title: Vitamin B12 and folate levels in healthy Swiss senior citizens: a prospective study evaluating reference intervals and decision limits.
abstract: BACKGROUND
  The vitamin B12 and folate status in nonanaemic healthy older persons needs attention the more so as decrease in levels may be anticipated from reduced haematinic provision and/or impaired intestinal uptake.
  
  
  METHODS
  A total of 1143 subjectively healthy Swiss midlands participants (637 females and 506 males), ≥60 years of age were included in this study. Levels of vitamin B12, holotranscobalamin (holoTC), methylmalonic acid (MMA), homocysteine (Hcy), serum folate, red blood cell (RBC) folate were measured. Further, Fedosov's wellness score was determined. Associations of age, gender, and cystatin C/creatinine-based estimated kidney function, with the investigated parameters were assessed. Reference intervals were calculated. Further, ROC analysis was done to assess accuracy of the individual parameters in recognizing a deficient vitamin B12 status. Finally, decision limits for sensitive, specific and optimal recognition of vitamin B12 status with individual parameters were derived.
  
  
  RESULTS
  Three age groups: 60-69, 70-79 and ≥ 80 had median B12 (pmol/L) levels of 237, 228 and 231 respectively (p = 0.22), holoTC (pmol/L) of 52, 546 and 52 (p = 0.60) but Hcy (μmol/L) 12, 15 and 16 (p < 0.001), MMA (nmol/L) 207, 221 and 244 (p < 0.001). Hcy and MMA (both p < 0.001), but not holoTC (p = 0.12) and vitamin B12 (p = 0.44) were found to be affected by kidney function. In a linear regression model Fedosov's wellness score was independently associated with kidney function (p < 0.001) but not with age. Total serum folate and red blood cell (RBC) folate drift apart with increasing age: whereas the former decreases (p = 0.01) RBC folate remains in the same bandwidth across all age groups (p = 0.12) A common reference interval combining age and gender strata can be obtained for vitamin B12 and holoTC, whereas a more differentiated approach seems warranted for serum folate and RBC folate.
  
  
  CONCLUSIONS
  Whereas the vitamin B12 and holoTC levels remain steady after 60 years of age, we observed a significant increment in MMA levels accompanied by increments in Hcy; this is better explained by age-related reduced kidney function than by vitamin B12 insufficiency. Total serum folate levels but not RBC folate levels decreased with progressing age.
authors.affiliation: Kantonsspital Graubünden, Zentrallabor, Loësstrasse 170, Chur, 7000, Switzerland. martin.risch@ksgr.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Risch
authors.affiliation: Labormedizinisches Zentrum Dr. Risch, Waldeggstrasse 37, Liebefeld, 3097, Switzerland. dominik_meier@me.com.
authors.forename: Dominik W
authors.initials: DW
authors.lastname: Meier
authors.affiliation: Labormedizinisches Zentrum Dr. Risch, Waldeggstrasse 37, Liebefeld, 3097, Switzerland. benjamin.sakem@risch.ch.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sakem
authors.affiliation: Labormedizinisches Zentrum Dr. Risch, Waldeggstrasse 37, Liebefeld, 3097, Switzerland. pedro.medina@risch.ch.
authors.forename: Pedro
authors.initials: P
authors.lastname: Medina Escobar
authors.affiliation: Labormedizinisches Zentrum Dr. Risch, Waldeggstrasse 37, Liebefeld, 3097, Switzerland. corina_risch@hotmail.com.
authors.forename: Corina
authors.initials: C
authors.lastname: Risch
authors.affiliation: Labormedizinisches Zentrum Dr. Risch, Waldeggstrasse 37, Liebefeld, 3097, Switzerland. urs.nydegger@risch.ch.
authors.forename: Urs
authors.initials: U
authors.lastname: Nydegger
authors.affiliation: Labormedizinisches Zentrum Dr. Risch, Waldeggstrasse 37, Liebefeld, 3097, Switzerland. lorenz.risch@risch.ch.|Private University Triesen, Triesen, 9495, Liechtenstein. lorenz.risch@risch.ch.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Risch
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D004906:Erythrocyte Count / Q000706:statistics & numerical data*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007677:Kidney Function Tests / Q000379:methods / Q000706:statistics & numerical data; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D012016:Reference Values; D012737:Sex Factors; D013557:Switzerland / Q000453:epidemiology; D014155:Transcobalamins / Q000032:analysis; D014805:Vitamin B 12 / Q000097:blood*; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D014155:Transcobalamins; D006710:Homocysteine; D008764:Methylmalonic Acid; D005492:Folic Acid; D014805:Vitamin B 12