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Impaired homocysteine metabolism in early-onset cerebral and peripheral occlusive arterial disease. Effects of pyridoxine and folic acid treatment.

Abstract
Severe homocysteinemia due to genetic defects either of pyridoxal 5-phosphate (PLP)-dependent cystathionine beta-synthase (CBS) or of enzymes in vitamin B12 and folate metabolism is associated with very early-onset vascular disease. Therefore, we studied homocysteine metabolism in 72 patients presenting before the age of 55 years with occlusive arterial disease of cerebral, carotid, or aorto-iliac vessels. Twenty patients (28%) had basal homocysteinemia; and 26 patients (36%) had abnormal increases of plasma homocysteine after peroral methionine loading, which exceeded the highest value for 46 comparable controls and was within the range for 20 obligate heterozygotes for homocystinuria due to CBS deficiency. Basal plasma homocysteine content was strongly and negatively correlated to vitamin B12 and folate concentrations. Plasma PLP was depressed in most patients but there was no correlation between PLP and homocysteine values. In 20 patients, treatment with pyridoxine hydrochloride (240 mg/day) and folic acid (10 mg/day) reduced fasting homocysteine after 4 weeks by a mean of 53%, and methionine response by a mean of 39%. These data show that a substantial proportion of patients with early-onset vascular disease have impaired homocysteine metabolism, which may contribute to vascular disease, and that the impaired metabolism can be improved easily and without side effects.
AuthorsL Brattström, B Israelsson, B Norrving, D Bergqvist, J Thörne, B Hultberg, A Hamfelt
JournalAtherosclerosis (Atherosclerosis) Vol. 81 Issue 1 Pg. 51-60 (Feb 1990) ISSN: 0021-9150 [Print] Ireland
PMID2407253 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Homocysteine
  • Folic Acid
  • Hydro-Lyases
  • Cystathionine beta-Synthase
  • Pyridoxine
Topics
  • Adult
  • Arterial Occlusive Diseases (drug therapy)
  • Cerebral Arterial Diseases (drug therapy)
  • Cystathionine beta-Synthase (metabolism)
  • Female
  • Folic Acid (therapeutic use)
  • Homocysteine (blood, metabolism)
  • Humans
  • Hydro-Lyases (metabolism)
  • Male
  • Middle Aged
  • Pyridoxine (therapeutic use)
  • Time Factors

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