The process of MPS plays a pivotal role in muscle function and serves as the structural basis for improvements in exercise performance.
Following a bout of exercise, the rate of MPS experiences an elevation for a brief period, known as the “anabolic window”. An increase in MPS has shown to facilitate muscle repair and mitigate post-exercise soreness and fatigue, leading to improved muscle strength, endurance, and anaerobic power recovery.
Research has demonstrated that exercise activates the protein kinase B/Mechanistic Target of Rapamycin (AKT/mTOR) signaling pathway. This activation stimulates mTOR1, thereby enhancing MPS efficiency as well as both short-term athletic ability and long-term muscle adaptation.
While whey protein supplementation has demonstrated to augment the post-exercise anabolic window, the optimal timing and dosage remain controversial.
Therefore, researchers in China conducted a systematic review and meta-analysis to evaluate the time-dependent pattern of whey protein supplementation combined with exercise on MPS, and to explore optimal supplementation strategies.
The primary outcomes measured included myofibrillar fractional synthetic rate (FSR) as a key quantitative indicator of MPS, and the activation of intracellular signaling pathways involved in MPS, such as AKT, mTOR, 70 kDa ribosomal protein S6 kinase (p70S6K), eukaryotic translation initiation factor 4E-binding protein-1 (4E-BP1), and ribosomal protein S6 (rpS6).
The findings showed that the combination of whey protein supplementation and exercise resulted in a significant rise in myofibrillar fractional synthetic rate (FSR), with increases ranging from 1.3 to 1.6 folds when consumed immediately after exercise, and up to 2.5 folds when taken 45 minutes prior to multiple-set resistance exercise.
In comparison to the placebo group, whey protein supplementation raised phosphorylation levels of the AKT/mTOR pathway and its downstream targets 4E-BP1, rpS6, and p70S6K at one to two hours post-exercise.
Four to five hours after exercise, phosphorylation levels of AKT and mTOR returned to baseline, while that of rpS6 and p70S6K decreased.
Furthermore, a dose-dependent increase in myofibrillar FSR was observed in response to whey protein supplementation.
“Consumption of 20 to 40g of whey protein before multiple sets of resistance exercise may enhance myofibrillar FSR and activate the AKT/mTOR pathway, thereby augmenting MPS and extending the anabolic window,” the researchers wrote.
Study profile
A total of 21 RCTs, involving 338 male participants and 33 female participants, were included in this systematic review. Sample sizes ranged from eight to 36 participants per study.
Seventeen studies incorporated participants who did resistance training at a frequency of one to three times per week, while four studies enrolled participants with no exercise experience.
All experimental groups received whey protein supplementation, with doses ranging from 10g to 60g per session. Some studies added supplements such as leucine, maltodextrin, and carbohydrates.
The control groups were provided with a variety of beverages, including artificially sweetened water, noncaloric placebo drinks, carbohydrate-based drinks, soy protein, milk, and blend protein.
The exercise protocols included leg press, leg extension, and knee extension exercises. These were typically performed at 70% to 80% of one-repetition maximum (1RM).
Some studies consisted of additional exercises, such as cycling sprints, chest press, lat pulldown, and whole-body resistance training, which were performed to volitional exhaustion.
Useful insights and notes for future
Widely utilized to improve muscle function and exercise performance, whey protein is rapidly broken down in the digestive tract, causing plasma amino acid levels to reach a high level 100 minutes after ingestion, particularly leucine.
Leucine is regarded as a pivotal branched-chain amino acid within whey protein and fulfils a regulatory function in muscle metabolic homeostasis.
Past research found leucine supplements to stimulate protein synthesis by activating the mTORC1 signaling pathway. The synergistic effect of leucine and insulin has also shown to enhance the net balance of protein synthesis and catabolism in skeletal muscle.
At the same time, milk proteins—encompassing milk, whey protein, yogurt, casein, and bovine colostrum—have shown to be efficacious in promoting gains in muscle mass and strength.
Some studies also discovered that whey protein supplementation led to the most consistent gains in muscular strength compared to other protein sources.
Notably, the present review found that whey protein supplementation was more effective than milk at improving MPS, and that a mixture of multiple nutrients had even greater effects.
“Our review demonstrated that the combination of whey protein supplementation and exercise significantly enhances post-exercise MPS. A six-week 25g/day whey protein supplementation and 4000 IU vitamin D3 supplements, in conjunction with a resistance training regimen, elicited significant improvements in muscle mass and strength in healthy young males.
“Acute 30g/day whey protein and omega-3 supplementation, particularly before exercise, improves strength and power and reduces delayed-onset muscle soreness in female futsal players,” the researchers said.
Nevertheless, findings from this review should be approached with caution.
Due to large variations in the dosage and intake timing across the studies, there is a need to further elucidate the potential mechanisms of whey protein supplementation and exercise interventions.
Future studies should be conducted with expanded sample sizes, and focus on the development of customized whey protein supplementation regimens and design of precise exercise protocols.
Source: Nutrients. 2025. doi: 10.3390/nu17162579. “Whey Protein Supplementation Combined with Exercise on Muscle Protein Synthesis and the AKT/mTOR Pathway in Healthy Adults: A Systematic Review and Meta-Analysis”. Authors: Xiaorong Ji et al.
