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

Abstract and Introduction


Epidemiological evidence shows that consumption of dairy products is associated with decreased prevalence of metabolic related disorders, whilst evidence from experimental studies points towards dairy protein as a dietary component which may aid prevention of type 2 diabetes (T2DM). Poor metabolic health is a common characteristic of overweight, obesity and aging, and is the forerunner of T2DM and cardiovascular disease (CVD), and an ever increasing global health issue. Progressive loss of metabolic control is evident from a blunting of carbohydrate, fat and protein metabolism, which is commonly manifested through decreased insulin sensitivity, inadequate glucose and lipid control, accompanied by a pro-inflammatory environment and hypertension. Adverse physiological changes such as excess visceral adipose tissue deposition and expansion, lipid overspill and infiltration into liver, muscle and other organs, and sarcopaenia or degenerative loss of skeletal muscle mass and function all underpin this adverse profile. 'Sarcobesity' and sarcopaenic diabetes are rapidly growing health issues. As well as through direct mechanisms, dairy protein may indirectly improve metabolic health by aiding loss of body weight and fat mass through enhanced satiety, whilst promoting skeletal muscle growth and function through anabolic effects of dairy protein-derived branch chain amino acids (BCAAs). BCAAs enhance muscle protein synthesis, lean body mass and skeletal muscle metabolic function. The composition and processing of dairy protein has an impact on digestion, absorption, BCAA kinetics and function, hence the optimisation of dairy protein composition through selection and combination of specific protein components in milk may provide a way to maximize benefits for metabolic health.


Poor metabolic health represents an ever increasing global epidemic based on estimates from countries as far ranging as the US and China.[1,2] Encompassed within metabolic health are the cluster of interrelated adverse metabolic markers of hyperglycaemia, dyslipidaemia and hypertension which alongside central or abdominal obesity have been termed the metabolic syndrome.[3,4] Individuals with metabolic syndrome are at twice the risk of developing cardiovascular disease (CVD) within 5–10 years, in addition to a 5-fold increase in risk of developing T2DM,[3] and therefore maintenance of good metabolic health is critically important.

A continuum of metabolic health exists from young, lean, healthy individuals with good physiological control to those with impaired metabolic regulation who are commonly overweight or obese, as well as older. Progressive loss of metabolic control is characterized by a range of physiological changes which include excess adipose deposition, lipid overspill, infiltration and accumulation in key organs such as liver and skeletal muscle, alongside blunting of carbohydrate (CHO), fat and protein metabolism, decreased insulin sensitivity and hyperglycaemia, dyslipidaemia, increased inflammation, impaired endothelial function,[5] and blunted muscle protein synthesis and decreased muscle mass, structure and function.[6] Multiple factors may contribute to the progressive loss of metabolic control, but obesity, ageing and physical inactivity are recognized as major drivers of these changes in metabolic health.[3,4]

Obesity is of particular importance and a prolonged positive energy balance with subsequent lipid deposition and expansion of adipose depots,[7] particularly visceral depots which secrete inflammatory cytokines, play a role in insulin resistance and decreased insulin-mediated glucose uptake.[8] Lipid turnover is decreased and mitochondrial oxidation is suppressed in obese subjects, promoting intracellular accumulation of lipids and the buildup of deleterious lipid metabolites in multiple tissues including skeletal muscle, liver, pancreatic beta cells, kidney and hypothalamus amongst others.[9] Subsequently, infiltration of inflammatory cells to clear toxic metabolic byproducts is accompanied by release of inflammatory cytokines that inhibit metabolic signaling pathways,[10] as well as promote cell death, tissue fibrosis and functional impairment. The recommended treatment to improve metabolic health includes changes in diet and physical activity, which promote adipose tissue loss, enhance metabolically active skeletal muscle mass and hence improve metabolic control.[5] Energy restricted diets are widely recommended for weight-loss in overweight or obese individuals with poor metabolic health, however ~25% of body weight loss can be attributable to decreases in skeletal muscle mass.[11–13] Loss of skeletal muscle is undesirable because it is essential for mobility and activities of daily living. In addition, skeletal muscle also plays a major role in glycaemic control accounting for up to 75% of tissue glucose uptake. Mitochondrial oxidative capacity is decreased in obese skeletal muscle, as well as in T2DM, possibly due to underlying physical inactivity.[14]

Advancing age and a sedentary lifestyle are also risk factors for a gradual loss of skeletal muscle mass, function and in turn muscle strength. The problem is commonly compounded by increased adipose tissue accumulation and myocellular lipid infiltration which provides the basis of sarcopenic (accelerated muscle loss) obesity, and which in turn may drive insulin resistance and increase metabolic risk.[15] Intramyocellular lipid accumulation in obese individuals appears to be difficult to reverse through weight-loss interventions.[16] Activation of skeletal muscle protein anabolism appears to be blunted in both the obese[17] and the elderly, although again this may be attributable to a common underlying physical inactivity and insulin resistance.[6,18] If metabolic health does not improve with diet or exercise interventions, pharmacological agents can be resorted to in order to manage dyslipidaemia, hypertension and hyperglycemia and loss of metabolic homeostasis.

Currently, there is considerable interest in the use of dairy proteins as supplements or in conjunction with lifestyle changes to improve metabolic health.[19–23] Evidence from some epidemiological studies suggest that greater consumption of dairy products is associated with lower risk of metabolic related disorders and CVD.[20,24] Multiple dairy components in milk such as whey protein, casein and minerals have been posited as drivers of these beneficial effects,[20] and there is a growing body of intervention studies assessing the effects of cow's milk-derived proteins[23] or peptides on metabolic health.[25] The focus of many of these interventions has been the whey component of milk, which may act to improve cardiometabolic risk factors. Whey protein has been shown to be an insulin secretagogue,[26] as well as to improve body weight and adiposity through increased satiety.[19] In addition to a dietary strategy to promote adipose loss, dairy proteins have also been shown to increase skeletal muscle mass through stimulation of muscle protein synthesis.[27] Peptides derived from dairy protein have also been widely investigated as potential inhibitors of angiotensin-converting enzyme (ACE), thereby regulating blood pressure,[28] and may influence activation of the innate immune system and inflammation.[29]