Protein type and caloric density of protein supplements modulate postprandial amino acid profile through changes in gastrointestinal behavior: A randomized trial

Background & aims: The requirement of leucine and essential amino acids (EAA) to stimulate muscle protein synthesis increases with age. To target muscle anabolism it is suggested that higher postprandial blood levels of leucine and EAA are needed in older people. The aim was to evaluate the impact of oral nutritional supplements with distinct protein source and energy density, resembling mixed meals, on serum amino acid profiles and on gastrointestinal behavior.

Methods: Four iso-nitrogenous protein (21 g) supplements were studied containing leucine-enriched whey protein with 150/320 kcal (W150/W320) or casein protein with 150/320 kcal (C150/C320); all products contained carbohydrates (10 or 32 g) and fat (3 or 12 g). Postprandial serum AA profiles were evaluated in twelve healthy, older subjects who participated in a randomized, controlled, single blind, cross-over study. Gastrointestinal behavior was studied in vitro by looking at gastric coagulation and cumulative intestinal protein digestion over time.

Results: The peak serum leucine concentration was twofold higher for W150 vs. C150 (521 ± 15 vs. 260 ± 15 μmol/L, p < 0.001), higher for W320 vs. C320 (406 ± 15 vs. 228 ± 15 μmol/L, p < 0.001), and higher for low-caloric vs. high-caloric products (p < 0.001 for pooled analyses; p < 0.001 for interaction protein source*caloric density). Similar effects were observed for the peak concentrations of EAA and total AA (TAA). In vitro gastric coagulation was observed only for the casein protein supplements. Intestinal digestion for 90 min resulted in higher levels of free TAA, EAA, and leucine for W150 vs. C150, for W150 vs. W320, and for C150 vs. C320 (p < 0.0125).

Conclusions: A low caloric leucine-enriched whey protein nutritional supplement provides a higher rise in serum levels of TAA, EAA and leucine compared to casein protein or high caloric products in healthy, elderly subjects. These differences appear to be mediated in part by the gastrointestinal behavior of these products.


Alex’s Notes: It has been well established that muscle protein synthesis (MPS) is driven by changes in the concentration of amino acids outside (extracellular), but not inside (intracellular), the muscle fibers. In other words, it is a change from low to high blood amino acid concentrations that stimulate MPS. As a result, the concept of “fast/slow” protein came about to indicate the postprandial profile of amino acids appearing in the blood. For instance, the dairy proteins whey and casein contain a similar amount of essential amino acids (EAAs), but blood EAA levels increased faster and to a higher level after the intake of whey protein.

Despite the abundance of research in this area, most studies use isolated protein mixtures when in reality most people consume mixed meals. To help fill this knowledge gap, the study at hand evaluated the postprandial blood amino acid (AA) profiles of healthy older adults consuming whey or casein with differing caloric content. Specifically, the protein drinks that had to be consumed within five minutes by 12 healthy older adults were composed of 20g of whey protein isolate or sodium caseinate and different amounts of carbohydrates and fats to change the caloric content (see table below).

  Whey (W) 150 Casein (C) 150 W320 C320
Kcal 150 150 320 320
Protein, g 21 (56%) 21 (56%) 21 (26%) 21 (26%)
Whey, g 20 -- 20 --
Casein, g -- 21 -- 21
Total leucine, g 3 2 3 2
Total EAA, g 10 9 10 9
Carbohydrate, g 11 (26%) 10 (26%) 33 (40%) 32 (40%)
Fat, g 3 (18%) 3 (18%) 12 (34%) 12 (34%)

Unfortunately, the use of caseinate prevents a proper comparison of fast vs slow proteins. As we have seen previously, whey isolates and caseinates do not differ in digestive speed and are both fast digesting unlike the coagulating micellar casein naturally found in milk products. Nonetheless, we are still able to see how caloric content affects the AA response of the popular whey protein isolate.

Regarding study protocol, the subjects consumed one of the four drinks in a blinded condition once every 7-10 days until each subject consumed all four drinks. They were fasted overnight and had blood drawn for the subsequent four hours after consumption. As for the carbohydrates and fats, the researchers say that they are similar to “medical nutrition supplements,” and are thus probably dextrose or sucrose and soybean oil, but we can’t know for sure.

Bottom line: calories matter

First and foremost, both whey drinks resulted in a greater postprandial AA response than the caseinate, suggesting that whey isolate is a better “fast” protein option in older adults. More importantly, however, the low-calorie drinks displayed significantly greater postprandial appearance of AAs compared to the high-calorie drinks. Not only did the extra calories blunt the peak concentration achieved by leucine and the EAAs in general, but it also reduced the overall AA appearance in the blood over the subsequent four hours and reduced the rate of AA appearance.

Previous research has shown the caloric content of meals to influence gastric emptying, and the study at hand appears to support this. What remains elusive is how the type of carbohydrate or fat influences this. Similarly, although a greater amount of calories slows gastric emptying, how would this be offset by eating more protein?

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