Subject(s)
Calcitriol/therapeutic use , Chronic Kidney Disease-Mineral and Bone Disorder/drug therapy , Dihydrotachysterol/therapeutic use , Growth Disorders/prevention & control , Anthropometry , Child , Child, Preschool , Chronic Kidney Disease-Mineral and Bone Disorder/complications , Clinical Protocols , Double-Blind Method , Growth Disorders/diagnostic imaging , Growth Disorders/etiology , Humans , Infant , Multicenter Studies as Topic , Nutritional Status , RadiographyABSTRACT
We investigated the biochemical and clinical efficacy of dietary erucic acid (C22:1) therapy for X-linked adrenoleukodystrophy (ALD). In a double-blind crossover study of patients who were on chronic oleic acid (C18:1) therapy, addition of erucic acid to the diet led to a further reduction in plasma hexacosanoic acid (C26:0) concentration. We treated 12 newly diagnosed ALD patients with a diet enriched with erucic acid and oleic acid for 2 to 19 months. Mean plasma C26:0 concentration decreased to normal by 4 weeks, and the C26:0 composition of plasma sphingomyelin and phosphatidylcholine became normal by 4 months on therapy. Fatty acid analysis of postmortem tissues from 1 boy treated for 10 months suggested that dietary erucic acid entered the heart, liver, adrenal gland, and brain. Eight patients remained on treatment long enough (mean, 12 +/- 3 months) to evaluate their clinical response; 6 of these patients with moderate to advanced disease deteriorated neurologically or showed progression of white matter disease on brain magnetic resonance imaging whereas 2 mildly affected patients remained clinically stable after 10 and 19 months. No adverse effects of the diet occurred. We conclude that dietary erucic acid therapy is effective in lowering plasma C26:0 to normal in ALD patients, and may prevent further demyelination in some mildly affected boys.
Subject(s)
Adrenoleukodystrophy/genetics , Diet , Diffuse Cerebral Sclerosis of Schilder/genetics , Erucic Acids/therapeutic use , Fatty Acids, Monounsaturated/therapeutic use , Genetic Linkage , X Chromosome , Adrenoleukodystrophy/diet therapy , Adrenoleukodystrophy/drug therapy , Clinical Trials as Topic , Erucic Acids/administration & dosage , Erucic Acids/adverse effects , Fatty Acids/blood , Humans , Lipids/blood , Magnetic Resonance Imaging , Nervous System/pathology , Nervous System/physiopathology , Oleic Acid , Oleic Acids/administration & dosage , Oleic Acids/therapeutic use , Time FactorsABSTRACT
To evaluate the effects of protein intake on renal tubular functions, seven metabolic studies were performed on five adolescents with mild, chronic renal insufficiency. After equilibration, patients were randomly assigned to two periods of four days each on either a high-protein diet (HPD) or a low-protein diet (LPD), with energy intakes remaining the same during both periods. High protein intake resulted in significantly higher mean (+/- SD) daily creatinine excretion and clearance rates. The HPD was associated with significantly increased excretion rates of potassium, phosphate, sulfate, and calcium. Net acid excretion with the HPD was nearly threefold higher than that observed with the LPD. These differences were unassociated with urinary pH, which remained similar with both diets. We conclude that different protein intakes affect urinary excretion of creatinine, potassium, phosphate, sulfate, calcium, and net acid.
Subject(s)
Dietary Proteins/administration & dosage , Kidney Failure, Chronic/diet therapy , Kidney/physiopathology , Adolescent , Calcium/metabolism , Child , Creatinine/metabolism , Female , Glomerular Filtration Rate , Humans , Hydrogen-Ion Concentration , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/physiopathology , MaleABSTRACT
Adrenoleukodystrophy (ALD) is an X-linked disorder characterized by demyelination, adrenal insufficiency, and accumulation of saturated very-long-chain fatty acids (VLFA), particularly hexacosanoate (C26:0). We treated 5 patients with adrenoleukodystrophy (3 males and 2 symptomatic female carriers) for 6 months with a diet enriched in oleic acid (C18:1) and moderately restricted in C26:0. Elevated plasma and erythrocyte levels of C26:0 decreased in a time-dependent manner during treatment. Total plasma C26:0 concentration was lowered by 50 +/- 9% (p less than 0.01); it became normal in the female carriers. The total erythrocyte level of C26:0 decreased (44 +/- 5%; p less than 0.001) into the normal range in all patients. Significant decreases were noted in the saturated VLFA composition of plasma and erythrocyte sphingomyelin and erythrocyte phosphatidylcholine during dietary treatment. In general, decreases in saturated VLFA levels were accompanied by increases in monounsaturated VLFA levels, while total VLFA values did not change. This novel approach to the treatment of adrenoleukodystrophy, in which there is an exchange of monounsaturated VLFA for the more toxic saturated VLFA, may prove clinically beneficial in this disorder.
Subject(s)
Adrenoleukodystrophy/diet therapy , Dietary Fats/therapeutic use , Diffuse Cerebral Sclerosis of Schilder/diet therapy , Fatty Acids/blood , Oleic Acids/administration & dosage , Peripheral Nervous System Diseases/genetics , Adrenoleukodystrophy/blood , Erythrocytes/analysis , Female , Heterozygote , Humans , Male , Oleic AcidABSTRACT
Six normal subjects were placed on a high carbohydrate diet (80%) and a high fat diet (60%) for 2 weeks each. Glucose tolerance testing with plasma immunoreactive insulin levels was performed along with insulin receptor quantitation after a control period and after each of the dietary manipulations. Despite improved carbohydrate tolerance and decreased plasma immuno-reactive insulin after the high carbohydrate diet (evidence for increased insulin sensitivity) insulin receptor number and affinity were unchanged. These studies suggest that the increased insulin sensitivity induced by a high carbohydrate diet is due to some adaptive change in postreceptor activity. Manipulations of dietary composition fail to alter insulin binding to peripheral mononuclear cells.
