Casein Protein

Background/Objectives: There is no consensus regarding the impacts of supplementation with milk proteins (MPs) on body composition (BC). This systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) assessed the effects of MP, casein protein (CP), and whey protein (WP) supplementation on BC and anthropometric parameters. Methods: A comprehensive search was performed in several databases to identify eligible RCTs published until October 2025. Random-effects models were applied to estimate the pooled effects of MP supplementation on anthropometric parameters. Results: A total of 150 RCTs were included. MP supplementation substantially increased lean body mass (LBM) (weighted mean difference (WMD): 0.41 kg; 95% CI: 0.19, 0.62; p < 0.001) and fat-free mass (FFM) (WMD: 0.67 kg; 95% CI: 0.40, 0.94; p < 0.001). It also significantly reduced body fat percentage (BFP) (WMD: -0.66%; 95% CI: -1.03, -0.28; p = 0.001), fat mass (FM) (WMD: -0.66 kg; 95% CI: -0.91, -0.41; p < 0.001), and waist circumference (WC) (WMD: -0.69 cm; 95% CI: -1.16, -0.22; p = 0.004). No considerable effects were observed for muscle mass (MM), body mass index (BMI), and body weight (BW). Dose-response analysis revealed that MP dosage was associated with significant changes in BFP, LBM, and MM. Conclusions: MP supplementation was associated with favorable modifications in body composition, including increases in LBM and FFM, as well as reductions in FM, BFP, and WC. These findings provide coherent and consistent evidence supporting the potential role of MP supplementation in targeted body composition management.

CONTEXT: It has been proposed that supplementation with milk protein (MP) may ameliorate lipid profiles, lower blood pressure (BP), reduce oxidative stress (OS), and regulate liver enzyme levels to prevent cardiovascular disease. OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) investigated the impacts of casein protein, whey protein, and MP supplementation on lipid profiles, BP, OS, and liver enzymes in adults. DATA SOURCES: A systematic search strategy was developed to determine relevant RCTs published up to September 2024 among several databases (Medline/PubMed, Web of Science, and Scopus). DATA EXTRACTION: The extracted data comprised a range of trial characteristics, including the study design, sample size, demographic data of participants, trial duration, pre- and post-assessments of the outcomes, and the dosage of MP supplements. DATA ANALYSIS: A random-effects meta-analysis was performed to determine the effects of MP supplementation on the measured outcomes. Heterogeneity across the trials was evaluated using the I2 statistic and Cochran's Q tests. The pooled analysis of 65 RCTs revealed that MP supplementation significantly reduced levels of total cholesterol (TC) (weighted mean difference [WMD]: -4.03 mg/dL; 95% CI: -7.91, -0.16; P = .042), systolic blood pressure (SBP) (WMD: -1.99 mmHg; 95% CI: -3.16, -0.82; P < .001), and triglycerides (TG) (WMD: -6.11 mg/dL; 95% CI: -9.78, -2.44; P = .001) in the MP group compared with the untreated group. However, there were no statistically substantial impacts on diastolic blood pressure, serum levels of glutathione, nitric oxide, apolipoprotein (Apo) A, high-density-lipoprotein cholesterol, Apo B, alanine transaminase, malondialdehyde, aspartate transaminase, and low-density-lipoprotein cholesterol. CONCLUSION: Supplementation with MP may have hypotensive and hypolipidemic effects, as indicated by reductions in SBP, TG, and TC. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42024621220. © The Author(s) 2025. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For commercial re-use, please contac

BACKGROUND: Impacts of milk proteins (MPs) on inflammation are uncertain. The current systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) evaluated the effects of whey protein (WP), casein protein (CP), or MP supplementation on serum levels of cytokines and adipokines in adults. METHODS: A comprehensive search of various online databases was conducted to find appropriate clinical trials published until September 2024. A random-effect statistical model was implemented. RESULTS: The meta-analysis included 53 RCTs. It was indicated that MP supplements had no substantial effects on serum values of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), adiponectin, and leptin. However, there were statistically significant decreases in serum levels of interleukin-6 (IL-6) following supplementation with MP (weighted mean difference (WMD): - 0.25 pg/mL, 95% CI - 0.48, - 0.03; P = 0.026) in the intervention group compared with the control group. CONCLUSION: This study revealed that MP supplementation may not have any considerable impacts on the levels of cytokines and adipokines. © 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

BACKGROUND: It is suggested that supplementation with milk protein (MP) has the potential to ameliorate the glycemic profile; however, the exact impact and certainty of the findings have yet to be evaluated. This systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) assessed the impact of MP supplementation on the glycemic parameters in adults. METHODS: A systematic search was carried out among online databases to determine eligible RCTs published up to November 2022. A random-effects model was performed for the meta-analysis. RESULTS: A total of 36 RCTs with 1851 participants were included in the pooled analysis. It was displayed that supplementation with MP effectively reduced levels of fasting blood glucose (FBG) (weighted mean difference (WMD): -1.83 mg/dL, 95% CI: -3.28, -0.38; P = 0.013), fasting insulin (WMD: -1.06 uU/mL, 95% CI: -1.76, -0.36; P = 0.003), and homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: -0.27, 95% CI: -0.40, -0.14; P < 0.001) while making no remarkable changes in serum hemoglobin A1c (HbA1c) values (WMD: 0.01%, 95% CI: -0.14, 0.16; P = 0.891). However, there was a significant decline in serum levels of HbA1c among participants with normal baseline body mass index (BMI) based on sub-group analyses. In addition, HOMA-IR values were significantly lower in the MP supplement-treated group than their untreated counterparts in short- and long-term supplementation (≤ 8 and > 8 weeks) with high or moderate doses (≥ 60 or 30-60 g/d) of MP or whey protein (WP). Serum FBG levels were considerably reduced upon short-term administration of a low daily dose of WP (< 30 g). Furthermore, the levels of serum fasting insulin were remarkably decreased during long-term supplementation with high or moderate daily doses of WP. CONCLUSION: The findings of this study suggest that supplementation with MP may improve glycemic control in adults by reducing the values of fasting insulin, FBG, and HOMA-IR. Additional trials with longer durations are required to confirm these findings. © 2023. BioMed Central Ltd., part of Springer Nature.

Background: Nutrient timing strategies may influence recovery and performance in athletes; however, the effects of ingesting casein protein before sleep versus immediately after exercise remain unclear. This study compared the acute effects of pre-sleep and post-exercise ingestion of casein on high-intensity anaerobic performance in highly trained soccer players. Methods: Twenty-four highly trained male soccer players (mean age: 20.6 ± 1.8 years) were randomly assigned to three groups: post-exercise casein ingestion group (PECIG; n = 8), pre-sleep casein ingestion group (PSCIG; n = 8), and control group (CG; n = 8). Following a standardized high-intensity resistance training protocol, participants consumed 30 g of micellar casein dissolved in 300 mL of water either immediately after exercise or 30-60 min before bedtime. Performance was assessed using the Countermovement Jump (CMJ), the Illinois Agility Test (IAT), and the Running-based Anaerobic Sprint Test (RAST), which were conducted both before and 24 h after the training session. Results: Repeated-measures ANOVA revealed significant group-by-time effects for CMJ (F = 8.21, p = 0.002, η2p = 0.36) and RAST performance variables, including peak power (F = 6.94, p = 0.003, η2p = 0.32), mean power (F = 7.42, p = 0.002, η2p = 0.34), and fatigue index (F = 5.87, p = 0.008, η2p = 0.28). Post hoc analyses showed that PSCIG significantly improved CMJ (Δ = +1.45 cm; p < 0.001, d = 2.04) and RAST mean power (Δ = +125.14 W; p = 0.002, d = 1.55) compared with the control condition. PECIG significantly enhanced RAST peak power (Δ = +205.79 W; p = 0.001, d = 1.64), mean power (Δ = +128.43 W; p = 0.013, d = 1.24), and fatigue index (Δ = +4.12 W/s; p = 0.010, d = 1.29) relative to CG. No performance differences were observed between PSCIG and PECIG timing conditions (all p > 0.05). Conclusions: Both pre-sleep and post-exercise casein ingestion enhanced anaerobic performance in highly trained soccer players, with each timing method favoring different performance outcomes. However, neither strategy demonstrated superiority over the other, suggesting that casein timing may be flexibly applied according to athletes' preferences a

Background: A higher protein diet (HPD) is recommended for older adults to support their muscle mass maintenance, but its cardiovascular protective effects in this population remain controversial, potentially due to differences in protein sources. Objective: To investigate the effects of HPDs with different sources within a healthy dietary pattern (HDP) on conventional cardiovascular disease (CVD) risk factors and vascular health-related outcomes in Singapore older adults. Methods: In this 16-week randomized controlled trial, 55 participants were assigned to one of the three groups: following a HDP alone (Control, n = 19), following a HDP supplemented with 20 g day-1 of either casein protein isolate powder (HPD-CP, n = 18) or soy protein isolate powder (HPD-SP, n = 18). Blood pressure, lipid-lipoprotein profiles and composite CVD risk indicators were evaluated at the baseline and post-intervention. Parameters of vascular function (flow-mediated dilation) and vascular regeneration (endothelial progenitor cell percentage and blood outgrowth cell functions) were also assessed. Results: The Control group exhibited significant increases in triglyceride levels (+0.33 ± 0.1 mmol L-1) and composite CVD risks (atherogenic index: +0.31 ± 0.11; Framingham predicted long-term CVD risk: +0.8 ± 0.43%). In contrast, both HPD groups showed maintenance of the lipid-lipoprotein profile and CVD risk predictors, with further significant reduction in the total cholesterol level in the HPD-SP group (-0.28 ± 0.12 mmol L-1). All groups showed significant increases in CD34+ cell expression, and particularly, the HPD-SP group demonstrated potential to enhance the angiogenic capacity of blood outgrowth endothelial cells. However, no changes were observed in other vascular functions and vascular regeneration parameters. Conclusions: Adherence to an HPD, particularly from soy protein, within an HDP supports the maintenance of the lipid-lipoprotein profile and CVD risk predictors among Singapore older adults. These findings highlight HPD as a potential dietary strategy to promote cardiovascular health when adhering to an HDP in older adults; however, the source of protein may influence its e

BACKGROUND: Probiotics comprise various strains that offer numerous health benefits. Researchers have recently focused on the relationship between probiotic consumption and improved gut microbiota function, enhanced digestion, increased nutrient absorption, and enhanced sports performance. Therefore, the present study investigated the effects of pre-sleep casein intake, coupled with probiotic strains, on soccer players' anaerobic power, lower-body-specific strength, and power performance. METHODS: A randomized, double-blinded, and placebo-controlled study was conducted with forty-four male soccer players (Age: 22.81 ± 2.76 years, Height: 177.90 ± 6.75 cm, Weight: 67.42 ± 8.44 kg). The participants underwent the isokinetic strength, Wall-squat, and running-based anaerobic sprint (RAST) tests initially; then, they were randomly divided into four groups: probiotics (PRO), casein (CAS), probiotics with casein (PRO+CAS), and placebo (PLA). The PRO groups were given one probiotic capsule (containing eight bacterial strains: Lactiplantibacillus plantarum BP06, Lacticaseibacillus casei BP07, Lactobacillus acidophilus BA05, Lactobacillus bulgaricus BD08, Bifidobacterium infantis BI04, Bifidobacterium longum BL03, Bifidobacterium breve BB02, and Streptococcus thermophilus BT01, with a total dose of 4.5 × 1011 CFU) during dinner, while the CAS groups consumed 20 grams of casein powder 45 minutes before bed. The PRO+CAS group was given one probiotic capsule during dinner and 20 grams of casein powder 45 minutes before bed. The participants in the PLA group were given one red capsule (containing 5 grams of starch) during dinner. All participants were instructed to take the supplements only on training days, three times a week for four weeks. Additionally, isokinetic strength parameters, including absolute peak torque (APT) and average rate of force development (AvRFD), were measured for the knee extensors (ext) and flexors (flx) muscles (concentric phase at angular velocities of 60°/s and 180°/s, using the dominant leg). One-way analysis of covariance (ANCOVA) or Quade tests with a significance level of p < 0.05 was used to analyze the collected data. RESULT: The current stu

BACKGROUND: The effects of consuming hemp seed protein (HSP) as well as its hydrolysate-derived bioactive peptide (HSP+) on blood pressure (BP) has not, to our knowledge, been investigated in humans. OBJECTIVES: We aimed to investigate how consumption of HSP and its hydrolysate modulates 24-h systolic (SBP) and diastolic BP (DBP) and plasma biomarkers of BP compared with casein. METHODS: In a double-blind, randomized, crossover design trial, 35 adults who had mild hypertension with SBP between 130 and 160 mmHg and DBP ≤110 mmHg were recruited. Participants were randomly assigned to varying sequences of 3 6-wk treatments, 50 g casein/d, 50 g HSP/d, or 45 g HSP plus 5 g HSP-derived bioactive peptides/d (HSP+), separated by a 2-wk washout period. Treatment effects were assessed with a linear mixed model with repeated measures. RESULTS: Compared with casein, after HSP+ consumption, 24-h SBP and 24-h DBP decreased from 135.1 and 80.0 mmHg to 128.1 ± 1.6 (P < 0.0001) and 76.0 ± 1.4 mmHg (P < 0.0001), respectively, whereas these values were 133.5 ± 1.6 and 78.9 ± 1.4 mmHg after HSP consumption (P < 0.0001). There were no differences between the HSP and HSP+ consumption in plasma angiotensin-converting enzyme (ACE) activity, renin, or nitric oxide (NO) concentrations. However, these 2 treatments were able to lower both ACE and renin activities and raise NO concentration in plasma compared with casein. CONCLUSIONS: These results suggest that hemp protein consumption, as well as in combination with bioactive peptides, may have a role in the dietary management of hypertension. This trial was registered at clinicaltrials.gov as NCT03508895.

Preliminary findings from multiple studies indicate that dietary intake of soy-derived isoflavones exert beneficial effects on the skin including defense against oxidant damage, stimulation of collagen synthesis, and increased hydration. This study aims to investigate how oral supplementation of a soy protein isolate with added isoflavones (SPII) affects components of photoaging such as facial wrinkles and dyspigmentation, and skin biophysical measures such as skin hydration and sebum excretion in postmenopausal women. This 6-month prospective, randomized double-blind controlled study was conducted on 44 postmenopausal women with Fitzpatrick skin types I, II, and III who were randomized to receive either casein protein or SPII. A high-resolution facial photography system was used to measure wrinkle severity and pigmentation at 0, 8, 16, and 24 weeks. Skin biophysical measurements included skin hydration and sebum production. The average wrinkle severity was decreased in the SPII intervention group at week 16 and week 24 by 5.9% and 7.1%, respectively, compared to the baseline. Compared to the casein group, average wrinkle severity was significantly decreased at week 16 (p < 0.05) and week 24 (p < 0.0001). Facial pigment intensity was decreased by -2.5% (p < 0.05) at week 24, whereas there was no significant change in the casein group. Compared to baseline, skin hydration in the SPII group was significantly increased by 39% and 68% on the left and right cheeks (p < 0.05), respectively, at 24 weeks. There were no significant differences in sebum production. Dietary soy protein supplementation with isoflavones may improve skin photoaging, including wrinkles and dyspigmentation, and increase skin hydration in postmenopausal women with Fitzpatrick skin types I, II, and III.

BACKGROUND: Casein protein ingestion prior to sleep has been shown to increase myofibrillar protein synthesis rates during overnight sleep. It remains to be assessed whether pre-sleep protein ingestion can also increase mitochondrial protein synthesis rates. Though it has been suggested that casein protein may be preferred as a pre-sleep protein source, no study has compared the impact of pre-sleep whey versus casein ingestion on overnight muscle protein synthesis rates. OBJECTIVE: We aimed to assess the impact of casein and whey protein ingestion prior to sleep on mitochondrial and myofibrillar protein synthesis rates during overnight recovery from a bout of endurance-type exercise. METHODS: Thirty-six healthy young men performed a single bout of endurance-type exercise in the evening (19:45 h). Thirty minutes prior to sleep (23:30 h), participants ingested 45 g of casein protein, 45 g of whey protein, or a non-caloric placebo. Continuous intravenous L-[ring-13C6]-phenylalanine infusions were applied, with blood and muscle tissue samples being collected to assess overnight mitochondrial and myofibrillar protein synthesis rates. RESULTS: Pooled protein ingestion resulted in greater mitochondrial (0.087 ± 0.020 vs 0.067 ± 0.016%·h-1, p = 0.005) and myofibrillar (0.060 ± 0.014 vs 0.047 ± 0.011%·h-1, p = 0.012) protein synthesis rates when compared with placebo. Casein and whey protein ingestion did not differ in their capacity to stimulate mitochondrial (0.082 ± 0.019 vs 0.092 ± 0.020%·h-1, p = 0.690) and myofibrillar (0.056 ± 0.009 vs 0.064 ± 0.018%·h-1, p = 0.440) protein synthesis rates. CONCLUSIONS: Protein ingestion prior to sleep increases both mitochondrial and myofibrillar protein synthesis rates during overnight recovery from exercise. The overnight muscle protein synthetic response to whey and casein protein does not differ. CLINICAL TRIAL REGISTRATION: NTR7251 . © 2023. The Author(s).

Oosthuyse, T, Florence, GE, Correia, A, Smyth, C, and Bosch, AN. Carbohydrate-restricted exercise with protein increases self-selected training intensity in female cyclists but not male runners and cyclists. J Strength Cond Res 35(6): 1547-1558, 2021-Carbohydrate-restricted training challenges preservation of euglycemia and exercise intensity that precludes ergogenic gains, necessitating countering strategies. We investigated the efficacy of ingesting casein protein hydrolysate in overnight-fasted male runners, male cyclists, and female cyclists. Twenty-four overnight-fasted athletes ingested 15.8 g·h-1 casein hydrolysate or placebo-water during exercise (60-80 minutes) comprising an incremental test to exhaustion, steady-state exercise (70% Vmax or 60% peak power output, 87 ± 4% HRmax), and 20-minute time trial (TT) in a double-blind randomized crossover design, with p < 0.05 accepted as significant. Ingesting protein vs. placebo increased metabolic demand {oxygen consumption, +4.7% (95% confidence interval [CI] ± 4%), p = 0.0297; +3.2% (95% CI ± 3.4%), p = 0.061}, heart rate (p = 0.0083; p = 0.007) and rating of perceived exertion (RPE) (p = 0.0266; p = 0.0163) in male cyclists and runners, respectively, but not female cyclists. Protein vs. placebo increased carbohydrate oxidation (+0.26 [95% CI ± 0.13] g·min-1, p = 0.0007) in female cyclists alone. Cyclists reported +2 ± 1 higher RPE than runners (p = 0.0062). Glycemia was maintained only in runners and increased with protein vs. placebo after 20 minutes of steady-state exercise (+0.63 [95% CI ± 0.56] mmol·L-1, p = 0.0285). TT performance with protein vs. placebo ingestion was modestly compromised in runners (-2.8% [95% CI ± 2.2%], p = 0.0018), unchanged in male cyclists (+1.9% [95% CI ± 5.6%], p = 0.5794), and modestly improved in female cyclists (+2.5% [95% CI ± 1.8%], p = 0.0164). Casein hydrolysate ingestion during moderate to hard carbohydrate-restricted exercise increases glycemia in runners, but not cyclists. Casein hydrolysate increases metabolic demand in male athletes and carbohydrate oxidation in female cyclists and is suitable for improving carbohydrate-restricted training intensity in female but

OBJECTIVES: Effects of repeated administration of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide were examined in rats fed a low-protein diet. METHODS: Rats were given a low (7% casein) or control (20% casein) protein diet for 21 days and administered Ginkgo biloba extract (100mg/kg per day) for the last 5 days. Tolbutamide was co-administered on the last day. Blood glucose and plasma tolbutamide concentrations were determined over the subsequent 12h and the activity of hepatic cytochrome P450s were determined at 12h after dosing. KEY FINDINGS: There were significant decreases in body weight, the ratio of liver to body weight, and plasma albumin concentrations in rats on the low-protein diet compared with controls. The hypoglycaemic effect of tolbutamide was significantly greater and the concentration of the drug in plasma was higher in the former group. The repeated administration of Ginkgo biloba extract had little influence on the hypoglycaemic effect of tolbutamide, but tended to decrease the drug concentration in plasma of control rats, while it reduced significantly the hypoglycaemic action and plasma concentration of tolbutamide in the protein-restricted rats. CONCLUSIONS: The effects of Ginkgo biloba extract on the pharmacokinetics and pharmacodynamics of tolbutamide were significantly enhanced in rats on the low-protein diet. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

Protein intake is an important factor for augmenting the response to resistance training in healthy individuals. Although food intake can help with anabolism during the day, the period of time during sleep is typically characterized by catabolism and other metabolic shifts. Research on the application of nighttime casein protein supplementation has introduced a new research paradigm related to protein timing. Pre-sleep casein supplementation has been attributed to improved adaptive response by skeletal muscle to resistance training through increases in muscle protein synthesis, muscle mass, and strength. However, it remains unclear what the effect of this nutritional strategy is on non-muscular parameters such as metabolism and appetite in both healthy and unhealthy populations. The purpose of this systematic review is to understand the effects of pre-sleep casein protein on energy expenditure, lipolysis, appetite, and food intake in both healthy and overweight or obese individuals. A systematic review following PRISMA guidelines was conducted in CINAHL, Cochrane, and SPORTDiscus during March 2021, and 11 studies met the inclusion criteria. A summary of the main findings shows limited to no effects on metabolism or appetite when ingesting 24-48 g of casein 30 min before sleep, but data are limited, and future research is needed to clarify the relationships observed.

CONTEXT: Various epidemiological studies suggest a positive association between exposure to cow's milk A1 β-casein protein and risk for noncommunicable chronic diseases. The consumption of A2 cow's milk is increasing, likely because A2 milk is postulated to have positive effects on digestive health. OBJECTIVE: A systematic review was conducted to investigate associations between A1 β-casein and health-related outcomes in humans. DATA SOURCES: Five electronic databases, 3 clinical trial registries, and the internet were searched systematically. STUDY SELECTION: Using predefined inclusion criteria, 2 authors independently selected studies investigating the effect of A1 β-casein or β-casomorphin-7 intake/exposure on any health-related outcome in humans. Discrepancies were resolved by consensus. DATA EXTRACTION: Two authors independently extracted data and assessed risk of bias. The certainty of evidence per outcome was evaluated using the GRADE approach. Discrepancies were resolved by consensus. RESULTS: Fifteen randomized controlled trials, 2 case-control studies, and 8 ecological studies were included. Most randomized controlled studies and case-control studies investigating a potential effect on various outcomes were based on intermediate markers and found no significant difference between the 2 milk types. In contrast, most ecological studies reported that population-level A1 β-casein exposure is associated with adverse health outcomes. The certainty of the evidence for the included outcomes, as assessed by the GRADE approach, was rated as moderate for digestive symptoms and as low to very low for all other outcomes. CONCLUSIONS: Human-based evidence from clinical trials and epidemiological studies published prior to October 2017 provides moderate certainty for adverse digestive health effects of A1 β-casein compared with A2 β-casein but low or very low certainty for other health effects. These conclusions may change in the future, given the emergent nature of this topic and the ongoing research in this area. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42016043795. © The Author(s) 2019. Published by Oxford University Press on behalf of the