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Serum milk fat globule-EGF factor 8 (MFG-E8) as a diagnostic and prognostic biomarker in patients with hepatocellular carcinoma.
Shimagaki, T, Yoshio, S, Kawai, H, Sakamoto, Y, Doi, H, Matsuda, M, Mori, T, Osawa, Y, Fukai, M, Yoshida, T, et al
Scientific reports. 2019;(1):15788
Abstract
Current serum hepatocellular carcinoma (HCC) biomarkers are insufficient for early diagnosis. We aimed to clarify whether serum MFG-E8 can serve as a diagnostic or prognostic biomarker of HCC. Serum MFG-E8 levels of 282 HCC patients, who underwent primary hepatectomy, were examined by ELISA. We also quantified serum MFG-E8 levels in patients with chronic hepatitis (CH), liver cirrhosis (LC), as well as in healthy volunteers (HVs). Serum MFG-E8 levels were significantly lower in HCC patients than in HVs regardless of the etiology of liver disease (3.6 ± 0.1 vs 5.8 ± 0.2 ng/mL, p < 0.0001), and recovered after treatment of HCC. Serum MFG-E8 levels in CH and LC patients were comparable to those in HVs. Serum MFG-E8 could detect HCCs, even α-fetoprotein (AFP)-negative or des-γ-carboxy prothrombin (DCP)-negative HCCs, in CH and LC patients. Our new HCC prediction model using MFG-E8 and DCP (Logit(p) = 2.619 - 0.809 × serum MFG-E8 + 0.0226 × serum DCP) distinguished HCC patients from CH and LC patients with an area under the curve of 0.923, a sensitivity of 81.1%, and a specificity of 89.8%. Futhermore, low preoperative serum MFG-E8 was an independent predictor of poor overall survival. Thus, serum MFG-E8 could serve as a feasible diagnostic and prognostic biomarker for HCC.
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Consumption of Milk Protein or Whey Protein Results in a Similar Increase in Muscle Protein Synthesis in Middle Aged Men.
Mitchell, CJ, McGregor, RA, D'Souza, RF, Thorstensen, EB, Markworth, JF, Fanning, AC, Poppitt, SD, Cameron-Smith, D
Nutrients. 2015;(10):8685-99
Abstract
The differential ability of various milk protein fractions to stimulate muscle protein synthesis (MPS) has been previously described, with whey protein generally considered to be superior to other fractions. However, the relative ability of a whole milk protein to stimulate MPS has not been compared to whey. Sixteen healthy middle-aged males ingested either 20 g of milk protein (n = 8) or whey protein (n = 8) while undergoing a primed constant infusion of ring (13)C₆ phenylalanine. Muscle biopsies were obtained 120 min prior to consumption of the protein and 90 and 210 min afterwards. Resting myofibrillar fractional synthetic rates (FSR) were 0.019% ± 0.009% and 0.021% ± 0.018% h(-1) in the milk and whey groups respectively. For the first 90 min after protein ingestion the FSR increased (p < 0.001) to 0.057% ± 0.018% and 0.052% ± 0.024% h(-1) in the milk and whey groups respectively with no difference between groups (p = 0.810). FSR returned to baseline in both groups between 90 and 210 min after protein ingestion. Despite evidence of increased rate of digestion and leucine availability following the ingestion of whey protein, there was similar activation of MPS in middle-aged men with either 20 g of milk protein or whey protein.
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Central adiposity and protein intake are associated with arterial stiffness in overweight children.
Arnberg, K, Larnkjær, A, Michaelsen, KF, Mølgaard, C
The Journal of nutrition. 2012;(5):878-85
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Abstract
Being overweight is associated with vascular abnormalities, which are important in the development of atherosclerosis. However, little is known about dietary and lifestyle determinants of vascular function in overweight children. In adults, dietary protein and milk intake are associated with reduced blood pressure and reduced risk of metabolic syndrome. This study examined the associations between dietary protein, milk intake, physical activity, and adiposity on arterial stiffness in overweight children. In a cross-sectional study, overweight children with habitual milk intakes ≤ 250 mL/d were examined by DXA scans, pedometer counts, anthropometry, and metabolic variables. Dietary intake was registered for 4 d. The outcomes were arterial stiffness measured by pulse wave velocity (PWV) (n = 182) and augmentation index (Aix) (n = 183). The PWV (mean ± SD) was 4.78 ± 0.72 m/s and the Aix was -0.77 ± 9.44%. In multivariate models, the android fat:gynoid fat and android fat:body fat ratios were positively associated with PWV (β = 1.49 and β = 10.3, both P < 0.05) and Aix (β = 28.3, P < 0.01 and β = 153, P < 0.05), whereas the gynoid fat:body fat ratio was negatively associated with the Aix (β = -134; P < 0.001). Protein intake (percentage energy) was positively associated with PWV (β = 0.05; P < 0.01). Milk intake (L/d) tended to be negatively associated with PWV (β = -0.64; P = 0.05). Pedometer counts were negatively associated with the Aix; however, the association became nonsignificant after controlling for HOMA, which was positively associated with the Aix (β = 0.95; P < 0.01). In conclusion, central adiposity and protein intake are associated with increased arterial stiffness measured as PWV in overweight children independent of blood pressure and heart rate. The effect of protein intake may be caused by meat, because the milk intake was low.
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Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling.
Atherton, PJ, Etheridge, T, Watt, PW, Wilkinson, D, Selby, A, Rankin, D, Smith, K, Rennie, MJ
The American journal of clinical nutrition. 2010;(5):1080-8
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BACKGROUND We previously showed that human muscle protein synthesis (MPS) increased during infusion of amino acids (AAs) and peaked at ≈120 min before returning to baseline rates, despite elevated plasma AA concentrations. OBJECTIVE We tested whether a protein meal elicited a similar response and whether signaling responses that regulate messenger RNA translation matched MPS changes. DESIGN Eight postabsorptive healthy men (≈21 y of age) were studied during 8.5 h of primed continuous infusion of [1,2-¹³C₂]leucine with intermittent quadriceps biopsies for determination of MPS and anabolic signaling. After 2.5 h, subjects consumed 48 g whey protein. RESULTS At 45-90 min after oral protein bolus, mean (± SEM) myofibrillar protein synthesis increased from 0.03 ± 0.003% to 0.10 ± 0.01%/h; thereafter, myofibrillar protein synthesis returned to baseline rates even though plasma essential AA (EAA) concentrations remained elevated (+130% at 120 min, +80% at 180 min). The activity of protein kinase B (PKB) and phosphorylation of eukaryotic initiation factor 4G preceded the rise of MPS and increases in phosphorylation of ribosomal protein kinase S6 (S6K1), and 4E-binding protein 1 (4EBP1) was superimposable with MPS responses until 90 min. However, although MPS decreased thereafter, all signals, with the exception of PKB activity (which mirrored insulin responses), remained elevated, which echoed the slowly declining plasma EAA profile. The phosphorylation of eukaryotic initiation factor 2α increased only at 180 min. Thus, discordance existed between MPS and the mammalian target of rapamycin complex 1 (mTORC1) and signaling (ie, S6K1 and 4EBP1 phosphorylation). CONCLUSIONS We confirm our previous findings that MPS responses to AAs are transient, even with oral protein bolus. However, changes in MPS only reflect elevated mTORC1 signaling during the upswing in MPS.
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A whey protein supplement decreases post-prandial glycemia.
Petersen, BL, Ward, LS, Bastian, ED, Jenkins, AL, Campbell, J, Vuksan, V
Nutrition journal. 2009;:47
Abstract
BACKGROUND Incidence of diabetes, obesity and insulin resistance are associated with high glycemic load diets. Identifying food components that decrease post-prandial glycemia may be beneficial for developing low glycemic foods and supplements. This study explores the glycemic impact of adding escalating doses of a glycemic index lowering peptide fraction (GILP) from whey to a glucose drink. METHODS Ten healthy subjects (3M, 7F, 44.4 +/- 9.3 years, BMI 33.6 +/- 4.8 kg/m2) participated in an acute randomised controlled study. Zero, 5, 10 and 20 g of protein from GILP were added to a 50 g glucose drink. The control (0 g of GILP) meal was repeated 2 times. Capillary blood samples were taken fasting (0 min) and at 15, 30, 45, 60, 90 and 120 minutes after the start of the meal and analyzed for blood glucose concentration. RESULTS Increasing doses of GILP decreased the incremental areas under the curve in a dose dependant manner (Pearson's r = 0.48, p = 0.002). The incremental areas (iAUC) under the glucose curve for the 0, 5, 10, and 20 g of protein from GILP were 231 +/- 23, 212 +/- 23, 196 +/- 23, and 138 +/- 13 mmol.min/L respectively. The iAUC of the 20 g GILP was significantly different from control, 5 g GILP and 10 g GILP (p < 0.001). Average reduction in the glucose iAUC was 4.6 +/- 1.4 mmol.min/L per gram of ingested GILP. CONCLUSION Addition of GILP to a oral glucose bolus reduces blood glucose iAUC in a dose dependent manner and averages 4.6 +/- 1.4 mmol.min/L per gram of GILP. These data are consistent with previous research on the effect of protein on the glycemic response of a meal.
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Effects of whey isolate, creatine, and resistance training on muscle hypertrophy.
Cribb, PJ, Williams, AD, Stathis, CG, Carey, MF, Hayes, A
Medicine and science in sports and exercise. 2007;(2):298-307
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PURPOSE Studies that have attributed gains in lean body mass to dietary supplementation during resistance exercise (RE) training have not reported these changes alongside adaptations at the cellular and subcellular levels. Therefore, the purpose of this study was to examine the effects of two popular supplements--whey protein (WP) and creatine monohydrate (CrM) (both separately and in combination)--on body composition, muscle strength, fiber-specific hypertrophy (i.e., type I, IIa, IIx), and contractile protein accrual during RE training. METHODS In a double-blind randomized protocol, resistance-trained males were matched for strength and placed into one of four groups: creatine/carbohydrate (CrCHO), creatine/whey protein (CrWP), WP only, or carbohydrate only (CHO) (1.5 g x kg(-1) body weight per day). All assessments were completed the week before and after an 11-wk structured, supervised RE program. Assessments included strength (1RM, three exercises), body composition (DEXA), and vastus lateralis muscle biopsies for determination of muscle fiber type (I, IIa, IIx), cross-sectional area (CSA), contractile protein, and creatine (Cr) content. RESULTS Supplementation with CrCHO, WP, and CrWP resulted in significantly greater (P < 0.05) 1RM strength improvements (three of three assessments) and muscle hypertrophy compared with CHO. Up to 76% of the strength improvements in the squat could be attributed to hypertrophy of muscle involved in this exercise. However, the hypertrophy responses within these groups varied at the three levels assessed (i.e., changes in lean mass, fiber-specific hypertrophy, and contractile protein content). CONCLUSIONS Although WP and/or CrM seem to promote greater strength gains and muscle morphology during RE training, the hypertrophy responses within the groups varied. These differences in skeletal muscle morphology may have important implications for various populations and, therefore, warrant further investigation.
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Clostridium difficile-associated diarrhoea: bovine anti-Clostridium difficile whey protein to help aid the prevention of relapses.
Numan, SC, Veldkamp, P, Kuijper, EJ, van den Berg, RJ, van Dissel, JT
Gut. 2007;(6):888-9
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Randomized controlled trial of the effects of soy protein containing isoflavones on vascular function in postmenopausal women.
Kreijkamp-Kaspers, S, Kok, L, Bots, ML, Grobbee, DE, Lampe, JW, van der Schouw, YT
The American journal of clinical nutrition. 2005;(1):189-95
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BACKGROUND The incidence of cardiovascular disease increases after menopause, possibly because of the decline in estrogen. Soy protein, a rich source of estrogen-like isoflavones, is hypothesized to improve vascular function. OBJECTIVE The objective of this study was to investigate whether supplementation with soy protein, a rich source of estrogen-like isoflavones, improves vascular function. DESIGN We performed a 12-mo double-blind randomized trial to compare the effects of soy protein containing 99 mg isoflavones/d (aglycone weights) with those of milk protein (placebo) on blood pressure and endothelial function in 202 postmenopausal women aged 60-75 y. RESULTS Changes in endothelial function during the intervention were not significantly different between the soy and the placebo groups. After the intervention, systolic blood pressure increased in the soy group significantly more than it did in the placebo group; the difference in change was 4.3 mm Hg (95% CI: 0.3, 8.4 mm Hg; P = 0.04) for systolic blood pressure, but only 2.0 mm Hg (95% CI: -0.74, 4.71 mm Hg; P = 0.15) for diastolic blood pressure. In the soy group only, systolic and diastolic blood pressure decreased and endothelial function improved in the equol producers, whereas systolic and diastolic blood pressure increased and endothelial function deteriorated in the equol nonproducers. CONCLUSIONS The results of this trial do not support the hypothesis that soy protein containing isoflavones have beneficial effects on vascular function in older postmenopausal women. Whether certain subgroups of women (eg, equol producers) do benefit from the intervention remains to be elucidated.
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Improved glutathione status in young adult patients with cystic fibrosis supplemented with whey protein.
Grey, V, Mohammed, SR, Smountas, AA, Bahlool, R, Lands, LC
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2003;(4):195-8
Abstract
BACKGROUND The lung disease of cystic fibrosis is associated with a chronic inflammatory reaction and an over abundance of oxidants relative to antioxidants. Glutathione functions as a major frontline defense against the build-up of oxidants in the lung. This increased demand for glutathione (GSH) in cystic fibrosis may be limiting if nutritional status is compromised. We sought to increase glutathione levels in stable patients with cystic fibrosis by supplementation with a whey-based protein. METHODS Twenty-one patients who were in stable condition were randomly assigned to take a whey protein isolate (Immunocal, 10 g twice a day) or casein placebo for 3 months. Peripheral lymphocyte GSH was used as a marker of lung GSH. Values were compared with nutritional status and lung parameters. RESULTS At baseline there were no significant differences in age, height, weight, percent ideal body weight or percent body fat. Lymphocyte GSH was similar in the two groups. After supplementation, we observed a 46.6% increase from baseline (P < 0.05) in the lymphocyte GSH levels in the supplemented group. No other changes were observed. CONCLUSION The results show that dietary supplementation with a whey-based product can increase glutathione levels in cystic fibrosis. This nutritional approach may be useful in maintaining optimal levels of GSH and counteract the deleterious effects of oxidative stress in the lung in cystic fibrosis.
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Maternal protein homeostasis and milk protein synthesis during feeding and fasting in humans.
Sunehag, AL, Haymond, MW
American journal of physiology. Endocrinology and metabolism. 2003;(2):E420-6
Abstract
Little is known about amino acid (AA) and protein metabolism in lactating women. We hypothesized: 1) AA sources other than the plasma acid pool provide substrate for milk protein synthesis in humans and 2) if albumin was one such source, then albumin fractional synthesis rate (FSR) is higher in the lactating women. To test these hypotheses, six healthy exclusively breast-feeding women [27 +/- 3 yr; body mass index (BMI) 26 +/- 2 kg/m2] between 6 wk and 3 mo postpartum and six healthy nonlactating women (28 +/- 2 yr; BMI 22 +/- 1 kg/m2) were studied two times, in random order, during 22 h fasting or 10 h of continuous feeding with a mixed nutrient drink. Protein metabolism was determined using [1-13C]leucine and [15N2]urea. In both the fed and fasted states, a significant portion of milk protein (20 +/- 5 and 31 +/- 6%, respectively) was derived from sources other than the plasma free AA pool. A 70% higher (P < 0.02) FSR of albumin was observed in lactating women during feeding, suggesting that albumin is a likely source of AA for milk protein synthesis. We conclude that plasma free AA contribute only 70-80% of the substrate for milk protein synthesis in humans and that albumin may be a significant source of amino acids for the remainder.