Effects of Whey Protein Supplementation on Sarcopenia and Frailty in Older Adults – A Narrative Review

1. Introduction

Sarcopenia and frailty are increasingly prevalent geriatric syndromes that substantially affect health outcomes and quality of life in older adults. These conditions are associated with the loss of muscle mass and strength, with malnutrition, aging, physical inactivity, and chronic diseases playing a key role in their pathogenesis [1] [2].

The main symptoms of sarcopenia include slower walking speed, increased fatigue, and weakness, which negatively affect psychological and social aspects. Frailty is a multidimensional geriatric syndrome characterized by reduced physiological reserve and increased vulnerability to stressors [1].

These conditions occur in approximately 5-10% of older adults with the highest prevalence among residents of care homes (15-30%), hospitalized patients (up to 37%), and those undergoing rehabilitation (up to 76%) [2], but they are also present in community-dwelling individuals, particularly those with low physical activity. Just three days of immobilization in an older adult can lead to a body mass reduction of over 1 kg. Both sarcopenia and frailty contribute to reduced quality of life and loss of independence [3].

The aim of this narrative review was to critically examine and discuss current evidence regarding whey protein-containing interventions in older adults with sarcopenia and frailty, with particular emphasis on their effects on muscle mass, muscle strength, physical performance, and their role within multimodal therapeutic strategies. Furthermore, this review highlights current limitations of the evidence base and identifies priorities for future research.

2. Literature Search and Narrative Synthesis Approach

This narrative review aimed to provide a comprehensive and clinically oriented overview of current evidence regarding the role of whey protein-containing interventions in the management of sarcopenia and frailty in older adults. The review focuses on the biological rationale for whey protein supplementation, its effects on muscle mass, muscle strength, and physical performance, as well as its role within multimodal intervention strategies.

Relevant literature was identified through searches of PubMed, Scopus, and Web of Science. Publications published between January 2014 and December 2025 were considered. Search terms included combinations of the following keywords: “sarcopenia”, “frailty”, “older adults”, “elderly”, “whey protein”, “protein supplementation”, “leucine”, “vitamin D”, “oral nutritional supplementation”, “muscle mass”, “muscle strength”, and “resistance training”.

The selection of literature prioritized randomized controlled trials, systematic reviews, meta-analyses, umbrella reviews, consensus statements, and clinically relevant narrative reviews. Additional articles were identified through manual screening of reference lists from key publications. Studies were selected based on their relevance to the scope of the review and their contribution to understanding the clinical implications of whey protein supplementation in older populations.

The evidence was narratively synthesized and organized into major thematic areas, including: (i) pathophysiological mechanisms underlying sarcopenia and frailty, (ii) biological rationale for whey protein supplementation, (iii) effects on muscle mass, (iv) effects on muscle strength and physical performance, (v) multimodal intervention strategies combining whey protein with exercise or additional anabolic nutrients, and (vi) practical considerations regarding supplementation dose, timing, and duration.

Because the objective of this article was to provide a critical narrative interpretation of the available literature rather than a formal evidence synthesis, no systematic review methodology, quantitative meta-analysis, or formal risk-of-bias assessment was performed. The findings should therefore be interpreted as a narrative overview of current knowledge rather than a comprehensive systematic evaluation of all available evidence.

3. Narrative Synthesis of Current Evidence

3.1. Characteristics of Included Studies

The review included 22 studies published between 2014 and 2025 that investigated the effects of whey protein-containing interventions in older adults with sarcopenia, frailty, or related muscle dysfunction. The studies differed substantially in terms of study design, participant characteristics, diagnostic criteria, intervention composition, protein dosage, intervention duration, and outcome measures. Of the 22 publications discussed throughout the review, Table 1 presents the most clinically relevant and representative studies. Additional studies are discussed in the narrative text.

As shown in Table 1, considerable heterogeneity was observed across the included studies regarding diagnostic criteria, protein supplementation protocols, intervention duration, and outcome assessment methods. Most interventions combined whey protein with additional anabolic components, such as leucine, vitamin D, or resistance exercise, which complicates the interpretation of the independent effects of whey protein.

3.2. Biological Rationale for Whey Protein Supplementation

A key pathophysiological mechanism underlying sarcopenia is impaired muscle protein synthesis. This phenomenon is closely associated with anabolic resistance, defined as a diminished skeletal muscle response to anabolic stimuli such as physical activity and dietary protein intake. In older adults, this phenomenon is further exacerbated by involutional changes within skeletal muscle (including impaired muscle perfusion), the presence of chronic diseases - often accompanied by chronic low - grade inflammation - progressive insulin resistance, and alterations in intracellular signaling pathways that regulate muscle protein metabolism. The coexistence of these factors reduces the efficiency of dietary amino acids in stimulating muscle protein synthesis. As a consequence, these processes accelerate the development and progression of sarcopenia. In this context, due to anabolic resistance, older adults require higher protein intake than younger individuals to effectively stimulate muscle protein synthesis [1]. Protein is a fundamental macronutrient necessary for tissue maintenance and regeneration, including skeletal muscle. Both the quantity and quality of protein are therefore critical for preserving muscle mass and function. Studies suggest that a daily protein intake of 1.0–1.2 g/kg body weight may have a preventive effect against muscle weakening, with an optimal minimum of 20 g of protein per meal [4]. The selection of high-quality protein, such as whey protein, may be particularly beneficial in the context of sarcopenia. Whey protein induces a pronounced anabolic response due to its rapid digestion- leading to a swift increase in circulating amino acid levels- as well as its high content of essential amino acids- particularly leucine, which independently stimulates muscle anabolism. Comparative studies have shown that whey protein enhances amino acid bioavailability and muscle protein synthesis more effectively than casein [5].

Given these metabolic properties, numerous clinical trials have investigated the effects of whey protein supplementation on muscle mass, strength, and physical performance in older adults with or without sarcopenia. These studies included hospitalized individuals, community-dwelling older adults, and participants enrolled in rehabilitation programs. The interventions varied across studies, encompassing whey protein supplementation alone or in combination with resistance exercise programs.

3.3. Effects of Whey Protein on Muscle Mass

Results from randomized clinical trials suggest that whey protein-containing interventions may improve muscle mass in selected older adults; however, the magnitude and consistency of these effects vary across studies. In one study [6], participants received a supplement containing 20 g of whey protein and 800 IU of vitamin D daily for a period of 13 weeks. This intervention resulted in an increase in limb muscle mass, and physical performance, assessed using the chair-stand test, also improved significantly in the intervention group compared with the control group.

Similarly, Hill et al. [7] reported that the consumption of 40 g of whey protein in the form of a supplement enriched with vitamin D and calcium led to increased muscle mass even in the absence of physical activity. The effects of whey protein supplementation were more pronounced than those observed with branched-chain amino acid (BCAA) supplementation, particularly in individuals with anabolic resistance.

Based on the findings of Gielen et al. [8], nutritional supplementation- especially with high-quality protein, essential amino acids (EAA), β-hydroxy-β-methylbutyrate (HMB), and vitamin D- should be considered as part of standard care for older adults at risk of sarcopenia. The conclusions of this study appear to be particularly relevant in the context of an aging population.

Al-Rawhani et al. reported that supplementation strategies including whey protein and leucine may improve body composition outcomes, including muscle mass. [9].

While the studies by Hill et al. and Gielen et al. indicated the possibility of increasing muscle mass without the involvement of exercise, more recent findings by Chang et al. [10] clearly emphasize the importance of combining supplementation with regular physical activity. The authors showed that supplementation with whey protein combined with leucine and vitamin D effectively increased limb muscle mass; however, improvements in muscle strength and physical performance were observed only when the nutritional intervention was combined with systematic physical exercise.

Furthermore, Giacosa et al. [2] reported that whey protein supplementation combined with omega-3 fatty acids and probiotics not only improves muscular function in older adults with sarcopenia but may also exert a preventive effect against the loss of muscle mass and strength. These effects were particularly pronounced when resistance training was included.

It should be noted, however, that not all studies have confirmed the beneficial effects of whey protein supplementation. Amasene et al. [11] reported that additional supplementation with whey protein and leucine did not result in statistically significant improvements in physical performance, body composition, or nutritional status when administered alongside a resistance training program.

In summary, the available evidence suggests that whey protein-containing interventions may contribute to the maintenance or improvement of muscle mass in some older adults, particularly when combined with resistance exercise or other nutrients; however, evidence remains inconsistent, the effectiveness of this intervention may depend on individual patient characteristics, its combination with physical activity, and the specific intervention protocols applied.

3.4. Effects on Muscle Strength and Physical Performance

Muscle strength is one of the key determinants of physical performance, particularly in older adults, including patients with sarcopenia. A decline in muscle strength is associated with an increased risk of falls, loss of independence, and reduced quality of life. It should be emphasized that an increase in muscle mass does not always directly translate into improved muscle strength, as strength adaptations require adequate neuromuscular stimuli. Although muscle strength and physical performance are closely related concepts, they reflect different aspects of muscle function- muscle strength refers to the ability to generate force, whereas physical performance also encompasses motor coordination, balance, and the capacity to perform activities of daily living. In the clinical context, physical performance is a key predictor of independence, risk of hospitalization, and mortality in the older population.

Some studies suggest that whey protein supplementation alone may contribute to the maintenance or improvement of physical performance in selected patient groups. Martinez et al. [12] reported that the use of high-protein dietary supplements based on whey protein is safe and effective in maintaining muscle mass, physical function, and quality of life in oncology patients with sarcopenia. Similar observations were reported by Li et al. [13], indicating that whey protein supplementation may positively influence various aspects of functional capacity in older adults with sarcopenia, contributing to an overall improvement in physical condition, although the effects on muscle strength were moderate.

Additional insights are provided by mechanistic and translational studies. Gilmartin et al. [14] showed that daily supplementation with 35 g of whey protein may improve selected biomarkers of sarcopenia in healthy older adults with features of frailty or sarcopenia. The authors emphasized that, in healthy older individuals, whey protein intake significantly enhances mTOR signaling in skeletal muscle; however, the greatest functional benefits for aging muscles are achieved through regular physical activity. In vitro studies further highlight the critical role of bioactive and bioavailable whey-derived peptides in modulating muscle aging processes.

Significantly greater improvements in muscle strength were observed in studies in which whey protein supplementation was combined with resistance training or rehabilitation programs. Chang et al. [10] found that supplementation with whey protein combined with leucine and vitamin D effectively increased appendicular muscle mass; however, improvements in muscle strength and physical performance were observed exclusively in groups where nutritional intervention was paired with regular physical activity. These findings clearly indicate that supplementation may support structural adaptations of muscle, whereas an exercise stimulus is essential for achieving functional improvements.

Similar conclusions were drawn by Englund et al. [15], who implemented a six-month resistance training program in older adults. This intervention led to improvements in body composition, reductions in subcutaneous and intramuscular adipose tissue, and increased muscle strength. Additional whey protein supplementation resulted in a further reduction in intramuscular fat volume and improved muscle density, suggesting that nutritional interventions may potentiate the beneficial effects of training.

The importance of high-quality complete protein in the context of muscle strength is also supported by recent evidence. Hey et al. [16] reported that supplementation with branched-chain amino acids (BCAAs) alone is insufficient, even in healthy individuals, with beneficial effects observed only when combined with complete protein and exercise. In the context of sarcopenia and chronic conditions such as liver cirrhosis, better outcomes were achieved with complete proteins such as whey protein, which provide a full amino acid profile and may improve nitrogen balance.

Findings by Liao et al. [17] further confirm that whey protein is an optimal supplement for counteracting sarcopenia in older adults undergoing resistance training. The authors emphasized that the synergistic combination of adequate protein intake and mechanical stimulus leads to greater improvements in muscle strength and function than either intervention applied alone.

The long-term benefits of this approach were found by Mori et al. [18], who showed that a combined intervention of resistance training and protein supplementation maintained the effects of sarcopenia treatment for up to 24 weeks after completion of the training program, compared with resistance training alone. The authors suggest that post-exercise protein intake may play a crucial role in sustaining muscle adaptations in older adults.

Mariangela et al. [3] also reported that consumption of a nutritional formula based on whey protein, enriched with leucine and vitamin D, improved physical performance and overall functional status, increased muscle mass, and reduced the intensity and costs of care. Similar results were obtained by Cereda et al. [19], suggesting that therapy using medical nutrition supplements containing, among other components, whey protein- administered alone or combined with an appropriate exercise program- constitutes an effective treatment strategy for older adults with sarcopenia.

However, it should be noted that not all studies confirmed such beneficial effects of whey protein supplementation. Cuyul-Vásquez et al. [20] found that whey protein supplementation was indeed more effective than placebo, but the observed effect was not clinically significant. Similarly, Amasene et al. [21] reported that despite overall improvements in most parameters related to muscle mass and strength, no significant differences were observed between the group receiving protein/amino acid supplementation and the group performing resistance training alone. Their findings suggest that a properly designed resistance training program was sufficient to improve physical function in older adults after hospitalization, without additional benefits from leucine-enriched whey protein supplementation.

Comparable results were reported by Björkman et al. [22]. In this long-term study (12 months of intervention and 43 months of follow-up), whey protein supplementation combined with low-intensity home-based exercise did not slow the decline in muscle strength or physical performance in older adults with sarcopenia. None of the supplements used in the intervention had a significant effect on physical performance outcomes.

3.5. Dose, Timing, and Duration of Whey Protein Supplementation

Across the included studies, whey protein doses typically ranged from approximately 20 g to 40 g per day. However, direct comparison of dose-related effects was limited due to differences in study design, intervention composition, and co-interventions. In many studies, whey protein was combined with leucine, vitamin D, or exercise, which further complicates the interpretation of dose-specific effects [2,3]. The duration of interventions varied from several weeks to several months, with most studies lasting between 8 and 24 weeks, although some longer-term studies were also identified. Timing of supplementation (e.g., post-exercise or between meals) was inconsistently reported [4,5]. Overall, studies using whey protein-containing interventions in combination with resistance exercise or other anabolic nutrients more frequently reported improvements in muscle-related outcomes. However, due to heterogeneity in dose, duration, and co-interventions, no definitive dose-response relationship can currently be established.

4. Discussion

The findings of this review indicate that whey protein-containing interventions may contribute to improvements in muscle-related outcomes in older adults; however, the observed benefits are most consistent when supplementation is combined with resistance exercise. The most consistent and clinically meaningful effects are observed when nutritional intervention is combined with a well-designed resistance training program, indicating a synergistic interaction between mechanical stimuli and the provision of high-quality protein. The findings further suggest that protein quality, the presence of key amino acids (particularly leucine), and the duration and intensity of physical activity are critical determinants of achieving sustained improvements in muscle strength and physical performance in older adults at risk of sarcopenia.

One of the major challenges in interpreting the available evidence is the difficulty in separating the effects of whey protein from those of accompanying interventions. In most studies, whey protein was administered together with leucine, vitamin D, resistance exercise, or other nutritional strategies. Consequently, the independent contribution of whey protein remains uncertain.

Nevertheless, the role of whey protein supplementation as a standalone intervention and its optimal application across different older populations require further well-designed clinical trials. The evidence should be interpreted cautiously. While several studies reported improvements in muscle mass or selected functional outcomes, others found no statistically significant or clinically meaningful additional benefit of whey protein-containing supplementation compared with exercise alone or placebo. Differences in baseline nutritional status, sarcopenia severity, intervention duration, adherence, protein dose, and co-interventions may partly explain the variability in outcomes. Therefore, the current evidence supports a potential role of whey protein-containing interventions as part of multimodal management rather than a consistently effective standalone treatment.

This review has several limitations. First, substantial heterogeneity across studies limited the possibility of conducting a meta-analysis. Second, many interventions were multimodal, making it difficult to isolate the independent effects of whey protein. Third, potential publication bias cannot be excluded. The lack of meta-analysis represents a limitation of this review. Although several outcomes were conceptually similar across studies, differences in study design, diagnostic criteria, intervention composition, dosing, duration, and outcome reporting limited the appropriateness of statistical pooling.

5. Strengths and Limitations

Strengths:

• focus on whey protein-containing interventions
• inclusion of recent meta-analyses
• clinical applicability

Limitations:

• narrative methodology
• no formal risk-of-bias assessment
• heterogeneity of studies
• inability to isolate whey protein effects

6. Clinical Implications

From a clinical perspective, whey protein-containing interventions may be considered as part of multimodal sarcopenia and frailty management, particularly in older adults with inadequate protein intake, reduced muscle mass, or limited anabolic response. The available evidence suggests that supplementation is most likely to be beneficial when combined with resistance exercise and, in selected populations, with additional anabolic nutrients such as leucine and vitamin D. However, clinicians should consider baseline nutritional status, renal function, comorbidities, physical activity level, and adherence when selecting supplementation strategies. Whey protein should not be presented as a standalone replacement for exercise-based interventions but rather as a nutritional strategy that may support muscle remodeling when adequate mechanical stimulus is provided.

7. Future Directions

Future trials should aim to distinguish the independent effects of whey protein from those of leucine, vitamin D, oral nutritional supplements, and resistance exercise. Standardized diagnostic criteria for sarcopenia and frailty should be applied, and studies should report baseline nutritional status, habitual protein intake, adherence, intervention timing, and clinically meaningful functional outcomes. Future research should also identify responder subgroups, including older adults with malnutrition, low physical activity, inflammatory comorbidities, post-hospitalization decline, or anabolic resistance. Longer follow-up periods are needed to determine whether changes in muscle mass translate into sustained improvements in strength, mobility, independence, and quality of life.

8. Conclusions

Whey protein-containing interventions may support the management of sarcopenia and frailty in older adults, particularly when combined with resistance exercise and anabolic nutrients such as leucine and vitamin D. The strongest evidence relates to improvements in muscle mass, while effects on muscle strength and physical performance are less consistent. Because most interventions were multimodal, the independent contribution of whey protein remains difficult to determine. Future randomized controlled trials should investigate standardized doses, intervention durations, and clinically relevant outcomes to better define the role of whey protein in sarcopenia and frailty management.