Metabolic Responses of Healthy or Prediabetic Adults to Bovine Whey Protein and Sodium Caseinate Do Not Differ

Background: Casein is considered a slowly digestible protein compared with whey protein, and this may cause differences in hormone responses and the kinetics of delivering amino acids into the circulation.

Objective: We investigated whether postprandial plasma hormone and metabolite responses were different when bovine casein or whey protein was co-administered with carbohydrates in healthy and prediabetic adults.

Methods: White healthy male adults (n = 15) and white, well-defined male and female prediabetic adults (n = 15) received test drinks randomly on 3 different occasions at least 2 d apart which contained 50 g of maltodextrin19 (MD19) alone or in combination with 50 g of whey protein isolate (WPI) or 50 g of sodium caseinate (SC). Blood samples were collected over a 240-min time period and were analyzed for hormone profiles and defined metabolites.

Results: No evidence was found that gastric emptying was different between the 2 protein drinks. Both proteins increased peak plasma insulin concentrations in prediabetic persons by 96% compared with MD19 (each, P < 0.05), which was accompanied by a reduction of peak venous blood glucose by 21% (each, P < 0.0001) without a difference between the 2 proteins. Peak plasma glucagon concentrations increased by 101% in both groups after the protein drinks (P < 0.05). The WPI drink also increased peak plasma glucose-dependent insulinotropic polypeptide concentrations in healthy volunteers by 56% (P < 0.01). Differences in plasma metabolite concentrations in volunteers could be attributed exclusively to the differences in the amino acid composition of the 2 proteins ingested.

Conclusion: The WPI and the SC drinks similarly reduced postprandial glucose excursions when ingested together with carbohydrates in healthy and prediabetic volunteers. Under our experimental conditions, however, no evidence was found that gastrointestinal processing of the 2 protein varieties differed substantially. 


Alex’s Notes: For those looking to manage postprandial glycemia, an important determinant of blood glucose elevations is the rate at which carbohydrates leave the stomach, as approximately one third of the variance in postprandial glucose is owed to the gastric emptying rate. It has been demonstrated that whey protein preloads are able to slow gastric emptying during a carbohydrate meal consumed 30 minutes afterwards, which may partially explain the benefits of whey protein on appetite regulation.

At the same time, however, casein is considered the “slow” milk protein because it forms clots within the stomach that are resistant to digestion and thus require more time to break down. Thus, the purpose of the current study was to investigate how whey and casein compared on modulating postprandial responses to carbohydrate intake.

Fifteen healthy normal-weight volunteers and 15 overweight prediabetics (confirmed by OGTT) underwent three blind challenges on three different days with a minimum of two days in between each. After a 12 hour overnight fast, the volunteers arrived at the lab to have a baseline blood draw followed by consumption of one of three test drinks (see table below) and further blood draws for the next four hours. It should be noted that all volunteers were white, with the healthy group being in their mid-20s and all men, and the prediabetic group averaging 62 years of age with ten men and five women.

Test Drink


WPI SC Maltodextrin


(measure kinetics and speed of amino acid absorption)

Lemon or vanilla flavor Lactulose (to assess transit time)
Whey Protein Isolate (WPI) 50g -- 50g 2g 10g 10g
Sodium Caseinate (SC) -- 50g 50g 2g 10g 10g
Placebo -- -- 50g 2g 10g 10g

Postprandial changes

  Healthy Prediabetic
WPI vs placebo SC vs placebo WPI vs SC WPI vs placebo SC vs placebo WPI vs SC
Blood glucose -- -- -- --
Insulin -- -- --
Glucagon -- --
C-peptide -- -- -- -- --
GIP -- --
GLP-1 -- -- -- -- -- --
Gastric transit time ↑ (slower) -- -- -- --
Plasma BCAAs -- --

As we can see in the table above, the effects were more pronounced in the prediabetic group, with little difference between whey and casein. Yet, casein is the slow protein right? And this is the intrinsic flaw with this study; the researchers used sodium caseinate rather than micellar casein. While micellar casein is usually obtained by micro- and ultrafiltration, caseinates are obtained by acid precipitation that increases their solubility and renders their digestive properties more akin to whey.

Nonetheless, this study does show that these fast absorbing proteins are beneficial for glycemic control, especially in the insulin resistant primarily through increasing insulin output. This study also supports the notion that if you want casein for slow digestion, then avoiding caseinates (calcium or sodium) is prudent. Also, I really must wonder why on Earth the researchers would choose caseinate over micellar casein given their objective. Perhaps they failed to do their research ahead of time, who knows.


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