Optimum Nutrition, Inc. Introduces Anabolic Milk ProteinWe previously observed in elderly subjects with Chronic Obstructive Pulmonary Disease COPD an enhanced anabolic response to milk protein sip feeding, associated with reduced splanchnic extraction SPE of phenylalanine. To study the effect of aging, the healthy elderly were compared to a group of healthy young subjects. Postabsorptive Raendo was not different for stanozolol rwr no paraguai of the measured amino acids between the healthy elderly and young anabolic milk protein, while anabolic milk protein feeding resulted in a reduction of Raendo of PHE. The enhanced anabolic response to milk protein sip feeding in normal-weight COPD patients is associated with a reduced splanchnic extraction of multiple amino acids including all anabolic milk protein amino acids. National Center for Biotechnology InformationU.
Optimum Nutrition, Inc. Introduces Anabolic Milk Protein | New Hope Network
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.
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 ].
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 ]. Loss of skeletal muscle is undesirable because it is essential for mobility and activities of daily living. 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 ]. 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 ]. All of these components have potential to contribute to the observed association between increased consumption of dairy products and decreased risk of metabolic disease observed in several epidemiological studies [ 20 , 30 , 31 ].
Milk is commonly separated into different protein fractions for different food applications [ 34 ]. Milk protein concentrate MPC , produced by ultrafiltration of skimmed milk, contains both casein and whey proteins in similar proportions to whole milk, but the total amount of protein, lactose and mineral content may vary between different MPC formulations.
Micellar casein can be extracted from milk protein concentrate by further ultrafiltration. Casein is produced from skim milk by acid precipitation or enzymatic coagulation, washing and drying. Hydrolysis with enzymes or acids provides a way to breakdown the structure of whey or casein. In metabolic-related studies a range of processed milk proteins have been used including milk protein concentrate, micellar casein, casein, sodium caseinate, calcium caseinate, casein hydrolysate, whey protein concentrate, whey protein isolate and whey protein hydrolysate, as well as a range of whey and casein peptides.
Whey protein and casein are both classified as high quality proteins based on human amino acid AA requirements, digestibility and their bioavailability. They contain a relatively high proportion of indispensible AAs, score higher than most other protein sources across a wide range of assessment methods including the protein digestibility corrected AA score PDCAAS [ 35 ] and recently developed digestible indispensable amino acid score DIAAS method [ 36 ].
Nevertheless, differences in the physiological effects of whey protein and casein have been attributed to differences in their AA composition [ 37 ]. Whey protein contains a higher proportion of the branched chain amino acids BCAA leucine, isoleucine and valine compared to casein [ 38 ].
Among the other indispensible or essential amino acids EAAs , casein contains a higher proportion of histidine, methionine, phenylalanine and valine than whey protein [ 38 ]. In addition, casein also contains a higher proportion of several non-EAAs including arginine, glutamic acid, proline, serine and tyrosine [ 38 ].
Whey protein is reported to be absorbed faster than casein [ 40 ]. The lower absorption rate of casein in its native micellar form is because the low pH conditions in the stomach cause casein to clot and delays gastric emptying [ 41 ].
Therefore, plasma AAs are more rapidly elevated following whey protein consumption, whereas changes in plasma AAs are lower and more sustained following micellar casein consumption [ 40 ]. Processing of whey protein or casein fractions via hydrolysis can markedly influence absorption and subsequent plasma AA profiles.
A casein hydrolysate is reported to be absorbed more rapidly than intact micellar casein, resulting in a greater increase in plasma AAs [ 42 ]. Conversely, whey protein hydrolysate intake is reported to result in similar plasma AA levels compared to whey protein concentrate [ 43 ], because of similar rapid rates of gastric emptying and absorption. The processing of micellar casein by acidification and then neutralization with alkali such as sodium hydroxide or calcium hydroxide to form caseinates also markedly alters plasma AA profiles compared to micellar casein [ 44 ].
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. 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. 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 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 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 ]. 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.
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. 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 ].
To date there have been few randomized controlled trials of longer-term whey protein or casein supplementation on glycaemic control. 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.
Dyslipidaemia is one of the main metabolic risk factors associated with CVD risk [ 60 ]. Even in the absence of overt dyslipidaemia in metabolic syndrome, postprandial lipaemia can cause transient impairment in endothelial function and other adverse outcomes [ 61 ].
Dairy proteins have potential to suppress postprandial lipaemia due to their insulinotropic effects, as insulin is known to inhibit hormone-sensitive lipase and release of FFA [ 62 ]. However, studies on the effects of milk protein ingestion on postprandial lipaemia and chronic dyslipidaemia have produced mixed findings [ 63 - 70 ]. Two studies in healthy normolipaemic young men and women reported that 50 g sodium caseinate suppressed the postprandial response following a 70 g fat bolus, decreasing diet-derived chylomicrons and FFAs independent of gastric emptying, compared to an oligosaccharide bolus [ 64 , 65 ].
In another study of normolipaemic young men and women, however, ingestion of a lower dose of 23 g casein did not significantly modulate the postprandial lipaemic response to a 40 g fat meal [ 63 ]. In a study of obese post-menopausal women, 45 g whey protein isolate or sodium caseinate with breakfast both decreased the postprandial appearance of chylomicron-derived TG as well as the TG: ApoB48 ratio [ 66 ].
Since postprandial effects appear to predominate, it was unsurprising that the cholesterol moieties did not change postprandially. When investigating the effect of different types of dairy proteins, also in obese individuals, a similar bolus of 45 g whey protein isolate, whey protein hydrolysate, alpha-lactalbumin or casein glycomacropeptide GMP did not differentially alter postprandial lipaemia following a fatty meal, although, whey hydrolysate marginally decreased postprandial suppression of FFAs relative to the other dairy fractions [ 68 ].
In T2DM patients, 45 g whey protein has been shown to suppress postprandial TG, FFA and rate of appearance of chylomicron-rich lipoproteins after a high-fat meal compared with casein and also non-dairy cod and gluten proteins [ 69 ], whilst a second study in T2DM patients found no response to 45 g casein on the postprandial TG response following a similar high-fat meal [ 67 ]. As yet the mechanism underpinning the effect of dairy protein on postprandial lipaemia is not well understood.
Nevertheless, the evidence of acute effects of dairy protein, particularly whey, on postprandial lipaemia provides a rationale for longer-term supplementation trials to manage dyslipidaemia. There have to date been few long-term randomized trials investigating fasting lipids in healthy individuals or those with adverse metabolic risk. Metabolic outcomes in this study may have been driven by weight loss since body weight also decreased following MPM supplementation.
In addition, dairy protein supplementation may provide an indirect way to improve blood lipid profiles when used in conjunction with low fat or low energy diets to induce weight-loss. Certainly there is experimental evidence that whey protein can decrease lipid infiltration into the liver, for example in rodent models of non-alcoholic fatty liver disease NAFLD [ 71 ], where hepatic TG is normalized through dietary treatment.
Dairy protein products appear to have potential to decrease dyslipidaemia in high-risk individuals, but more studies are needed.
In epidemiological studies, consumption of dairy products including milk and yogurt is associated with decreased risk of hypertension, purported to be driven by a high content of bioactive peptides [ 20 , 72 ]. Whey protein and casein both contain the bioactive peptides lactokinins or caseinkinins respectively.
In-vitro experiments indicate these peptides can inhibit ACE activity [ 25 ]. ACE is a rate limiting enzyme in the conversion of angiotensin I to angiotensin II responsible for vasoconstriction. Therefore, lactokinins or caseinkinins both have potential to lower blood pressure. Vascular reactivity is important for glucose disposal and regulation of blood flow, but is impaired in patients with metabolic syndrome due to decreased insulin-stimulated vasodilation via the eNOS pathway and suppressed NO production in the vascular endothelium [ 73 ].
In a recent study of older overweight adults with impaired vascular endothelial function, 5 g of a novel whey protein-derived extract increased brachial artery flow-mediated dilation over a 2 hour period compared to a placebo [ 74 ], although notably without inhibition of ACE activity or alteration of circulating endothelium factors including plasma NO, prostacyclin metabolites or endothelin-1 [ 74 ].
Evidence for improvements in blood pressure has been steadily growing in the majority [ 75 - 80 ], although not all trials [ 81 ].