Restriction Of Dietary Protein Intake Research Articles

Protein restriction for diabetic kidney disease.

Diabetic kidney disease (DKD) continues to be the leading cause of kidney failure across the world. For decades dietary protein restriction has been proposed for patients with DKD with the aim to retard the progression of chronic kidney disease (CKD) towards kidney failure. However, the relative benefits and harms of dietary protein restriction for slowing the progression of DKD have not been addressed. To determine the efficacy and safety of low protein diets (LPD) (0.6 to 0.8 g/kg/day) in preventing the progression of CKD towards kidney failure and in reducing the incidence of kidney failure and death (any cause) in adult patients with DKD. Moreover, the effect of LPD on adverse events (e.g. malnutrition, hyperglycaemic events, or health-related quality of life (HRQoL)) and compliance were also evaluated. We searched the Cochrane Kidney and Transplant Register of Studies up to 17 November 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We included randomised controlled trials (RCTs) or quasi-RCTs in which adults with DKD not on dialysis were randomised to receive either a LPD (0.6 to 0.8 g/kg/day) or a usual or unrestricted protein diet (UPD) (≥ 1.0 g/kg/day) for at least 12 months. Two authors independently selected studies and extracted data. Summary estimates of effect were obtained using a random-effects model. Results were summarised as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised MD (SMD) with 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We identified eight studies involving 486 participants with DKD. The prescribed protein intake in the intervention groups ranged from 0.6 to 0.8 g/kg/day. The prescribed protein intake in the control groups was ≥ 1.0 g/kg/day, or a calculated protein intake ≥ 1.0 g/kg/day if data on prescribed protein intake were not provided. The mean duration of the interventions was two years (ranging from one to five years). Risks of bias in most of the included studies were high or unclear, most notably for allocation concealment, performance and detection bias. All studies were considered to be at high risk for performance bias due to the nature of the interventions. Most studies were not designed to examine death or kidney failure. In low certainty evidence, a LPD may have little or no effect on death (5 studies, 358 participants: RR 0.38, 95% CI 0.10 to 1.44; I² = 0%), and the number of participants who reached kidney failure (4 studies, 287 participants: RR 1.16, 95% CI 0.38 to 3.59; I² = 0%). Compared to a usual or unrestricted protein intake, it remains uncertain whether a LPD slows the decline of glomerular filtration rate over time (7 studies, 367 participants: MD -0.73 mL/min/1.73 m²/year, 95% CI -2.3 to 0.83; I² = 53%; very low certainty evidence). It is also uncertain whether the restriction of dietary protein intake impacts on the annual decline in creatinine clearance (3 studies, 203 participants: MD -2.39 mL/min/year, 95% CI -5.87 to 1.08; I² = 53%). There was only one study reporting 24-hour urinary protein excretion. In very low certainty evidence, a LPD had uncertain effects on the annual change in proteinuria (1 study, 80 participants: MD 0.90 g/24 hours, 95% CI 0.49 to 1.31). There was no evidence of malnutrition in seven studies, while one study noted this condition in the LPD group. Participant compliance with a LPD was unsatisfactory in nearly half of the studies. One study reported LPD had no effect on HRQoL. No studies reported hyperglycaemic events. Dietary protein restriction has uncertain effects on changes in kidney function over time. However, it may make little difference to the risk of death and kidney failure. Questions remain about protein intake levels and compliance with protein-restricted diets. There are limited data on HRQoL and adverse effects such as nutritional measures and hyperglycaemic events. Large-scale pragmatic RCTs with sufficient follow-up are required for different stages of CKD.

P1455PRIORITIZATION BY MEDICAL DIRECTORS OF NUTRITIONAL PROTEIN VERSUS DIETARY PHOSPHORUS CONTROL IN HEMODIALYSIS PATIENTS: ASSOCIATION WITH MORTALITY IN THE DIALYSIS OUTCOMES AND PRACTICE PATTERNS STUDY (DOPPS)

Abstract Background and Aims Patients undergoing dialysis for end-stage kidney disease (ESKD) have poorer nutritional status than the general population, and worse nutritional status is associated with poor clinical outcomes. Hyperphosphatemia is common in dialysis patients owing to abnormal mineral and bone metabolism. Nephrologists manage hyperphosphatemia by prescribing phosphate binders and/or recommending restriction of dietary protein intake; the latter may, however, adversely affect nutritional status. In this analysis, we address the hypothesis that, even in the presence of hyperphosphatemia, liberalizing dietary protein leads to better patient outcomes. Method The analysis includes 11,628 hemodialysis (HD) patients in 12 countries in DOPPS phase 4 (2009-2011), from 254 facilities where the medical director completed a survey reporting facility practices. Demographic data, comorbid conditions, laboratory values, and medications were abstracted from patient records. Mortality was assessed during study follow-up. The primary exposure variable was response to the following question: “For patients with serum albumin 3.0 g/dL and phosphate 6.0 mg/dL, do you typically recommend to (A) increase or (B) not change or decrease dietary protein intake?” The primary outcome was all-cause mortality, analyzed by Cox regression, stratified by country, accounting for facility clustering using robust sandwich covariance estimators, and adjusted for case-mix and laboratory values. Linear regression was used to model the associations between the exposure variable and intermediate nutritional markers including serum albumin, creatinine, and phosphorus. We used multiple imputation to replace missing values for model covariates. Results Median follow-up was 1.4 years. In the case scenario, 91% of medical directors in North America recommended to increase protein intake compared to 58% in Europe (range=36-83% across 7 countries) and 56% in Japan (Figure). Advice to increase dietary protein intake was associated with 0.33 mg/dL higher serum creatinine levels (95% CI: 0.08-0.57) after adjustment for case mix, while clinically meaningful associations were not observed for serum albumin and phosphorus. Advice to increase dietary protein intake was weakly associated with lower mortality [HR (95% CI): 0.89 (0.77-1.03)]. The association with survival was stronger in patients with age 70+ years [HR (95% CI): 0.81(0.68-0.96), P=0.08 for interaction] and for those without diabetes [HR (95% CI): 0.81(0.66-0.98), P=0.20 for interaction] Conclusion In this large international cohort study, the medical director’s stated preference to recommend an increase in dietary protein intake for HD patients with low albumin and high phosphorus levels was most common in North America and was associated with higher patient serum creatinine levels and potentially lower all-cause mortality. Additional research into the possible benefits of protein intake liberalization for HD patients, even in the presence of hyperphosphatemia, is warranted. This abstract was directly supported by Kyowa Kirin Co.,Ltd..

Homeostatic sensing of dietary protein restriction: A case for FGF21.

Restriction of dietary protein intake increases food intake and energy expenditure, reduces growth, and alters amino acid, lipid, and glucose metabolism. While these responses suggest that animals 'sense' variations in amino acid consumption, the basic physiological mechanism mediating the adaptive response to protein restriction has been largely undescribed. In this review we make the case that the liver-derived metabolic hormone FGF21 is the key signal which communicates and coordinates the homeostatic response to dietary protein restriction. Support for this model centers on the evidence that FGF21 is induced by the restriction of dietary protein or amino acid intake and is required for adaptive changes in metabolism and behavior. FGF21 occupies a unique endocrine niche, being induced when energy intake is adequate but protein and carbohydrate are imbalanced. Collectively, the evidence thus suggests that FGF21 is the first known endocrine signal of dietary protein restriction.

Con: The role of diet for people with advanced Stage 5 CKD.

Restriction of dietary protein intake has been used in the management of chronic kidney disease (CKD) for many decades, yet remains controversial, with marked variations in its application in clinical practice. There is extensive literature on the subject, with some expert opinion advocating the use of protein restriction based on the balance of the available evidence. The largest randomized trial of low-protein diets is the Modification of Diet in Renal Disease study. Despite multiple secondary analyses, the essential intention-to-treat analysis failed to demonstrate a benefit in the primary outcome of rate of decline of glomerular filtration rate. There are criticisms of many published studies and meta-analyses, including the likelihood of publication bias and unsuitable biochemical endpoints that may be affected by dietary restriction in the absence of effects on kidney function, leading to false positive findings. It is also uncertain whether any benefits observed in these often older studies would be derived in patients undergoing modern standards of CKD management, including blood pressure control and renin-angiotensin blockade. Thus it is unclear whether, even in the strictly controlled environment of a clinical study, low-protein diets significantly slow CKD progression. Important questions exist regarding the applicability of these diets in routine clinical practice. Even in carefully selected study populations with intensive dietetic input, adherence to low-protein diets is poor. It is likely that only a small minority of CKD patients in routine practice could adhere to these diets, and although risks of malnutrition arising from protein restriction are uncertain, they will be greater in less supervised care outside of studies.

Keto acid-supplemented low-protein diet for treatment of adult patients with hepatitis B virus infection and chronic glomerulonephritis

An open-label, randomized, controlled, single-centre clinical trial to evaluate the effects of low-protein intake, with or without keto acid supplementation, on nutritional status and proteinuria, in patients with hepatitis B virus (HBV) and early stage chronic glomerulonephritis. Patients with chronic glomerulonephritis and HBV infection were randomized to receive a low-protein diet (0.6-0.8 g/kg ideal body weight [IBW] per day) either without (LP group) or with (sLP group) keto acid supplementation (0.1 g/kg IBW per day), for 12 months. Nutritional, clinical and safety parameters were recorded. The study included 17 patients (LP group n = 9; sLP group n = 8). Proteinuria and microalbuminuria were significantly lower in the sLP group at 6 and 12 months compared with baseline, and at 12 months compared with the LP group. There were no significant differences in serum creatinine level or estimated glomerular filtration rate. Nutritional parameters (serum albumin and prealbumin) were significantly improved at 12 months, compared with baseline, in the sLP group. Restriction of dietary protein intake to 0.6-0.8 g/kg IBW per day appears to have an acceptable safety profile. Supplementation with keto acids is associated with decreased urine protein excretion.

Restricting Protein Intake not Beneficial

Zhan and Stremmel correctly draw attention to minimal hepatic encephalopathy (MHE), a frequently unrecognized complication of cirrhosis. They highlight the dilemma that restriction of dietary protein intake further reduces muscle mass in patients who are already severely malnourished. In the section on nutritional therapy, however, the authors fail to make clear statements. The European Society for Clinical Nutrition and Metabolism (Europaische Gesellschaft fur Stoffwechselforschung und klinische Ernahrung, ESPEN) guideline recommending a protein rich diet is based on evidence from randomized controlled trials (1) and should not be dismissed. Even in patients with recurrent encephalopathy, protein restriction—as previously recommended—is not beneficial (2). The often reiterated recommendation of protein restriction is based on a collection of cases reported by Sherlock and colleagues in 1954. Here they described a selected subgroup of five patients with cirrhosis and encephalopathy, four of whom suffered from portal vein thrombosis and two of whom were treated with ammonium chloride as a diuretic. „Meat intoxication“ as a precipitating factor of hepatic encephalopathy is a rare event nowadays and listing excessive protein intake as item number 2 in the box showing precipitating factors is not appropriate. Infections are far more important in that respect and should be systematically and rapidly sought for and treated; indeed, infections should be at the top of the list. Furthermore, an effect of lactulose on ammonia generation from the glutamine metabolism of the small intestinal mucosa can only be exerted by small bowel evacuation but not by a specific effect on glutamine uptake (3). The work of Egberts and Schomerus on the effect of branched-chain amino acids on driving capacity seems to have escaped the authors' attention when compiling the list of randomized controlled trials.

Adiponectin,leptin: focus on low-protein diet supplemented with keto acids in chronic glomerulonephritis with hbv patients

Leptin and adiponectin come from adipose tissue, which can reflect patients' inflammation and status of lipid metabolism. Our study is aim to evaluate the effects of short-term restriction of dietary protein intake (DPI) supplemented with keto acids on nutrition and lipid metabolic disturbance in chronic glomeruloneph-ritis with HBV patients. 17 patients were randomized to either low DPI with keto acid-supplemented (sLP) or low DPI (LP) group for 12 weeks. Low-protein diet (LPD) wasindividualized with protein intake of 0.6–0.8 g/kg/day and keto acids were supplied in 0.1 g/kg/day. Nutritional index other clinical index were measured to evaluate the effect and safey respectively. Serum levels of adiponectin, leptin were determined by ELISA assay.The urine protein excretion level was significantly decreased after 12 weeks in the sLP group compared to the basal value and the LP group (baseline:4.52±1.74,4 weeks:3.19±1.52 g,8 weeks: 2.19±1.1 g,12 weeks:1.64±0.77 g, P In conclusion: Short-term restriction of DPI 0.6–0.8 g of protein/ kg IBW/day is safe, when combined with keto acids, is associated with decreased of urinary protein and improvement of lipid metabolism

Protein-Restricted Diets Plus Keto/Amino Acids - A Valid Therapeutic Approach for Chronic Kidney Disease Patients

Chronic kidney disease (CKD) is increasingly common, and there is an increasing awareness that every strategy should be used to avoid complications of CKD. Restriction of dietary protein intake has been a relevant part of the management of CKD for more than 100 years, but even today, the principal goal of protein-restricted regimens is to decrease the accumulation of nitrogen waste products, hydrogen ions, phosphates, and inorganic ions while maintaining an adequate nutritional status to avoid secondary problems such as metabolic acidosis, bone disease, and insulin resistance, as well as proteinuria and deterioration of renal function. This supplement focuses on recent experimental and clinical findings related to an optimized dietary management of predialysis, dialysis, and transplanted patients as an important aspect of patient care. Nutritional treatment strategies are linked toward ameliorating metabolic and endocrine disturbances, improving/maintaining nutritional status, as well as delaying the renal replacement initiation and improving outcomes in CKD patients. A final consensus states that dietary manipulations should be considered as one of the main approaches in the management program of CKD patients and that a reasonable number of patients with moderate or severe CKD benefit from dietary protein/phosphorus restriction.

Effect of Short-Term Low-Protein Diet Supplemented with Keto Acids on Hyperphosphatemia in Maintenance Hemodialysis Patients

Aim: To evaluate the effects of short-term restriction of dietary protein intake (DPI) supplemented with keto acids on hyperphosphatemia in maintenance hemodialysis (MHD) patients. Methods: Forty MHD patients with uncontrolled hyperphosphatemia were randomized to either low DPI with keto acid-supplemented (sLP) or normal DPI (NP) group for 8 weeks. After 8 weeks, the sLP group was shifted to NP for another 8 weeks. Low-protein diet (LPD) was individualized with total caloric intake 30–35 kcal/kg/day, protein intake of 0.8 g/kg/day and phosphate intake of 500 mg/day. Keto acids were supplied in a dosage of 12 pills per day. Calcium phosphorous metabolism index and nutritional index (serum albumin, total protein, somatometric measurements, 3-day diaries and Mini-Nutritional Assessment score) were recorded. C-reactive protein, CO₂ combining power and Kt/V were measured to evaluate the inflammation, metabolic acidosis and dialysis adequacy, respectively. Results: Serum phosphorus level and calcium-phosphate product were significantly decreased at the end of the first 8 weeks in the sLP group compared to the basal value and the NP group (p < 0.001). No difference was observed in C-reactive protein, Kt/V and nutritional index, while CO₂ combining power was significantly higher at week 8 in the sLP group (p < 0.001). Conclusion: Short-term restriction of DPI supplemented with keto acids could decrease hyperphosphatemia and calcium-phosphate product, while keeping stable nutritional status among MHD patients.

New era in treatment for phenylketonuria: Pharmacologic therapy with sapropterin dihydrochloride

Oral administration of sapropterin hydrochloride, recently approved for use by the US Food and Drug Administration and the European Commission, is a novel approach for the treatment of phenylketonuria (PKU), one of the most common inborn errors of metabolism. PKU is caused by an inherited deficiency of the enzyme phenylalanine hydroxylase (PAH), and the pathophysiology of the disorder is related to chronic accumulation of the free amino acid phenylalanine in tissues. Contemporary therapy is based upon restriction of dietary protein intake, which leads to reduction of blood phenylalanine levels. This therapy is difficult to maintain throughout life, and dietary noncompliance is commonplace. Sapropterin dihydrochloride is a synthetic version of tetrahydrobiopterin, the naturally occurring pterin cofactor that is required for PAH-mediated phenylalanine hydroxylation. In a subset of individuals with PAH deficiency, sapropterin administration leads to reduction in blood phenylalanine levels independent of dietary protein. For these individuals, sapropterin is an effective novel therapy for PKU.

Nutrition in Hepatic Encephalopathy

Protein calorie malnutrition (PCM) is a well-known complication of chronic liver disease (CLD). A major contribution to PCM in CLD is restriction of dietary protein intake. After many decades of injudicious reduction in dietary protein, cirrhotic patients are now prescribed appropriate amounts of protein. PCM in CLD is known to be associated with life-threatening complications. In the general approach to these patients, the initial and most important step for the clinician is to recognize the extent of malnutrition. Most patients tolerate a normal amount of dietary protein without developing hepatic encephalopathy (HE). Oral branched-chain amino acids (BCAAs) have a limited role in HE. Patients who exhibit dietary protein intolerance originally were thought to be best treated with BCAA formulations. Mixed evidence has been reported in multiple studies. In keeping with other reports, this article shows that in animal protein-intolerant patients, even those with advanced cirrhosis, vegetable protein-based diets are well tolerated. Another approach to management of apparent dietary intolerance is to optimize HE treatment with available medications. This article reviews the causes of HE, minimal HE, and PCM; examines nutrition requirements and assessment; and discusses treatment options for malnutrition in HE.

Effect of Dietary Factors on Proteinuria and Endothelial Dysfunction in Renal Patients

ENDOTHELIAL DYSFUNCTION is a common feature in patients with chronic kidney disease (CKD), and an early precursor of atherosclerosis. Effective pharmacologic and nonpharmacologic interventions are needed to reduce the disproportionate cardiovascular risk in CKD patients. Nutritional treatment plays a central role in the conservative management of CKD patients. It includes the restriction of dietary protein intake, and a reduced intake of phosphorus and sodium. The requirement of essential amino acids must always be guaranteed, as well as adequate energy intake.

Les déficits du cycle de l’urée chez les patients adultes

Urea cycle disorders (UCD) usually present after 24 h to 48 h of life with failure to thrive, lethargy and coma leading to death, but milder forms may occur from infancy to adulthood. Survival of children with UCD has significantly improved and the need for transitional care to adulthood has emerged. Adult onset UCD present with chronic or acute neurological, psychiatric and digestive symptoms associated with protein avoidance. Ornithine transcarbamylase (OTC) deficiency, which is inherited as an X-linked disorder, is the most well-described UCD in adults. Acute decompensations associate the triad of encephalopathy, respiratory alkalosis and hyperammonemia. Acute encephalopathy is characterized by brain edema, which is life-threatening without treatment. Specific urea cycle enzyme deficiency can be suspected in the presence of abnormal plasma amino acids concentrations and urinary excretion of orotic acid. A measurement enzyme activity in appropriate tissue, or DNA analysis if available, is required for diagnosis. Treatment requires restriction of dietary protein intake and the use of alternative pathways of waste nitrogen excretion with sodium benzoate and sodium phenylbutyrate. Patients with acute forms may need hemodialysis or hemodiafiltration. Therapeutic goals for OTC deficiency are to maintain plasma ammonia<80 micromol/L, plasma glutamine<1,000 micromol/L, argininemia 80-150 micromol/L and branched chain amino acids within the normal range, in order to prevent episodes of potentially lethal acute hyperammonemia. Potentially fatal acute hyperammonemia may occur in male or female patients at any age. Ammonia should be measured promptly in case of acute neurological and psychiatric symptoms or coma.

Skeletal muscle protein mobilization during the progression of lactation

To investigate changes in muscle metabolism during lactation, serial biopsy of the triceps brachii was conducted in first-parity sows subjected to three degrees of selective protein mobilization through restriction of dietary protein intake (see Clowes EJ, Aherne FX, Foxcroft GR, and Baracos VE. J Anim Sci 81: 753-764, 2003). Muscle biopsies were taken 7 days before parturition and at 12 and 23 days of lactation. The following changes occurred after parturition, were progressive, and were significantly magnified in animals under the greatest degree of dietary protein restriction and hence of protein mobilization. Decreased RNA-to-DNA ratio (capacity for protein synthesis) was observed. The presence of increased expression of several elements of the ubiquitin proteasome proteolytic pathway suggested a robust catabolic response. However, as lactation progressed, and especially under conditions of increased dietary protein restriction, protein mobilization increased, muscle RNA-to-DNA ratio fell further, protease gene expression continued to rise, tissue free glutamine levels rose dramatically, and essential amino acid levels, especially branched-chain amino acids and threonine, fell to below prepartum levels.

Hormonal modulation of proteinuria in the nephrotic syndrome.

Proteinuria is the primary manifestation of a variety of glomerular diseases which are characterized clinically by the nephrotic syndrome. In many cases there is little effective treatment for the primary disease process. However, reduction of proteinuria can frequently improve the hypoalbuminemia, hyperlipidemia and edema which are responsible for the morbidity of the nephrotic syndrome. Proteinuria can be reduced in nephrotic humans and experimental animal models by restriction of dietary protein intake, nonsteroidal anti-inflammatory drug, and by angiotensin-converting enzyme inhibitors. Each of these therapies modifies the activity of locally acting glomerular hormones, autocoids, suggesting that there is a component of proteinuria which is hormonally mediated. The effects of dietary protein, nonsteroidal anti-inflammatory drugs, and angiotensin-converting enzyme inhibitors on nephrotic proteinuria and their potential hormonal mechanisms of action is the subject of this review.

Reducing dietary protein intake to retard progression of diabetic nephropathy.

End-stage renal disease is a frequent complication of insulin-dependent diabetes mellitus. Recent studies have demonstrated that abnormal intrarenal hemodynamics contribute to the progression of chronic renal failure in several models of renal disease, including the diabetic rat. Restriction of dietary protein intake has been demonstrated to normalize these abnormalities and retard progression of renal failure. Limited studies in human subjects suggest a similar beneficial effect, and trials are now underway in diabetic patients with renal failure to clearly establish efficacy of this approach.

Plasma testosterone levels and Leydig cell function in male uremic rats after restriction of dietary protein intake

Journal Article Plasma testosterone levels and Leydig cell function in male uremic rats after restriction of dietary protein intake Get access M R Müller, M R Müller Institut für Physiologische Chemie II, Universität Düsseldorf Search for other works by this author on: Oxford Academic Google Scholar N Kühn-Velten, N Kühn-Velten Institut für Physiologische Chemie II, Universität Düsseldorf Search for other works by this author on: Oxford Academic Google Scholar W Staib W Staib Institut für Physiologische Chemie II, Universität Düsseldorf Search for other works by this author on: Oxford Academic Google Scholar Acta Endocrinologica (Norway), Volume 117, Issue 4_Supplement, Apr 1988, Page S207, https://doi.org/10.1530/acta.0.117S207 Published: 01 April 1988

Reduced Albuminuria After Dietary Protein Restriction in Insulin-Dependent Diabetic Patients With Clinical Nephropathy

Recent clinical investigations have demonstrated that an early restriction of dietary protein intake may reduce the rate of progression of chronic renal failure in humans. In this study the effects of a restricted-protein diet on kidney function in type I diabetic patients with clinical nephropathy were evaluated. Sixteen patients (9 men, 7 women) with mean age 37.1 +/- 9.8 yr, mean duration of diabetes 17.7 +/- 6.6 yr, proteinuria greater than 0.5 g/24 h, and serum creatinine concentration of 0.7-1.9 mg/dl were studied. Patients were randomly divided into two groups. The low-protein diet (LPD) group comprised seven patients who were kept for 4.5 +/- 1 mo on a diet containing 0.71 +/- 0.12 g X kg-1 X day-1 protein. The normal-protein diet (NPD) group comprised nine patients as controls maintained for 11.7 +/- 7 mo on their usual diabetic diet containing 1.44 +/- 0.12 g X kg-1 X day-1 protein. All patients were studied every 1-2 mo. Metabolic control was assessed by evaluation of 5-8 blood glucose determinations/day and by glycosylated hemoglobin, whereas renal function was evaluated by albumin, IgG and beta 2-microglobulin urinary excretion rates, serum creatinine concentration, and creatinine clearance. At each visit, serum concentrations of total protein, albumin, phosphate, calcium, and electrolytes and weight and blood pressure were also measured. A significant reduction (434 +/- 244 to 205 +/- 212 micrograms/min, mean +/- SD) in albumin excretion rate was found in all LPD patients after dietary protein restriction, with a significant reincrease (689 +/- 201 micrograms/min) in the same patients several months after interruption of diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous catabolism is the major source of toxic metabolites in isovaleric acidemia

A patient with isovaleryl-coenzyme A dehydrogenase deficiency was given a synthetic oral feed containing L-(2H3-methyl)-leucine of high isotopic purity as the only dietary precursor to the defective enzyme. Metabolites derived from this source were readily distinguished from their unlabeled endogenous counterparts by mass spectrometry. During 6 consecutive days of labeled leucine ingestion, the average daily excretion of labeled metabolites was only about 10% of the total derived from leucine. It is suggested that therapy should be directed toward the control of endogenous protein turnover rather than the restriction of dietary protein intake.