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(Circulation. 2002;105:1810.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Does Oral Folic Acid Lower Total Homocysteine Levels and Improve Endothelial Function in Children With Chronic Renal Failure?

K. Bennett-Richards, MB, BS, MRCP; M. Kattenhorn, BSc, Hons; A. Donald, AVT; G. Oakley, RGN, MSc; Z. Varghese, PhD, FRCPath; L. Rees, MD, FRCP, FRCPCH; J.E. Deanfield, FRCP

From the Departments of Nephrology and Vascular Physiology, Great Ormond Street Hospital for Children NHS Trust and Institute of Child Health (K.B.-R., M.K., A.D., G.O., L.R., J.E.D.), London, UK; and the Royal Free Hospital Renal Research Unit, Royal Free and University College Medical School (Z.V.), London, UK.

Correspondence to Dr Katy Bennett-Richards, Vascular Physiology Unit, 34 Great Ormond St, London WC1 3JH, UK. E-mail KatyJBR{at}aol.com

Background— Accelerated vascular disease is common in chronic renal failure (CRF) and accounts for significant mortality and morbidity. Elevated homocysteine levels may contribute by an effect on endothelial function.

Methods and Results— We performed a double-blind placebo-controlled randomized crossover trial of folic acid at 5 mg/m² in 25 normotensive children 12±3 (7 to 17) years of age with CRF (glomerular filtration rate 26.8±13.2 mL/min per 1.73 m²) of noninflammatory etiology. Each subject underwent two 8-week periods of folic acid and placebo separated by an 8-week washout period. The effect of folic acid on homocysteine levels, LDL oxidation, and both endothelial-dependent and -independent vascular function were measured. After oral folic acid, serum folate levels rose from 11.7±4.25 to 635±519 µg/L (P=0.001), red cell folate levels rose from 364±195 to 2891±2623 µg/L (P<0.001), and total homocysteine levels fell from 10.28±4.16 to 8.62±2.32 µmol/L (P=0.03). In addition, there was a significant improvement in flow-mediated dilatation (FMD) (endothelial-dependent dilatation) from 7.21±2.8% to 8.47±3.01% (P=0.036) with no change in response to glyceryl trinitrate (endothelial-independent dilatation). There was no significant change in FMD or glyceryl trinitrate during the placebo phase. There was, however, no significant difference in final FMD after placebo or folic acid. Lag times for LDL oxidation were prolonged during the treatment phase (58.4±18.7 to 68.1±25.9 minutes, P=0.01).

Conclusion— Folic acid supplementation in children with CRF may improve endothelial function with an increased resistance of LDL to oxidation.

Key Words: homocysteine • folic acid • renal failure • endothelium

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