Introduction
Ageing is associated with sarcopenia [
1] that ultimately results from an imbalance between rates of muscle protein synthesis and breakdown. Both physical activity and nutrient availability represent potent anabolic stimuli for adult muscle, however, the ability of elderly muscle to mount a robust increase in myofibrillar protein synthesis (MPS) in response to amino acids [
2,
3] and resistance exercise [
4] is attenuated compared to that seen in the young; a phenomenon termed ‘anabolic resistance’ [
2]. Previous studies have shown that both protein dose [
2,
5,
6] and source (i.e., plant vs. animal) [
7‐
11] are important in determining the postprandial response of MPS, which may be of particular relevance to the elderly. For example, we have recently demonstrated greater increases in post-exercise MPS in the elderly following bolus ingestion of 40 g vs. 20 g of whey protein [
6]; a finding in contrast to our data from young adults who show a maximal MPS response with 20 g protein and no further increase with 40 g [
5]. Thus, it appears that higher doses of protein [
6,
12], and/or leucine [
13,
14] to promote a greater aminoacidemia or leucinemia [
7] are required by the elderly to maximize the response of MPS to protein ingestion.
The mechanisms underpinning the differential capacity of proteins from different sources to support increased rates of protein synthesis are not fully understood [
15]. Whey protein [
7,
9,
10] and bovine milk [
8] (~20% whey protein) appear to stimulate greater rates of muscle protein synthesis than do proteins such as micellar casein or soy both at rest and following resistance exercise. This is somewhat counter-intuitive given that soy, whey, and casein are all defined as high quality proteins based on their protein digestibility corrected amino acid scores (PDCAAS; for review see [
16]). However, the digestion kinetics of these proteins is markedly different, and protein digestibility has been established as an important factor regulating whole-body protein synthesis and breakdown [
17,
18]. Both whey [
18] and soy [
19] are acid soluble, a characteristic that facilitates rapid digestion and results in a large but transient increase in aminoacidemia. These so-called ‘fast’ proteins induce a rapid aminoacidemia and appear to support greater increases in MPS. On the other hand ‘slow’ proteins, such as micellar casein (which clots in the acidic pH of the stomach) is slowly digested and induces a more moderate but sustained aminoacidemia than whey [
7,
10].
Knowledge of the capacity of proteins from different sources to stimulate MPS in the elderly is warranted in view of the importance of preserving skeletal muscle mass in ageing. Therefore, the aim of the current study was to examine the effects of different doses (20 g and 40 g) of soy protein isolate on MPS at rest and following the potent anabolic condition of resistance exercise in elderly men, and compare these findings to our previous work examining the effects of graded intakes of whey protein isolate on MPS in the elderly [
6].
Discussion
In the present study, we show that ingestion of 20 g (S20) and 40 g (S40) of soy protein isolate does not stimulate increased rates of MPS under resting conditions in the elderly. However, when combined with the potent anabolic stimulus of resistance exercise, 40 g but not 20 g, of soy protein isolate has a modest effect on increasing post-exercise rates of MPS when compared to a group who performed resistance exercise without subsequent protein intake (Figure
5). These data are in contrast to what was observed following equivalent doses of whey protein, as 20 g (W20) effectively stimulated MPS at rest, while both 20 g and 40 g (W40) increased post-exercise MPS in a stepwise manner (i.e. 40 g > 20 g) [
6]. Thus, when comparing our current findings on soy protein with our previous work examining graded doses of whey protein [
6], soy appears less effective than whey protein at promoting increases in MPS in the elderly (Figure
5). Further, our results confirm that the elderly benefit from significantly greater doses of protein after exercise [
6,
12] than do the young, who we have shown mount a maximal MPS response with ingestion of ~20 g protein [
5] or ~10 g EAA [
2].
We have previously reported that soy protein is less effective than whey [
9] and bovine milk protein [
8] at increasing rates of post-exercise muscle protein synthesis in young subjects. Whey protein appears superior in its ability to stimulate muscle protein synthesis not only when compared to soy, but also when compared to other dairy protein sources such as intact [
7,
9,
10] or hydrolyzed [
10] casein. The mechanism(s) underpinning differences in the capacity of these proteins to support increased rates of MPS has not been fully elucidated. Previous research in rats reported greater increases in the phosphorylation status of mTOR(Ser 2448) and p70S6k (Thr 389), critical proteins involved in regulating translation initiation of protein synthesis, following whey compared with soy protein intake after endurance exercise [
30]. Other important factors may relate to important differences in the leucine content of the respective proteins (~12% in whey and ~8% in soy) [
16], and/or to differences in their digestion/absorption kinetics and the subsequent aminoacidemia [
17,
18,
31]. For example, protein digestibility has been established as an important factor regulating whole-body protein synthesis and breakdown [
17,
18]; rapidly digested proteins have been shown to elicit a large increase in whole-body protein synthesis, whereas ‘slow’ proteins reduce rates of whole-body proteolysis [
17,
18,
32]. More recent work has extended these findings at the whole-body level by showing that a fast protein, such as whey, also stimulates greater rates of skeletal muscle protein synthesis than does a slow protein, such as casein, both in both young and elderly subjects [
7,
9,
10]. However, although whey and soy are relatively rapidly digested dietary proteins [
19,
33], previous studies have demonstrated that the amino acids from soy are partitioned for use within the body by more rapidly turning-over gut (i.e. splanchnic) proteins, and are converted to urea to a greater extent than amino acids from dairy based proteins which are partitioned to the periphery for use by skeletal muscle tissue [
19,
34].
In the present study, we observed protein source-dependent differences in rates of leucine oxidation (Figure
4). When expressed relative to lean body mass, rates of leucine oxidation were significantly greater for S20 than W20 (Figure
4). The higher rates of leucine oxidation in S20 vs. W20 suggest that a greater proportion of the amino acids from soy protein were diverted towards oxidation, and were thus unavailable as substrate for protein synthesis. Overall, although they are considered to be equivalent high quality proteins from the perspective of the truncated PDCAAS scoring system [
16], there are clearly important differences in the capacity of soy and whey protein to stimulate MPS and promote anabolism. This point is of particular importance to the elderly in whom preserving skeletal muscle mass is of importance. Previous work showing that nitrogen balance is attainable with long-term diets containing moderate amounts of soy [
35] would appear to be incongruent with our data; however, these data [
35] are confounded by weight loss in a number of the subjects and due to the age of subjects in this study not being entirely comparable. Our data would, in contrast to previous conclusions regarding the adequacy of soy protein [
35‐
37], suggest that long-term consumption of soy protein may not attenuate sarcopenic muscle loss.
The mechanisms underpinning the ‘anabolic resistance’ of elderly muscle to nutrient provision are not entirely clear. Given the results of the current study, and previous studies demonstrating that MPS responds favorably to higher doses of protein in the elderly [
6,
12] as compared to the young [
5], it appears that the muscle of older persons has a higher anabolic aminoacidemic ‘threshold’ [
6,
9,
38] that can be surpassed by ingesting either greater quantities of protein/amino acids or possibly greater leucine [
13]. The greater rates of MPS observed with equivalent doses of whey as compared to soy protein suggest that protein source is an important factor in reaching and surpassing the anabolic threshold (Figure
5). The branched chain amino acid leucine has been shown to be a key activator of muscle protein synthesis through its ability to regulate mRNA translation initiation through the mTOR signaling pathway [
39,
40]. For example, Katsanos and colleagues [
13] reported that while 6.7 g of EAA containing ~26% leucine failed to stimulate MPS in the elderly, increasing the leucine content to ~41% increased MPS in the elderly such that measured rates were not different from that seen in the young. Based on results from the present study, there were no protein source dependent differences in leucine area under the curve (AUC) at either the 20 g or 40 g dose (Figure
3), however, the temporal response of blood leucine was different following whey and soy at both protein doses (Figure
2) with the response of whey being greater in amplitude than that observed following soy. To overcome the confounding influence of amino acid composition when comparing different proteins, we recently manipulated the pattern of postprandial aminoacidemia using a bolus versus a pulsed feeding pattern with whey protein [
41]. Despite equivalent leucine and EAA AUC (i.e., net exposure) the bolus feeding pattern and the associated rapid aminoacidemia stimulated greater rates of post-exercise MPS than pulse feeding, which elicited a moderate but sustained rise in aminoacidemia [
41]. Further, supplementation of soy protein with the BCAA has been shown to increase the anabolic effect of this protein in both the elderly and clinical COPD patients [
42]. Thus, the higher leucine content and more rapid leucinemia with whey as opposed to soy may in part explain the observed differences in resting and post-exercise MPS between the two proteins.
In summary, we report that soy protein isolate is relatively ineffective in its capacity to stimulate MPS in the elderly when compared to whey protein. The mechanisms underpinning the reduced anabolic effect of soy as compared to whey likely relate to its relatively lower leucine content (~12% in whey and ~8% in soy) [
16] and reduced leucinemia as a result of subtle differences in digestion/absorption between soy and whey protein. It is unlikely these differences have a marked impact on protein nutrition in all but the elderly or clinical populations [
42]. Differences in postprandial amino acid oxidation rates may also be important as lower doses of soy (S20) resulted in greater increases in leucine oxidation than equivalent doses of whey protein. Our results have implications for nutrient formulations designed to support increased muscle protein anabolism in the elderly and suggest that whey protein offers clear advantages to soy protein in its capacity to support both rested and post-exercise increases in MPS.
Acknowledgments
We are grateful to Todd Prior and Tracy Rerecich for their technical assistance during data collection.
Funding
This work was funded by a research award from the US Dairy Research Institute to SMP, Grants from the Canadian Natural Science and Engineering Research Council (NSERC) to SMP and a graduate scholarship to TACV, and The Canadian Institutes for Health Research (CIHR) to SMP. YY, TACV, NAB, MAT, and SMP have no conflicts of interest, financial or otherwise, to declare.
Competing interests
YY, TACV, NAB, LB, MAT, and SMP declare that they have no competing interests.
Authors’ contributions
YY and SMP designed the research; YY, TACV, NAB, MAT and SMP conducted the research; YY and SMP analyzed the data; YY, TACV, LB, and SMP wrote and edited the manuscript; SMP had primary responsibility for the final content. All authors read and approved the final content.