Dietary sources of long-chain n-3 PUFA

Commonly consumed food sources rich in n-3 PUFA include oily fish such as mackerel, sardines, trout and salmon (Fig. 1). In comparison, canned tuna contains a lower n-3 PUFA content and is no longer categorised as an oil-rich fish source. While other non-fish food sources such as walnuts also contain n-3 PUFA, the n-3 PUFA are shorter chain (often α-linolenic acid) which, in human subjects, are poorly converted to EPA and then DHA through processes of elongation and desaturation. Interestingly, this conversion is poorer in men than in women^{(Reference Burdge and Calder7)}.

Fig. 1.

Commonly consumed n-3 PUFA-rich food sources in the UK diet. Data extracted from the composition of foods integrated dataset (CoFID)⁽⁷⁰⁾. n-3 PUFA, very long-chain n-3 PUFA; ALA, α-linoleic acid.

Dietary guidelines in the UK recommend two, 140 g, portions of fish per week, one of which should be of oily source⁽⁸⁾. However, the latest National Diet and Nutrition Survey⁽⁹⁾ indicates that, on average, adults aged 19–64 years consume only 56 g oily fish on a weekly basis (excluding canned tuna), while older adults aged 65+ consume 84 g oily fish per week. While the average oily fish intake falls alarmingly short of this 140 g recommendation, also noteworthy is the median intake for both age groups is 0 g per week, with the majority of UK adults avoiding dietary intake of oily fish altogether. Evidence from the EPIC-Norfolk study highlights that cod liver oil (a source of n-3 PUFA) was the most popular supplement consumed by 32 % of men and 45 % of women^{(Reference Lentjes, Keogh and Welch10)}. However, it is worth noting that over-the-counter fish oil preparations do not always contain the dose advertised on the label, and that the fatty acids can often be extensively oxidised, compromising their proposed biological function^{(Reference Albert, Derraik and Cameron-Smith11,Reference Heller, Gemming and Tung12)} .

The Scientific Advisory Committee on Nutrition recommends a long-chain n-3 PUFA intake of 450 mg/d. In comparison, UK intakes of EPA and DHA are estimated at 244 mg/d (131 mg/d from oil-rich fish)^{(Reference Gibbs, Rymer and Givens13)}, with potentially lower intakes in ethnic minority groups. Hence, there is ample scope to explore strategies to increase n-3 PUFA intakes in the UK diet, potentially through enrichment strategies targeting foods such as dairy and meat (especially poultry)^{(Reference Gibbs, Rymer and Givens13)}, with a view to improving cardio-metabolic health. While n-3 PUFA intake is low in the Western population, n-6 PUFA consumption remains comparatively high, through regular intake of seed oils and food products. It is understood that the ratio of n-6 : n-3 PUFA has recently shifted from a balanced 1:1 to about 20:1, with implications for metabolism, specifically the production of pro-inflammatory molecules, such as prostaglandins and leukotrienes^{(Reference Simopoulos14)}.

Importance of skeletal muscle tissue for cardio-metabolic health and physical function

The term cardio-metabolic risk describes a family of risk factors of metabolic origin that increase the risk of developing CVD such as CHD, stroke, type 2 diabetes mellitus and chronic kidney disease. Skeletal muscle tissue plays a crucial, albeit often underappreciated, role in maintaining cardio-metabolic health and offsetting morbidities commonly associated with advancing age^{(Reference Wolfe15)}. Accounting for about 40 % of total body mass^{(Reference Kim, Wang and Heymsfield16)}, skeletal muscle is described as a plastic tissue that is capable of (mal)adaptation to physical (in)activity and diet. As the primary site of blood glucose disposal, skeletal muscle accounts for about 80 % of postprandial glucose uptake^{(Reference Meyer, Dostou and Welle17)}. Low muscle mass is associated with a reduced RMR that can lead to the accumulation of fat mass^{(Reference Wolfe15)}. Therefore, the maintenance of skeletal muscle mass over the lifecourse is critical in regulating blood glucose homeostasis and reducing the risk of type 2 diabetes mellitus, as well as other associated cardio-metabolic diseases. In addition, skeletal muscle serves as the body's primary storage site for amino acids and, during starvation or in the context of conditions such as AIDS by providing gluconeogenic precursors that are crucial for survival^{(Reference Kotler, Tierney and Wang18)}. Beyond metabolic health, it is widely recognised that skeletal muscle is crucial in preserving physical function, mobility and ultimately independence during older age.

An inevitable, albeit partially modifiable, feature of the ageing process concerns the progressive decline in skeletal muscle mass, strength and function. Muscle atrophy begins as early as the fourth decade of life^{(Reference Janssen, Heymsfield and Wang19)}, continues at a rate of about 1 % of total muscle mass per year until age 70 years^{(Reference Mitchell, Williams and Atherton20)}, and increases to about 1·5 % of total muscle mass per year above age 80 years^{(Reference Delmonico, Harris and Visser21)}. Alarmingly, the decline in muscle strength with advancing age typically exceeds the decline in muscle mass, with annual declines of 3–4 % in strength commonly reported^{(Reference Goodpaster, Park and Harris22)}. Once the decline in muscle strength and muscle mass falls below critical thresholds, older adults are classified as sarcopenic^{(Reference Cruz-Jentoft, Bahat and Bauer23)}. This condition is associated with a 2–3 fold increase in the risk of falling, bone fractures, loss of independence and increased mortality^{(Reference Landi, Liperoti and Fusco24,Reference Janssen, Heymsfield and Ross25)} . According to a recent report, additional health and social care costs associated with sarcopenia in the UK are currently estimated to be £2·5 billion annually^{(Reference Pinedo-Villanueva, Westbury and Syddall26)}.

In 2016, sarcopenia was recognised as an independent geriatric condition, with its own International Classification of Disease code. Compounding this progressive loss of functional ability, the age-related decline in muscle mass and strength is associated with an increased cardio-metabolic health risk. In this regard, a recent study demonstrated that low muscle strength was associated with an increased risk of all-cause mortality and mortality from CVD, cancer and respiratory disease^{(Reference Celis-Morales, Welsh and Lyall27)}. Similarly, low muscle strength has been associated with a higher incidence of type 2 diabetes mellitus^{(Reference Celis-Morales, Welsh and Lyall27)}, with findings more equivocal for low muscle mass^{(Reference Hong, Chang and Jung28,Reference Li, Wittert and Vincent29)} . Furthermore, the increased risk of CVD mortality observed in patients with type 2 diabetes mellitus is attenuated in those individuals with greater grip strength^{(Reference Celis-Morales, Petermann and Hui30)}. Taken together, these observational data provide compelling evidence that the maintenance of muscle mass and strength with advancing age is critical for the management of cardio-metabolic health risk.

The decline in muscle mass with advancing age often occurs in concert with an increase in fat mass. This age-related phenomenon is referred to as sarcopenic obesity. It is well established that obesity independently increases the risk of many cardio-metabolic health outcomes such as myocardial infarction, stroke, some cancers and all-cause mortality^{(Reference Lauby-Secretan, Scoccianti and Loomis31–Reference Wormser and Kaptoge33)}. Evidence also suggests that when sarcopenia and obesity are combined, the debilitating effects are additive. For example, whilst sarcopenia and obesity are independently associated with an increased risk of all-cause mortality (sarcopenia hazard ratio 1·41 (95 % CI 1·22, 1·63)) and obesity hazard ratio 1·21 (95 % CI 1·03, 1·42) compared to lean non-sarcopenic individuals, all-cause mortality risk is even greater (hazard ratio 1·72 (95 % CI 1·35–2·18)) in sarcopenic obese men^{(Reference Atkins, Whincup and Morris34)}. Therefore, it seems prudent to target the maintenance/increase of muscle mass, strength and function alongside the loss of fat mass to optimal levels in older adult populations. Before establishing targeted interventions to offset the age-related decline in muscle mass and increase in fat mass, it is important to understand the causal mechanism(s) that underpin the decline in muscle mass with advanced age.

Causal mechanisms that underpin the decline in muscle mass, strength and function with age

Although sarcopenia affects about 10–30 % of community-dwelling men and women aged 60+ worldwide, the underlying pathology of this clinical condition is not fully understood. Clearly, the underlying cause of sarcopenia is multifactorial, with interconnected and complex contributing factors. In terms of muscle atrophy, contributing factors include, but are not limited to, chronic low-grade inflammation, elevated levels of oxidative stress, DNA damage, mitochondrial dysfunction and hormonal changes^{(Reference Morley35)}. Ultimately however, from a metabolic standpoint, the decline in muscle mass with advanced age is underpinned by a state of negative muscle protein balance.

Two possible metabolic drivers of negative muscle protein balance exist. First, an impaired stimulation of muscle protein synthesis (MPS), defined as the rate by which freely available amino acids in the blood or muscle amino acid pools are incorporated into functional muscle protein. Secondly, an up-regulation of muscle protein breakdown, defined as the rate by which muscle protein is degraded into amino acid precursors. There is a general consensus that basal, post-absorptive rates of MPS are comparable between young and older adults^{(Reference Markofski, Dickinson and Drummond36–Reference Cuthbertson, Smith and Babraj38)}. In contrast, several studies have reported suppressed postprandial rates of MPS in response to amino acid feeding in older adults compared with their younger counterparts^{(Reference Wall, Gorissen and Pennings39)}. The concept of this so-called anabolic resistance has been conceived from this observation and describes the age-related impairment in response of MPS to ingesting a meal-like (about 20 g) quantity of protein and/or other typically robust anabolic stimuli such as mechanical loading, i.e. structured exercise training. At the molecular level, this age-related impairment in MPS appears to be mediated by a dysregulation in the Akt-mTOR (mechanistic target of rapamycin) cell signalling cascade that controls the rate-limiting translation initiation step of MPS^{(Reference Guillet, Prod'homme and Balage40)}. As such, anabolic resistance is widely regarded as one of the key drivers of sarcopenia. Moreover, as further evidence of the interplay between mechanisms underlying sarcopenia, animal studies have demonstrated that low-grade inflammation, which is particularly prevalent in sarcopenic obese individuals, impairs the stimulation of MPS in response to food intake^{(Reference Balage, Averous and Remond41)}. Hence, there is a clear biological rationale to establish non-pharmacological lifestyle-friendly interventions that target overcoming both anabolic resistance and low-grade inflammation in older adults.

In practical terms, the progressive decline in muscle mass and strength is exacerbated by periods of muscle disuse^{(Reference Wall, Snijders and Senden42,Reference Bell, von Allmen and Devries43)} . Examples of skeletal muscle disuse range in duration and severity from short-term periods of limb immobilisation caused by injury (i.e. accidental falls) to longer-term periods of bedrest inflicted by illness and/or cardio-metabolic disease. A reduction in physical activity, as typically quantified by step count, provides another important, albeit less extreme, example of muscle disuse. Accordingly, age-related anabolic resistance is exacerbated by reducing physical activity levels^{(Reference Breen, Stokes and Churchward-Venne44)}, limb immobilisation^{(Reference Wall, Snijders and Senden42,Reference Wall, Dirks and Snijders45)} and bedrest^{(Reference Ferrando, Lane and Stuart46)}. Moreover, recent evidence suggests that age-related anabolic resistance is further exacerbated in overweight and/or obese older adults^{(Reference Smeuninx, Mckendry and Wilson47)} (Fig. 2) and in response to a period of high-fat feeding^{(Reference Stephens, Chee and Wall48)}. Thus, it follows that optimising diet and lifestyle strategies for maintaining muscle health is of critical importance in sarcopenic older adults. In this regard, given the potent anti-inflammatory properties of n-3 PUFA^{(Reference Calder49)} and recent evidence that n-3 PUFA exhibit anabolic properties^{(Reference Kamolrat and Gray50,Reference McGlory, Galloway and Hamilton51)} , the role of dietary n-3 PUFA intake in combating sarcopenia has received considerable recent attention.

Fig. 2.

Theoretical model of muscle ‘anabolic resistance’ associated with ageing and obesity. Data are generated from citations denoted by number in parentheses:^{(Reference Witard, Jackman and Breen65)} young (18–35 years) adults ingested 10, 20 or 40 g whey protein;^{(Reference Yang, Breen and Burd71)} older (65–75 years) ingested 10 g whey protein;^{(Reference Yang, Churchward-Venne and Burd72)} older (65–75 years) ingested 20 or 40 g soya protein;^{(Reference Smeuninx, Mckendry and Wilson47)} older (66–73 years) obese (BMI > 30) adults ingested 15 g milk protein isolate;^{(Reference Beals, Sukiennik and Nallabelli73)} young (23–30 years) obese (BMI > 33) adults ingested 170 g pork containing 36 g protein. Small protein feed, 10 g protein; moderate protein feed, 20 g protein, large protein feed, 36–40 g protein. MPS, muscle protein synthesis; Yg, young adults; Old, older adults.

Diverse biological roles of long-chain n-3 fatty acids

A key determinant of physiological function at the cellular level includes the fatty acid composition of the phospholipid cell membrane. Membrane fatty acid composition is modulated by metabolic, genetic and hormonal factors, and of particular relevance to this review, dietary intake of fatty acids. As detailed earlier, the western diet is generally rich in n-6 PUFA (e.g. linoleic acid) relative to n-3 PUFA. This pattern is reflected in the constituent fatty acid composition of cell membranes which typically range from 10 to 20 % for n-6 PUFA and 2 to 5 % for n-3 PUFA^{(Reference Calder52)}. The membrane composition of n-3 PUFA can be elevated in a dose-dependent manner by dietary intake of n-3 PUFA^{(Reference Rees, Miles and Banerjee53)}. Functionally, the most important n-3 PUFA are EPA and DHA and many research studies have investigated the physiological properties of EPA/DHA, primarily due to their potential to reduce inflammation^{(Reference Calder52)}.

Whilst inflammation is an important defence mechanism of the immune system to protect human subjects from infection, unresolved pathological inflammation can result in damage and disease. For example, and as detailed previously, low-grade chronic inflammation has been implicated in the aetiology of sarcopenia but also many cardio-metabolic conditions. There is a host of research demonstrating that increasing n-3 PUFA intake serves to reduce inflammation, as reviewed previously^{(Reference Calder52)}. As inflammation has been associated with many cardio-metabolic conditions, it has been suggested that n-3 PUFA supplementation may be of therapeutic use. For example, early observational studies in Inuits demonstrated that even though this population consumed very high-fat diets, the prevalence of heart disease was low, with this inverse relationship attributed to the high dietary n-3 PUFA intake^{(Reference Ebbesson, Ebbesson and Swenson54,Reference Bang, Dyerberg and Sinclair55)} . In contrast, a recent meta-analysis demonstrated that increasing EPA and DHA consumption has minimal, or no effect, on mortality or cardiovascular health^{(Reference Abdelhamid, Brown and Brainard56)}, with the authors calling for a halt in further studies until ongoing large trials are fully reported.

In addition to their anti-inflammatory properties and role in regulating immune function, n-3 PUFA exhibit other physiological roles due to their incorporation into all cell types. Therefore, it is not surprising that the physiological roles of EPA and DHA are not limited to the immune system. For example, DHA is vital for fetal brain and retinal development given the high propensity for DHA incorporation in the brain and retinal membrane phospholipids that are crucial for the functional development of these tissues^{(Reference Greenberg, Bell and Ausdal57)}. Since the recent observation that EPA and DHA supplementation results in an increased incorporation of EPA and DHA in muscle cells^{(Reference McGlory, Galloway and Hamilton51)}, there has been a growing interest in the physiological effects of such a change for muscle health with advancing age.

Role of long-chain n-3 fatty acids in prevention and treatment of sarcopenia

Dietary n-3 PUFA have received considerable recent attention in the context of optimising diet for the management of sarcopenia. Extending early epidemiological data which found that fatty fish consumption was positively associated, in a dose–response manner, with grip strength^{(Reference Robinson, Jameson and Batelaan58)}, two seminal experimental studies in healthy young, middle-aged and older adults sparked interest in the potential muscle anabolic action of n-3 PUFA^{(Reference Smith, Atherton and Reeds59,Reference Smith, Atherton and Reeds60)} . These proof-of-principle, acute metabolic, studies were conducted under controlled laboratory conditions and measured rates of MPS under basal (fasted and rested) and simulated fed conditions before and after 8 weeks of fish oil (4 g/d) derived n-3 PUFA supplementation (1·86 g EPA, 1·50 g DHA daily). Amino acids and insulin were infused intravenously to partially mimic the ingestion of a protein-rich mixed macronutrient meal. Whereas the basal response of MPS was not modulated by n-3 PUFA, the feeding-induced increase in MPS was potentiated by 30–60 % after 8 weeks of fish oil supplementation compared with before supplementation^{(Reference Smith, Atherton and Reeds59,Reference Smith, Atherton and Reeds60)} .

Perhaps surprisingly, at least from a mechanistic standpoint, in these studies^{(Reference Smith, Atherton and Reeds59,Reference Smith, Atherton and Reeds60)} no changes in TNFα or C-reactive protein concentrations, as systemic markers of inflammation, were observed over the 8-week period of fish oil supplementation. However, the phosphorylation status of intramuscular cell signalling proteins known to up-regulate MPS (e.g. mTORC1-p70S6k1) was potentiated in response to simulated feeding following dietary fish oil supplementation. Consistent with this observation, our laboratory reported an increase in the proportion of n-3 PUFA, specifically EPA, in the muscle cell following 4 weeks of fish oil (5 g/d) derived n-3 PUFA supplementation in healthy young men^{(Reference McGlory, Galloway and Hamilton51)}. Such structural modifications to the muscle cell membrane were also associated with an increased phosphorylation of mTORC1 (a nutrient-sensitive intramuscular cell signalling protein and focal adhesion kinase) a mechanically sensitive kinase known to regulate MPS. Therefore, the primary causal mechanism that appears to underpin the anabolic action of n-3 PUFA relates to modifying the lipid profile of the muscle phospholipid membrane and subsequently up-regulating the activity of intracellular signalling proteins, rather than an anti-inflammatory response.

In recent years, we^{(Reference Da Boit, Sibson and Sivasubramaniam61,Reference McGlory, Wardle and Macnaughton62)} and others^{(Reference Lalia, Dasari and Robinson63)} have extended these acute metabolic studies to investigate the anabolic and/or anti-catabolic potential of n-3 PUFA in young and older adults using more physiologically relevant experimental study designs (Fig. 3). Rather than the intravenous infusion of amino acids and insulin to simulate feeding, anabolic stimuli included either an orally ingested dose of intact protein, a standardised mixed macronutrient meal and/or a resistance exercise session(s) administered over a period of 1–4 d. Informed by our in vitro experiment with fully differentiated C2C12 cells whereby EPA, rather than DHA, was shown to both up-regulate the MPS response to a leucine stimulus and down-regulate muscle protein breakdown^{(Reference Kamolrat, Gray and Thivierge64)}, these studies have primarily administered high-dose (3–5 g/d) fish oil supplements that are rich in EPA content. Accordingly, Lalia et al.^{(Reference Lalia, Dasari and Robinson63)} reported that fish oil supplementation (3·9 g/d) augmented the acute response of MPS to conducting a single bout of resistance exercise alongside feeding a protein-containing meal by about 30 % in older adults. As a note of caution, data values for MPS (expressed as fractional synthesis rate) were remarkably high in this study, calling into question the validity of these findings.

Fig. 3.

Overview of findings from experimental studies that investigated the influence of fish oil-derived n-3 PUFA supplementation on the response of muscle protein synthesis (MPS) to amino acid provision in young and older adults. Data generated from citations denoted by number in parentheses:^{(Reference Smith, Atherton and Reeds60)} young and middle-aged (about 39 years) adults consumed fish oil (4 g/d; 1·86 g/d EPA and 1·50 g/d DHA) capsules over 8 weeks and MPS was measured pre and post supplementation in response to the intravenous infusion of amino acids and insulin.^{(Reference Smith, Atherton and Reeds59)} Older (≥65 years) adults consumed fish oil (4 g/d; 1·86 g/d EPA and 1·50 g/d DHA) or maize oil capsules over 8 weeks and MPS was measured in response to the intravenous infusion of amino acids and insulin.^{(Reference McGlory, Wardle and Macnaughton62)} Young (about 21 years) adults consumed fish oil (5 g/d; 3·5 g/d EPA and 0·9 g/d DHA) or coconut oil capsules over 8 weeks and MPS was measured in response to ingesting 30 g whey protein at rest and following resistance exercise.^{(Reference Lalia, Dasari and Robinson63)} Older (65–85 years) adults consumed fish oil (3·9 g/d) capsules over 16 weeks and MPS was measured in response to an acute bout of resistance exercise.^{(Reference Smeuninx, Mckendry and Wilson47)} MPS was measured in response to ingesting 15 g milk protein isolate in older (66–73 years) obese (BMI > 30) adults. FSR, fractional synthesis rate; Yg, young adults, Old, older adults; AA, amino acid, WP, whey protein; REx, resistance exercise.

However, study findings regarding the influence of n-3 PUFA supplementation on postprandial rates of MPS have been equivocal, which may be attributed to differences in study design (i.e. the duration and dose of n-3 PUFA supplementation, choice of control supplement and technique used to measure MPS) and/or participant characteristics. For instance, we observed no differences in p70S6K1 kinase activity or free-living integrated rates of MPS measured over 4 d (assessed by recently re-introduced and less invasive orally administered ²H oxide tracer methodology) between two groups of older adults that combined resistance training with either fish oil (3 g/d) or safflower oil (3 g/d) supplementation^{(Reference Da Boit, Sibson and Sivasubramaniam61)}. In addition, we demonstrated that 8 weeks of fish oil (5 g/d) derived n-3 PUFA (3·5 g/d EPA) did not modulate the 4 h (as measured by the precursor-product method with intravenous infusion of labelled phenylalanine) MPS response to ingestion of a 30 g whey protein bolus under both rested and post-exercise conditions in trained young men^{(Reference McGlory, Wardle and Macnaughton62)}. Follow-up studies designed with a mechanistic focus are warranted to further explore these findings. We cannot discount the possibility that ingesting 30 g whey protein saturated the muscle protein synthetic machinery in our cohort of ‘nutrient-sensitive’ trained young men^{(Reference Witard, Jackman and Breen65)}, and although more relevant to are warranted to further explore these findings. We can-not discount the possibility that ingesting 30g whey protein saturated the muscle protein synthetic machinery in our cohort of ‘nutrient-sensitive’ trained young men^{(Reference Witard, Jackman and Breen65)}, and although more relevant to simulating daily lifestyle patterns, free-living measurements of MPS integrating postabsorptive and postprandial physiological states might have diluted the chance of detecting any subtle, but physiological relevant, anabolic action of n-3 PUFA^{(Reference Da Boit, Sibson and Sivasubramaniam61)}. Taken together, based on currently available evidence, these data indicate the anabolic action of n-3 PUFA may confer greater application to older adults who exhibit a state of anabolic resistance (Fig. 3).

The anabolic action of n-3 PUFA in ageing muscle has been partially supported by a series of longitudinal studies that obtained clinically-relevant endpoint measurements of muscle mass, strength and function, particularly when older women were studied. Expanding upon their initial work, Smith et al. ^{(Reference Smith, Julliand and Reeds4)} have demonstrated that daily ingestion of n-3 PUFA (1·86 g EPA and 1·50 g DHA) over 6 months increased thigh volume by about 3·5 % and handgrip strength by about 6 % in older adults, despite the absence of structured exercise training. The clinical implications of these remarkable data are particularly significant given that, as mentioned previously, handgrip strength^{(Reference Celis-Morales, Welsh and Lyall27)} and general strength^{(Reference Metter, Talbot and Schrager66)} are known predictors of all-cause mortality. Moreover, we demonstrated that improvements in muscle strength and quality (calculated as peak torque relative to muscle anatomical cross-sectional area), but not muscle mass, following 18 weeks of structured bi-weekly resistance exercise training were augmented with dietary fish oil-derived n-3 PUFA supplementation in older women^{(Reference Da Boit, Sibson and Sivasubramaniam61)}. However, no such benefit of n-3 PUFA ingestion was observed when older men were studied. Consistent with this observation, an earlier study supplemented older women with 2 g/d fish oil during 90 d resistance training and reported greater strength gains compared with training alone^{(Reference Rodacki, Rodacki and Pereira5)}. However, we contend that these data from Rodacki et al. ^{(Reference Rodacki, Rodacki and Pereira5)} should be treated with caution since no placebo group was included in the study design, the changes in blood n-3 PUFA composition were minimal, and no direct measures of muscle mass or MPS were collected. It follows that further studies are warranted to first confirm this apparent sex-difference in the muscle adaptive response to resistance training with n-3 PUFA ingestion, and second, determine the mechanism(s) that underpins this apparent sexual dimorphism in response to ingested n-3 PUFA.

Accumulating evidence also substantiates a protective role for n-3 PUFA ingestion during short-term periods of muscle disuse. In this regard, an elegant recent study by McGlory et al. ^{(Reference McGlory, Gorissen and Kamal67)} investigated the influence of n-3 PUFA supplementation on changes in muscle mass and integrated rates of MPS following 2 weeks of limb immobilisation in young women. The decline in muscle volume elicited by short-term limb immobilisation was attenuated by approximately 6 % with n-3 PUFA supplementation (a decrease of 8 %) v. the sunflower oil control (a decrease of 14 %). Moreover, following 2 weeks of rehabilitation whereby study participants resumed their habitual physical activity levels, muscle volume returned to baseline levels with n-3 PUFA supplementation, but remained below baseline in the control group. Accompanying the retention of muscle volume during simulated muscle disuse atrophy was a higher integrated response of MPS both at the immediate cessation of limb immobilisation and following 2 weeks of remobilisation. Interestingly, n-3 PUFA supplementation had no protective effect on the decline in muscle strength. Consistent with this observation, albeit using an animal model, rats fed an n-3 PUFA-rich diet during hindlimb suspension (simulating leg immobilisation) demonstrated an attenuated loss of muscle mass v. rats fed a maize oil-rich diet^{(Reference You, Park and Song68)}. Taken together, based on multiple lines of evidence, the preponderance of available data suggests that the optimal diet for maintaining muscle mass with age should consider the dietary intake of n-3 PUFA. Future studies are warranted to investigate the impact of n-3 PUFA ingestion on age-related changes in body composition in sarcopenic, obese, population groups.