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- Lewerin, Catharina, 1961, et al.
(author)
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Glomerular filtration rate as measured by serum cystatin C is an important determinant of plasma homocysteine and serum methylmalonic acid in the elderly
- 2007
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In: J Intern Med. - 0954-6820. ; 261:1, s. 65-73
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To explore the dependence of glomerular filtration rate (GFR) on plasma total homocysteine (tHcy) and serum methylmalonic acid (MMA), as well as the consequences for the diagnosis of cobalamin and/or folic acid deficiency in an elderly community-dwelling population. DESIGN AND SETTING: Population-based study of 209 community-dwelling subjects, mean age 76 years. INTERVENTIONS: Four months' treatment study with oral vitamin B(12), folic acid and B(6) or placebo. MAIN OUTCOME MEASURES: Determinants of tHcy and MMA: cystatin C as a marker of GFR and serum/plasma concentrations of vitamin B(12) and folate, age and sex. RESULTS: Elevated cystatin C (>1.55 mg L(-1)) was found in 31.3% (men) and 13.0% (women). Elevated tHcy (> or = 16 micromol L(-1)) occurred in 53% and elevated MMA (> or = 0.34 micromol L(-1)) in 11% of all subjects. When GFR was taken into consideration, the proportion of elevated tHcy was reduced to 10% (20/209), whilst the proportion of elevated MMA was unchanged. Cystatin C was correlated with tHcy (r = 0.45, P < 0.001) and with MMA (r =0.28, P < 0.001), independently of vitamin B(12)- and folate status. According to multiple regression, independent predictors for tHcy were plasma folate (15%), cystatin C (11%) and vitamin B(12) (4%), and for MMA, cystatin C (8%) and vitamin B(12) (2%). CONCLUSIONS: The prevalence of elevated tHcy may be overestimated in elderly populations unless GFR is taken into account. Nomograms for evaluation of tHcy and MMA in relation to both cystatin C and serum creatinine are presented.
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- Lewerin, Catharina, 1961, et al.
(author)
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Significant correlations of plasma homocysteine and serum methylmalonate with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy: a placebo controlled randomized study
- 2005
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In: American Journal of Clinical Nutrition. - 0002-9165. ; 81:5, s. 1155-1162
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Journal article (peer-reviewed)abstract
- BACKGROUND: Deficiencies of vitamin B-12, folic acid, and vitamin B-6-as de-fined by laboratory measures-occur in 10-20% of elderly subjects. The clinical significance remains unresolved. OBJECTIVE: The objective was to explore any association between vitamin status and vitamin treatment and movement and cognitive performance in elderly subjects. DESIGN: Community-dwelling sub-jects (n = 209) with a median age of 76 y were randomly assigned to daily oral treatment with 0.5 mg cyanocobalamin, 0.8 mg folic acid, and 3 mg vitamin B-6 or placebo (double blind) for 4 mo. Movement and cognitive performance tests were performed before and after treatment. RESULTS: A high plasma total ho-mocysteine (tHcy) concentration (> or =16 micromol/L) was found in 64% of men and in 45% of women, and a high serum methylmalonic acid (MMA) concentra-tion (> or =0.34 micromol/L) was found in 11% of both sexes. Movement time, digit symbol, and block design (adjusted for age, sex, smoking, and creatinine) correlated independently with plasma tHcy (P < 0.01, < 0.05, and < 0.01, respec-tively); the simultaneity index and block design correlated with serum MMA (P < 0.05 for both). Vitamin therapy significantly decreased plasma tHcy (32%) and serum MMA (14%). No improvements were found in the movement or cognitive tests compared with placebo. Neither vitamin therapy nor changes in plasma tHcy, serum MMA, serum vitamin B-12, plasma folate, or whole-blood folate cor-related with changes in movement or cognitive performance. CONCLUSIONS: High plasma tHcy and serum MMA were prevalent and correlated inversely with movement and cognitive performance. Oral B vitamin treatment normalized plasma tHcy and serum MMA concentrations but did not affect movement or cognitive performance. This might have been due to irreversible or vitamin-independent neurocognitive decline or to an insufficient dose or duration of vita-mins.
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- Lewerin, Catharina, 1961
(author)
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Vitamin B12 and folate depletion in the elderly. Diagnosis, clinical correlates and causes
- 2006
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Doctoral thesis (other academic/artistic)abstract
- Subclinical vitamin B12 and folate deficiency is common in the elderly. The clinical significance remains unresolved. There is not a universally accepted set of laboratory criteria for diagnosis, however subclinical deficiency is important to diagnose since it is easy to treat. Currently available measures of vitamin concentrations are, except in pronounced deficiency, unreliable. Plasma tHcy and serum MMA are potentially more reliable markers of intracellular vitamin status. The overall aim was to estimate the prevalence of B-vitamin deficiency and atrophic gastritis, to calculate health related reference intervals for plasma tHcy/serum MMA, to explore the dependence of glomerular filtration rate on these metabolites, and to study the effect of oral B-vitamin therapy both on biochemical and clinical outcome.The thesis is based on a population-based study of 209 community-dwelling subjects, mean age 76 years. The study included a double-blind placebo controlled intervention with an oral daily combination of vitamin B12 (0.5mg), folic acid (0.8mg) and B6 (3mg) during four months.Elevated plasma tHcy and serum MMA was found in 53% and 11%. Vitamin B12 deficiency occurred in 7.2%, folate deficiency in 11%, atrophic gastritis in up to 14%. Health- related upper reference limits for the metabolites were higher than those commonly used. After adjustment for glomerular filtration rate also within it s normal range, the fraction of subjects with elevated plasma tHcy diminished significantly. Plasma tHcy and serum MMA correlated inversely with movement and cognitive performance. Vitamin therapy significantly decreased plasma tHcy (32%) and serum MMA (14%) but failed to improve movement or cognitive performance. Atrophic gastritis did not cause reduced vitamin absorption.In conclusion, elevated levels of plasma tHcy and serum MMA were common and more frequent than actual B-vitamin deficiency. The prevalence of elevated plasma tHcy may be overestimated unless adjusted for glomerular filtration rate. Atrophic gastritis was not uncommon and correlated to inferior B-vitamin status. Short-term oral B vitamin treatment normalized plasma tHcy and serum MMA levels also in subjects with atrophic gastritis, but did not affect movement or cognitive performance.
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