Milk Protein for Improved Metabolic Health

A Review of the Evidence

Robin A McGregor; Sally D Poppitt


Nutr Metab. 2013;10(46) 

In This Article

Milk Proteins, Insulin Secretion and Glucose Control

Insulinotropic Effects

Insulin is sensitive to both the composition and concentration of plasma AAs, hence both whey and casein ingestion stimulate increased insulin secretion.[45,46] Ingestion of whey protein leads to more rapid secretion of insulin than micellar casein,[40] however, hydrolysis of casein speeds up the absorption of AAs and secretion of insulin relative to the micellar form of casein.[42] Insulin has wide-ranging direct and indirect effects on CHO, fat and protein metabolism, including stimulation of glucose uptake, glycogen synthesis, lipid uptake, triglyceride (TG) synthesis, protein synthesis and inhibition of protein breakdown, lipolysis and gluconeogenesis. Therefore, the stimulation of insulin secretion by different milk proteins may make a significant contribution to metabolic effects in insulin sensitive tissues and in particular skeletal muscle anabolism. Prolonged, elevated fasting glucose is a key metabolic risk factor, one of the main characteristics of T2DM and associated with an increased risk of CVD.[47] Hyperglycaemia develops with increased insulin resistance and failure of insulin secretion.

Postprandial Glycaemia

Management of non-fasting or postprandial glucose response is important to minimize prolonged exposure to high blood glucose levels in individuals both with and without T2DM.[48] Plasma glucose can increase protein glycosylation, nonenzymatic glycation products and the generation of free radicals, as well as decrease nitric oxide production leading to damage to the macro- and microvasculature.[48] Of significant importance to dairy are the milk proteins whey and casein which stimulate insulin release, and have the potential to alter tissue glucose uptake and suppress postprandial blood glucose excursions.[43,45,46,49–51]

Many of the studies on the insulinotropic inducing properties of whey protein or casein have been conducted in healthy men rather than individuals with impaired glucose control.[43,45,46,49–51] The AA profile of whey protein is suggested to contribute to its insulinotropic effects, however, the protein format has been shown to have variable effects on insulin secretion. AA-supplemented drinks containing several insulinotropic AAs found at high levels in whey protein (e.g. leucine, isoleucine, valine, lysine, threonine) are reported to result in similar insulinaemic and glycaemic responses.[46] A recent study showed co-ingestion of these AAs with 9 g whey protein however did not further augment the suppression of postprandial glucose after a CHO meal,[52] which may be due to a ceiling in the stimulation of insulin by free AAs and AAs derived from intact protein. One study has shown that insulinotropic effects between intact whey protein and whey protein hydrolysate does not vary in healthy individuals at doses of 20–50 g protein.[43] Conversely, in a different study whey protein concentrate but not hydrolysate decreased postprandial blood glucose and insulin responses in a dose dependent manner (10–40 g) following an ad libitum mixed meal, although the authors noted that this was most likely because food intake was decreased at this free choice meal,[49] hence confounding these effects.

In individuals with T2DM, 18 g whey protein added to breakfast or lunch resulted in greater insulinotropic responses, circulating levels of the gut peptide glucose-dependent insulinotropic polypeptide (GIP), and suppression of postprandial glycaemia than following an isoenergetic non-dairy protein (lean ham and lactose).[53] 55 g whey protein ingested before or with a CHO lunch also suppressed postprandial glucose in T2DM patients,[54] triggering greater insulinotropic, and gut peptide (GIP and cholecystokinin, CCK) responses.[54] Gastric emptying was only inhibited with pre-meal whey protein ingestion, although there was no evidence that this was any more effective for postprandial glycaemic control than ingestion with a meal.[54] It is of considerable interest that the acute effects of whey protein on postprandial blood glucose are comparable to sulfonylureas and other insulin secretagogues used for the pharmaceutical management of hyperglycaemia in T2DM. Sulfonylureas stimulate increased secretion of (pro) insulin by binding to ATP-dependent potassium channels in pancreatic β-cells.[55] Therefore, there is a rationale for regular whey protein ingestion before or with meals to manage postprandial glycaemic responses in individuals with poor metabolic control or T2DM.

Effects of casein may be less consistent. In an overweight group with T2DM, consumption of a casein hydrolysate (~30 g) and leucine (~10 g) beverage after breakfast, lunch and dinner decreased prevalence of hyperglycaemia over the course of 24 hours.[56] Yet in another study of patients with long-standing T2DM, higher 40 g dose casein hydrolysate given at each main meal did not improve the prevalence of hyperglycemia over 24 hours,[57] possibly attributable to β-cell impairment characteristic of long-term T2DM. Although, even in long-standing T2DM however, there is some evidence that the insulin secretory mechanism is retained and can be re-activated by ingestion of free AA and protein mixtures including free leucine, free phenylalanine and wheat protein hydrolysate.[58] Possibly whey protein or casein could improve hyperglycemia over 24 hours in individuals with metabolic syndrome or early T2DM characterized by insulin resistance but still functional β-cells.

Chronic Fasting Glycaemia

To date there have been few randomized controlled trials of longer-term whey protein or casein supplementation on glycaemic control. In the only study of which we are aware in overweight and obese individuals, 12 weeks of 54 g/day whey protein isolate or sodium caseinate supplementation without any lifestyle intervention resulted in a decrease in fasting blood insulin levels and insulin resistance, but not fasting blood glucose levels,[59] compared to 12 weeks of glucose supplementation. Most individuals at the start of the trial had borderline impaired glucose tolerance (IGT) as well as other metabolic risk factors including high TG, low HDL-C and high waist circumference.[59] Further long-term trials of whey protein or casein in individuals with IGT are warranted based on the evidence from acute trials showing milk proteins suppress postprandial glycaemia chronic fasting hyperinsulinaemia and insulin resistance.