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Randomized Controlled Trial
. 2012 Jul 1;303(1):E152-62.
doi: 10.1152/ajpendo.00106.2012. Epub 2012 May 8.

Coingestion of Whey Protein and Casein in a Mixed Meal: Demonstration of a More Sustained Anabolic Effect of Casein

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Randomized Controlled Trial

Coingestion of Whey Protein and Casein in a Mixed Meal: Demonstration of a More Sustained Anabolic Effect of Casein

Mattias Soop et al. Am J Physiol Endocrinol Metab. .
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Abstract

When consumed separately, whey protein (WP) is more rapidly absorbed into circulation than casein (Cas), which prompted the concept of rapid and slow dietary protein. It is unclear whether these proteins have similar metabolic fates when coingested as in milk. We determined the rate of appearance across the splanchnic bed and the rate of disappearance across the leg of phenylalanine (Phe) from coingested, intrinsically labeled WP and Cas. Either [¹⁵N]Phe or [¹³C-ring C₆]Phe was infused in lactating cows, and the labeled WP and Cas from their milk were collected. To determine the fate of Phe derived from different protein sources, 18 healthy participants were studied after ingestion of one of the following: 1) [¹⁵N]WP, [¹³C]Cas, and lactose; 2) [¹³C]WP, [¹⁵N]Cas, and lactose; 3) lactose alone. At 80-120 min, the rates of appearance (R(a)) across the splanchnic bed of Phe from WP and Cas were similar [0.068 ± 0.010 vs. 0.070 ± 0.009%/min; not significant (ns)]. At time 220-260 min, Phe appearance from WP had slowed (0.039 ± 0.008%/min, P < 0.05) whereas Phe appearance from Cas was sustained (0.068 ± 0.013%/min). Similarly, accretion rates across the leg of Phe absorbed from WP and Cas were not different at 80-120 min (0.011 ± 0.002 vs. 0.012 ± 0.003%/min; ns), but they were significantly lower for WP (0.007 ± 0.002%/min) at 220-260 min than for Cas (0.013 ± 0.002%/min) at 220-260 min. Early after meal ingestion, amino acid absorption and retention across the leg were similar for WP and Cas, but as rates for WP waned, absorption and assimilation into skeletal muscle were better retained for Cas.

Figures

Fig. 1.
Fig. 1.
Study outline. FFM, fat-free mass.
Fig. 2.
Fig. 2.
Arterial plasma concentrations of insulin (A), glucagon (B), glucose (C), and total amino acids (D) in subjects ingesting isocaloric meals containing protein and lactose ([15N]WP/[13C]Cas and [13C]WP/[15N]Cas groups; n = 6 and 6, respectively) or lactose alone (lactose group; n = 6). Group × time interactions: P = 1.0 (A), P = 0.0013 (B), P < 0.0001 (C), and P < 0.0001 (D). WP, whey protein; Cas, casein.
Fig. 3.
Fig. 3.
Regional plasma flow rates (A) and phenylalanine concentrations (B) in subjects ingesting isocaloric meals containing protein and lactose ([15N]WP/[13C]Cas and [13C]WP/[15N]Cas groups; n = 6 and 6, respectively) or lactose alone (lactose group; n = 6). Group × time interactions: P = 0.92 for hepatic vein plasma flow and P = 0.62 for femoral vein plasma flow (A); P < 0.0001 for phenylalanine concentrations in the hepatic vein, femoral artery, and femoral vein (B).
Fig. 4.
Fig. 4.
Regional plasma isotopic enrichment of tracers [15N]Phe (A) and [13C]Phe (B) in subjects ingesting isocaloric meals containing differentially labeled milk protein fractions ([15N]WP/[13C]Cas and [13C]WP/[15N]Cas groups; n = 6 and 6, respectively). Group × time interactions: for [15N]Phe enrichments, P = 0.096 at the hepatic vein, P = 0.029 at the femoral artery, and P = 0.043 at the femoral vein (A); for [13C]Phe enrichments, P = 0.062 at the hepatic vein, P = 0.18 at the femoral artery, and P = 0.074 at the femoral vein (B).
Fig. 5.
Fig. 5.
A: comparison of hepatic venous enrichments of phenylalanine tracers from WP and Cas in subjects ingesting isocaloric meals containing differentially labeled milk protein fractions ([15N]WP/[13C]Cas and [13C]WP/[15N]Cas groups; n = 6 and 6, respectively). Group × time interactions: P = 0.096 for [15N]Phe (left) and P = 0.074 for [13C]Phe (right). Insets: mean enrichments during “early” (20–80 min) and “late” (100–420 min) periods. Student's t-tests for comparisons between groups of [15N]Phe enrichments: P = 0.55 during early period, *P = 0.041 during late period; for [13C]Phe enrichment, P = 0.71 during early period, **P = 0.0031 during late period. B, left: mean rates of appearance (Ra) across the splanchnic region of phenylalanine from WP and Cas in subjects ingesting isocaloric meals containing differentially labeled milk protein fractions ([15N]WP/[13C]Cas and [13C]WP/[15N]Cas groups; n = 6 and 6, respectively) during time periods 0, 80–120, 220–260, and 380–420 min. Student's t-test between WP and Cas: P = not significant during the 80- to 120-min period, *P = 0.0498 during 220- to 260-min period. Inset: mean rates calculated from areas under curve of raw data during early (20–80 min) and late (100–420 min) phases. No significant differences between WP and Cas; Student's t-test. B, right: mean rates of retention across the leg of phenylalanine from the 2 protein fractions during time periods 0, 80–120, 220–260, and 380–420 min. Student's t-test between WP and Cas, P = 0.6 during the 80- to 120-min period, **P = 0.002 during the 220- to 260-min period. Inset: mean rates calculated from areas under curve of raw data during “early” (20–80 min) and “late” (100–420 min) phases. No significant differences between WP and Cas; Student's t-test.
Fig. 6.
Fig. 6.
Plasma concentrations of lysine (A) and isotopic enrichment of [15N]lysine (B) at the femoral artery and vein in subjects ingesting isocaloric meals containing protein and lactose ([15N]WP/[13C]Cas and [13C]WP/[15N]Cas groups; n = 6 and 6, respectively) or lactose alone (lactose group; n = 6). Group × time interactions: P < 0.001 for arterial and venous plasma concentrations of lysine, P < 0.001 for arterial and venous isotopic enrichment of [15N]lysine.
Fig. 7.
Fig. 7.
A: arteriovenous balances of lysine across leg (left) and splanchnic region (right) in subjects ingesting isocaloric meals containing milk protein and lactose (protein meals; n = 12) or lactose alone (lactose meals; n = 6). Group × time interactions: P = 0.0057 across splanchnic region, P < 0.0001 across leg. B, left: rates of appearance of lysine (Ra Lys) across leg in subjects ingesting isocaloric meals containing milk protein and lactose (protein group; n = 12) or lactose alone (lactose group; n = 6). Student's t-tests between groups, P = 0.16 during 80- to 120-min period, P = 0.94 during 220- to 260-min period. Inset: rates calculated on the areas under curve of the raw data during early (20–80 min) and late (100–420 min) periods. Student's t-test, protein vs. lactose groups; *P = 0.025. B, right: rates of disappearance of lysine (Rd Lys) across leg. Student's t-test between groups; P = 0.62 during 80- to 120-min period, P = 0.063 during 220- to 260-min period. Inset: rates calculated on the areas under curve of the raw data during early (20–80 min) and late (100–420 min) phases. Student's t-test, protein vs. lactose groups; ***P < 0.0001, *P = 0.011.
Fig. 8.
Fig. 8.
Fractional synthesis rates (FSR) in mixed muscle protein (MMP), mitochondrial protein (mito), and sarcoplasmic protein (sarco) during the period between the 2 biopsies (120 and 420 min) in subjects ingesting isocaloric meals containing milk protein and lactose (protein groups; n = 12) or lactose alone (lactose groups; n = 6). *P < 0.05 and **P < 0.01, Student's t-test between groups.

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