Mild hyperhomocysteinemia is recognized as a risk factor for premature arteriosclerotic disease. A few vitamins and other substances have been reported to reduce blood homocysteine levels, but normalization of elevated blood homocysteine concentrations with any of these substances has not been reported. Therefore, we screened 421 patients suffering from premature peripheral or cerebral occlusive arterial disease by oral methionine loading tests for the presence of mild hyperhomocysteinemia. Thirty-three percent of patients with peripheral and 20% of patients with cerebral occlusive arterial disease were identified with mild hyperhomocysteinemia (14% of the men, 34% of the premenopausal women, and 26% of the postmenopausal women). Mildly hyperhomocysteinemic patients were administered vitamin B 6 250 mg daily. After 6 weeks methionine loading tests were again assessed to evaluate the effect of treatment. Patients with nonnormalized C lassic homocystinuria, due to homozygosity for cystathionine synthase (CS) deficiency, is characterized by severe accumulation of homocysteine in the blood and tissues. The incidence of this hereditary dysfunction varies geographically and is estimated as 1:200 000 worldwide.1 Homocystinuria is generally considered to cause premature arteriosclerosis and thromboembolism. It is treated with high-dose administration of vitamin B 6 , the active form of which, pyridoxal phosphate, functions as a cofactor in the conversion of homocysteine to cystathionine (Fig 1). The marked homocysteine-lowering effect of vitamin B 6 is attributable to its stimulation of the residual activity of the cystathionine synthase enzyme.14 Additionally, folic acid and betaine, both involved in the remethylation of homocysteine into methionine, can lower or even normalize elevated homocysteine levels in patients who respond poorly or not at all to vitamin B 6 treatment. 13 The incidence of vascular accidents is significantly reduced after initiating homocysteine-lowering treatment, revealing the clinically beneficial effect of such intervention in homozygous patients. 4 Mild hyperhomocysteinemia, with homocysteine concentrations equivalent to those found in individuals heterozygous for CS deficiency, is characterized by Received September 30, 1993; revision accepted November 22, 1993.From the Department of Medicine, Division of Endocrinology (D.G.F., G.H.J.B., P.W.C.K.), and the Department of Pediatrics (H.J.B., F.J.M.T.) of the University Hospital Nijmegen, Nijmegen, the Netherlands.Reprint requests to Dr G.HJ. Boers, Department of Medicine, University Hospital Nijmegen, Post Box 9101, 6500 HB Nijmegen, the Netherlands. homocysteine concentrations were further treated with vitamin B 6 250 mg daily and/or folic acid 5 mg daily and/or betaine 6 g daily, solely or in any combination. Vitamin B 6 treatment normalized the afterload homocysteine concentration in 56% of the treated patients (71% of the men, 45% of the premenopausal women, and 88% of the postmenopausal women). Further treatment resulted in a n...

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The prevalence of mild hyperhomocysteinemia in young patients with arterial occlusive disease is high. Simple and inexpensive therapy with vitamin B6 plus folic acid will normalize homocysteine metabolism, as assessed by the homocysteine plasma level after methionine loading, in virtually all these patients.

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Previous studies have shown that elevated basal homocysteine levels are correlated among family members of patients with coronary vascular disease and juvenile venous thrombosis. This suggests the possibility of the presence of inherited basal mild hyperhomocysteinemia (mHH). We studied homocysteine levels, fasting as well as after methionine load, among 96 family members of 21 post-load hyperhomocysteinemic vascular index patients, i.e. 6 parents, 27 offspring, 38 siblings, 19 uncles and aunts and 6 cousins. In 15 out of 21 screened families post-load ml-IH was esti in at least one family member. Fa:>ting and post-load mHH was observed in 19 out of 89 (21%) screened family members (fasting homocysteine levels not measured in seven family members), and 31 out of 96 screened family members (32%), respectively. In 40% of all family members, post-load mHH was not accompanied by fasting mHH.conclude that both fasting and post-load mHH seems to be inherited in the majority of ic vascular patients.