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Thirty-four adults undergoing long-term parenteral nutrition (TPN) were treated either with or without intravenous taurine for less than or equal to 24 mo. Statistical comparisons were carried out in eight patients randomly assigned to receive intravenous taurine, usually 10 mg.kg-1.d-1, and 10 patients not receiving taurine. Compared with normal adults, baseline plasma taurine and urine taurine-creatinine ratios were decreased in both groups and platelet taurine was reduced in the taurine-treated group. During taurine treatment the mean of the mean values for taurine became normal in plasma and platelets and remained normal in erythrocytes, granulocytes, and lymphocytes; urine taurine-creatinine ratios rose to approximately five times normal. During follow-up, patients not given taurine had plasma, erythrocyte, and granulocyte taurine and urine taurine-creatinine ratios below normal values and the concentrations of taurine-treated patients. Their platelet taurine was also subnormal. Thus, 10 mg taurine.kg-1.d-1 intravenously normalizes plasma and blood cell taurine concentrations in long-term TPN patients.

To evaluate the effects of long-term total parenteral nutrition (TPN) on eye function, 27 adults and 12 children in the UCLA Home TPN Clinic underwent ophthalmoscopic examination and visual-function testing. Direct inspection of the fundus showed a marked granularity of the retinal pigmented epithelium in some patients. About one-half of the children and one-third of the adults tested had at least one and usually two abnormalities in their electroretinogram. Determination of blood nutrients thought to affect vision revealed that zinc and vitamin E were within normal range. Vitamin A concentrations were above normal in 10 of 19 adults and selenium concentrations were below normal in 10 of 10 children and 17 of 21 adults tested. Linoleic and linolenic acid concentrations were low; plasma, platelet, and urine taurine concentrations were significantly lower than normal. Despite these diffuse nutrient abnormalities, only zinc and vitamin E concentrations correlated significantly with any index of visual function.

People in developed nations such as the United States and Canada have an increased risk of colon cancer. Fecal mutagens have been detected in the feces of individuals at high risk for colon cancer. We describe a rapid, sensitive, reliable, reproducible high-pressure liquid chromatography (HPLC) method for detecting fecapentaenes, the most active and chief mutagen found in human stool. We found fecapentaene in all the stool samples of adults on typical high-fat, low-fiber Western diets. These fecapentaene concentrations remained largely constant when subjects consumed constant diets. Fecapentaene concentrations were reduced for total-parenteral-nutrition (TPN) patients with severe intestinal malabsorption. This finding with TPN patients may reflect changes in important variables of gut microflora in fecapentaene production. Studies with newborns and children showed that fecapentaenes appeared very early in life but are not present in stool at birth.

Chronic renal failure is associated with many abnormalities in plasma amino acids. Since patients with renal failure are frequently deficient in vitamin B-6, this study examined whether vitamin B-6 deficiency may be a cause of any of the abnormal plasma amino acid concentrations observed in chronic renal failure. Sham-operated and chronically azotemic rats were pair-fed diets deficient in or replete with vitamin B-6 for 21 d. By the end of 21 d, the EGOT index rose significantly in the B-6-deficient rats but not in the B-6-replete animals. There were several differences in plasma amino acid concentrations between azotemic and control rats. Azotemia and B-6 deficiency each lowered the plasma serine concentration and raised the glycine-to-serine ratio. Plasma glycine was affected by a two-way interaction between azotemia and vitamin B-6 deficiency whereby the highest values were found in the sham-operated vitamin B-6-deficient animals. Plasma alanine and asparagine were reduced by B-6 deficiency and unchanged by azotemia. These results suggest that vitamin B-6 deficiency may contribute to several of the abnormalities in the plasma aminograms observed in chronic renal failure.

The plasma sulfur amino acid status of maintenance hemodialysis (MHD) patients has not previously been comprehensively investigated. We measured plasma sulfur amino acid levels in 24 MHD patients (12 fasted, 12 nonfasted) both before and after a routine 4-h hemodialysis and in 13 normal individuals (seven fasted, six nonfasted). Plasma free cystine, homocystine, cysteine-homocysteine-mixed disulfide (MDS), methionine, and taurine and protein-bound cysteine and homocysteine were measured. In nonfasted patients, plasma homocystine and MDS were not measured. Fasted patients predialysis had elevated plasma free cystine, homocystine, MDS, methionine, and taurine; all of these, except taurine, fell during dialysis. In nonfasted patients, plasma free cystine was elevated. Protein-bound cysteine and homocysteine were elevated predialysis and postdialysis in all patients; protein-bound cysteine fell during dialysis but remained above normal. In MHD patients predialysis, plasma free cystine levels correlated with plasma MDS, protein-bound cysteine, and age. These findings indicate pervasive alterations in plasma sulfur amino acid levels in MHD patients.

Taurine concentrations were measured in plasma and blood cells of 40 adults undergoing long-term parenteral nutrition, without intravenous taurine, for 43.8 +/- 35.1 (SD) mo. Patients were classified into Group 1 (21 patients) or Group 2 (19 patients) according to whether their estimated enteral absorption of calories was less or greater than 25% of their daily requirement, respectively. In Group 1, taurine concentrations were reduced to 35-49% of normal control values in plasma (p less than 0.01), platelets (p less than 0.001), lymphocytes (p less than 0.005), and erythrocytes (p less than 0.001). Granulocyte taurine was not different from normal. A smaller decrease in taurine concentration was found in Group 2 patients; however, taurine levels were significantly below normal in their plasma and red cells. Thus, many patients undergoing long-term parenteral nutrition with little or no taurine intake are depleted of taurine in plasma and most blood cells. These findings suggest that taurine may be essential for these patients and should be added to solutions used for long-term parenteral nutrition.

In healthy adult humans, eight amino acids (isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine) were shown classically by nitrogen balance studies to be indispensable. Subsequent studies classifying histidine as indispensable are reviewed in this article. We also review the evidence that in certain nutritional or disease states or in certain stages of development otherwise dispensable amino acids may become indispensable. Arginine, citrulline, ornithine, cysteine, and tyrosine thus may be considered as acquired indispensable amino acids. Evidence for the indispensability of taurine is also considered. We propose a classification of the indispensability of amino acids based on clinical and therapeutic considerations.

Although nondialyzed, chronically uremic patients and patients undergoing maintenance hemodialysis often show evidence for wasting and calorie malnutrition and have low dietary energy intakes, their energy expenditure has never been systematically evaluated. It is possible that low energy intakes are an adaptive response to reduced energy needs; alternatively, energy expenditure could be normal or high and the low energy intakes would be inappropriate. Energy expenditure was therefore measured by indirect calorimetry in 12 normal individuals, 10 nondialyzed patients with chronic renal failure, and 16 patients undergoing maintenance hemodialysis. Energy expenditure was measured in the resting state, during quiet sitting, during controlled exercise on an exercise bicycle, and for four hours after ingestion of a test meal. Resting energy expenditure (kcal/min/1.73 m2) in the normal subjects, chronically uremic patients and hemodialysis patients was, respectively, 0.94 +/- 0.24 (SD), 0.91 +/- 0.20, and 0.97 +/- 0.10. There was also no difference among the three groups in energy expenditure during sitting, exercise, or the postprandial state. Within each group, energy expenditure during resting and sitting was directly correlated. During bicycling, energy expenditure was directly correlated with work performed, and the regression equation for this relationship was similar in each of the three groups. These findings suggest that for a given physical activity, energy expenditure in nondialyzed, chronically uremic patients and maintenance hemodialysis patients is not different from normal. The low energy intakes of many of these patients may be inadequate for their needs.

Taurine levels were measured in adult cats consuming casein-based diets supplemented with 0.2, 0.05, 0.02, 0.01 or 0% (wt/wt) taurine or with 0% taurine plus 5.0% L-cystine. Taurine concentrations in plasma, platelets, granulocytes and erythrocytes declined significantly with decreased dietary taurine. In the cats that did not receive the 5.0% cystine supplement, the relationship between dietary taurine intake and plasma and blood cell taurine level was nonlinear. The greatest increment in taurine concentrations occurred between the 0.02 and 0.05% taurine intakes. These findings suggest that the dietary taurine requirement for adult cats may be between 0.02 and 0.05%. Supplementation of the 0% taurine diet with 5.0% L-cystine raised taurine levels above those of the taurine-deficient diets in plasma and all blood cell types. The result of this study therefore suggest a close relationship between dietary taurine intake and blood cell taurine levels in cats. Five percent L-cystine stimulates taurine synthesis in these animals.

Plasma taurine levels and urinary taurine excretion were measured in 12 strict vegetarian (vegan) males who had maintained a vegan diet for 53 +/- 26 mo (SD) and in 14 male nonvegetarian control subjects. Plasma taurine levels differed (45 +/- 7 vs 58 +/- 16 mumol/L, respectively). Urinary taurine excretion was lower (266 +/- 279 vs 903 +/- 580 mumol/d), urinary N pi-methylhistidine was barely detectable, and urinary N tau-methylhistidine was significantly reduced (296 +/- 87 vs 427 +/- 19 mumol/d) in the vegans. Analysis of 3-d dietary diaries kept by the vegans indicated marginal to adequate intake of protein, carbohydrate, vitamin B-6, methionine, and cystine; inadequate intake of zinc; and negligible intake of taurine. Prolonged absence of dietary taurine intake causes decreased plasma taurine and severely restricted urinary taurine output.

Although maintenance hemodialysis (MHD) patients are often wasted, little is known about their dietary energy needs. We studied four men and two women in a clinical research center while they received diets providing 45, 35 and 25 kcal/kg desirable body weight/day; diets were fed, in random order, for 21 to 23 days each. Protein intake, 1.13 +/- 0.02 (SEM) g protein/kg/day, was similar with all three diets. Body weight rose with 45 and 35 kcal/kg/day (P less than 0.05) and fell with 25 kcal/kg/day (P less than 0.05). Nitrogen balance, adjusted for estimated unmeasured losses, was neutral with 45 and 35 kcal/kg/day and negative with 25 kcal/kg/day. Balance was neutral or positive in 6 of 6, 4 of 6, and 0 of 6 patients fed 45, 35, 25 kcal/kg/day, respectively. Nitrogen balance, many plasma amino acids and changes in body weight, mid-arm circumference, mid-arm muscle area and body fat each correlated with energy intake. Resting energy expenditure was normal. The energy intake estimated from regression equations to maintain neutral nitrogen balance was 38.5 kcal/kg desirable weight/day; for body fat and weight, it was 32 kcal/kg/day. These data suggest that MHD patients have normal energy expenditure and approximately normal requirements for maintenance of protein balance, body weight and body fat. An average energy intake of about 38 kcal/kg desirable weight/day may be necessary to maintain nitrogen balance in these patients.