title: Advanced age as a risk factor for folate-associated functional cobalamin deficiency.
abstract: OBJECTIVE
  To determine whether high serum folate levels contribute to metabolite changes in elderly subjects with normal cobalamin levels.
  
  
  METHODS
  Case series.
  
  
  METHODS
  Outpatient clinic at a university-based staff model health maintenance organization.
  
  
  METHODS
  Two hundred thirty-three ambulatory individuals without diabetes mellitus with normal renal function and normal cobalamin levels evaluated for cobalamin deficiency.
  
  
  METHODS
  Cobalamin, serum folate, methylmalonic acid (MMA), and homocysteine.
  
  
  RESULTS
  Older individuals (≥60) with low-normal cobalamin levels (201-300 pg/mL) had higher MMA and lower homocysteine levels when serum folate levels were high (>20 ng/mL) than when serum folate levels were normal (P < .02), but serum folate levels within the normal range were not a determinant of either metabolite. In younger subjects with low-normal cobalamin levels, high serum folate levels were not associated with significant differences in either metabolite. At mid-normal cobalamin levels (301-600 pg/mL), high serum folate levels were associated with lower homocysteine levels in older adults (P < .001) but not with differences in MMA in either age group. Cobalamin therapy decreased or normalized MMA and homocysteine in 89% or more of participants even at pretherapy cobalamin levels greater than 600 pg/mL.
  
  
  CONCLUSIONS
  High serum folate levels are associated with higher MMA levels when cobalamin levels are low-normal, and this effect is age dependent, not progressive within the normal serum folate range (suggesting a threshold effect), and reversed by cobalamin therapy. Because MMA may be neurotoxic, these findings suggest caution in the use of folic acid supplements in elderly adults.
authors.affiliation: Section of Palliative Care, Department of Medicine, School of Medicine, Yale University, New Haven, CT 06520, USA. lawrence.solomon@yale.edu
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Solomon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015984:Causality; D003072:Cognition Disorders / Q000453:epidemiology; D015897:Comorbidity; D005260:Female; D005492:Folic Acid / Q000097:blood*; D015577:Geriatric Assessment; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood*; D012307:Risk Factors; D012720:Severity of Illness Index; D014805:Vitamin B 12 / Q000097:blood*; D014806:Vitamin B 12 Deficiency / Q000097:blood* / Q000453:epidemiology / Q000517:prevention & control
chemical_list: D006710:Homocysteine; D008764:Methylmalonic Acid; D005492:Folic Acid; D014805:Vitamin B 12