Whey contains a unique collection of bioactive components ideal for elite and recreational athletes. Literally hundreds of scientific studies have been conducted on this perfect protein for active people. One of the positive outcomes of ingesting whey protein is improved body composition. Training-induced improvements in body composition are coordinated by a complex network of metabolic pathways, many of which are favorably influenced by the unique nutrient matrix in whey protein. Whey is naturally high in essential amino acids (EAA) for stimulating the protein synthetic machinery. Beyond the high EEA content, whey is also packaged with an assortment of distinctive nutrients to support recovery from exercise and adaptations to training. These benefits and the many health promoting attributes of whey are reviewed here.
Whey and casein are the two primary proteins in milk. Casein is the major milk protein representing about 80% and whey the remaining 20%. Both milk proteins have all the essential amino acids, which makes it score well on all methods of protein quality. Whey protein however is more soluble in an acid environment, whereas casein molecules are relatively insoluble in the aqueous environment of milk. Casein forms a curd during the cheese making process. The liquid remaining is separated and represents whey. The liquid whey actually contains additional nutrients besides protein such as lactose, vitamins, minerals, and small amounts of fat. There are several other types of protein contined within whey. The major one is beta-lactoglobulin comprising about one-third of the total protein. Protiens of smaller abundance in whey include alpha-lactalbumin, glycomacropeptide, proteose peptone, immunoglobulins, serum albumin, lactoferrin, and lactoperoxidase. These whey proteins have each been investigated separately and shown to have a variety of health promoting actions. On whole it can be said that whey is a complex protein protein source. A distinguishing feature of whey protein is the complex protein source with a high prevalence of EAA, indispensable for stimulating skeletal muscle protein synthesis(1-4) and physiologic responses to resistance training. Compared to soy protein, whey contains a higher proportion of EAA, especially branched chain amino acids (leucine, isoleucine, and valine), potent nutrient modulators of protein synthesis(5).
A Unique Aspect of Protein Quality: Digestion Rate
Proteins are unique for many reasons - they contain nitrogen, and they provide amino acids that serve as building blocks for the formation of new proteins. But not all dietary proteins are equal in their biological effects. An emerging concept in protein quality is that digestion rate has a major impact on protein effects in the body. This has led to the classification of proteins as either slow or fast. Some proteins are digested slowly, whereas others are digested quickly and results in quite different effects. Whey protein is digested and absorbed quickly resulting in a more rapid increase in plasma amino acids compared to casein, which significantly alters muscle protein kinetics(6) and probably other physiologic aspect attributed to whey such as satiety.
Whey Acutely Stimulates Protein Synthesis
Ingestion of whey protein alone stimulates muscle protein synthesis(6,7), and when provided before or after exercise augments the anabolic response to resistance training(8,9). The high degree of branched-chain amino acids in whey (~10g per 100 g of protein) is especially critical for stimulating protein anabolism, particularly leucine(10,11). The important role of leucine has been laid out in a series of elegant experiments. Researchers directly examined muscle protein synthesis after feeding animals various formulations of amino acids and compared them to glucose ingestion. When a complete protein was consumed (one that contains all the amino acids), protein synthesis was increased. When just essential amino acids were provided and the nonessential ones left out, the same increase was noted indicating nonessential amino acids are not required to stimulate protein synthesis. When just the BCAA were given, again there was the same increase in protein synthesis. Finally when just leucine was consumed, yet again protein synthesis increased to the same magnitude. These findings provided strong evidence that leucine was the driving force behind the ability of dietary protein to stimulate protein synthesis. Cutting edge work in the last few years has revealed how leucine directly activates a critical compound in muscle cells called the mammalian target of rapamycin (mTOR). It turns out mTOR is like a molecular switch that turns on the protein synthetic machinery in muscle and leucine is one of the major activators of mTOR. Thus, leucine not only provides the building blocks for protein synthesis, it also has a critical role in up-regulating the process. The application of all this work is that adding additional leucine to typical protein beverages is an effective strategy to maximize muscle anabolism after resistance exercise. Stimulation of protein synthesis with intake of EEA post-exercise translates into improved protein balance when measured over an entire day(12). Thus whey protein, which has a higher proportion of EEA and leucine than other protein sources, consumed after resistance exercise provides a greater overall anabolic effect on skeletal muscle.
Timing of Whey Protein Around Exercise
Timing of protein intake has been shown to be an important variable for maximizing its effects. Prior work had indicated that when free amino acids plus carbohydrate were taken before resistance exercise, it resulted in a more anabolic response compared to consumption after resistance exercise. This was an exciting finding because it showed the value of ingesting amino acids before a workout for maximizing protein synthesis. However no work had validated these findings using an intact whey protein. A recently study examined whether the timing of whey protein was important in terms of promoting anabolism(8). Healthy subjects were placed into a group that received 20 g of whey protein immediately before, or a group that received the same whey protein immediately after a bout of resistance exercise. The anabolic response (muscle protein balance) was increased in both groups whether taken before or after exercise. Some subjects had a significantly greater anabolic response when whey protein was consumed before exercise, but the average responses were similar. The researchers suggested a better time to ingest whey protein before exercise might be 30 to 45 min before exercise in order to allow for digestion and absorption of the amino acids into the circulation. The logical conclusion from this research is to consume whey protein at both time points (both pre and post-exercise) for maximizing protein synthesis and protein balance.
Whey Protein is Preferentially Diverted to Skeletal Muscle
Enahcincing protein synthesis is critically important important for athletes, but the key is to specifically target skeletal muscle to enhance muscle growth rather than other tissues. There are differences between protein sources in regards to the tissue-responsiveness to protein. In particular, there are considerable differences in the fate of soy and intact milk proteins (ie, combination of both whey and casein)(13-15). In comparison to milk, when soy protein is digested the amino acids are directed toward deamination pathways rather than protein synthesis and splanchnic regions (internal organs) rather than skeletal muscle. Milk protein on the other hand appears to be preferentially directed toward peripheral tissues thereby having greater potential to augment skeletal muscle protein synthesis. For example, healthy men who consumed milk protein immediately after resistance exercise had a markedly greater uptake of amino acid nitrogen compared to subjects who consumed an isocaloric and isonitrogenous soy protein beverage(16). Another recent study examined skeletal muscle protein synthesis and translation initiation following consumption of soy and whey protein after exercise in rats(17). Whey and soy protein both increased skeletal muscle protein synthesis and translation initiation following exercise, but whey protein resulted in significantly greater circulating levels of leucine and specific phosphorylation of mTOR and S6K1 demonstrating greater molecular signaling for protein synthesis.
Chronic Effects of Whey and Lean Body Mass
There is evidence that supplementation with whey protein alone(18) or a combination of whey and casein(19,20) are more effective than a carbohydrate supplement at augmenting lean body mass responses to resistance training. In comparison to casein, ingestion of whey protein during resistance training has been shown to promote greater increases in lean body mass and reductions in body fat(21). In that study Australian researchers compared whey isolate to casein protein in bodybuilders. Both groups supplemented their diets with 1.5 g per kilogram body weight per day of the whey or casein supplement while performing their normal resistance training for 10 weeks. The whey group had a greater increase in lean body mass (5.0 kg) compared to the casein group (0.8 kg). In addition, the whey group lost more fat (-1.5 kg) compared to the casein group (0.2 kg). The greater increases in lean body mass translated into greater strength gains over the 10 weeks in the whey group. Another recent study showed no difference between whey and soy protein on lean body mass responses to resistance, but the very short intervention (6 wk) was likely not long enough to observe subtle differences in the anabolic potential of these two protein sources(18).
Whey Protein Promotes Weight Loss and Fat Loss
In addition to promoting muscle anabolism and strength, there is evidence that whey protein may also promote body weight and fat loss. In a preliminary study(22), ninety overweight men and women were assigned to one of three supplement groups: 1) 60 g per day of whey protein, 2) 60 g per day of soy protein, or 3) 60 g per day of carbohydrate. After 6 mo, the whey protein group lost significantly more weight and body fat than the carbohydrate supplement group with no other changes in habitual diet and exercise habits. Whey consumption in conjunction with training has been shown to improve the efficiency of exercise to decrease adiposity(23). Greater weight and fat loss could be attributed to an increased thermogenesis. Higher quality animal proteins induce greater 24 hr thermic effects compared to soy and isocaloric amounts of carbohydrate(24). Since whey is nutrient dense but relatively low in energy (~4 kcal/g), supplementation is an efficient method to promote skeletal muscle anabolism while promoting catabolism in adipocytes and therefore is hypothesized to improve both muscle growth and fat loss. The high leucine content of whey is important in regards to promoting weight loss. Researchers at the University of Illinois have conducted studies that examined weight loss diets that contained 10 g/day of leucine and 125 g total protein per day with a minimum of 2.5 g leucine at each meal. In two separate studies, this group demonstrated that the high leucine diets resulted in greater weight loss, greater fat loss, and better preservation of lean body mass. In these studies, the high leucine diets also resulted in better glucose control. A recent animal study provided some important details on the cellular mechanisms by which leucine regulated body fat. In this study animals that doubled their leucine intake were resistant to diet-induced obesity and improved a host of metabolic disturbances. The higher leucine intake caused an increase in energy expenditure and an increased expression of uncoupling protein 3, which causes energy to be given off as heat rather than stored as fat. These studies all support the use of whey protein to maximize fat loss and spare muscle loss during weight loss. Another mechanism to explain greater weight and fat loss is decreased food intake. Several studies have shown peptides and other components of whey are involved in the regulation of food intake and satiety(25).
Whey Protein Supplements Improve Blood Glucose Control
Eating meals high in simple carbohydrates causes large changes in blood sugar and insulin. Meals with a high glycemic index (high in simple sugars) increase blood sugar rapidly, which triggers the release of insulin. Insulin binds with cell receptors that work like locks and keys to allow sugar into the cell. The blood sugar control system doesn't work very well in people with type 2 diabetes, which triggers a host of health problems called the Metabolic Syndrome. Metabolic Syndrome includes high blood pressure, elevated cholesterol, blood clotting abnormalities and abdominal fat deposition. Swedish researchers found that supplementing with whey protein during breakfast or lunch caused less fluctuation in blood sugar during the day(26). In this study, subjects were provided a breakfast (bread, ham, and lactose) and lunch (mashed potatoes, meatballs, ham, and lactose) with fast-absorbing high-glycemic index carbohydrates and the glucose and insulin responses to the meals were measured. On another occasion, the same test meals were consumed, but whey protein (18.2 g protein and 5.3 g lactose) was exchanged for the lactose and ham so that energy, protein, carbohydrate, and fat were identical. Compared to the normal meals, the whey containing meals resulted in a significantly higher insulin response at breakfast (31%) and lunch (57%), which led to a significantly lower glucose response at lunch (-21%). Thus, whey protein augments insulin secretion, which led to improved disposal of glucose. Insulin also promotes disposal of amino acids, although this was not measured in this study. The implications of this research are that whey protein is an ideal supplement to include with meals and as a post-exercise drink because it augments insulin-mediated disposal of glucose and amino acids. In addition to better glucose control, whey may also positively effect glycogen levels. A recent report found that whey protein increased glycogen levels in both the liver and skeletal muscle of exercise-trained rats more so than other types of protein. Glycogen is a crucial energy source to perform high intensity exercise(26).
Antioxidant and Immunotropic Functions of Whey
Exercise causes an increase in the generation of reactive oxygen species (ROS) that if not balanced appropriately by antioxidant defense systems contributes to fatigue, suboptimal recovery, and impaired muscle growth responses to training. Whey is a unique rich source of cysteine and thiol groups (3-4 times higher than soy) that are rate-limiting for synthesis of glutathione (GSH), one of the most important nonenzymatic antioxidant defense systems. The GSH-dependent detoxification of reactive oxygen species is integrated with other antioxidants such as vitamin C and vitamin E. Suboptimal cellular levels of GSH contribute to excessive oxidative stress that can amplify the biochemical stress response to exercise and impair recovery. Supplementation with whey protein is an effective cysteine delivery vehicle as shown by increased GSH in immune deficiency states such as cancer(27), HIV(28,29) and chronic intense exercise training(30). Increased GSH translates into better anti-oxidant capacity, reduced oxidative stress and increased exercise performance(31,32). Adequate cysteine and GSH are also linked with protein metabolism either through better maintenance of protein synthesis or reduced protein catabolism(33-36).
Whey also has positive effects on immune function. The GSH antioxidant system is the principal protective mechanism of the cell and is a crucial factor in regulating the exercise-induced immune response(37). Reviews addressing the immunoregulatory activities of whey in animals and humans have revealed widespread immunotropic functions that could be attributed to a variety of whey fractions such as lactoferrin, glutamine, immunoglobulins, and other peptides (eg, lysozome, beta-lactoglobulin, and alpha-lactalbumin)(38-42). Lactoferrin is an iron-binding glycoprotein with known immunological functions (41) that has been shown to be absorbed intact in adult humans(43). Its anti-microbial activity is due to its ability to chelate iron, an essential element for many microorganisms. This same property may contribute to its ability to reduce oxidative stress. In addition, lactoferrin is known to activate NK cells and neutrophils (40). Whey also contains immunoglobulins and is rich in the amino acid glutamine; both can decrease with intense exercise and therefore are important for a healthy immune system which is vital not only for optimal health but important to muscle tissue remodeling after exercise.
Hypotensive Effects of Whey
Several peptides from whey protein have been shown to possess hypotensive properties (reviewed in(44)). The most likely mechanism for this blood pressure-lowering effect is inhibition of angiotensin-converting enzyme (ACE) activity because milk has been shown to be a rich source of ACE inhibitory peptides(44). Inhibition of ACE prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. Whey derived peptides showing ACE inhibitory effects are released during normal digestion in the gastrointestinal tract by proteases. Peptides can be absorbed intact through the intestine by paracellular and transcellular routes, and there is evidence that a heptapeptide from whey with ACE inhibitory activity is transported through the intestines and detectable in blood(45). A recent paper in the Journal of Hypertension evaluated the effects of a whey hydrolysate in 30 subjects with mild hypertension(46). Subjects were randomly assigned to a whey hydrolysate group (20 g/day) or a control group who ingested the same amount of an unmodified whey protein. After 6 weeks of treatment the whey hydrolysate group significantly reduced systolic blood pressure by 8 mm Hg and diastolic blood pressure by 6 mm Hg compared to control. An additional benefit of lower LDL cholesterol and C-reactive protein (a marker of inflammation) was also noted in the whey hydrolysate group. The magnitude of reduction in blood pressure in just 6 weeks would be considered very clinically relevant and on par with some drugs used to treat blood pressure.
Whey protein is an excellent, high-quality protein source with advantages over other proteins. Research supports whey may support greater increases in lean body mass and decreases fat as part of a resistance training program. Certain constituents of whey may also promote antioxidant status and a healthy immune system. Since exercise, in particular excessive exercise, can result in compromised antioxidant and immune status, whey might be particularly effective in individuals who exercise intensely on a regular basis. In addition, whey offers benefits for individuals just wanting to maintain or enhance health.
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