No Native Advantage: RCT Compares High-Leucine "Native" Whey to Regular Concentrate - Finds NO Difference in MPS

Is the literally "raw" raw material that's used to manufacture "native whey" worth the extra bucks the final products cost? Native whey fails the real world test.

In February this year, I already predicted that the "benefits" of "native whey" will probably turn out to be practically irrelevant. In the corresponding article "Native Whey, a Superior Muscle Builder? Recently Observed Impressive Absorption Rates Tell You Nothing About 'Gains'" (re-read it).

Back in the day, I made a point that the improved amino acid kinetics, i.e. the more rapid appearance of amino acids Hamarsland et al. observed in their first study this year (Hamarsland 2017) for native compared to 'regular' whey protein was unlikely to trigger significant differences in actual protein synthesis - let alone long-term gains.

Now, a recent study by Hamarsland et al. (2017b) confirms just that - as early as in the title, by the way: "Native whey protein with high levels of leucine results in similar post-exercise muscular anabolic responses as regular whey protein: a randomized controlled trial" (Hamarsland 2017b).
As the researchers point out in the introduction to their paper, protein is not just needed as a substrate for protein synthesis and thus the accrual of lean muscle mass, it can also stimulate protein synthesis. In this context, leucine has been found to be one of, if not the main agent to drive the increase in mTOR, a protein that controls the process of protein synthesis.

Native whey has more leucine than regular whey, so it should be more anabolic, no?

The authors' hypothesis in the study at hand was that "native whey[, which is produced by the filtration of unprocessed raw milk and has been found to induce greater leucine blood concentrations than WPC-80 (Hamarsland 2017a), would be [a more potent stimulator of MPS than WPC-80] (Hamarsland 2017b).

Accordingly, the authors compared the time-dependent changes in mTORC1 substrate signal in response to either native whey protein or a regular whey protein concentrate (WPC80) when both were ingested at a dosage of 2 × 20 g after a resistance exercise session and controlled to the effects of milk providing 20g of protein at even lower relative amounts of leucine than WPC80.

Figure 1: Authors' illustration of the experimental design (Hamarsland 2017b)

The study was a double-blinded, partial crossover, randomized control trial. Each participant was assigned to one of two groups. The randomization was stratified based on lean body mass. The milk group did the protocol once, whereas the whey group was exposed to the protocol two times, once consuming WPC-80 and once consuming native whey, in a randomized order, approximately two weeks apart.

Exercise protocol: leg training, only

3 h after a standardized breakfast participants performed an intense bout of high-load leg-resistance exercise. 20 g of protein from milk, WPC-80 or native whey, were ingested both immediately after, and again 2 h after exercise. Blood samples were collected from an antecubital vein to measure changes in blood concentrations of amino acids, glucose, insulin, urea and creatine kinase (CK). MPS and related intracellular signaling were measured during a 5-h recovery period combining biopsies and tracer infusion of [2H5]phenylalanine. In addition, we measured recovery of muscle force-generating capacity by maximal isometric voluntary contractions (MVC) for 24 h after exercise.

The results were quite unequivocal: real benefits of "nativity" couldn't be observed

In line with the results of the previously discussed study, native whey increases the blood leucine concentrations to a greater extent than WPC-80 and milk (P < 0.05). What it did not do, however, was to trigger a significant increase of the phosphorylation of p70S6K, an mTOR target protein that controls the actual rate of protein synthesis - for p70S6K, an advantage was only observed over milk and that only 180 min after exercise (P = 0.03).

Figure 2: The increased phosphorylation of p70S6k did not translate to sign. increased rates of protein synthesis; * different from resting values. # different from milk at the corresponding time point, p < 0.05 (Hamarsland 2017b).

What is even more important, though, is that the actually measured muscle protein synthesis rates did not differ between the whey groups. For both whey proteins, the protein synthesis increased significantly 1–3 h hours after the exercise - with WPC-80 (0.119%), and 1–5 h after exercise with native whey (0.112%).

The only thing that is noteworthy, here, is that this increase in protein synthesis appears to be non-significantly more sustained in the native vs. concentrate group. That's probably also why only the native whey group saw a statistically significant increase over milk during the whole 1–5 h period after the workouts (0.112% vs. 0.064, P = 0.023), while the overall increase in FSR in the concentrate group didn't reach statistical significance (the difference we see here is yet practically irrelevant, for the practitioner one won't have an advantage over the other... after all, there's almost no and certainly no statistically relevant difference between native and whey concentrate).
References:

• Hamarsland, Håvard, et al. "Native whey induces higher and faster leucinemia than other whey protein supplements and milk: a randomized controlled trial." BMC Nutrition 3.1 (2017a): 10.
• Hamarsland, H. et al. "Native whey protein with high levels of leucine results in similar post-exercise muscular anabolic responses as regular whey protein: a randomized controlled trial." Journal of the International Society of Sports Nutrition (2017b) 14:43.