Casein Hydrolysate

What Is Casein Hydrolysate?

Casein hydrolysate is a pharmaceutical-grade milk protein consisting of two and three amino-acid (di- and tri-) peptides. The body's peptide transporters quickly and easily absorb the mixture without further digestion. Casein hydrolysate is significantly more effective in stimulating muscle protein synthesis than conventional casein or whey.*

Benefits of Casein Hydrolysate

• Increases muscle gain by 70% over whey hydrolysate (Demling RH, 2000).*
• Doubles fat loss over whey hydrolysate (Demling RH, 2000).*
• Enhances nutrient uptake in muscle, directly affecting AMP-activated protein kinase signaling in the cell (Iwasa M, 2020).*
• Improves VO2 max performance significantly and reduces exercise-induced muscle soreness (Saunders MJ, 2009).*
• Increases levels of powerful metabolic regulator FGF-21, which improves insulin sensitivity in muscle (Fangmann D, 2020).*

What You Need to Know About Casein Hydrolysate

Casein hydrolysate is a refined di- and tri-peptide complex that's absorbed intact and doesn't require further digestion, making it at least 30% more effective in stimulating muscle protein synthesis than other milk-based proteins. Casein hydrolysate's fast-acting amino acids also make it ideal for peri- or intra-workout consumption.

Casein hydrolysate is also more insulinogenic than fast-acting whey proteins. Insulinogenic means it boosts insulin, which is ideal during the peri-workout period because insulin shuttles amino acids to working muscles.

Casein hydrolysate is among the most expensive proteins in the world. Still, they're also quite economical, considering casein hydrolysate stimulates muscle protein synthesis much more significantly than conventional proteins.

Research on Casein Hydrolysate

1. Boire Y et al. Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci USA. 1997, Dec 23;94(26):1493-5.
2. Koopman R et al. Ingestion of protein hydrolysate is accompanied by an accelerated in vivo digestion and absorption rate when compared to its intact protein. Am J Clin Nutr. 2009 90: 106-115.
3. Manninen A. Protein hydrolysates in sports nutrition, Nutrition and Metabolism. 2009 6:38 doi: 10.1186/1743-7075-6-38.
4. Iwasa M et al. The milk casein hydrolysate-derived peptide enhances glucose uptake through AMP-activated protein kinase signaling pathway in skeletal muscle cells. Exp Physiol. 2020 Dec 28. PMID: 33369793 DOI: 10.1113/EP088770. New findings: What is the central question of this study? Previously, we have shown that supplementation of Lactobacillus helveticus-fermented milk and milk casein hydrolysate (MCH) improves glucose metabolism in exercised mice and humans. Common active ingredients contained in both Lactobacillus helveticus-fermented milk and MCH may enhance glucose metabolism, but the details are yet to be clarified. What is the main finding and its importance? MCH enhanced glucose uptake in skeletal muscle cells by stimulating AMP-activated kinase (AMPK), but not insulin signaling. Moreover, the MCH-derived specific peptide, Ile-Pro-Pro, mimicked this effect, suggesting a mechanism for the MCH-induced metabolic improvement. ABSTRACT: Improvement of glucose metabolism in the skeletal muscle has a key role in exercise performance and prevention of metabolic diseases. In our previous study, we had shown that intake of milk casein hydrolysate improves glucose metabolism in humans, but the mechanism of action was not elucidated. In this study, we aimed to investigate the mechanism of action of milk casein hydrolysate and its derived peptides on glucose uptake and glucose metabolic signaling in cultured skeletal muscle cells. Differentiated C2C12 myotubes were used for the experiments. The differentiated cells were incubated with milk casein hydrolysate, valine-proline-proline, and isoleucine-proline-proline. Subsequently, the rate of 2-deoxy-glucose uptake and the phosphorylation levels of insulin-dependent and -independent signaling factors were examined. We found that the rate of 2-deoxy-glucose uptake in both milk casein hydrolysate and isoleucine-proline-proline-treated cells was higher than that in the control cells. Immunoblotting assays showed that the phosphorylation levels of AMP-activated protein kinase, a rate-limiting factor in insulin-independent signaling, and that of liver kinase B1, an upstream factor of AMP-activated protein kinase, in both milk casein hydrolysate and isoleucine-proline-proline-treated cells were higher than those in the control cells. Such significant effects were not observed after treatment with valine-proline-proline. Moreover, the insulin-dependent signaling was not significantly affected under the different conditions. The findings of our study suggest that milk casein hydrolysate enhances glucose uptake by activating insulin-independent AMP-activated protein kinase signaling in skeletal muscle cells, which might be mediated by a milk casein hydrolysate-derived peptide, namely, isoleucine-proline-proline.
5. Saunders MJ et al. Carbohydrate and protein hydrolysate coingestions improvement of late-exercise time-trial performance. Int J Sport Nutr Exerc Metab. 2009 Apr;19(2):136-49. PMID: 19478339 DOI: 10.1123/ijsnem.19.2.136. ABSTRACT: This study examined whether a carbohydrate + casein hydrolysate (CHO+ProH) beverage improved time-trial performance vs. a CHO beverage delivering approximately 60 g CHO/hr. Markers of muscle disruption and recovery were also assessed. Thirteen male cyclists (VO2peak = 60.8 +/- 1.6 ml . kg-1 . min-1) completed 2 computer-simulated 60-km time trials consisting of 3 laps of a 20-km course concluding with a 5-km climb (approximately 5% grade). Participants consumed 200 ml of CHO (6%) or CHO+ProH beverage (6% + 1.8% protein hydrolysate) every 5 km and 500 ml of beverage immediately postexercise. Beverage treatments were administered using a randomly counterbalanced, double-blind design. Plasma creatine phosphokinase (CK) and muscle-soreness ratings were assessed immediately before and 24 hr after cycling. Mean 60-km times were 134.4 +/- 4.6 and 135.0 +/- 4.0 min for CHO+ProH and CHO beverages, respectively. All time differences between treatments occurred during the final lap, with protein hydrolysate ingestion explaining a significant (p < .05) proportion of between-trials differences over the final 20 km (44.3 +/- 1.6, 45.0 +/- 1.6 min) and final 5 km (16.5 +/- 0.6, 16.9 +/- 0.6 min). Plasma CK levels and muscle-soreness ratings increased significantly after the CHO trial (161 +/- 53, 399 +/- 175 U/L; 15.8 +/- 5.1, 37.6 +/- 5.7 mm) but not the CHO+ProH trial (115 +/- 21, 262 +/- 88 U/L; 20.9 +/- 5.3, 32.2 +/- 7.1 mm). Late-exercise time-trial performance was enhanced with CHO+ProH beverage ingestion compared with a beverage containing CHO provided at maximal exogenous oxidation rates during exercise. CHO+ProH ingestion also prevented increases in plasma CK and muscle soreness after exercise.
6. Demling RH et al. Increased protein intake during the recovery phase after severe burns increases body weight and muscle function. J. Burn Care Rehab. 1998;19:161-168.
7. Demling RH et al. Effect of a hypocaloric diet, increased protein intake and resistance training on lean mass gains and fat mass loss in overweight police officers. Ann Nutr Metab. 2000;44(1):21-9. PMID: 10838463 DOI: 10.1159/000012817. ABSTRACT: We compare the effects of a moderate hypocaloric, high-protein diet and resistance training, using two different protein supplements, versus hypocaloric diet alone on body compositional changes in overweight police officers. A randomized, prospective 12-week study was performed comparing the changes in body composition produced by three different treatment modalities in three study groups. One group (n = 10) was placed on a nonlipogenic, hypocaloric diet alone (80% of predicted needs). A second group (n = 14) was placed on the hypocaloric diet plus resistance exercise plus a high-protein intake (1.5 g/kg/day) using a casein protein hydrolysate. In the third group (n = 14) treatment was identical to the second, except for the use of a whey protein hydrolysate. We found that weight loss was approximately 2.5 kg in all three groups. Mean percent body fat with diet alone decreased from a baseline of 27 +/- 1.8 to 25 +/- 1.3% at 12 weeks. With diet, exercise and casein the decrease was from 26 +/- 1.7 to 18 +/- 1.1% and with diet, exercise and whey protein the decrease was from 27 +/- 1.6 to 23 +/- 1.3%. The mean fat loss was 2. 5 +/- 0.6, 7.0 +/- 2.1 and 4.2 +/- 0.9 kg in the three groups, respectively. Lean mass gains in the three groups did not change for diet alone, versus gains of 4 +/- 1.4 and 2 +/- 0.7 kg in the casein and whey groups, respectively. Mean increase in strength for chest, shoulder and legs was 59 +/- 9% for casein and 29 +/- 9% for whey, a significant group difference. This significant difference in body composition and strength is likely due to improved nitrogen retention and overall anticatabolic effects caused by the peptide components of the casein hydrolysate.
8. Fangmann D et al. Differential effects of protein intake versus intake of a defined oligopeptide on FGF-21 in obese human subjects in vivo. Clin Nutr. 2020 Jun 17;S0261-5614(20)30296-X. PMID: 32600859 DOI: 10.1016/j.clnu.2020.06.006. ABStrACT: Background: FGF-21 is described as a powerful metabolic regulator with beneficial effects including glucose-lowering and improvement of insulin sensitivity without hypoglycaemia. On the other hand, FGF-21 is activated when muscle and other tissues are stressed by external effects or internal cellular pathogens that lead to shortcomings in metabolic balance. Previous results suggested that FGF-21 could be a promising target to develop future metabolic therapeutics. Purpose: The present study was performed to gain deeper insight into the regulation of FGF-21 by protein metabolism in obese human subjects. Methods: FGF-21 serum concentrations were measured in a cohort of n = 246 obese humans ± type 2 diabetes mellitus (T2DM) (median age 53.0 [46.0; 60.0] years and BMI 40.43 [35.11; 47.24] kg/m2) and related to the nutritional protein intake. In addition, the effect of a novel oligopeptide purified from a β-casein hydrolysate on FGF-21 was examined in vitro in liver cells and in vivo in a human intervention study with the main focus on metabolic inflammation including 40 mainly obese subjects (mean age 41.08 ± 9.76 years, mean BMI 38.29 ± 9.4 kg/m2) in a randomized 20 weeks double-blind cross-over design. Main findings: In the cohort analysis, FGF-21 serum concentrations were significant lower with higher protein intake in obese subjects without T2DM but not in obese subjects with T2DM. Furthermore, relative methionine intake was inversely related to FGF-21. While global protein intake in obesity was inversely associated with FGF-21, incubation of HepG2 cells with a β-casein oligopeptide increased FGF-21 expression in vitro. This stimulatory effect was also present in vivo, since in the clinical intervention study treatment of obese subjects with the β-casein oligopeptide for 8 weeks significantly increased FGF-21 serum levels from W0 = 23.86 pg/mL to W8 = 30.54 pg/mL (p < 0.001), while no increase was found for placebo. Conclusion: While the total nutritional protein intake is inversely associated with FGF-21 serum levels, a purified and well characterised oligopeptide is able to induce FGF-21 serum levels in humans. These findings suggest a differential role of various components of protein metabolism on FGF-21, rather than this factor being solely a sensor of total nutritional protein intake.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.