High homocystiene levels in elderly

Karin Björkegren was born 1950 in Stockholm and achieved university education and training in Uppsala from 1970. She taught in nine-year compulsory school and midwifery up to 1982. She became MD 1992, and specialist in family medicine 1997, full-time work as general practitioner. Main non-professional interests: four grown-up children, husbond, house, physical training. Since about 10 years, she has worked with an own scientifc project at the Department of Public Health and Caring Sciences, Section of Family Medicine and Epidemiology, University of Uppsala. Johan Hultdin summarizes the main structure of her research.

Clinical testing of homocysteine (Hcy) in elderly people (older than 70 years) constantly reveals a large number of individuals with elevated values, the significance of which is subject of debate. A population-based study from the borough Älvkarleby with demographic profile close to Swedish average is expected to elucidate the problem of homocysteine interpretation in elderly (cf. 1,2). It is reasonable to assume that the results obtained in Älvkarleby reflect general features of postindustrial societies with analogous demographic profiles.

Swedish residents are subject to an efficient registration system, which promotes epidemiological studies (cf. 1,2). Thus, a stratified and randomized sample of residents was invited to testing for deficiency of cobalamin and folate in the period 1993-95. The sample size was moderate (n=266), the response rate 88% (n=235). The probands were more or less in their last decile of life, median age 77 years. Thus, eleven of them were too weak for participation and had to be excluded. The final sample comprised 224 persons.

Out of the 224 remaining persons, 38 (17%) had already reached the stage of diagnosed deficiency, and were treated with pharmacological doses of cobalamin and/or folate. Among non-treated persons (n=186), 69 probands (37%) were eligible for a treatment trial due to serum cobalamin below 300 pmol/L (primary inclusion criterion), and serum methylmalonic acid (S-MMA) above 0.37 micromol/L or plasma homocysteine above 15 micromol/L (secondary inclusion criteria).

Folate and cobalamin are coupled in a series connection (cf 3,4) in the cellular metabolism. The clinical consequences are the possibility of excess folate masking hematological symptoms of cobalamin deficiency at least temporarily, and the trapping of serum folate by isolated cobalamin deficiency. This series connection of folate and cobalamin was utilized in the treatment trial of the Älvkarleby study (1). All 69 persons with preclinical deficiency were treated with cobalamin monotherapy for six months. During this period, S-MMA became normal in 13 out of 15 persons, Hcy in 15 out of 56 persons. Remaining homocysteine values were normalized by oral folic acid, 5 mg daily, for three months.

From Hultdin J. Down syndrome – should we increase homocysteine? [debate]. Rondel 2001; 9. URL: http://www.rondellen.net debate09_eng.htm

The Älvkarleby studies highlight the biochemical, cellular and clinical liaison between folate and cobalamin. Thus, it is suggested that combination therapy with both cobalamin and folate should be considered in the treatment of "monodeficiency" states.

Johan Hultdin

References

4. Norberg B. Neuropsychiatric disorders caused by vitamin B12 deficiency in the absence of anaemia or macrocytosis – an explaining hypothesis [debate]. Rondel 2001; 8. URL: http://www.rondellen.net debate08_eng.htm

Published January 14, 2003