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 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.

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 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.