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J Intern Med. 1999 Sep;246(3):317-24.

Elevated serum levels of methylmalonic acid and homocysteine in elderly people. A population-based intervention study.

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  • 1Uppsala University, Department of Public Health and Caring Sciences, Family Medicine Section, University Hospital, Sweden.



There is uncertainty amongst clinicians about the definitions of cobalamin and folate deficiency and therefore about the indications for treatment. In this report we present the results of systematic cobalamin and folic acid treatment based upon serum cobalamin, total homocysteine (tHcy) and methylmalonic acid (MMA) analyses in a population-based sample.


A 20% random sample of persons 70 years or older in a defined geographical area were invited to a survey (n = 266). Sixty-nine persons who had serum cobalamin < 300 pmol L-1 and serum MMA >/=0.37 micromol L-1 or serum tHcy >/=15 micromol L-1 and who had no cobalamin or folic acid substitution were selected for treatment.


Initially all 69 patients were given cobalamin orally or intramuscularly. Those who remained high in tHcy were in addition given folic acid treatment.


Serum cobalamin, serum MMA and serum tHcy.


After 6 months of cobalamin treatment, serum MMA became normal in 13 out of 15 persons. Mean serum tHcy decreased but was normalized in only 15 out of 56 persons. After 3 months of folic acid treatment added to those who still had an abnormal serum tHcy, serum tHcy had normalized in all but one person.


Cobalamin treatment normalizes increased MMA values and combined cobalamin and folic acid treatment normalizes tHcy, suggesting a pretreatment deficiency of tissue cobalamin and folate in spite of normal serum cobalamin and folate values in the majority of cases.

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