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.

Conclusion: 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.

Fig. 1

Chart representing all the recruited participants with those retained and those excluded from the study (n = number of participants). *Some participants fulfill several exclusion criteria

Fig. 2

Vitamin B12 and holoTC serum levels in three arbitrarily defined advanced age groups classified according to sex. The box plot representation with vitamin B12 (panel a) and holoTC (panel b) as appearing in three age groups. The difference of vitamin B12 concentrations among males and females is significant in 70–79 year old (p = 0.001) and not significant in the participants aged 60–69 (p = 0.07) and ≥ 80 years (p = 0.69). The same comparisons of holoTC concentrations are significant for participants aged 60–69 and 70–79 (both p < 0.001), and not significant in the particpants ≥ 80 years (p = 0.77)

Fig. 3

Receiver operating characteristic (ROC) curves of vitamin B12, holoTC, MMA and Hcy. The Fedosov wellness parameter ω = −0.5 was used as a separator of the groups assumed deficient and assumed healthy