Ranges of phenotypic flexibility in healthy subjects.

BACKGROUND: A key feature of metabolic health is the ability to adapt upon dietary perturbations. A systemic review defined an optimal nutritional challenge test, the "PhenFlex test" (PFT). Recently, it has been shown that the PFT enables the quantification of all relevant metabolic processes involved in maintaining or regaining homeostasis of metabolic health. Furthermore, it was demonstrated that quantification of PFT response was more sensitive as compared to fasting markers in demonstrating reduced phenotypic flexibility in metabolically impaired type 2 diabetes subjects. METHODS: This study aims to demonstrate that quantification of PFT response can discriminate between different states of health within the healthy range of the population. Therefore, 100 healthy subjects were enrolled (50 males, 50 females) ranging in age (young, middle, old) and body fat percentage (low, medium, high), assuming variation in phenotypic flexibility. Biomarkers were selected to quantify main processes which characterize phenotypic flexibility in response to PFT: flexibility in glucose, lipid, amino acid and vitamin metabolism, and metabolic stress. Individual phenotypic flexibility was visualized using the "health space" by representing the four processes on the health space axes. By quantifying and presenting the study subjects in this space, individual phenotypic flexibility was visualized. RESULTS: Using the "health space" visualization, differences between groups as well as within groups from the healthy range of the population can be easily and intuitively assessed. The health space showed a different adaptation to the metabolic PhenFlex test in the extremes of the recruited population; persons of young age with low to normal fat percentage had a markedly different position in the health space as compared to persons from old age with normal to high fat percentage. CONCLUSION: The results of the metabolic PhenFlex test in conjunction with the health space reliably assessed health on an individual basis. This quantification can be used in the future for personalized health quantification and advice.

Epigallocatechin gallate (EGCG) (TEAVIGO) does not impair nonhaem-iron absorption in man.

A number of studies have shown that tea catechins can inhibit intestinal iron absorption, mostly iron in the nonhaem form. This randomized, double-blind, placebo-controlled, 3-periods cross-over study examined the degree of inhibition of nonhaem iron absorption by pure crystalline epigallocatechin gallate (EGCG). The study was designed to show the maximum inhibitory action of EGCG by selecting 30 healthy women with low iron stores. Treatments were 150 mg, 300 mg EGCG and placebo each for 8 consecutive study days with a wash-out period of 14 days between treatments. Iron incorporation was assessed by supplying 57Fe orally and 58Fe intravenously. Differences in fractional nonhaem iron absorption between the treatments were evaluated by using two-sided ANOVA. Results showed a relative nonhaem iron absorption reduction of 14% with 150mg EGCG and 27% for 300mg EGCG treatment compared to placebo. Differences were statistically significant (p < or = 0.05) between the placebo and the 300mg EGCG treatments and between the 150 and 300 mg EGCG treatments. The inverse relation between EGCG dose and fractional nonhaem iron absorption was linear (p = 0.0002). In this study the magnitude of the inhibitory action of EGCG on nonhaem iron absorption was found to be much lower than that reported in the literature for black tea and similar compounds. The doses of EGCG in supplements, which will be lower than those used in this study, are not expected to have any health relevant effects on iron absorption in subjects with normal iron stores.

Changes in energy metabolism in relation to physical activity due to fermentable carbohydrates in group-housed growing pigs.

Fermentable nonstarch polysaccharides (dietary fiber) affect energy retention in group-housed growing pigs by reducing physical activity. This study assessed the effects of fermentation and bulkiness of dietary carbohydrates on physical activity in relation to energy metabolism. Eight clusters of 14 pigs were fed one of four diets in a 2x2 factorial arrangement. Factors included 1) gastrointestinal fermentation and 2) dietary bulkiness. Contrasts in fermentation were created by exchanging gelatinized maize starch with raw potato starch on a volume basis. Bulkiness was altered by adding 15% milled wheat straw to the diets. Apart from these differences, amounts of other dietary ingredients fed to the pigs were similar. Pigs were housed in groups. Nitrogen and energy balances were measured per cluster during a 14-d period. Dietary bulkiness did not affect ME intake, heat production, or energy retention. Metabolizability decreased when maize starch was replaced with raw potato starch (P< .01), resulting in a lower energy retention on the potato starch diets (P<.01). However, the lower ME intake on the potato diets was partially compensated by a reduced energy expenditure on physical activity (P< .01), which was 17.6% lower than that of pigs fed the maize starch diets. Dietary bulkiness did not affect physical activity. The effect of fiber-rich diets (nonstarch polysaccharides) on activity in growing group-housed pigs seems to be related to fermentation in the gastrointestinal tract, and not to bulkiness (volume).

Non-starch polysaccharides in pig feeding.

In pigs and humans, the nutrients starch, protein, fat and some minerals need to be digested prior to the terminal ileum for optimal use of these nutrients. In contrast, the non-starch polysaccharides (NSP) are mainly fermented by microbes in the hindgut. Results of experiments in pigs showed that NSP negatively affected apparent digestion of protein, fat and some minerals. In addition, large amounts of fermented NSP increased the empty weight of the hindgut. Because tissue of organs like the intestinal tract are metabolically very active, it may have required more energy for maintenance, hence leaving less energy for growth. Despite all the negative effects as mentioned above, including NSP-rich ingredients in pig diets also has quite a lot of advantages. Their energy supply can cover the energy requirements for maintenance. In addition, positive effects on the well-being and health of pigs, and on the excretion of ammonia are claimed. In conclusion, in future pig diet formulation not only the nutritional aspects of NSP-rich ingredients should be taken into account, but also their non-nutritional aspects. This might be realized by developing nutrient based feed evaluation systems, rather than the energy based systems which are presently used.

Dietary carbohydrates alter the fecal composition and pH and the ammonia emission from slurry of growing pigs.

We investigated the effects of dietary carbohydrates on the composition and pH of fecal material and on the ammonia emission from the slurry of growing pigs. Thirty-four barrows (BW approximately 40 kg) were randomly allotted to 1 of 10 diets. A basal diet was formulated to meet all requirements for protein, amino acids, minerals, and vitamins. The control diet was composed of the basal diet plus heat-treated cornstarch. In the other diets, the cornstarch in the control diet was replaced with three levels of either coconut expeller, soybean hulls, or dried sugar beet pulp. Feces were collected separately from urine in a balance experiment. Feces were mixed with a standardized urine (ratio of 1:2.5, wt/wt) to form a slurry. A sample of this slurry was placed in an in vitro system to determine the pH and the ammonia emission for 16 d at 20 degrees C. The fecal and slurry DM contents decreased (P < .001) and the total VFA concentrations increased (P < .001) when the level of dietary carbohydrates increased. The pH and the ammonia emission decreased as the level of carbohydrates increased (P < .001). The addition of soybean hulls to the diet had the greatest effect on reducing the pH and ammonia emission (P < .001), and the effects of sugar beet pulp and coconut expeller were approximately the same. A linear relationship was found between the intake of dietary nonstarch polysaccharides (NSP) and the ammonia emission (P < .001). For each 100-g increase in the intake of dietary NSP, the slurry pH decreased by approximately .12 unit and the ammonia emission from slurry decreased by 5.4%. We conclude that replacing cornstarch in the diet with components that have a high concentration of fermentable carbohydrates increases the VFA concentration of feces and slurry and reduces the pH and ammonia emission from the slurry of growing pigs.

Effect of resistant starch on net portal-drained viscera flux of glucose, volatile fatty acids, urea, and ammonia in growing pigs.

Net portal-drained viscera (PDV) flux of glucose, VFA, ammonia, and urea was determined in pigs fed diets with or without resistant starch. Diets consisted of 65% cornstarch (diet CS), 32.5% cornstarch and 32.5% raw potato starch (diet CPS), or 65% raw potato starch (diet PS); the remaining 35% supplied all amino acids, fat, fiber, minerals, and vitamins. The diets contained twice the maintenance requirement for energy and were fed twice daily to four barrows (initial BW 56 kg) in three periods in a crossover design. The pigs were fitted with catheters in a mesenteric vein, a mesenteric-artery, and the portal vein, and net PDV flux was calculated by multiplying portal-arterial concentration differences and corresponding portal vein flow. Net PDV flux of glucose was significantly less after feeding diets CPS and PS, and portal absorption of ileally digested glucose was 89, 66, and 41% for diets CS, CPS, and PS, respectively. Net PDV flux of VFA was lowest after feeding diet CS and three to four times higher after feeding diets CPS and PS. Net PDV flux of ammonia was highest for diet CS and almost halved after feeding diets CPS and PS. There was a small negative net PDV flux of urea for diets CS and CPS, which significantly increased after feeding diet PS. These results suggest that excretion of nitrogen is shifted from urine to feces primarily by reduction of the net PDV flux of ammonia when resistant starch is fed.

Apparent digestibility of nutrients in diets with different energy density, as estimated by direct and marker methods for pigs with or without ileo-cecal cannulas.

The objective of this study were a) to compare the apparent total tract digestibility (TD) between non-cannulated (intact) and cannulated (steered ileo-cecal valve technique, SICV) pigs fed diets differing in energy density (Exp. 1) and b) to compare the direct vs marker (Cr2O3) methods for estimation of the TD and apparent ileal digestibility (ID) in SICV-cannulated pigs (Exp. 2). In Exp. 1, 24 intact and 18 SICV-cannulated castrates of approximately 40 kg initial BW were randomly assigned to six treatments in a 2 x 3 x 2 factorial arrangement (two pig types, three carbohydrate sources, and two fat levels). In Exp. 2, the same SICV-cannulated pigs from Exp. 1 were given those treatments in a 2 x 3 x 2 factorial arrangement (two methods of digestibility estimation, three carbohydrates sources, and two fat levels). In both experiments either cornstarch, soybean hulls, or pure cellulose, without or with fat, were incorporated into a barely-soybean meal based diet to alter energy density. Daily diets were isoenergetic (based on NEf), and water supply was .33 L/MJ of NEf. In Exp. 1, the pig type effect on the TD of DM, OM, CP, and the pig type x carbohydrate interactions for the TD of DM, OM, and crude fiber (CF) were significant (P < .05), merely due to a larger difference found for the diet enriched with cellulose. In Exp. 2, the TD and ID evaluated with the marker method were significantly lower (except for the TD of CF) than with the direct method, mainly because Cr recovery was below 100%. Overall, the marker method seems to be superior because the TD means obtained from Cr ratios were closer to the TD obtained from intact pigs. In general, the SICV technique seems to be suitable for long-term digestibility studies to measure the TD and ID in the same pig fed low-or high-fiber diets.

Biochemical lung maturity, static respiratory compliance, and pulmonary gas transfer in intubated preterm infants with and without respiratory distress syndrome.

We investigated the relationship between tests of biochemical lung maturity [lecithin/sphingomyelin ratio (L/S ratio)], static compliance of the respiratory system (Crs), and estimates of pulmonary gas transfer [venous admixture and arterial/alveolar (a/A) ratio] in a group of intubated preterm infants with and without respiratory distress syndrome (RDS). Thirty infants were studied once (n = 26) or twice (n = 4). The L/S ratio was obtained by means of high-performance thin-layer chromatography and determination of the phosphorus content. Crs was obtained by the multiple occlusion technique. Transcutaneous blood gases and the percentage of oxygen in the inspired gas were recorded and estimates of pulmonary gas transfer were calculated using algorithms. L/S ratio and Crs correlated well (r = 0.73), indicating a higher compliance in biochemically more mature lungs. Both the a/A ratio and venous admixture correlated significantly with the L/S ratio and Crs (P < 0.001). Crs, L/S ratio, and a/A ratio decreased with increasing severity of radiological RDS, and the percentage venous admixture increased (P < 0.001). Sequential measurements in four infants during the acute phase and after RDS resolved indicated that clinical improvement coincided with improvements in biochemical lung maturity, Crs, and estimates of pulmonary gas transfer.

Development of a human lung surfactant, derived from extracted amniotic fluid.

Using a surfactant preparation of human origin for the treatment of the respiratory distress syndrome (RDS) instead of an animal-derived surfactant will minimize immunological problems. Therefore we isolated surfactant material from human amniotic fluid. Protein and phospholipid fractions of extracted human amniotic fluid (HAFS) were separated by Lipidex 5000 or acidulated LH20 liquid chromatography systems. Fractions of HAFS, the phospholipid or the recombined phospholipid-protein fractions, were tested in the 27-day fetal rabbit model. The results were compared with the results of the corresponding fractions of extracted ovine lung lavage (EOS) and of the already clinically tested surfactant Curosurf. The in situ surface activity of HAFS, EOS, and of their combined phospholipid + protein fractions (200 mg/kg body wt.) resulted in a lung compliance which was significantly higher than the control (saline) values. The compliances of HAFS, EOS, their combined fractions, and Curosurf were similar, but the lung stability values (V5) differed significantly among these surfactant extracts. The best V5 values (greater than or equal to 0.020 ml/g body wt.) were found after installing EOS or its LH20 phospholipid + protein fractions. HAFS had a poor stabilizing capacity which increased significantly after Lipidex chromatography and even more after enrichment of the Lipidex material with 10% palmitic acid. The Lipidex HAFS + 10% palmitic acid surfactant is at present the best obtainable human surfactant extract. Further development is in progress for the clinical application of this surfactant in preterm neonates.