daily intake of approximately 6 microg vitamin B-12 appears to saturate all the vitamin B-12-related variables in Danish postmenopausal women. Am J Clin Nutr. 2006 Jan; 83 (1): 52-58. PMID: 16400049.
      • Dhonukshe-Rutten RA, van Zutphen M, de Groot LC, Eussen SJ, Blom HJ, van Staveren WA. Effect of supplementation with cobalamin carried either by a milk product or a capsule in mildly cobalamin-deficient elderly Dutch persons. Am J Clin Nutr. 2005 Sep; 82 (3): 568-574. PMID: 16155269.
      • Eussen SJ, de Groot LC, Clarke R, Schneede J, Ueland PM, Hoefnagels WH, van Staveren WA. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: A dose-finding trial. Arch Intern Med. 2005 May 23; 165 (10): 1,167-1,172.
      • Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998 Aug 15; 92 (4): 1,191-1,198.
      • McKay DL, Perrone G, Rasmussen H, Dallal G, Hartman W, Cao G, Prior RL, Roubenoff R, Blumberg JB. The effects of a multivitamin/mineral supplement on micronutrient status, antioxidant capacity and cytokine production in healthy older adults consuming a fortified diet. J Am Coll Nutr. 2000 Oct; 19 (5): 613-621. PMID: 11022875.
      • Rajan S, Wallace JI, Brodkin KI, Beresford SA, Allen RH, Stabler SP. Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults. J Am Geriatr Soc. 2002 Nov; 50 (11): 1,789-1,795. PMID: 12410896.
      • Seal EC, Metz J, Flicker L, Melny J. A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. J Am Geriatr Soc. 2002 Jan; 50 (1): 146-151. PMID: 12028259.
  • Search Plan and Results: NSUP: Vitamin B12 2007
     
  Are serum cobalamin concentrations associated with cognitive function in older adults?

  • Conclusion

    Research is inconclusive regarding specific serum cobalamin levels associated with cognitive function in older adults. Five studies (one RCT, one non-randomized controlled trial, two cross-sectional studies and one prospective cohort study) found an association between low serum cobalamin levels and impaired cognitive function in older adults. Four studies (one cross-sectional, three RCTs) found no significant difference in cognitive function in individuals with normal and deficient cobalamin levels. One additional study (RCT) found a decline in cognitive function with supplementation in cobalamin deficient adults compared to placebo and another study (cross-sectional) found deteriorating cognitive function in cobalamin- and folate-deficient individuals.

    Current research is limited by lack of a standardized definition of vitamin B₁₂ deficiency and lack of standardized measures of cognitive function. Further research is needed to establish the role of vitamin B₁₂ in cognitive function in older adults.

  • Grade: III
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: Serum Cobalamin Concentrations and Cognitive Function in Older Adults
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      • Assantachai P, Yamwong P, Chongsuphaijaisiddhi T. Relationships of vitamin B1, B12, folate and the cognitive ability of the Thai rural elderly. J Med Assoc Thai. 1997; 80 (11): 700-705.
      • Baker H, De Angelis B, Baker ER, Frank O, Jaslowdagger SP. Lack of effect of one year intake of a high-dose vitamin and mineral supplement on cognitive function of elderly women. Gerontology. 1999; 45: 195-199. PMID: 10394075.
      • Eussen SJ, de Groot LC, Joosten LW, Bloo RJ, Clarke R, Ueland PM, Schneede J, Blom HJ, Hoefnagels WH, van Staveren WA. Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial. Am J Clin Nutr. 2006 Aug; 84 (2): 361-370.
      • Hvas AM, Juul S, Lauritzen L, Nexo E, Ellegaard J. No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study. J Affect Disord. 2004; 81 (3): 269-273.
      • Kwok T, Tang C, Woo J, Lai WK, Law LK, Pang CP. Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels. Int J Geriatr Psychiatry. 1998 Sep; 13 (9): 611-616. PMID: 9777425.
      • Lindeman RD, Romero LJ, Koehler KM, Liang HC, LaRue A, Baumgartner RN, Garry PJ. Serum Vitamin B12, C and Folate Concentrations in the New Mexico Elder Health Survey: Correlations with Cognitive and Affective Functions. J Am Coll Nutr. 2000; 19: 68-76.
      • Morris MS, Jacques PF, Rosenberg IH and Selhub J. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr. 2007, 85: 193-200.
      • 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: 609-614.
      • Robins Wahlin TB, Wahlin A, Winblad B, Backman L. The influence of serum vitamin B12 and folate status on cognitive functioning in very old age. Biol Psychol. 2001;56:247–265. PMID: 11399353
      • Tucker KL, Qiao N, Scott T, Rosenberg I, Spiro A 3rd. High homocysteine and low B vitamins predict cognitive decline in aging men: the Veterans Affairs Normative Aging Study. Am J Clin Nutr. 2005; 82 (3): 627-635.
      • Wouters-Wesseling W, Wagenaar LW, Rozendaal M, Deijen JB, de Groot LC, Bindels JG, van Staveren WA. Effect of an enriched drink on cognitive function in frail elderly persons. J Gerontol A Biol Sci Med Sci. 2005 Feb; 60 (2): 265-270. PMID: 15814873.
  • Search Plan and Results: NSUP: Vitamin B12 2007