Rice protein-based infant formula: current status and future development.

Rice is the world's leading staple cereal food and is the major source of protein for many parts of the world. Rice is among the first solid foods fed to infants in many cultures, in part because of its hypoallergenicity from lack of gluten. Nutritional quality of rice protein compares favorably with other cereal proteins including wheat, oat and barley. It is rich in methionine and cystine, although as is the case for other cereals, it is an incomplete protein source for human infants with lysine and threonine being the primary limiting amino acids. Fortification of rice proteins with these two limiting amino acids improves its protein quality. Rice protein-based infant formulas (RPF) were initially based on high protein rice flours, but more recently are based on rice protein concentrates, isolates or hydrolysates, fortified with lysine and threonine. Hypoallergenicity efficacy, particularly for hydrolyzed rice protein-based formulas, has been reported, and limited data indicated that rice protein based infant formula may provide potentially adequate alternative if standard milk- or soy protein-based formulas are not tolerated. Unlike the rice-protein based infant formula, rice beverage formulas made from rice flour are nutritionally inadequate for infants. Reports have indicated stunted growth in infants/children fed rice beverage formulas. Future development for the RPF include those based on genetically improved rice with high lysine and threonine content, supplementation with appropriate mineral and fat blend, and long-term clinical studies in infants to confirm its efficacy and safety.

Growth of newborn, term infants fed soy formulas for 1 year.

Few studies have measured long-term growth in infants fed soy protein-based formulas. The effect of nucleotide (NT) supplementation of soy protein-based infant formulas on growth is unknown. Growth was therefore evaluated in healthy term infants fed a soy protein-based formula (SOY; n = 73), SOY with added NT (72 mg added NT/L) at human milk (HM) levels (SOYN, n = 73), or mixed feeding (MF, n = 67) in a randomized, masked, parallel 1-year feeding study. The MF group (a nonrandomized reference group) was fed HM exclusively from birth to 2 months of age followed by HM and/or a standard milk-based formula (Similac with Iron with no supplemental NTs) to 1 year of age. Results indicated that growth (weight, length, and head circumference) was normal and comparable among the three groups. All three groups had similar plasma albumin (at 2 months of age) and hemoglobin levels (at 12 months of age). Thus, this study demonstrated similar growth in the first year of life among infants fed MF feeding or soy formula with or without supplemental NTs.

Alteration of plasma lipids in the rat by fractionation of modified milk fat (butterfat).

Our objective was to determine the nutritional effects of defined fat fractions of modified milk fat, or butterfat (anhydrous butter without the milk fat globule membrane) on lipid and lipoprotein cholesterol concentrations in plasma of rats fed diets containing 16% fat and two amounts of cholesterol. Five dietary fats were compared: 1) intact butterfat, 2) a liquid butterfat fraction enriched in oleic acid and unsaturated triacylglycerols with < 40 carbon atoms, 3) a solid butterfat fraction enriched in palmitic and stearic acids, 4) corn oil, and 5) palm oil. The extent of diet-induced hypercholesterolemia was the greatest with palm oil, followed by solid butterfat, corn oil, intact butterfat, and the lowest with liquid butterfat. Triacylglycerol concentrations in plasma were greater for rats fed palm oil than for those fed corn oil or liquid or intact butterfat. Among the high cholesterol dietary groups, ingestion of the liquid butterfat diet resulted in similar lipoprotein cholesterol and very low density lipoprotein concentrations relative to the corn oil diet, and ingestion of the solid butterfat diet resulted in similar lipoprotein cholesterol and very low density lipoprotein concentrations relative to the palm oil diet. These results suggest that changes in the triacylglycerol and fatty acid composition of butterfat by fractionation processes may improve its nutritional profile.

Total parenteral nutrition containing medium- vs. long-chain triglyceride emulsions elevates plasma cholesterol concentrations in rats.

Male Fischer 344 rats (235-246 g) were fed for 6-14 d by intravenous or intragastric infusion with total parenteral nutrition (TPN) solutions providing 40 or 65% of nonprotein energy as fat from long-chain triglyceride (LCT) or a 3:1 admixture of medium-chain triglyceride (MCT) and LCT emulsions. In three separate experiments, plasma cholesterol concentrations were significantly greater (24-32%) with intravenous infusion of TPN solutions containing MCT-LCT rather than LCT. Plasma cholesterol concentrations in rats were not significantly different with intragastric infusion of TPN solutions containing MCT-LCT rather than LCT. Hepatic total lipid and triglyceride concentrations were not significantly different. Hepatic total cholesterol and esterified cholesterol concentrations were significantly lower in animals given 65% of energy from MCT-LCT rather than LCT emulsions (main effects, two-way ANOVA). The concentration of individual hepatic acyl-CoA esters reflected the fatty acid profiles of the lipid emulsions infused. Total hepatic acyl-CoA concentrations suggested differences in utilization of acyl-CoA esters with intravenous infusion of MCT-LCT rather than LCT and were consistent with rapid oxidation of MCT. These data demonstrate that MCT-LCT elevates plasma cholesterol concentrations compared with LCT emulsions with intravenous, but not with intragastric, infusion of TPN solutions in rats.

Energy expenditure in rats maintained with intravenous or intragastric infusion of total parenteral nutrition solutions containing medium- or long-chain triglyceride emulsions.

Energy expenditure was determined in male Fischer 344 rats (235-246 g) fed by intravenous (IV) or intragastric (IG) infusion with total parenteral nutrition solutions providing 65% of nonprotein energy as fat from long-chain triglyceride (LCT) or a 3:1 admixture of medium-chain triglyceride (MCT) and LCT emulsions. Respiratory gas exchange and somatomotor activity were assessed continuously for 24 h during d 5 and 11 of infusion feeding. The MCT infusion resulted in one-third the weight gain noted with LCT infusion (MCT, 10 +/- 2 g/14 d; LCT, 32 +/- 4 g/14 d; P less than 0.0001). Insulin concentration was 60% higher with IV than with IG infusion and approximately 100% higher with IV-MCT than with IG-MCT or LCT infusion (P less than 0.05). Rats receiving IV infusion of MCT displayed similar levels of motor activity but 8-13% greater daily energy expenditure (kJ.kg-0.75.kJ intake-1) than rats receiving IG-MCT or LCT infusion (P less than 0.05). The MCT infusion also resulted in an elevation in respiratory quotient after cessation of nutrient infusion (MCT, 0.87-0.92; LCT, 0.83-0.85; P less than 0.05). Total and resting energy expenditure decreased approximately 13% from 5 to 11 d of infusion feeding. The lower weight gain and greater energy expenditure seen with MCT- compared with LCT-supplemented total parenteral nutrition may be mediated by higher insulin concentrations.

In vivo determination of triglyceride secretion using radioactive glycerol in rats fed different dietary saturated fats.

Our objective was to determine the relative rates of in vivo triglyceride (TG) secretion and the composition of very low density lipoproteins (VLDL) in rats fed different dietary saturated fats. Male Sprague-Dawley rats (150-200 g) were fed diets containing 16% corn oil, or 14% butterfat, 14% beef tallow, 14% olive oil, or 14% coconut oil plus 2% corn oil for 5 wk. Changes in plasma TG specific radioactivity were determined in individual, unanesthetized fasted rats after injection of 100 microCi [2-3H]glycerol. Nonlinear regression analysis using a 2-compartment model was used to determine the fractional rate constant for TG turnover in plasma. The plasma TG pool was 33-40% larger with beef tallow than with corn, olive or coconut oil feeding (p less than 0.05), and 20% larger with beef tallow than with butterfat feeding. The rate of TG secretion into plasma (mg/min/100 g body weight) was 60% higher in animals fed beef tallow than corn or coconut oil (p less than 0.05) and 26-33% higher in animals fed beef tallow than olive oil or butterfat. Differences in VLDL composition (% wt) were also noted. Our data suggest that greater TG secretion is the primary factor contributing to the larger TG pool with ingestion of beef tallow relative to butterfat, corn or coconut oil. These results suggest that different dietary saturated fats have unique effects on TG metabolism in rats.

Interrelationship of plasma triglycerides and HDL size and composition in rats fed different dietary saturated fats.

We investigated the relative effects of different dietary saturated fats on the size distribution, apolipoprotein (apo) and chemical composition of HDL in fasted rats. Male Sprague-Dawley rats (174 +/- 2 g) were fed diets containing 0.035% cholesterol and 16% fat (wt/wt) from corn oil (CO diet) or from 2% CO plus 14% butterfat (BF diet), beef tallow (BT diet), palm oil (PO diet) or coconut oil (CN diet) for 6 wk. Apparent lipid digestibility was significantly lower with the PO and BT diets vs. the CO, BF and CN diets. Plasma total cholesterol levels were significantly higher in rats fed the PO and BT diets than in rats fed the BF and CN diets but were not different among the PO-, BT- and CO-fed groups. Nondenaturing gradient gel electrophoresis immunoblot analysis indicated that HDL apo A-I and E resided on particles with significantly smaller modal diameters in rats fed all saturated fats compared with those fed the CO diet. Chemical analyses indicated that HDL generally contained proportionately less protein and more triglyceride, free cholesterol and apo E with saturated fat feeding than with CO diet feeding. Significantly higher plasma and VLDL triglyceride levels were noted with ingestion of the BT, PO or CN diet than with the CO diet. Butterfat feeding resulted in lower plasma triglycerides and HDL-esterified cholesterol than did feeding the other saturated fats. Very low density lipoprotein triglyceride concentrations were inversely correlated with HDL modal diameter of apo E containing lipoproteins (P less than 0.005). These data provide further evidence of the interrelationship of triglyceride and HDL metabolism and suggest that mechanisms independent of cholesterol ester transfer protein may mediate this response in rats.

Mammary tumor lipids and plasma lipoproteins in DMBA-intubated rats fed olive or safflower oils.

The effects of feeding olive and safflower oils on lipid and fatty acid composition of mammary tumors, plasma lipids and lipoproteins, and the nuclear magnetic resonance (NMR) spectra of plasma were investigated in rats. 7-12-Dimethylbenz[a]anthracene (DMBA)- and placebo-intubated male Sprague-Dawley rats were fed 20% fat diets containing 18:2n-6 (wt/wt) from either high-linoleic safflower oil (SL, 14.6% 18:2n-6), high oleic safflower oil (SO, 3.4% 18:2n-6), olive oil (OO, 1.1% 18:2n-6), or olive oil supplemented with 18:2n-6 (OL, 3.4% 18:2n-6) for 16 weeks. Our result indicated that tumor composition of 18:1n-9 and 18:2n-6 reflected the diet, but tumor neutral lipid (NL) was more reflective of diet than was tumor phospholipid (PL). The 20:4n-6 content of tumor PL was constant in all of the dietary groups despite threefold higher levels of 18:2n-6 in tumor PL from animals fed SL than from those fed SO, OO, or OL diets. This suggests a possible feedback inhibition of delta 6-desaturase by the higher content of 18:2n-6 associated with SL feeding No diet effects were obtained for tumor total lipid, NL, PL, cholesterol, and triglyceride contents. Plasma lipoprotein changes were more reflective of diet than tumorigenesis except for apolipoprotein-E, which was lower, and for very low-density lipoprotein cholesterol and low-density lipo protein, which were higher in tumor-bearing rats. Plasma NMR analysis indicated no difference in the average line widths of the methyl and methylene resonances for tumor-bearing and nontumor-bearing rats fed any of the diets.

Dietary olive and safflower oils in promotion of DMBA-induced mammary tumorigenesis in rats.

Interpretation of studies comparing the efficacy of different dietary fat sources in promoting 7,12-dimethylbenz[a]-anthracene (DMBA)-induced rat mammary tumorigenesis often ignores the fact that about 4% (wt/wt) linoleic acid (18:2n-6) is required for optimal tumor promotion. We therefore fed DMBA-intubated or placebo-intubated female, Sprague-Dawley rats 20% fat diets containing 18:2n-6 (wt/wt) from either high-linoleic safflower oil (SL, 14.6% 18:2n-6), high-oleic safflower oil (SO, 3.4% 18:2n-6), olive oil (OO, 1.1% 18:2n-6), or OO supplemented with 18:2n-6 (OL, 3.4% 18:2n-6) for 16 weeks. Results indicated that OO-fed rats had longer tumor-free time, fewer tumors per rat, and lower tumor incidence compared with SO and OL. Addition of 2.3% 18:2n-6 to OO enhanced tumor promotion (p less than 0.04); SL, SO, and OL demonstrated similar tumor-enhancement effect. About 74% of observed mammary tumors were adenocarcinomas; a greater number of tumors appeared in the thoracic and inguinal than in the cervical and abdominal regions irrespective of diet. These results indicate that once an optimal amount of linoleic acid is provided in the diet, oleic- or linoleic-rich oils have similar effects on promotion of mammary tumors in the rat.

Relative effects of dietary oleic- and linoleic-rich oils on plasma lipoprotein composition in rats.

Plasma lipoprotein composition and hepatic lipid content were investigated in male Sprague-Dawley rats (104 +/- 2 g) fed diets containing 12% olive oil [OO, 70% 18:1(n-9)], 12% high oleic safflower oil [SO, 70% 18:(ln-9)] or 12% high linoleic safflower oil [SL, 73% 18:2(n-6)] for periods of up to 10 wk. Fasting plasma triglycerides were significantly higher after feeding oleic-rich diets than after feeding SL for 3, 5 and 6 wk. At 6 wk VLDL triglycerides were two- to threefold higher in rats fed OO or SO than in those fed SL, but by 10 wk both plasma and VLDL triglycerides were similar. A greater proportion of HDL2 (diameter 8.0-12.1 nm), a lower proportion of HDL1 (diameter 12.2-17.0 nm) and lower HDL apo E content occurred in rats fed OO and SO than in those fed SL at both 6 and 10 wk. LDL and HDL protein and cholesterol concentrations were not different with feeding SO or SL. After 10 wk of feeding the experimental diets, rats fed OO had significantly lower HDL protein, cholesterol and apo E concentrations and significantly higher hepatic triglyceride content compared to rats fed SO or SL, P less than 0.05. These data suggest that HDL and hepatic lipid content are determined by some property of the dietary oil other than its oleic acid content.

Effect of dietary fat on individual long-chain fatty acyl-CoA esters in rat liver and skeletal muscle.

The effect of dietary fat on the long-chain acyl-CoA ester profile of liver and skeletal muscle was investigated by feeding weanling rats 12%-fat diets composed of high-linoleic safflower oil (73% 18:2n-6), high-oleic safflower oil (70% 18:1n-9) or olive oil (70% 18:1n-9) for six and ten weeks. Approximately 50% of both hepatic and skeletal muscle acyl-CoA esters comprised linoleoyl-CoA or oleoyl-CoA with high-linoleic or oleic feeding, respectively. Total hepatic acyl-CoA ester concentration was 40% higher (p less than 0.05) in rats fed 12% fat compared with controls fed a 4%-fat diet. These data demonstrate that the long-chain acyl-CoA ester profile of liver and skeletal muscle reflects the dietary fatty acid profile.

Soluble oat fiber tends to normalize lipoprotein composition in cholesterol-fed rats.

The effect of oat fiber on VLDL, LDL and HDL composition was investigated by feeding male Sprague-Dawley rats diets containing 1.0% cholesterol and 0.2% cholic acid, and 6% dietary fiber from oat bran, high-fiber oat flour or a processed oat product for 20 d. Compared to cholesterol-fed cellulose controls, all oat fibers altered the response to cholesterol feeding as indicated by 25-45% lower total lipoprotein cholesterol, 40-60% lower VLDL + LDL cholesterol, and 25-40% higher HDL cholesterol contents, P less than 0.01. The effect of the oat fibers on VLDL composition was especially pronounced as demonstrated by 30-65% lower VLDL protein, VLDL apo E and plasma apo B concentrations. The processed oat product which contained 40% more soluble fiber than oat bran or oat flour normalized the lipoprotein profile associated with ingestion of the atherogenic diet significantly more than oat bran or oat flour. Concentration of total lipoprotein cholesterol and distribution of apo E among the VLDL and LDL fractions in the processed oat product group were similar to controls not fed cholesterol. These data indicate that ingestion of oat fiber tends to normalize the lipoprotein profile induced by feeding an atherogenic diet in the rat, and that the hypocholesterolemic effect of oat fiber is associated with its soluble fiber content.