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Metabolic bone disease of total parenteral nutrition: course after changing from casein to amino acids in parenteral solutions with reduced aluminum content.

Bone disease with total parenteral nutrition (TPN) has been attributed to aluminum loading or vitamin D therapy. We studied 17 patients who first received TPN containing casein hydrolysate with high Al and ergocalciferol (25 micrograms/d) for 6-72 mo followed by TPN containing amino acids with reduced Al and ergocalciferol (5 micrograms/d) for 9-58 mo. We also did a cross-sectional study of 22 patients receiving casein and ergocalciferol (25 micrograms/d) compared with 46 patients receiving amino acids and ergocalciferol (5 micrograms/d) for 6-58 mo. Bone formation was higher and osteoid area, bone-surface stainable Al and total bone Al were lower with amino acid TPN than with casein TPN. Bone formation varied inversely with both plasma Al and bone-surface Al, suggesting that plasma or bone-surface Al, acquired during TPN, can reduce bone formation and lead to patchy osteomalacia. Serum levels of iPTH and 1,25-dihydroxyvitamin D were higher with amino acid TPN.

Aluminum↗

Soy protein and casein in cholesterol-enriched diets: effects on plasma lipoproteins in normolipidemic subjects.

The effect of dietary plant protein vs animal protein on plasma lipoproteins was investigated in a crossover study. Eleven normal subjects consumed formula diets containing 20% of calories as soy protein or casein, 27% as fat, and 53% as carbohydrate: the average cholesterol intake was 500 mg/d. After an initial decrease in plasma cholesterol and low-density-lipoprotein cholesterol (LDL-C) on both diets, the concentration of LDL-C stabilized during the soy-protein diet at a 16% lower level than on the casein diet (p less than 0.02) whereas the concentration of high-density-lipoprotein cholesterol (HDL-C) was 16% higher (p less than 0.01). In a similar earlier study with a cholesterol intake of less than 100 mg/d, casein and soy protein had indistinguishable effects on lipoprotein levels. Our two studies together suggest that the level of cholesterol intake may determine whether plant and animal dietary proteins have similar or different effects on plasma LDL and HDL concentrations.

Caseins↗

Relative importance of carbohydrate and protein sources in the differential effects of soy-based vs casein-based formulas on bone minerals in rats.

Studies reported here examine the extent to which differences in the source of protein (soy vs casein) and of carbohydrate (absence or presence of lactose) may be responsible for differential effects of soy-based and casein-based infant formulas on bone minerals. Growth and bone minerals were measured in rats fed casein-based or soy-based diets with or without lactose. Analysis of variance indicated that presence of lactose in the diets increased calcium, phosphorus, magnesium, and zinc concentrations in the vertebrae (P less than 0.02) and also increased magnesium (P less than 0.01) and zinc (P less than 0.05) in femur and tibia-fibula. In contrast, the source of protein had an effect only on bone magnesium concentration, with the soy protein resulting in lower magnesium retention in all bones studied (P less than 0.05). These data suggest that differences in lactose content rather than in the source of protein may be mainly responsible for the differential effects of milk-based and soy-based infant formulas on bone minerals.

Animals↗

Gastrojejunal kinetics and the digestion of [15N]beta-lactoglobulin and casein in humans: the influence of the nature and quantity of the protein.

The evolution and luminal effects of different quantities of casein and beta-lactoglobulin were investigated in the upper jejunum of 35 volunteers who ingested 400 mL water with either beta-lactoglobulin or casein in either low or high doses (72.6 mmol N, Lbetalg; 71.7 mmol N, LCas; 368.2 mmol N, Hbetalg; 386.8 mmol N, HCas). The flow rate of the liquid effluents as well as the nitrogen movements were measured and the exogenous ([15N]) and endogenous nitrogen fractions analyzed in the upper jejunum after milk protein ingestion. The basal jejunal liquid flow rate (mL/min) was 3.88+/-1.84 and peaked in the 0-20 min period for water (9.92+/-3.72) and Lbetalg (7.27+/-3.08) and during the 20-40 min period for LCas (5.69+/-2.49), HCas (6.32+/-1.85), and Hbetalg (6.11+/-2.31). One hour after water, LCas, Lbetalg, Hbetalg, and HCas ingestion, 100%, 95%, 85%, 71%, but only 38% of the liquid phase of the meal were passed through the jejunum, respectively. The flow rate of the endogenous nitrogen was 12.93+/-5.22 mmol N/h before meal ingestion; remained unchanged after water, LCas or Hbetalg ingestion; but increased significantly (P<0.05) after Lbetalg and HCas ingestion. The net disappearance of exogenous nitrogen in the upper jejunum 240 min after HCas, Lbetalg, LCas and Hbetalg ingestion was 82.6+/-9.5%, 61.6+/-9.6%, 58.4+/-14.7%, and 44.7%+/-24.4%, respectively. The exogenous fraction of protein nitrogen recovered in the upper intestinal lumen represented 43.3% of the ingested Hbetalg nitrogen, but only 4.9% of the ingested HCas nitrogen. In conclusion, casein and beta-lactoglobulin present differences in both the intestinal kinetics of amino acid delivery and in the nature of the products in the intestinal lumen. These differences have to be taken into account from both nutritional and physiologic points of view for the utilization of these proteins in humans.

Adult↗

A comparison of the effects of 2 doses of soy protein or casein on serum lipids, serum lipoproteins, and plasma total homocysteine in hypercholesterolemic subjects.

BACKGROUND: Studies have shown that soy protein reduces some atherogenic lipid and lipoprotein concentrations, although lipoprotein(a) concentrations may be increased. The dose response of soy protein has not been established; neither has its effect on plasma total homocysteine. OBJECTIVE: Our objective was to evaluate the effect of 2 doses of soy protein on lipid, lipoprotein, and homocysteine concentrations. DESIGN: Four to 24 wk after being instructed to consume a lipid-lowering diet, 130 men and women with LDL-cholesterol concentrations > or = 4 mmol/L were studied during a parallel group trial in which 4 interventions were assigned randomly. Thirty grams isolated soy protein (ISP) and 10 g cotyledon fiber or 50 g ISP and 16.6 g cotyledon fiber or equivalent doses of casein and cellulose were consumed daily as a beverage for 16 wk. RESULTS: When the 2 groups who consumed ISP were compared with the 2 groups who consumed casein, the differences in the net changes from baseline to week 16 in the concentrations of LDL cholesterol and plasma total homocysteine were -0.26 mmol/L (95% CI: -0.43, -0.09 mmol/L; P = 0.01) and -0.8 micromol/L (-1.4, -0.2 micromol/L; P = 0.005), respectively. The effect of the ISP dose was not significant. There were no significant differences between the 2 ISP and the 2 casein groups in changes in lipoprotein(a), HDL-cholesterol, or triacylglycerol concentrations. CONCLUSIONS: Adding 30-50 g soy protein/d to a lipid-lowering diet significantly reduced LDL-cholesterol concentrations without increasing lipoprotein(a) concentrations. Plasma total homocysteine concentrations also decreased, suggesting a novel, possibly antiatherosclerotic effect.

Adult↗

Characterization of O-linked glycosylation motifs in the glycopeptide domain of bovine kappa-casein.

kappa-Casein is the major glycoprotein in bovine milk. It has a proteinase-sensitive (chymosin) site which cleaves the glycoprotein into two segments: N-terminal para-kappa-casein domain and the C-terminal kappa-casein macroglycopeptide domain which is highly heterogeneous in oligosaccharide content. We have identified six sites of O-glycosylation on the macroglycopeptide by solid-phase Edman degradation: Thr121, Thr131, Thr133, Thr136 (A variant only), Thr142 and Thr165. No Ser residues are glycosylated. The glycosylation status of 15 of 17 potential O-glycosylation sites in the B variant was accurately predicted using the four peptide motifis previously proposed for the glycosylation of human glycophorin A (Pisano, A., Redmond, J.W., Williams, K.L. and Gooley, A.A., Glycobiology, 3, 429-435, 1993), provided one additional assumption is made concerning an inhibitory role for a nearby Ile.

Amino Acid Sequence↗

Utilization of nitrogen from soybean meal, casein, zein, and urea by mature sheep.

The utilization of nitrogen contained in soybean meal, casein, zein, and urea was studied in 12 mature wethers. Net microbial synthesis rates during the 6-hour period after feeding corresponded to ruminal ammonia concentrations, suggesting that the ruminal ammonia level in these experiments was a limiting factor in microbiol protein synthesis. Maximum conversion of dietary nitrogen to microbial nitrogen in the rumen during a 24-hour period was estimated to be 62.5, 85.3, 40.9, and 90.1%, respectively, for soybean meal, casein, zein, and urea. Estimated production rates of acetic, propionic, butyric, isovaleric, and valeric acids during the first 6 hours after feeding suggested that zein supported the lowest microbial activity in the rumen, and that urea supplementation resulted in isovaleric and valeric acids production rates equivalent to or greater than rates when the other nitrogen supplements were present in the diet. Daily endogenous urinary and metabolic fecal nitrogen determined by regression analysis utilizing soybean meal as the only nitrogen supplement were 72 mg/kg body weight0.75 and 340 mg/100 g of dry matter intake. Biological values of 84.8, 78.3, 84.3, and 76.4 were obtained for soybean meal, casein, zein, and urea, respectively.

Animal Feed↗

Supplementation of a semipurified casein diet for catfish with free amino acids and gelatin.

Semipurified diets with casein as the sole protein source were supplemented with gelatin, arginine, cystine, methionine or tryptophan, and fed to channel catfish (Ictalurus punctatus) fingerlings. Increasing the arginine level from 1.1% to 1.7% of diet by the isonitrogenous substitution of gelatin for casein resulted in a significant enhancement of growth. However, the addition of free arginine, cystine, tryptophan or methionine to casein had little effect on growth or food conversion. These data substantiate a previous report that suggested catfish were similar to carp in their inability to utilize free amino acids.

Amino Acids↗

Long term pancreatic response to feeding heat damaged casein in rats.

Rats were fed a heat damaged casein (autoclaved 24 hours, 121 degrees, 2 atm) diet to determine the effect of poorly digested protein on pancreatic enzyme levels and response to a meal. After 10 days of feeding, the pancreas showed no signs of atrophy, however, chymotrypsin and amylase activities were lower in proportion to body weight. An estimation of secretion during the meal was similar or slightly lower in rats fed heated casein (HC) as compared to the casein diet (C), but a greater levels of enzyme activity was found in the intestinal contents of rats fed HC relative to control rats. These results suggest that the turnover of enzymes in the gut is reduced when a less digestible protein is fed, and that the endogenous pancreatic secretions and the dietary protein are not digested and absorbed as well.

Amylases↗

Incorporation of [14C]leucine into protein of perfused liver of rats fed diets containing casein or lactalbumin.

The livers of rats (190-210 g) fed casein (a phosphoprotein) or lactalbumin (non-phosphoprotein) diets (200 g protein/kg diet) were perfused for 20, 40, or 60 minutes with 5 microCi of [14C]leucine. We determined the amount of radioactivity in the protein and non-protein (free amino acid) fractions of the liver and perfusate supernatant. The wet weight, total protein and protein: DNA ratio of the livers was also determined. The livers of the group fed casein were significantly lighter and contained less protein than the lactalbumin-fed group. However, more [14C]leucine was incorporated into protein of the liver plus perfusate supernatant of the casein-fed group than the lactalbumin group. We concluded that protein metabolism in the liver of rats appears to be increased when the rats were fed a diet containing phosphoprotein as the sole source of protein.

Animals↗

Studies on the mechanism of antihypercholesterolemic action of soy protein and soy protein-type amino acid mixtures in relation to the casein counterparts in rats.

Given evidence of a hypocholesterolemic effect in rats, soy protein compared with casein showed the following effects on cholesterol dynamics: a) lower cholesterol absorption and greater fecal steroid excretion, b) more rapid turnover of serum cholesterol, c) a marked size reduction of the rapidly exchangeable cholesterol pool (pool A) through a significant increase in the removal rate in that compartment without influencing the production rate, and d) greater hepatic sterogenesis both in vitro and in vivo. In contrast, the amino acid mixture equivalent to soy protein compared with casein-type mixture showed: a) no effects on cholesterol absorption and fecal steroid excretion, b) no effects on the turnover of serum cholesterol, c) the reduction of pool A size as a result of decreased production, and d) the reduction of hepatic steroidogenesis in vitro, but not in vivo. These results indicate that decreased intestinal absorption of cholesterol, and increased fecal steroid excretion are primarily responsible for the antihypercholesterolemic effect of soy protein compared with casein. The fecal loss of steroids far outweighs the activation of hepatic steroidogenesis. In the case of the soy protein-type amino acid mixture, the depression of hepatic cholesterol synthesis seems accountable for reducing serum cholesterol levels.

Absorption↗

Lactational response to exogenous growth hormone and abomasal infusion of a glucose- sodium caseinate mixture in high-yielding dairy cows.

Milk production responses to 1) growth hormone injections (51.5 IU/day), 2) a mixture of glucose (274 g/day) and sodium caseinate (441 g/day) infused into the abomasum, 3) a combination treatment, and 4) a placebo treatment were determined in 4 cows in a 4 x 4 Latin square design. Treatment periods were 10 days, and production responses were based on the last 5 days of each treatment. Growth hormone administration increased milk yield 15.2% without changing milk composition or feed intake. Infusions of glucose-sodium caseinate into the abomasum increased milk yield 3.9% and milk protein yield 6.4% but when combined with growth hormone treatment did not stimulate a greater response than observed for growth hormone alone. Plasma concentrations of growth hormone were increased 4-fold with growth hormone injections but were not affected by the infusion of glucose-sodium caseinate into the abomasum. There were no significant changes in plasma concentrations of glucose, free fatty acids, insulin, glucagon, prolactin, triiodothyronine, thyroxine or cortisol with any of the treatments. Growth hormone increased milk synthesis and the efficiency of milk production, but its effect was not enhanced by the postruminal supply of additional nutrients.

Animals↗

Biliary steroid excretion in rats fed soybean protein and casein or their amino acid mixtures.

Male Wistar rats were fed 1% fat, cholesterol-free semipurified diets containing soybean protein isolate and casein or amino acid mixtures simulating these proteins for 28-30 days. The animals then underwent surgery for biliary diversion, and bile was collected for 2 hours. The rate of bile flow was not influenced by the type of dietary protein. The concentration and output of biliary cholesterol in rats fed soybean protein were significantly higher than in those fed casein, while biliary bile acid excretion was comparable. The group given the soy protein-type amino acid mixture also tended to excrete more biliary cholesterol relative to the casein-type amino acid mixture, although the difference was not significant, while biliary bile acid output was comparable. When 5% fat diets containing 0.5% cholesterol were given to rats, concentrations of both biliary cholesterol and bile acid were elevated significantly on a vegetable protein diet. In these experiments, there was a significant negative correlation between serum cholesterol and biliary cholesterol levels. Stimulation of the biliary excretion of cholesterol seems at least relevant to the cholesterol-lowering action of soybean protein.

Amino Acids↗

Effect of casein and beta-casomorphins on gastrointestinal motility in rats.

The effect of bovine casein and synthetic beta-casomorphins on the motility of rat gastrointestinal tract was studied by noninvasive techniques using the nonabsorbable marker 141Ce. Casein suspensions (CAS) or whey protein suspensions (WPS) were labeled with 141Ce and fed by gastric tube. Gastric emptying rate (GER) as well as gastrointestinal transit time (GITT) of the tracer were significantly longer with feeding CAS compared to WPS. The differences between the CAS and the WPS groups were partly (GER) or completely (GITT) abolished by pretreating the animals with the specific opiate-receptor antagonist naloxone. It is assumed that opioid peptides released from casein during digestion slowed gastrointestinal motility by direct interaction with gut opiate receptors. To prove whether beta-casomorphins, when given by gastric tube, can affect motility, different synthetic beta-casomorphins in doses between 1 and 10 mg were added to the WPS. The beta-casomorphin-4 (Tyr-Pro-Phe-Pro-NH2) showed no effect on GITT. The D-Ala substituted D-Ala-beta-casomorphin-4 (Tyr-D-Ala-Phe-Pro-NH2) and D-Ala-beta-casomorphin-5 (Tyr-D-Ala-Phe-D-Ala-Tyr-NH2), which are more resistant to proteolytic attack and have higher opioid potency than beta-casomorphin-4, slowed GITT in a dose-dependent manner.

Amino Acid Sequence↗

Essential amino acids in relation to hypercholesterolemia induced in rabbits by dietary casein.

Rabbits fed a cholesterol-free, semi-purified diet containing 25% casein amino acids (25% AA) for 2 wk had significantly higher serum total and low density lipoprotein (LDL) cholesterol levels than animals fed the same diet containing 11.2% casein amino acids (11.2% AA). These results were similar to those obtained by feeding diets containing 27% and 12% casein, respectively. When rabbits were fed the 11.2% AA diet supplemented with essential amino acids to the 25% level (11.2% AA + essential AA), their LDL cholesterol level was significantly higher than that in animals fed the 11.2% AA diet supplemented with nonessential amino acids to the 25% level (11.2% AA + nonessential AA). LDL protein and phospholipid levels were significantly higher in rabbits fed the 25% AA diet than in those fed 11.2% AA and tended to be elevated in animals fed 11.2% AA + essential AA compared to those fed 11.2% AA + nonessential AA. Fecal excretion of bile acids and cholesterol was similar with all dietary regimens, and the level of liver lipids showed no correlation with the degree of hypercholesterolemia produced by dietary amino acid mixtures.

Amino Acids↗

The hypocholesterolemic effect of dietary soybean protein vs. casein in hamsters fed cholesterol-free or cholesterol-enriched semipurified diets.

Golden Syrian hamsters fed a cholesterol-free diet containing 25% casein had higher plasma total triglyceride and cholesterol levels and VLDL + LDL cholesterol levels than animals fed a 25% soybean protein diet. Hamsters fed the cholesterol-free casein diet also had higher HDL cholesterol levels than animals fed the soybean protein diet, but these differences were not statistically significant. Addition of cholesterol to the diets caused even greater mean differences between the animals fed different types of protein, but the increased inter-animal variability of response to the added cholesterol resulted in less statistically significant differences. Although less responsive than the nonhybrid Golden Syrian hamsters, hybrid F1B hamsters showed similar effects of dietary casein vs. soybean protein on plasma lipids. These results indicate that the hamster may be a useful model to examine the effect of different types of protein and the interaction with dietary cholesterol on various plasma lipids and lipoproteins.

Animals↗

Abomasal infusion of casein enhances nitrogen retention in somatotropin-treated steers.

The effects of bovine somatotropin (bST) administration and abomasal protein infusion on nitrogen metabolism were investigated using four abomasally-cannulated Holstein steers in a 4 x 4 Latin square design. Treatments were factorially arranged to include daily abomasal infusion (water or casein, 0.9 g/kg body wt) and daily bST injection (0 or 200 micrograms/kg body wt). Each treatment period lasted for 23 d and consisted of an adjustment period (d 1 to 7), casein infusion (d 8 to 23) and bST treatment (d 10 to 23). Nitrogen metabolism and serum insulin-like growth factor-I (IGF-I) profiles were characterized on d 16-22. Animals were fed a total mixed diet balanced to achieve 0.75 kg gain/d and supplemented to provide 115% of requirements for crude protein and minerals. Nitrogen retention was increased by casein and bST individually (21 and 33%, respectively) or in combination (75%). Somatotropin treatment increased the biological value of absorbed N, which was consistent with reductions in plasma urea nitrogen. Circulating IGF-I was increased by bST and was highly correlated (r = 0.73) with N retention. Overall, bST altered requirements so that less absorbed N was required per unit of N retained. However, results also demonstrated that because of limitations in amino acids supplied from microbial and ruminal escape protein in young growing cattle, amino acid supply may limit the magnitude of N retention response to bST under many situations.

Abomasum↗

Labeling with 15N as compared with homoarginine suggests a lower prececal digestibility of casein in pigs.

Calculations of prececal protein digestibility based on the stable isotope 15N and the chemical label homoarginine were compared, using casein doubly-labeled with both markers. After food was withheld overnight 24 miniature pigs were given a meal containing 15 g/100 g casein, including 4 g/100 g doubly-labeled protein, and chromic oxide as an indigestible marker. The intestine of eight animals each was removed 3, 6 or 12 h later, divided into 3 sections of equal length, and chyme was collected. Kjeldahl-N, 15N and homoarginine were determined in diet and chyme. Digestibility of casein in the distal third of the small intestine was 93.5 +/- 0.5% and 97.6 +/- 0.3% (P < 0.05) according to 15N and homoarginine label, respectively. Potential causes for this systematic difference were assessed. The data suggest that incorporation of 15N into endogenous proteins and re-entry into the intestinal lumen via secreta and desquamations is the major cause for the 4.2 +/- 0.4% lower digestibility based on the 15N as compared with the homoarginine labeling technique. A preferential occurrence of homoarginine in more easily digestible sections of the protein, faster release during the digestive process and absorption of homoarginine, or incorporation of 15N into proteins of intestinal bacteria are less likely to cause this difference.

Animals↗