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Enhanced Lacto-Tri-Peptide Bio-Availability by Co-Ingestion of Macronutrients.

Ten Have GA, van der Pijl PC, Kies AK, Deutz NE - PLoS ONE (2015)

Bottom Line: In a second experiment (n=10), we compared the CasH-containing protein matrix with a CasH-containing meal matrix and the modifying effects of macronutrients in a meal on the availability (high carbohydrates, low quality protein, high fat, and fiber).Low protein quality and fiber increased XPP systemic bioavailability further (respectively 1.5 and 1.4 times).We conclude that the amount and quality of the protein, and the presence of fiber in a meal, are the main factors that increase the systemic bioavailability of food-derived XPP.

View Article: PubMed Central - PubMed

Affiliation: Center for Translational Research in Aging & Longevity, Department of Health & Kinesiology, Texas A&M University, College Station, TX, United States of America; Department of Surgery, Nutrition and Toxicology Institute Maastricht, Maastricht University, Maastricht, The Netherlands.

ABSTRACT
Some food-derived peptides possess bioactive properties, and may affect health positively. For example, the C-terminal lacto-tri-peptides Ile-Pro-Pro (IPP), Leu-Pro-Pro (LPP) and Val-Pro-Pro (VPP) (together named here XPP) are described to lower blood pressure. The bioactivity depends on their availability at the site of action. Quantitative trans-organ availability/kinetic measurements will provide more insight in C-terminal tri-peptides behavior in the body. We hypothesize that the composition of the meal will modify their systemic availability. We studied trans-organ XPP fluxes in catheterized pigs (25 kg; n=10) to determine systemic and portal availability, as well as renal and hepatic uptake of a water-based single dose of synthetic XPP and a XPP containing protein matrix (casein hydrolyte, CasH). In a second experiment (n=10), we compared the CasH-containing protein matrix with a CasH-containing meal matrix and the modifying effects of macronutrients in a meal on the availability (high carbohydrates, low quality protein, high fat, and fiber). Portal availability of synthetic XPP was 0.08 ± 0.01% of intake and increased when a protein matrix was present (respectively 3.1, 1.8 and 83 times for IPP, LPP and VPP). Difference between individual XPP was probably due to release from longer peptides. CasH prolonged portal bioavailability with 18 min (absorption half-life, synthetic XPP: 15 ± 2 min, CasH: 33 ± 3 min, p<0.0001) and increased systemic elimination with 20 min (synthetic XPP: 12 ± 2 min; CasH: 32 ± 3 min, p<0.0001). Subsequent renal and hepatic uptake is about 75% of the portal release. A meal containing CasH, increased portal 1.8 and systemic bioavailability 1.2 times. Low protein quality and fiber increased XPP systemic bioavailability further (respectively 1.5 and 1.4 times). We conclude that the amount and quality of the protein, and the presence of fiber in a meal, are the main factors that increase the systemic bioavailability of food-derived XPP.

No MeSH data available.


Related in: MedlinePlus

Systemic levels of XPP peptides—Effect of protein matrix.Post-prandial arterial concentrations after intra-gastric administration of control salt solution (Control), synthetic XPP’s (XPP), casein hydrolysate rich in XPP (CasH) and spiked CasH (CasH + XPP). A: Isoleucine-proline-proline (IPP). B: Leucine-proline-proline (LPP). C: Valine-proline-proline (VPP). Respective number of observations for Control, XPP, CasH and CasH +XPP are for graph A: n = 9, 10, 9 and 10; graph B: n = 10, 10, 9 and 10; graph C: n = 8, 10, 9 and 10. Values are mean ± SEM. Statistics: repeated measures two-way ANOVA, mixed model, planned comparisons. All curves are significantly different from the XPP mixture: effect test mixture p<0.001; effect time p<0.001; interaction p<0.001.
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pone.0130638.g001: Systemic levels of XPP peptides—Effect of protein matrix.Post-prandial arterial concentrations after intra-gastric administration of control salt solution (Control), synthetic XPP’s (XPP), casein hydrolysate rich in XPP (CasH) and spiked CasH (CasH + XPP). A: Isoleucine-proline-proline (IPP). B: Leucine-proline-proline (LPP). C: Valine-proline-proline (VPP). Respective number of observations for Control, XPP, CasH and CasH +XPP are for graph A: n = 9, 10, 9 and 10; graph B: n = 10, 10, 9 and 10; graph C: n = 8, 10, 9 and 10. Values are mean ± SEM. Statistics: repeated measures two-way ANOVA, mixed model, planned comparisons. All curves are significantly different from the XPP mixture: effect test mixture p<0.001; effect time p<0.001; interaction p<0.001.

Mentions: Systemic (= arterial) concentrations of XPP in time (Fig 1) showed no measurable baseline/post-absorptive endogenous XPP (Control group, tested with Wilcoxon). The XPP concentrations in the CasH groups were not back to baseline at 90 min post-prandial (one-way ANOVA with Dunnett’s post-hoc test: IPP p<0.002; LPP p<0.001; VPP p<0.05). The calculated systemic absolute bioavailability (fabs (%) = fraction dose absorbed, Table 3) was increased in the protein based CasH group (IPP: 4.7 times, p<0.0004; LPP: 2.5 times, p<0.002; VPP: 121 times, p<0.0001). The spiked CasH group (CasH+XPP) showed lower systemic bioavailability for VPP (65 times, p<0.0001) in comparison to CasH. There was a delay in the time to maximum XPP plasma concentration (tmax) with the CasH groups compared to the XPP test mixture (12 min, p<0.0001, Wilcoxon matched pairs signed rank test). The calculated absorption half-life (t½,a) and elimination half-life (t½,e) was delayed significantly in CasH groups (resp. 6 min and 20 min, p<0.0001, Wilcoxon matched pairs signed rank test). Plasma concentrations of the dipeptides LP, IP, VP and PP in the post-prandial period, measured in a limited set of samples, were in the range of 1–7 μM, compared to 1–30 nM for XPP’s in this sample set (S1 Table. Dipeptide/tripeptide ratio—Study 1.).


Enhanced Lacto-Tri-Peptide Bio-Availability by Co-Ingestion of Macronutrients.

Ten Have GA, van der Pijl PC, Kies AK, Deutz NE - PLoS ONE (2015)

Systemic levels of XPP peptides—Effect of protein matrix.Post-prandial arterial concentrations after intra-gastric administration of control salt solution (Control), synthetic XPP’s (XPP), casein hydrolysate rich in XPP (CasH) and spiked CasH (CasH + XPP). A: Isoleucine-proline-proline (IPP). B: Leucine-proline-proline (LPP). C: Valine-proline-proline (VPP). Respective number of observations for Control, XPP, CasH and CasH +XPP are for graph A: n = 9, 10, 9 and 10; graph B: n = 10, 10, 9 and 10; graph C: n = 8, 10, 9 and 10. Values are mean ± SEM. Statistics: repeated measures two-way ANOVA, mixed model, planned comparisons. All curves are significantly different from the XPP mixture: effect test mixture p<0.001; effect time p<0.001; interaction p<0.001.
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pone.0130638.g001: Systemic levels of XPP peptides—Effect of protein matrix.Post-prandial arterial concentrations after intra-gastric administration of control salt solution (Control), synthetic XPP’s (XPP), casein hydrolysate rich in XPP (CasH) and spiked CasH (CasH + XPP). A: Isoleucine-proline-proline (IPP). B: Leucine-proline-proline (LPP). C: Valine-proline-proline (VPP). Respective number of observations for Control, XPP, CasH and CasH +XPP are for graph A: n = 9, 10, 9 and 10; graph B: n = 10, 10, 9 and 10; graph C: n = 8, 10, 9 and 10. Values are mean ± SEM. Statistics: repeated measures two-way ANOVA, mixed model, planned comparisons. All curves are significantly different from the XPP mixture: effect test mixture p<0.001; effect time p<0.001; interaction p<0.001.
Mentions: Systemic (= arterial) concentrations of XPP in time (Fig 1) showed no measurable baseline/post-absorptive endogenous XPP (Control group, tested with Wilcoxon). The XPP concentrations in the CasH groups were not back to baseline at 90 min post-prandial (one-way ANOVA with Dunnett’s post-hoc test: IPP p<0.002; LPP p<0.001; VPP p<0.05). The calculated systemic absolute bioavailability (fabs (%) = fraction dose absorbed, Table 3) was increased in the protein based CasH group (IPP: 4.7 times, p<0.0004; LPP: 2.5 times, p<0.002; VPP: 121 times, p<0.0001). The spiked CasH group (CasH+XPP) showed lower systemic bioavailability for VPP (65 times, p<0.0001) in comparison to CasH. There was a delay in the time to maximum XPP plasma concentration (tmax) with the CasH groups compared to the XPP test mixture (12 min, p<0.0001, Wilcoxon matched pairs signed rank test). The calculated absorption half-life (t½,a) and elimination half-life (t½,e) was delayed significantly in CasH groups (resp. 6 min and 20 min, p<0.0001, Wilcoxon matched pairs signed rank test). Plasma concentrations of the dipeptides LP, IP, VP and PP in the post-prandial period, measured in a limited set of samples, were in the range of 1–7 μM, compared to 1–30 nM for XPP’s in this sample set (S1 Table. Dipeptide/tripeptide ratio—Study 1.).

Bottom Line: In a second experiment (n=10), we compared the CasH-containing protein matrix with a CasH-containing meal matrix and the modifying effects of macronutrients in a meal on the availability (high carbohydrates, low quality protein, high fat, and fiber).Low protein quality and fiber increased XPP systemic bioavailability further (respectively 1.5 and 1.4 times).We conclude that the amount and quality of the protein, and the presence of fiber in a meal, are the main factors that increase the systemic bioavailability of food-derived XPP.

View Article: PubMed Central - PubMed

Affiliation: Center for Translational Research in Aging & Longevity, Department of Health & Kinesiology, Texas A&M University, College Station, TX, United States of America; Department of Surgery, Nutrition and Toxicology Institute Maastricht, Maastricht University, Maastricht, The Netherlands.

ABSTRACT
Some food-derived peptides possess bioactive properties, and may affect health positively. For example, the C-terminal lacto-tri-peptides Ile-Pro-Pro (IPP), Leu-Pro-Pro (LPP) and Val-Pro-Pro (VPP) (together named here XPP) are described to lower blood pressure. The bioactivity depends on their availability at the site of action. Quantitative trans-organ availability/kinetic measurements will provide more insight in C-terminal tri-peptides behavior in the body. We hypothesize that the composition of the meal will modify their systemic availability. We studied trans-organ XPP fluxes in catheterized pigs (25 kg; n=10) to determine systemic and portal availability, as well as renal and hepatic uptake of a water-based single dose of synthetic XPP and a XPP containing protein matrix (casein hydrolyte, CasH). In a second experiment (n=10), we compared the CasH-containing protein matrix with a CasH-containing meal matrix and the modifying effects of macronutrients in a meal on the availability (high carbohydrates, low quality protein, high fat, and fiber). Portal availability of synthetic XPP was 0.08 ± 0.01% of intake and increased when a protein matrix was present (respectively 3.1, 1.8 and 83 times for IPP, LPP and VPP). Difference between individual XPP was probably due to release from longer peptides. CasH prolonged portal bioavailability with 18 min (absorption half-life, synthetic XPP: 15 ± 2 min, CasH: 33 ± 3 min, p<0.0001) and increased systemic elimination with 20 min (synthetic XPP: 12 ± 2 min; CasH: 32 ± 3 min, p<0.0001). Subsequent renal and hepatic uptake is about 75% of the portal release. A meal containing CasH, increased portal 1.8 and systemic bioavailability 1.2 times. Low protein quality and fiber increased XPP systemic bioavailability further (respectively 1.5 and 1.4 times). We conclude that the amount and quality of the protein, and the presence of fiber in a meal, are the main factors that increase the systemic bioavailability of food-derived XPP.

No MeSH data available.


Related in: MedlinePlus