New Insights Into the Difference Between Whey, Casein, Cod & Wheat Proteins: Increased Dopamine, Decreased Gastric Emptying, Unknown Hydroxy-Fatty Acids & More

This is not your average protein shoot-out - the amount of leucine and the mTOR and protein synthetic response were not even measured.

It's actually rare to read the phrease "in contrast to previous studies" in a study about whey protein. There have been dozens,... ah, what do I see, hundreds of studies that have investigated almost all aspects of the biochemical, digestive, and health properties of whey proteins and still, there it is: The sentence-starter "in contrast to previous studies" in a paper that's about to be published in one of the upcoming issues of the Journal of Proteome Research.

The proteome, by the way, is the entire set of proteins expressed by a genome, cell, tissue or organism at a certain time and a study that compares the acute differential effects between whey isolate, cod and gluten (=wheat) protein on postprandial amino acid, and lipid levels, as well as other metabolites is not what I would be looking for in this journal.
But alas! I am happy that the research by Jan Stanstrup, Simon Stubbe Schou, Jens Holmer-Jensen, Kjeld Hermansen, and Lars O. Dragsted got published at all; I mean "in contrast to previous studies" - that certainly sounds promising, doesn't it?

So what was in contrast to previous studies, then?

Quite a good question, well... ok, I am not going to keep you on the tenderhooks any longer. The surprise finding the researchers made, when they conducted this randomized, single-blinded, crossover meal study with 11 obese non-diabetics, aged 40 – 68 years with BMI 30.3 – 42.0, is after all mentioned in the title of the paper, as well:

"Whey protein delays gastric emptying and suppresses plasma fatty acids and their metabolites compared to casein, gluten and fish protein." (Stanstrup. 2014).

As a regular at the SuppVersity it should be easy for you to identify what is odd here: The digestion speed of the isocaloric test meals which consisted of an energy-free soup with 100 g of good Danish butter, 25 g of raw leek and 45 g of either whey isolate (WI), casein (CAS), cod protein isolate (COD), or a wheat protein (GLUT) and was served with white bread (total carbohydrate content 45 g) was different from what it should have been.

Figure 1: Amino acid composition of the 4 protein sources used in the study (Stanstrup. 2014)

As a well-versed student of the SuppVersity you do of course know that one of the characteristic qualities of whey isolate is that it passes through the gut at lightning speed - so fast, in fact, that some people develop diarrhea, but that's a topic for a different SuppVersity article. Accordingly, it's not surprising that Stanstrup et al. state that the delayed gastric emptying for whey isolate was

"[...] surprising since β-lactoglobulin (the major whey protein) was found to be highly soluble in the gastric juices and rapidly emptied from the stomach when compared to other protein sources such as casein, which coagulates in acidic environments and is therefore retained in the stomach." (Stanstrup. 2014)

On the other hand, others have reported similar rates of gastric emptying for whey and casein (Calbet. 2005), before - albeit in a scenario, where they were administered alone and not in combination with a meal.

Figure 2: The digestion process (Stanstrup. 2014)

If you take a closer look at the graphical illustration in Figure 2 you will see that what appears to be counter-intuitive at first, is eventually only logical. The slow(er) transit of the whey protein through the gastrointestinal tract does after all leave more time for the complete assimilation of the amino acid content, which - and this is something you knew already - is particularly fast, because whey is easier to disassemble than casein for example.

You also know that the increased influx of amino acids goes hand in hand with an insulin spike that's more pronounced than it would be for white bread (learn more).

Many of you will probably also know (some by experience) that this spike in insulin leads to an increase in glucose uptake that leaves many low carbers notoriously hypoglycemic and makes them feel tired, shaky and miserable. What you probably didn't know, though, is that the increased glucose clearance goes hand in hand with a decrease in the amount of various fatty acids in the blood, while the cheap (see Table 1) wheat gluten meal caused elevated levels of a number of unidentified hydroxy fatty acids and dicarboxylic fatty acids, which is somewhat scary, since increases in linolic acid derived hydroxy fatty acids in human low density lipoproteins have also been observed in atherosclerotic patients (Jira. 1998; note: it's not clear whether the HCFs Stanstrup et al. observed were identical to the ones Jira et al. associated with atherosclerosis).

You can tell me whatever you want: Wheat gluten is not "kosher"

In the results section of their paper, the researchers from the University of Copenhagen and the University Hospital in Aarhus, also point out that dopamine-3-O-sulfate (the predominant form of dopamine in plasma) levels increase above baseline at 2 h for the GLU meal. In spite of the fact that the plasma levels returned to baseline again at 4 h, this appears to be in contrast to previous findings that a gluten-free diet increased major serotonin and dopamine metabolite concentrations in brain (Hallert. 1983). What Stanstrup et al. forget to mention, though, is that Hallert et al. observed this effect in patients with celiac disease; and unlike the average Internet guru tries to make you believe, we don't all suffer from gluten intolerance, let alone full-blown celiac disease.

Table 1: Wheat gluten is the cheapest form of protein - no wonder it's so popular among food manufacturers (Day. 2006)

It's still not impossible that "these findings suggest that gluten causesdecreased uptake of dopamine into the brain with concomitant increase in plasma dopamine" (Stanstrup. 2014), on the other hand there are a dozen of other possible mechanisms to explain the appearance of increased levels of dopamine-3-O-sulfate in response to the ingestion of the wheat protein isolate. This, as well as the effects of the Dicarboxylic and hydroxy fatty acids elevation after the wheat (=gluten) protein meal certainly need further investigation, though.
References:

• Calbet, Jose AL, and Jens J. Holst. "Gastric emptying, gastric secretion and enterogastrone response after administration of milk proteins or their peptide hydrolysates in humans." European journal of nutrition 43.3 (2004): 127-139.
• Day, Li, et al. "Wheat-gluten uses and industry needs." Trends in Food Science & Technology 17.2 (2006): 82-90.
• Hallert, Claes, and Göran Sedvall. "Improvement in central monoamine metabolism in adult coeliac patients starting a gluten-free diet." Psychol Med 13.2 (1983): 267-71.
• Jira, Wolfgang, et al. "Strong increase in hydroxy fatty acids derived from linoleic acid in human low density lipoproteins of atherosclerotic patients." Chemistry and physics of lipids 91.1 (1998): 1-11.
• Stanstrup, Jan, et al. "Whey protein delays gastric emptying and suppresses plasma fatty acids and their metabolites compared to casein, gluten and fish protein." Journal of Proteome Research (2014).