Are different reference intervals for methylmalonic acid and total homocysteine necessary in elderly people?

To determine whether age-adjusted reference intervals for methymalonic acid (MMA) and total homocysteine (tHcy) are necessary, data from 2 previous studies were used. First, the reference intervals for serum vitamin B12, folate, methylmalonic acid and total homocysteine were determined in 2 reference sample groups: 99 healthy adults and 64 selected healthy elderly subjects living at home. Secondly, health-related reference limits were estimated in 143 elderly subjects after supplementing the nutritional status with a combination of vitamin B12, vitamin B6 and folate during a 3-wk period. In the latter group, the adjusted reference intervals for MMA (46-288 nmol/L) as well as for tHcy (5-13.6 mumol/L) are different with considerably lower upper reference limits than that estimated with the original reference values (72-476 nmol/L for MMA; 6.8-21 mumol/L for tHcy) in the elderly subjects. Our data suggest that the MMA and tHcy levels increase with age. Moreover, the upper reference limit for MMA and tHcy, conventionally defined as the mean +2 SD in healthy elderly reference sample group without supplementing the nutritional status, might result in falsely high values due to a high prevalence of an inadequate vitamin B12, vitamin B6 and folate status.