Therapeutic applications of whey protein.
Whey, a protein complex derived from milk, is being touted as a functional food with a number of health benefits. The biological components of whey, including lactoferrin, beta-lactoglobulin, alpha-lactalbumin, glycomacropeptide, and immunoglobulins, demonstrate a range of immune-enhancing properties. In addition, whey has the ability to act as an antioxidant, antihypertensive, antitumor, hypolipidemic, antiviral, antibacterial, and chelating agent. The primary mechanism by which whey is thought to exert its effects is by intracellular conversion of the amino acid cysteine to glutathione, a potent intracellular antioxidant. A number of clinical trials have successfully been performed using whey in the treatment of cancer, HIV, hepatitis B, cardiovascular disease, osteoporosis, and as an antimicrobial agent. Whey protein has also exhibited benefit in the arena of exercise performance and enhancement.
Altern Med Rev. 2004 Jun;9(2):136-56
Effect of whey protein isolate on strength, body composition and muscle hypertrophy during resistance training.
PURPOSE OF REVIEW: Sarcopenia (skeletal muscle wasting with aging) is thought to underlie a number of serious age-related health issues. While it may be seen as inevitable, decreasing this gradual loss of muscle is vital for healthy aging. Thus, it is imperative to investigate exercise and nutrition-based strategies designed to build a reservoir of muscle mass as early as possible. RECENT FINDINGS: Elderly individuals are still able to respond to both resistance training and the anabolic signals provided by protein ingestion, provided specific amino acids, such as leucine, are present. Whey proteins are a rich source of these essential amino acids and rapidly elevate plasma amino acids, thus providing the foundations for preservation of muscle mass. Several studies involving supplementation with whey protein have been shown to be effective in augmenting the effects of resistance exercise, particularly when supplementation occurs in the hours surrounding the exercise training. SUMMARY: While further work is required, particularly in elderly people, simple dietary and exercise strategies that may improve the maintenance of skeletal muscle mass will likely result in a decrease in the overall burden of a number of diseases and improve the quality of life as we age.
Curr Opin Clin Nutr Metab Care. 2008 Jan;11(1):40-4
The effect of whey protein supplementation with and without creatine monohydrate combined with resistance training on lean tissue mass and muscle strength.
Our purpose was to assess muscular adaptations during 6 weeks of resistance training in 36 males randomly assigned to supplementation with whey protein (W; 1.2 g/kg/day), whey protein and creatine monohydrate (WC; 0.1 g/kg/day), or placebo (P; 1.2 g/kg/day maltodextrin). Measures included lean tissue mass by dual energy x-ray absorptiometry, bench press and squat strength (1-repetition maximum), and knee extension/flexion peak torque. Lean tissue mass increased to a greater extent with training in WC compared to the other groups, and in the W compared to the P group (p < .05). Bench press strength increased to a greater extent for WC compared to W and P (p < .05). Knee extension peak torque increased with training for WC and W (p < .05), but not for P. All other measures increased to a similar extent across groups. Continued training without supplementation for an additional 6 weeks resulted in maintenance of strength and lean tissue mass in all groups. Males that supplemented with whey protein while resistance training demonstrated greater improvement in knee extension peak torque and lean tissue mass than males engaged in training alone. Males that supplemented with a combination of whey protein and creatine had greater increases in lean tissue mass and bench press than those who supplemented with only whey protein or placebo. However, not all strength measures were improved with supplementation, since subjects who supplemented with creatine and/or whey protein had similar increases in squat strength and knee flexion peak torque compared to subjects who received placebo.
Int J Sport Nutr Exerc Metab. 2001 Sep;11(3):349-64
Whey protein ingestion in elderly persons results in greater muscle protein accrual than ingestion of its constituent essential amino acid content.
It is recognized that both whey protein (WY) and essential amino acids (EAA) are stimuli for muscle protein anabolism. The aim of the present study was to determine if the effects of WY ingestion on muscle protein accrual in elderly persons are due solely to its constituent EAA content. Fifteen elderly persons were randomly assigned to ingest a bolus of either 15 g of WY, 6.72 g of EAA, or 7.57 g of nonessential amino acids (NEAA). We used the leg arteriovenous model to measure the leg phenylalanine balance, which is an index of muscle protein accrual. Phenylalanine balance (nmol x min(-1) kg lean leg mass(-1)) during the 3.5 hours after the bolus ingestion improved in the WY (-216 +/- 14 vs -105 +/- 19; P < .05) but not in the EAA (-203 +/- 21 vs -172 +/- 38; P > .05) or NEAA groups (-203 +/- 19 vs -204 +/- 21; P > .05). The insulin response (uIU x mL(-1) 210 min(-1)) during the same period was lower in both the NEAA (48 +/- 40) and EAA (213 +/- 127) when compared to the WY (1073 +/- 229; P < .05). In conclusion, WY ingestion improves skeletal muscle protein accrual through mechanisms that are beyond those attributed to its EAA content. This finding may have practical implications for the formulation of nutritional supplements to enhance muscle anabolism in older individuals.
Nutr Res. 2008 Oct;28(10):651-8
Creatine supplementation improves muscular performance in older men.
PURPOSE: Creatine supplementation has been shown to enhance muscle strength and power after only 5-7 d in young adults. Creatine supplementation could therefore benefit older individuals because aging is associated with a decrease in muscle strength and explosive power. METHODS: We examined the effects of 7 d of creatine supplementation in normally active older men (59-72 yr) by using a double-blind, placebo-controlled design with repeated measures. After a 3-wk familiarization period to minimize learning effects, a battery of tests was completed on three occasions separated by 7 d (T1, T2, and T3). After T1, subjects were matched and randomly assigned into creatine (N = 10) and placebo (N = 8) groups. After T2, subjects consumed supplements (0.3 g x kg(-1) x d(-1)) for 7 d until T3. All subjects were tested for maximal dynamic strength (one-repetition maximum leg press and bench press), maximal isometric strength (knee extension/flexion), upper- and lower-body explosive power (6 x 10-s sprints on a cycle ergometer), and lower-extremity functional ability (timed sit-stand test and tandem gait test). Body composition was assessed via hydrostatic weighing, and blood samples were obtained to assess renal and hepatic responses and muscle creatine concentrations. RESULTS: No significant increases in any performance measures were observed from T1 to T2 with the exception of isometric right-knee flexion in the placebo group indicating stability in the testing protocols. Significant group-by -time interactions indicated the responses from T2 to T3 were significantly greater (P <or= 0.05) in the creatine compared with the placebo group, respectively, for body mass (1.86 and -1.01 kg), fat-free mass (2.22 and 0.00 kg), maximal dynamic strength (7-8 and 1-2%), maximal isometric strength (9-15 and -6 to 1%), lower-body mean power (11 and 0%), and lower-extremity functional capacity (6-9 and 1-2%). No adverse side effects were observed. CONCLUSION: These data indicate that 7 d of creatine supplementation is effective at increasing several indices of muscle performance, including functional tests in older men without adverse side effects. Creatine supplementation may be a useful therapeutic strategy for older adults to attenuate loss in muscle strength and performance of functional living tasks.
Med Sci Sports Exerc. 2002 Mar;34(3):537-43
Effect of a pre-exercise energy supplement on the acute hormonal response to resistance exercise.
The effect of a pre-exercise energy sport drink on the acute hormonal response to resistance exercise was examined in eight experienced resistance trained men. Subjects were randomly provided either a placebo (P: maltodextrin) or the supplement (S: combination of branched chain amino acids, creatine, taurine, caffeine, and glucuronolactone). Subjects performed 6 sets of no more than 10 repetitions of the squat exercise at 75% of their 1 repetition maximum (1RM) with 2 minutes of rest between sets. Blood draws occurred at baseline pre-exercise, immediately post- (IP), 15 minutes post- (15P), and 30-minutes post (30P) exercise for measurement of serum growth hormone, total and free testosterone, cortisol, and insulin concentrations. Although significant differences were seen only at set 5, the total number of repetitions and training volume tended (p = 0.08) to be higher with S compared to P. Serum growth hormone and insulin concentrations were significantly higher at 15P and IP, respectively, in S compared to P. Results suggest that a pre-exercise energy S consumed 10 minutes before resistance exercise can enhance acute exercise performance by increasing the number of repetitions performed and the total volume of exercise. The enhanced exercise performance resulted in a significantly greater increase in both growth hormone and insulin concentrations, indicating an augmented anabolic hormone response to this pre-exercise S.
J Strength Cond Res. 2008 May;22(3):874-82
Therapeutic considerations of L-glutamine: a review of the literature.
The most abundant amino acid in the bloodstream, L-glutamine fulfills a number of biochemical needs. It operates as a nitrogen shuttle, taking up excess ammonia and forming urea. It can contribute to the production of other amino acids, glucose, nucleotides, protein, and glutathione. Glutamine is primarily formed and stored in skeletal muscle and lungs, and is the principal metabolic fuel for small intestine enterocytes, lymphocytes, macrophages, and fibroblasts. Supplemental use of glutamine, either in oral, enteral, or parenteral form, increases intestinal villous height, stimulates gut mucosal cellular proliferation, and maintains mucosal integrity. It also prevents intestinal hyperpermeability and bacterial translocation, which may be involved in sepsis and the development of multiple organ failure. L-glutamine use has been found to be of great importance in the treatment of trauma and surgery patients, and has been shown to decrease the incidence of infection in these patients. Cancer patients often develop muscle glutamine depletion, due to uptake by tumors and chronic protein catabolism. Glutamine may be helpful in offsetting this depletion; however, it may also stimulate the growth of some tumors. The use of glutamine with cancer chemotherapy and radiotherapy seems to prevent gut and oral toxic side-effects, and may even increase the effectiveness of some chemotherapy drugs.
Altern Med Rev. 1999 Aug;4(4):239-48
Glutamine and the immune system.
Glutamine is utilised at a high rate by cells of the immune system in culture and is required to support optimal lymphocyte proliferation and production of cytokines by lymphocytes and macrophages. Macrophage-mediated phagocytosis is influenced by glutamine availability. Hydrolysable glutamine dipeptides can substitute for glutamine to support in vitro lymphocyte and macrophage functions. In man plasma and skeletal muscle glutamine levels are lowered by sepsis, injury, burns, surgery and endurance exercise and in the overtrained athlete. The lowered plasma glutamine concentrations are most likely the result of demand for glutamine (by the liver, kidney, gut and immune system) exceeding the supply (from the diet and from muscle). It has been suggested that the lowered plasma glutamine concentration contributes, at least in part, to the immunosuppression which accompanies such situations. Animal studies have shown that inclusion of glutamine in the diet increases survival to a bacterial challenge. Glutamine or its precursors has been provided, usually by the parenteral route, to patients following surgery, radiation treatment or bone marrow transplantation or suffering from injury. In most cases the intention was not to stimulate the immune system but rather to maintain nitrogen balance, muscle mass and/or gut integrity. Nevertheless, the maintenance of plasma glutamine concentrations in such a group of patients very much at risk of immunosuppression has the added benefit of maintaining immune function. Indeed, the provision of glutamine to patients following bone marrow transplantation resulted in a lower level of infection and a shorter stay in hospital than for patients receiving glutamine-free parenteral nutrition.
Amino Acids. 1999;17(3):227-41
Glutamine, exercise and immune function. Links and possible mechanisms.
Glutamine is the most abundant free amino acid in human muscle and plasma and is utilised at high rates by rapidly dividing cells, including leucocytes, to provide energy and optimal conditions for nucleotide biosynthesis. As such, it is considered to be essential for proper immune function. During various catabolic states including surgical trauma, infection, starvation and prolonged exercise, glutamine homeostasis is placed under stress. Falls in the plasma glutamine level (normal range 500 to 750 mumol/L after an overnight fast) have been reported following endurance events and prolonged exercise. These levels remain unchanged or temporarily elevated after short term, high intensity exercise. Plasma glutamine has also been reported to fall in patients with untreated diabetes mellitus, in diet-induced metabolic acidosis and in the recovery period following high intensity intermittent exercise. Common factors among all these stress states are rises in the plasma concentrations of cortisol and glucagon and an increased tissue requirement for glutamine for gluconeogenesis. It is suggested that increased gluconeogenesis and associated increases in hepatic, gut and renal glutamine uptake account for the depletion of plasma glutamine in catabolic stress states, including prolonged exercise. The short term effects of exercise on the plasma glutamine level may be cumulative, since heavy training has been shown to result in low plasma glutamine levels (< 500 mumol/L) requiring long periods of recovery. Furthermore, athletes experiencing discomfort from the overtraining syndrome exhibit lower resting levels of plasma glutamine than active healthy controls. Therefore, physical activity directly affects the availability of glutamine to the leucocytes and thus may influence immune function. The utility of plasma glutamine level as a marker of overtraining has recently been highlighted, but a consensus has not yet been reached concerning the best method of determining the level. Since injury, infection, nutritional status and acute exercise can all influence plasma glutamine level, these factors must be controlled and/or taken into consideration if plasma glutamine is to prove a useful marker of impending overtraining.
Sports Med. 1998 Sep;26(3):177-91
Plasma amino acid concentrations in the overtraining syndrome: possible effects on the immune system.
Overtraining and long-term exercise are associated with an impairment of immune function. We provide evidence in support of the hypothesis that the supply of glutamine, a key fuel for cells of the immune system, is impaired in these conditions and that this may contribute to immunosuppression. Plasma glutamine concentration was decreased in overtrained athletes and after long-term exercise (marathon race) and was increased after short-term, high intensity exercise (sprinting). Branched chain amino acid supplementation during long-term exercise was shown to prevent this decrease in the plasma glutamine level. Overtraining was without effect on the rate of T-lymphocyte proliferation in vitro or on the plasma levels of interleukin-1 and -6, suggesting that immune function is not impaired in this condition. Given the proposed importance of glutamine for cells of the immune system, it is concluded that the decrease in plasma glutamine concentration in overtraining and following long-term exercise, and not an intrinsic defect in T lymphocyte function, may contribute to the immune deficiency reported in these conditions.
Med Sci Sports Exerc. 1992 Dec;24(12):1353-8
Depression of plasma glutamine concentration after exercise stress and its possible influence on the immune system.
OBJECTIVE: To determine whether plasma glutamine levels can be used as an indicator of exercise-induced stress, and to consider the possible effects of low plasma glutamine concentrations on the immune system. METHODS: We used two exercise regimens: in Trial 1 seven male subjects were randomly stressed on a treadmill at 0, 30%, 60%, 90% and 120% of their maximal oxygen uptake (VO2max); in Trial 2 five highly trained male subjects underwent intensive interval training sessions twice daily for ten days, followed by a six-day recovery period. RESULTS: Plasma glutamine concentrations decreased significantly from an average of 1,244 +/- 121 mumol/L to 702 +/- 101 mumol/L after acute exercise at 90% VO2max (P < 0.05) and to 560 +/- 79 mumol/L at 120% VO2max (P < 0.001). Four of the five subjects showed reduced plasma glutamine concentrations by Day 6 of the overload training trial, with all subjects displaying significantly lower glutamine levels by Day 11. However, glutamine levels showed a variable rate of recovery over the six-day recovery period, with two subjects’ levels remaining low by Day 16. CONCLUSIONS: Reduced plasma glutamine concentrations may provide a good indication of severe exercise stress.
Med J Aust. 1995 Jan 2;162(1):15-8