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June 03, 2021 13 min read

Maintaining skeletal muscle and physical function are absolutely critical throughout the aging process. But beginning as early as the fourth decade of life, and detectable at ~50 years, skeletal muscle mass (which is called sarcopenia) and strength/power (dynapenia) are estimated to deteriorate from ~0.8–1% and ~2–3% per year, respectively (1).

The progression of sarcopenia is associated with and increased risk of falls and fractures, metabolic dysfunction, cardiac and respiratory disease development, early mortality, and overall decrease in quality of life (3).

The health risks stated above make it very clear why people looking to progress into their later years unburdened by age-associated complications, stay as functional as possible and should regularly incorporate exercise and nutrition strategies to offset the decrements in skeletal muscle mass and physical function.

It’s difficult to assess the prevalence of sarcopenia...

However, recent estimates indicate that up to 30% of older adults fall under the categorization of having low muscle mass (2).

As we all know, resistance exercise is a potent stimulus to increase muscle mass, and nutrition plays a crucial role in the adaptive response of skeletal muscle to resistance training. We know that resistance exercise sensitizes skeletal muscle to dietary protein provision causing more of the ingested protein to be directed towards and utilized within skeletal muscle for anabolism.

This is also true in older individuals, but aging causes a reduced sensitivity (i.e., anabolic resistance) to conventional anabolic stimuli (4) and dietary protein ingestion (5), which makes the task of maintaining muscle mass in older individuals particularly challenging.

The identification and utilization of proper nutritional strategies to overcome the blunted anabolism in skeletal muscle of older individuals may serve to increase muscular hypertrophy or at least help maintain muscle mass.  

Below is a schematic illustration of the mechanisms through which the nutritional supplements discussed in this article may function to promote skeletal muscle adaptation.

Adapted from McKendry et al. 2020 (3)


Let’s examine the most recent evidence surrounding the interaction between resistance exercise and various nutritional strategies as a means to augment muscle protein synthesis, promote muscle protein accumulation, and mitigate the progression of sarcopenia. 

The best supplements to help fight off age-related muscle loss


The postprandial (after eating) large increase in blood levels of amino acids (known as hyperaminoacidemia) that occurs from protein ingestion initiates and results in the stimulation of muscle protein synthesis.

This is due specifically to the increase in essential amino acids (EAAs) which leucine has independently shown to stimulate muscle protein synthesis, and protein sources higher in leucine content typically produce a greater stimulation of muscle protein synthesis. 

For instance, higher doses of leucine (41%, 2.7 g vs 26%, 1.7g) in an EAA mixture increased muscle protein synthesis above baseline in older adults (6). In addition, different doses of total protein (25 g vs 10 g), containing the same leucine content (3g) generated similar increase in acute muscle protein synthesis in older adults (7).

In order to maximally stimulate muscle protein synthesis; additional leucine confers no significant benefit when a sufficient bolus of protein is provided (>35 g) (8). 

However, supplementing a sub-optimal dose of protein with leucine in older adults can rescue the deficit in muscle protein synthesis, similar to consuming a much greater dose of protein (6).

Therefore, boosting a sub-optimal protein dose with additional leucine might be an efficient nutritional strategy to counteract muscle mass loss for older adults and can potentially mitigate the increased cost and burden associated with the consumption of a larger amounts of protein.

Most estimates show that ingestion of ≥30 g of protein is needed to increase post-exercise muscle protein synthesis in older adults (9), however, when you compare a sub-optimal dose of milk protein (15 g) that contains a lower (~1.3 g) and higher (~4.2 g) of leucine; the higher dose resulted in a larger increase in muscle protein synthesis after resistance exercise (10). 

In support of this notion; in older females, 10 g of milk protein with 3 g of leucine led to greater acute muscle protein synthesis than 24 g of whey protein (7). 

It’s clear that leucine is important for stimulating muscle protein synthesis and particularly in older persons where anabolic resistance of muscle appears can be overcome to some degree by leucine supplementation (3).

It’s important to note that in a free-living environment, protein is typically consumed with other macronutrients (i.e., carbs and fats), which may influence amino acid absorption. Plasma EAA concentration is lower following consumption of a mixed-macronutrient meal (11). Therefore, it’s recommended that older adults should consume a higher leucine dose (≥4.5 g) when consuming mixed macronutrient meals (12). 

In addition, older adults absolutely need the stimulus of resistance training to maximize the benefits of leucine which together can be a very effective approach to counteract sarcopenia.  More research is needed utilizing long-term suboptimal protein ingestion enriched with leucine in order to ascertain the resistance exercise-induced increase in lean mass accretion in older individuals.

Omega-3 polyunsaturated fatty acids (n3-PUFA)

Omega-3 polyunsaturated fatty acids (n3-PUFA), commonly referred to as fish oil, contains two or more double bonds and performs an important role in normal metabolic function.

The most biologically active n3-PUFAs are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are considered conditionally essential fatty acids, due to the low conversion rate from Alpha-linolenic acid (ALA); therefore, increasing dietary (e.g., oily fish) and/or supplemental (e.g., fish oil) intake is recommended (13).

EPA and DHA possess anti-inflammatory properties and serve as critical components of phospholipids in cellular membranes, therefore increasing n3-PUFA consumption may theoretically, benefit any bodily tissue – skeletal muscle included (14). 

Daily supplementation with EPA and DHA in older adults for 8 weeks increased muscle protein synthesis in response to a constant infusion of insulin and amino acids (15). 

More work is required to corroborate the potential use of EPA and DHA to combat anabolic resistance in older adults. Notably, no studies have investigated the potential synergistic effects of n3-PUFA and resistance exercise training in older adults with sarcopenia, and this warrants further investigation.

In addition to aging, periods of physical inactivity (e.g., bed rest, muscle disuse, step reduction) contribute to the development of anabolic resistance and sarcopenia progression (16).

Young healthy women supplementing with EPA (2.97 g/day) and DHA (2.03 g/day) had greater integrated rates of muscle protein synthesis during 2 weeks of single-leg immobilization and following 2 weeks of recovery, compared to a control group ingesting sunflower oil (17).

Additionally, EPA and DHA supplementation not only lessen muscle atrophy during immobilization, but also enabled the full return of skeletal muscle volume after 2 weeks of passive recovery (17).

These findings highlight the potential efficacy of EPA and DHA intake to mitigate disuse-induced skeletal muscle atrophy.  Further work to address whether n3-PUFA can mitigate muscle disuse atrophy in older adults is justified.

Vitamin D

Vitamin D is a fat-soluble nutrient that plays an important role in the maintenance of skeletal muscle health and function.

Following exposure to sunlight, vitamin D is synthesized in the skin, and is essential to support healthy bone, kidney, intestine, and muscle function (18).

In older adults, the RDA for vitamin D is 800 IU/day, with a goal of elevating blood vitamin D to >50 nmol/L, to maintain skeletal health (19). 

It seems that vitamin D and the vitamin D receptor may play a role in modulating satellite cell activity, protein synthesis, mitochondrial metabolism, as well as energy production through various protein pathways that play a role in maintaining skeletal muscle mass and function (20).

Older individuals are at greater risk for vitamin D deficiency due to poor intestinal absorption, reduced sun exposure (especially in countries farther away from equator), and impaired hydroxylation metabolism in the liver and kidneys (21).

The impairment of vitamin D synthesis in older individuals could contribute to the progression of sarcopenia and an increased risk of falls and fractures (22).

Early observational studies suggested a positive association between vitamin D and muscle function in elderly individuals (21).

Indeed, a 3-year observational study demonstrated that older individuals with serum concentration vitamin D below 25 nmol/L are twice as likely to develop muscle wasting (23).

When resistance training is paired with vitamin D supplementation, in deficient individuals, the improvement in muscle strength and physical function (assessed by the timed up and go test) are greater than exercise alone (24). 

Therefore, older adults looking to maintain skeletal muscle mass and function should avoid vitamin D insufficiency (<50 nmol/L) and deficiency (<25–30 nmol/L). However, supplementation to further augment serum vitamin D concentration above sufficiency (>50 nmol/L) likely confers no additional benefit to muscle health.


We have all heard of creatine and its benefits to strength, muscle size and anaerobic type events (i.e. sprinting, football). 

But what exactly is creatine and how does it work?

Creatine is a naturally occurring, nitrogenous, organic acid composed of the amino acids methionine, arginine, and glycine. Creatine is found in many bodily tissues (e.g., heart, brain, eyes), but predominantly (~95%) within skeletal muscle as either phosphocreatine (PCr) or free creatine, which comprise two-thirds and one-third of stored creatine, respectively (25).

Creatine plays an integral role within the phosphocreatine energy system, of which the primary function is to facilitate the transfer of high-energy phosphates in the production, and rapid regeneration, of adenosine triphosphate (ATP).

Creatine supplementation exerts an ergogenic effect through increasing PCr stores and subsequently delaying their depletion, facilitating the rapid re-synthesis of PCr, acting as an energy buffer and potentially the modification of lactic acid production (26).

Approximately 1–2 g per day of muscle-stored creatine is converted to creatinine and lost through urinary excretion. As skeletal muscle has no creatine biosynthesizing capacity, creatine must be obtained endogenously (i.e., inside the body) through de novo (i.e., from new) synthesis by the kidneys and liver or exogenously (i.e., outside the body) via the consumption of creatine-containing dietary sources such as meat or fish or as a supplement.

The most effective dosing strategy to augment skeletal muscle stores of creatine is to use ~5 g of creatine monohydrate four times daily for 5–7 days (27) followed by a maintenance dose of 3–5 g/day; however, a more conservative dosing strategy can be employed such as consuming 3 g/day for 28 days.

It should also be noted that the co-ingestion of creatine with other macronutrients (i.e., carbohydrate or carbohydrate and protein) may stimulate greater muscle creatine retention (27).

There is a substantial amount of evidence documenting the benefits of creatine supplementation in a young, healthy, population.

Specifically, creatine has been shown to augment performance in repetitive, explosive tasks, such as sprinting and resistance exercise and facilitates increased lean body mass. Therefore, creatine supplementation may confer a meaningful benefit on skeletal muscle mass and function in an older population.

Creatine supplementation in an older population has been shown to elicit improvements in body composition, (28) and to enhance exercise performance (29).

Recently, a number of meta-analyses have concluded that creatine supplementation leads to increased lean tissue mass (~1.5 kg) and upper- and lower-body muscular strength when provided alongside resistance training (≥6 weeks), compared with resistance training alone (29).

Creatine and resistance training may act synergistically to promote improvements in body composition and performance, therefore the benefits of supplementation in the absence of resistance training may be limited (30).

The magnitude by which skeletal muscle creatine content can be increased displays significant discrepancy, and is likely impacted by pre-supplementation levels, exercise training history, diet, and possibly fiber-type composition (31). Therefore, not all studies demonstrate a benefit of creatine supplementation in older individuals.

For example, creatine content is ~12% greater in type II compared with type I muscle fibers (31) and following supplementation both fiber types exhibit a similar relative increase (~15%) in creatine content. Importantly, evidence for adverse effects with creatine supplementation is scarce, and in the absence of benefits for skeletal muscle, the physiological improvements induced by creatine supplementation may extend to bone and brain tissue (32).

Despite some apparent variability, creatine supplementation offers a safe, well-tolerated, and effective nutritional strategy to augment skeletal muscle adaptations when carried out in concert with resistance training.

In summary

It’s very clear that skeletal muscle is critical for the maintenance of physical, functional and metabolic health; therefore, conditions such as sarcopenia are a significant concern in aging individuals.

Despite the complex and multifaceted nature of sarcopenia, resistance training performed with a high degree of effort offers the most potent non-pharmacological strategy to ameliorate the progression of sarcopenia and offer numerous health-related quality of life benefits. 

The take home message is that we absolutely, one hundred percent need resistance training as a catalyst to ensure the supplementation strategies mentioned above are able to exert their benefits on our bodies to their fullest effect.

It’s clear that the influence of resistance training on skeletal muscle in older adults can be augmented by incorporating rational evidence-based nutritional support strategies.

Besides specific dietary components such as protein, specific nutritional supplements such as leucine, omega-3 polyunsaturated fatty acids, and creatine show evidence-based support to enhance resistance training induced adaptations.

Consuming sufficient high-quality, leucine rich protein in concert with resistance training appears to be the primary, and arguably most well-supported, way to improve, or at least maintain, skeletal muscle mass and function with advancing age.

Despite the importance of leucine content in triggering and sustaining an optimal muscle protein synthesis response, leucine supplementation alone is unlikely to confer a significant benefit for skeletal muscle—excluding its capacity to rescue deficits in muscle protein synthesis from lower quality protein sources.

It’s quite clear from all the available evidence that other established (i.e., creatine) and promising (i.e., n3-PUFAs) nutrition-based strategies appear to provide valuable tools to overcome anabolic resistance and augment resistance exercise-induced adaptations and ultimately impede sarcopenia progression. In contrast, evidence to support vitamin D (outside of preventing deficiency/insufficiency), and antioxidant supplementation to augment resistance training adaptations are lacking.

Further exploration of the efficacy of the aforementioned supplements within clinical or sarcopenic populations would yield valuable insights.




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Dr. Paul Henning

About Dr. Paul

I'm currently an Army officer on active duty with over 15 years of experience and also run my own health and wellness business. The majority of my career in the military has focused on enhancing Warfighter health and performance. I am passionate about helping people enhance all aspects of their lives through health and wellness. Learn more about me