RCTTop journalHigh evidence score
Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health
Luigi Fontana, Nicole E. Cummings, Sebastian I. Arriola Apelo +21 more · Cell Reports · 2016 · 476 citations
Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet.
RCTLeading journalHigh evidence score
A high whey protein–, leucine-, and vitamin D–enriched supplement preserves muscle mass during intentional weight loss in obese older adults: a double-blind randomized controlled trial
A.M. Verreijen, Sjors Verlaan, Mariëlle F. Engberink +3 more · American Journal of Clinical Nutrition · 2014 · 227 citations
ObservationalTop journalModerate
Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality
Mingyang Song, Teresa T. Fung, Frank B. Hu +4 more · JAMA Internal Medicine · 2016 · 710 citations
IMPORTANCE: Defining what represents a macronutritionally balanced diet remains an open question and a high priority in nutrition research. Although the amount of protein may have specific effects, from a broader dietary perspective, the choice of protein sources will inevitably influence other components of diet and may be a critical determinant for the health outcome. OBJECTIVE: To examine the associations of animal and plant protein intake with the risk for mortality. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study of US health care professionals included 131 342 participants from the Nurses' Health Study (1980 to end of follow-up on June 1, 2012) and Health Professionals Follow-up Study (1986 to end of follow-up on January 31, 2012). Animal and plant protein intake was assessed by regularly updated validated food frequency questionnaires. Data were analyzed from June 20, 2014, to January 18, 2016. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) for all-cause and cause-specific mortality. RESULTS: Of the 131 342 participants, 85 013 were women (64.7%) and 46 329 were men (35.3%) (mean [SD] age, 49 [9] years). The median protein intake, as assessed by percentage of energy, was 14% for animal protein (5th-95th percentile, 9%-22%) and 4% for plant protein (5th-95th percentile, 2%-6%). After adjusting for major lifestyle and dietary risk factors, animal protein intake was not associated with all-cause mortality (HR, 1.02 per 10% energy increment; 95% CI, 0.98-1.05; P for trend = .33) but was associated with higher cardiovascular mortality (HR, 1.08 per 10% energy increment; 95% CI, 1.01-1.16; P for trend = .04). Plant protein was associated with lower all-cause mortality (HR, 0.90 per 3% energy increment; 95% CI, 0.86-0.95; P for trend < .001) and cardiovascular mortality (HR, 0.88 per 3% energy increment; 95% CI, 0.80-0.97; P for trend = .007). These associations were confined to participants with at least 1 unhealthy lifestyle factor based on smoking, heavy alcohol intake, overweight or obesity, and physical inactivity, but not evident among those without any of these risk factors. Replacing animal protein of various origins with plant protein was associated with lower mortality. In particular, the HRs for all-cause mortality were 0.66 (95% CI, 0.59-0.75) when 3% of energy from plant protein was substituted for an equivalent amount of protein from processed red meat, 0.88 (95% CI, 0.84-0.92) from unprocessed red meat, and 0.81 (95% CI, 0.75-0.88) from egg. CONCLUSIONS AND RELEVANCE: High animal protein intake was positively associated with cardiovascular mortality and high plant protein intake was inversely associated with all-cause and cardiovascular mortality, especially among individuals with at least 1 lifestyle risk factor. Substitution of plant protein for animal protein, especially that from processed red meat, was associated with lower mortality, suggesting the importance of protein source.
RCTHigh evidence score
The effects of dietary protein intake on appendicular lean mass and muscle function in elderly men: a 10-wk randomized controlled trial.
Mitchell CJ, Milan AM, Mitchell SM +8 more · Am J Clin Nutr · 2017 · 132 citations
StudyModerate
Protein intake and exercise for optimal muscle function with aging: Recommendations from the ESPEN Expert Group
Nicolaas E.P. Deutz, Jürgen M. Bauer, Rocco Barazzoni +11 more · Clinical Nutrition · 2014 · 1,611 citations
RCTHigh evidence score
Physiological effects beyond the significant gain in muscle mass in sarcopenic elderly men: evidence from a randomized clinical trial using a protein-rich food
Heliodoro Alemán-Mateo, Liliana Macias, Julián Esparza‐Romero +2 more · Clinical Interventions in Aging · 2012 · 89 citations
BACKGROUND: Sarcopenia is strongly associated with an inadequate intake of dietary protein. Dietary protein supplementation boosts muscle-protein synthesis and increases muscle mass in the elderly. This study tested whether adding a protein-rich food, ricotta cheese, to the habitual diet increased total appendicular skeletal muscle mass and strength in elderly people. METHODS: Participants (n = 40), were sarcopenic elderly men and women over 60 years of age. Two comparison groups were formed at random and followed for 3 months: the intervention group received 210 g/day of ricotta cheese plus the habitual diet, while the control group followed the habitual diet with no additional intervention. Total appendicular skeletal muscle (TASM) was assessed by dual-energy X-ray absorptiometry, while strength was measured using a handheld dynamometer at baseline and after the intervention period. The primary outcomes were the percentage of relative change in TASM and strength. RESULTS: The percentage of relative change in TASM was not significant between the groups after the intervention period. Muscle strength improved in the intervention group, but showed only a tendency towards significance (P = 0.06). Secondary analysis showed that the men in the intervention group gained 270 g in TASM compared to those in the control group, and improved their fasting insulin levels (P = 0.05), muscle strength, lean body mass in the arms, and body weight variables. CONCLUSION: The results of this study indicate that a nutritional intervention using a high-quality protein food, specifically ricotta cheese, in order to increase the amount of protein intake might not be regarded as fully promising in elderly men and women with sarcopenia. However, the gender effects on muscle strength, lean tissue in the arms, homeostatic assessment of insulin resistance, and body weight detected in this study suggest that additional research is needed on elderly male subjects with sarcopenia.
RCTHigh evidence score
The effects of varying protein and energy intakes on the growth and body composition of very low birth weight infants
Juan Antonio Costa-Orvay, J. Figueras Aloy, Gerardo Romera +2 more · Nutrition Journal · 2011 · 84 citations
OBJECTIVE: To determine the effects of high dietary protein and energy intake on the growth and body composition of very low birth weight (VLBW) infants. STUDY DESIGN: Thirty-eight VLBW infants whose weights were appropriate for their gestational ages were assessed for when they could tolerate oral intake for all their nutritional needs. Thirty-two infants were included in a longitudinal, randomized clinical trial over an approximate 28-day period. One control diet (standard preterm formula, group A, n = 8, 3.7 g/kg/d of protein and 129 kcal/kg/d) and two high-energy and high-protein diets (group B, n = 12, 4.2 g/kg/d and 150 kcal/kg/d; group C, n = 12, 4.7 g/kg/d and 150 kcal/kg/d) were compared. Differences among groups in anthropometry and body composition (measured with bioelectrical impedance analysis) were determined. An enriched breast milk group (n = 6) served as a descriptive reference group. RESULTS: Groups B and C displayed greater weight gains and higher increases in fat-free mass than group A. CONCLUSION: An intake of 150 kcal/kg/d of energy and 4.2 g/kg/d of protein increases fat-free mass accretion in VLBW infants.
Meta-analysisWikiHigh evidence score
Weight gain during the menopause transition: Evidence for a mechanism dependent on protein leverage
Stephen J. Simpson, David Raubenheimer, Kirsten Black +1 more · BJOG An International Journal of Obstetrics & Gynaecology · 2022 · 17 citations
Weight gain during menopause is not primarily caused by oestrogen decline or metabolic slowdown, but by a shift in eating behaviour driven by the body's prioritisation of protein intake — women unknowingly increase total calorie consumption to maintain absolute protein intake as their protein requirements rise, leading to fat gain.
Read the breakdown →StudyLeading journalModerate
Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity
A. R. Skov, S Toubro, Birgitte Rønn +2 more · International Journal of Obesity · 1999 · 743 citations
RCTHigh evidence score
Dietary protein intake does not modulate daily myofibrillar protein synthesis rates or loss of muscle mass and function during short-term immobilization in young men: a randomized controlled trial.
Kilroe SP, Fulford J, Jackman S +4 more · Am J Clin Nutr · 2021 · 39 citations
RCTModerate
Replacement of carbohydrate by protein in a conventional-fat diet reduces cholesterol and triglyceride concentrations in healthy normolipidemic subjects.
B. M. Wolfe, L A Piché · PubMed · 1999 · 76 citations
OBJECTIVE: To determine the effect on plasma lipid profiles of replacement of dietary carbohydrate by low-fat, high-protein foods. DESIGN: Cross-over randomized controlled trial. PARTICIPANTS: Ten healthy, normolipidemic subjects (8 women and 2 men). INTERVENTIONS: Subjects were randomly allocated to either a low-protein (12%) or high-protein (22%) weight-maintaining diet for 4 weeks and then switched to the alternate diet for 4 more weeks. The first 2 weeks of each diet served as an adjustment/washout period. Fat was maintained at 35% of energy, mean cholesterol intake at 230 mg per day and mean fibre intake at 24 g per day. Compliance was promoted by the use of written dietary protocols based on the food preferences of the subjects and weekly dietary consultation as required. OUTCOME MEASURES: Mean plasma levels of total, very-low-density-lipoprotein (VLDL), low-density-lipoprotein (LDL), and high-density-lipoprotein (HDL) cholesterol, and of total and very-low-density-lipoprotein (VLDL) triglycerides. Satiety levels were self-rated on a 10-point scale. RESULTS: Consumption of the high- versus the low-protein diet resulted in significant reductions in mean plasma levels of total cholesterol (3.8 v. 4.1 mmol/L, p < 0.05), VLDL cholesterol (0.20 v. 0.26 mmol/L, p < 0.02), LDL cholesterol (2.4 v. 2.6 mmol/L, p < 0.05), total triglycerides (0.69 v. 0.95 mmol/L, p < 0.005) and VLDL triglycerides (0.35 v. 0.57 mmol/L, p < 0.001), as well as in the ratio of total cholesterol to HDL cholesterol (3.1 v. 3.5, p < 0.01). A trend towards an increase in HDL cholesterol (1.26 v. 1.21 mmol/L, p = 0.30) was observed but was not statistically significant. Satiety levels tended to be higher among those eating the high-protein diet (6.1 v. 5.4, p = 0.073). CONCLUSIONS: Moderate replacement of dietary carbohydrate with low-fat, high-protein foods in a diet containing a conventional level of fat significantly improved plasma lipoprotein cardiovascular risk profiles in healthy normolipidemic subjects.
StudyLeading journalModerate
Quantity and source of dietary protein influence metabolite production by gut microbiota and rectal mucosa gene expression: a randomized, parallel, double-blind trial in overweight humans
Martín Beaumont, Kevin Portune, Nils Steuer +14 more · American Journal of Clinical Nutrition · 2017 · 250 citations
StudyTop journalModerate
Ingestion of Casein and Whey Proteins Result in Muscle Anabolism after Resistance Exercise
Kevin D. Tipton, Tabatha A. Elliott, Melanie Cree‐Green +3 more · Medicine & Science in Sports & Exercise · 2004 · 349 citations
PURPOSE: Determination of the anabolic response to exercise and nutrition is important for individuals who may benefit from increased muscle mass. Intake of free amino acids after resistance exercise stimulates net muscle protein synthesis. The response of muscle protein balance to intact protein ingestion after exercise has not been studied. This study was designed to examine the acute response of muscle protein balance to ingestion of two different intact proteins after resistance exercise. METHODS: Healthy volunteers were randomly assigned to one of three groups. Each group consumed one of three drinks: placebo (PL; N = 7), 20 g of casein (CS; N = 7), or whey proteins (WH; N = 9). Volunteers consumed the drink 1 h after the conclusion of a leg extension exercise bout. Leucine and phenylalanine concentrations were measured in femoral arteriovenous samples to determine balance across the leg. RESULTS: Arterial amino acid concentrations were elevated by protein ingestion, but the pattern of appearance was different for CS and WH. Net amino acid balance switched from negative to positive after ingestion of both proteins. Peak leucine net balance over time was greater for WH (347 +/- 50 nmol.min(-1).100 mL(-1) leg) than CS (133 +/- 45 nmol.min(-1).100 mL(-1) leg), but peak phenylalanine balance was similar for CS and WH. Ingestion of both CS and WH stimulated a significantly larger net phenylalanine uptake after resistance exercise, compared with the PL (PL -5 +/- 15 mg, CS 84 +/- 10 mg, WH 62 +/- 18 mg). Amino acid uptake relative to amount ingested was similar for both CS and WH (approximately 10-15%). CONCLUSIONS: Acute ingestion of both WH and CS after exercise resulted in similar increases in muscle protein net balance, resulting in net muscle protein synthesis despite different patterns of blood amino acid responses.
StudyModerate
Exercising before protein intake allows for greater use of dietary protein-derived amino acids for de novo muscle protein synthesis in both young and elderly men.
Pennings B, Koopman R, Beelen M +3 more · Am J Clin Nutr · 2011 · 308 citations
StudyTop journalModerate
Effect of low-protein diets on growth performance and body composition of broiler chicks
Kristjan Bregendahl, JL Sell, DR Zimmerman · Poultry Science · 2002 · 340 citations
Three experiments were conducted to investigate effects of dietary manipulations to improve growth performance and whole-body composition of broiler chicks fed low-protein diets supplemented with crystalline amino acids. In all experiments, male chicks (1 d old) were fed a common corn-soybean meal diet (23% CP) for 7 d and subsequently allotted to treatment diets in a completely randomized design (10 chicks per floor pen, six replications). Chicks had free access to the isoenergetic diets (3,200 kcal MEn/kg) for 2 wk, after which chicks were weighed and then fasted for 24 h, and the whole-body DM, N, and ether extract contents of two chicks per pen (and six baseline chicks) were determined. In Experiment 1, Gln or Asn replaced 1% triammonium citrate in the low-protein diet (19% CP). In Experiments 2 and 3, dietary concentrations of crystalline essential and nonessential amino acids, respectively, were increased incrementally in the low-protein diets (19 to 20% CP). In all experiments, chicks fed low-protein diets grew slower, used feed less efficiently, and retained less N and more ether extract than chicks fed the control diets (P < or = 0.05), despite additions of crystalline Gln or Asn and despite increased dietary concentrations of crystalline essential and nonessential amino acids. Chicks fed low-protein diets excreted less N (P < 0.001) than did chicks fed the high-protein diets, and N excretion increased linearly (P < 0.001) with N intake. In summary, low-protein diets failed to support equal growth performance to that of high-protein control diets.
StudyModerate
Muscle protein synthesis in cancer patients can be stimulated with a specially formulated medical food.
Deutz NE, Safar A, Schutzler S +5 more · Clin Nutr · 2011 · 204 citations
StudyModerate
The role of dietary protein intake in the prevention of sarcopenia of aging.
Beasley JM, Shikany JM, Thomson CA · Nutr Clin Pract · 2013 · 187 citations
RCTHigh evidence score
Effect of 1-year daily protein supplementation and physical exercise on muscle protein synthesis rate and muscle metabolome in healthy older Danes: a randomized controlled trial.
Bülow J, Khakimov B, Reitelseder S +5 more · Eur J Nutr · 2023 · 7 citations
StudyModerate
The effects of consuming a high protein diet (4.4 g/kg/d) on body composition in resistance-trained individuals
José António, Corey A. Peacock, Anya Ellerbroek +2 more · Journal of the International Society of Sports Nutrition · 2014 · 116 citations
BACKGROUND: The consumption of dietary protein is important for resistance-trained individuals. It has been posited that intakes of 1.4 to 2.0 g/kg/day are needed for physically active individuals. Thus, the purpose of this investigation was to determine the effects of a very high protein diet (4.4 g/kg/d) on body composition in resistance-trained men and women. METHODS: Thirty healthy resistance-trained individuals participated in this study (mean ± SD; age: 24.1 ± 5.6 yr; height: 171.4 ± 8.8 cm; weight: 73.3 ± 11.5 kg). Subjects were randomly assigned to one of the following groups: Control (CON) or high protein (HP). The CON group was instructed to maintain the same training and dietary habits over the course of the 8 week study. The HP group was instructed to consume 4.4 grams of protein per kg body weight daily. They were also instructed to maintain the same training and dietary habits (e.g. maintain the same fat and carbohydrate intake). Body composition (Bod Pod®), training volume (i.e. volume load), and food intake were determined at baseline and over the 8 week treatment period. RESULTS: The HP group consumed significantly more protein and calories pre vs post (p < 0.05). Furthermore, the HP group consumed significantly more protein and calories than the CON (p < 0.05). The HP group consumed on average 307 ± 69 grams of protein compared to 138 ± 42 in the CON. When expressed per unit body weight, the HP group consumed 4.4 ± 0.8 g/kg/d of protein versus 1.8 ± 0.4 g/kg/d in the CON. There were no changes in training volume for either group. Moreover, there were no significant changes over time or between groups for body weight, fat mass, fat free mass, or percent body fat. CONCLUSIONS: Consuming 5.5 times the recommended daily allowance of protein has no effect on body composition in resistance-trained individuals who otherwise maintain the same training regimen. This is the first interventional study to demonstrate that consuming a hypercaloric high protein diet does not result in an increase in body fat.
StudyModerate
Dose-response effects of dietary protein on muscle protein synthesis during recovery from endurance exercise in young men: a double-blind randomized trial.
Churchward-Venne TA, Pinckaers PJM, Smeets JSJ +7 more · Am J Clin Nutr · 2020 · 103 citations
StudyModerate
Coingestion of carbohydrate with protein does not further augment postexercise muscle protein synthesis
René Koopman, Milou Beelen, Trent Stellingwerff +5 more · American Journal of Physiology-Endocrinology and Metabolism · 2007 · 150 citations
The present study was designed to assess the impact of coingestion of various amounts of carbohydrate combined with an ample amount of protein intake on postexercise muscle protein synthesis rates. Ten healthy, fit men (20 +/- 0.3 yr) were randomly assigned to three crossover experiments. After 60 min of resistance exercise, subjects consumed 0.3 g x kg(-1) x h(-1) protein hydrolysate with 0, 0.15, or 0.6 g x kg(-1) x h(-1) carbohydrate during a 6-h recovery period (PRO, PRO + LCHO, and PRO + HCHO, respectively). Primed, continuous infusions with L-[ring-(13)C(6)]phenylalanine, L-[ring-(2)H(2)]tyrosine, and [6,6-(2)H(2)]glucose were applied, and blood and muscle samples were collected to assess whole body protein turnover and glucose kinetics as well as protein fractional synthesis rate (FSR) in the vastus lateralis muscle over 6 h of postexercise recovery. Plasma insulin responses were significantly greater in PRO + HCHO compared with PRO + LCHO and PRO (18.4 +/- 2.9 vs. 3.7 +/- 0.5 and 1.5 +/- 0.2 U.6 h(-1) x l(-1), respectively, P < 0.001). Plasma glucose rate of appearance (R(a)) and disappearance (R(d)) increased over time in PRO + HCHO and PRO + LCHO, but not in PRO. Plasma glucose R(a) and R(d) were substantially greater in PRO + HCHO vs. both PRO and PRO + LCHO (P < 0.01). Whole body protein breakdown, synthesis, and oxidation rates, as well as whole body protein balance, did not differ between experiments. Mixed muscle protein FSR did not differ between treatments and averaged 0.10 +/- 0.01, 0.10 +/- 0.01, and 0.11 +/- 0.01%/h in the PRO, PRO + LCHO, and PRO + HCHO experiments, respectively. In conclusion, coingestion of carbohydrate during recovery does not further stimulate postexercise muscle protein synthesis when ample protein is ingested.
StudyLeading journalModerate
The role of dietary protein in optimizing muscle mass, function and health outcomes in older individuals
Robert R. Wolfe · British Journal Of Nutrition · 2012 · 181 citations
The determination of whether increased dietary protein can positively affect health outcomes is hindered by the absence of prospective, randomized trials directly addressing this issue in which all pertinent variables are controlled. Consequently, we can only address the question deductively by considering the support for the rationale underlying the notion of a beneficial effect of increased dietary protein intake. With regard to health outcomes, we have focused on older individuals. Muscle mass and function are progressively lost with aging, so that by the age of 60 many individuals have reached a threshold where function begins to be affected. An association between reduced muscle mass and strength and unfavourable health outcomes is more likely to be revealed in individuals who have significant decrements in muscle mass and strength. In this article support for the rationale underlying the notion of a beneficial effect of increased dietary protein intake is considered. Dietary protein intake, and the resulting increased availability of plasma amino acids, stimulates muscle protein synthesis. If all other variables are controlled, increased muscle protein synthesis leads to improved muscle mass, strength and function over time. Increased muscle mass, strength and function are related to improved health outcomes in older individuals. Since adverse effects of reasonable increases in protein intake above the recommended dietary allowance (RDA) of 0·8 g protein/kg/day have not been reported, it is reasonable to conclude that the optimal protein intake for an older individual is greater than the RDA.
StudyModerate
Citrulline modulates muscle protein metabolism in old malnourished rats
Sylwia Osowska, T. Duchemann, Stéphane Walrand +4 more · American Journal of Physiology-Endocrinology and Metabolism · 2006 · 146 citations
Protein energy malnutrition is common in the elderly, especially in hospitalized patients. The development of strategies designed to correct such malnutrition is essential. Our working hypothesis was that poor response to nutrition with advancing age might be related to splanchnic sequestration of amino acids, which implies that fewer amino acids reach the systemic circulation. Administration of citrulline, which is not taken up by the liver, can offer a means of increasing whole body nitrogen availability and, hence, improve nutritional status. Thirty old (19 mo) rats were submitted to dietary restriction (50% of food intake) for 12 wk. They were randomized into three groups: 10 rats (R group) were killed and 20 others refed (90% of food intake) for 1 wk with a standard diet (NEAA group) or a citrulline-supplemented diet (Cit group). Before being killed, the rats were injected with [(13)C]valine, and the absolute protein synthesis rate (ASR) was measured in the tibialis using the flooding-dose method. When the rats were killed, the tibialis was removed for protein content analysis. Blood was sampled for amino acid and insulin analysis. The standard diet did not have any effect on protein synthesis or on the protein content in the muscle. Citrulline supplementation led to higher protein synthesis and protein content in muscle (117 +/- 9, 120 +/- 14, and 163 +/- 4 mg/organ for protein content in R, NEAA, and Cit groups, P < 0.05). The ASR were 0.30 +/- 0.04, 0.31 +/- 0.04, and 0.56 +/- 0.10 mg/h in the three groups, respectively (R and NEAA vs. Cit, P < 0.05). Insulinemia was significantly higher in the Cit group. For the first time, a realistic therapeutic approach is proposed to improve muscle protein content in muscle in frail state related to malnutrition in aging.
StudyTop journalModerate
Effects of jugular-infused lysine, methionine, and branched-chain amino acids on milk protein synthesis in high-producing dairy cows
J.A.D.R.N. Appuhamy, J.R. Knapp, O. Bečvář +2 more · Journal of Dairy Science · 2011 · 97 citations
In addition to lysine and methionine, current ration-balancing programs suggest that branched-chain amino acid (BCAA) supply may also be limiting in dairy cows. The objective of this study was to investigate whether BCAA, leucine, isoleucine, and valine become limiting for milk protein synthesis when methionine and lysine supply were not limiting. Nine multiparous Holstein cows with an average milk production of 53.5±7.1 kg/d were randomly assigned to 7-d continuous jugular infusions of saline (CTL), methionine and lysine (ML; 12 g and 21 g/d, respectively), or ML plus leucine, isoleucine, and valine (ML+BCAA; 35 g, 15 g, and 15 g/d, respectively) in a 3×3 Latin square design with 3 infusion periods separated by 7-d noninfusion periods. The basal diet consisted of 40% corn silage, 14% alfalfa hay, and a concentrate mix, and respectively supplied lysine, methionine, isoleucine, leucine, and valine as 6.1, 1.8, 4.7, 8.9, and 5.3% of metabolizable protein. Dry matter intake (23.9 kg/d), milk yield (52.8 kg/d), fat content (2.55%), fat yield (1.33 kg/d), lactose content (4.77%), lactose yield (2.51 kg/d), and milk protein efficiency (0.38) were similar across treatments. Protein yield and protein content were not significantly different between ML (1.52 kg/d and 2.88%, respectively) and ML+BCAA (1.51 kg/d and 2.83%, respectively), but they were significantly greater than that of CTL (1.39 kg/d and 2.71%). Cows that received ML+BCAA had less milk urea nitrogen content (10.9 mg/dL) compared with milk of CTL cows (12.4 mg/dL) and ML cows (11.8 mg/dL). Whereas high-producing cows responded positively to methionine and lysine supplementation, no apparent benefits of BCAA supplementation in milk protein synthesis were found. Infusion of BCAA may have stimulated synthesis of other body proteins, probably muscle proteins, as evidenced by decreased milk urea nitrogen.
RCTLeading journalHigh evidence score
Post-Exercise Whey Protein Supplementation: Effects on IGF-1, Strength, and Body Composition in Pre-Menopausal Women, a Randomised Controlled Trial.
Murray M, Vlietstra L, Best AMD +3 more · Nutrients · 2025 · 4 citations
StudyModerate
Functional impact of high protein intake on healthy elderly people
Stéphane Walrand, Kevin R. Short, Maureen L. Bigelow +3 more · American Journal of Physiology-Endocrinology and Metabolism · 2008 · 121 citations
Decline in muscle mass, protein synthesis, and mitochondrial function occurs with age, and amino acids are reported to enhance both muscle protein synthesis and mitochondrial function. It is unclear whether increasing dietary protein intake corrects postabsorptive muscle changes in aging. We determined whether a 10-day diet of high [HP; 3.0 g protein x kg fat-free mass (FFM)(-1) x day(-1)] vs. usual protein intake (UP; 1.5 g protein x kg FFM(-1) x day(-1)) favorably affects mitochondrial function, protein metabolism, and nitrogen balance or adversely affects insulin sensitivity and glomerular filtration rate (GFR) in 10 healthy younger (24+/-1 yr) and 9 older (70+/-2 yr) participants in a randomized crossover study. Net daily nitrogen balance increased equally in young and older participants, but postabsorptive catabolic state also increased, as indicated by higher whole body protein turnover and leucine oxidation with no change in protein synthesis. Maximal muscle mitochondrial ATP production rate was lower in older people, with no change occurring in diet. GFR was lower in older people, and response to HP was significantly different between the two groups, with a significant increase occurring only in younger people, thus widening the differences in GFR between the young and older participants. In conclusion, a short-term high-protein diet increased net daily nitrogen balance but increased the postabsorptive use of protein as a fuel. HP did not enhance protein synthesis or muscle mitochondrial function in either young or older participants. Additionally, widening differences in GFR between young and older patients is a potential cause of concern in using HP diet in older people.
StudyLeading journalModerate
Ingestion of Insect Protein Isolate Enhances Blood Amino Acid Concentrations Similar to Soy Protein in A Human Trial
Mathias T. Vangsoe, Rebekka Thøgersen, Hanne Christine Bertram +2 more · Nutrients · 2018 · 74 citations
BACKGROUND: Increased amino acid availability stimulates muscle protein synthesis (MPS), which is critical for maintaining or increasing muscle mass when combined with training. Previous research suggests that whey protein is superior to soy protein in regard to stimulating MPS and muscle mass. Nevertheless, with respect to a future lack of dietary protein and an increasing need for using eco-friendly protein sources it is of great interest to investigate the quality of alternative protein sources, like insect protein. OBJECTIVE: Our aim was to compare the postprandial amino acid (AA) availability and AA profile in the blood after ingestion of protein isolate from the lesser mealworm, whey isolate, and soy isolate. DESIGN: Six healthy young men participated in a randomized cross-over study and received three different protein supplementations (25 g of crude protein from whey, soy, insect or placebo (water)) on four separate days. Blood samples were collected at pre, 0 min, 20 min, 40 min, 60 min, 90 min, and 120 min. Physical activity and dietary intake were standardized before each trial, and participants were instructed to be fasting from the night before. AA concentrations in blood samples were determined using ¹H NMR spectroscopy. RESULTS: < 0.05). Area under the curve (AUC) analysis and AA profile revealed comparable AA concentrations for soy and insect protein, whereas whey promoted a ~97% and ~140% greater AUC value than soy and insect protein, respectively. A tendency towards higher AA concentrations beyond the 120 min period was observed for insect protein. CONCLUSION: We report that ingestion of whey, soy, and insect protein isolate increases blood concentrations of EAA, BCAA, and leucine over a 120 min period (whey > insect = soy). Insect protein induced blood AA concentrations similar to soy protein. However, a tendency towards higher blood AA concentrations at the end of the 120 min period post ingestion was observed for insect protein, which indicates that it can be considered a "slow" digestible protein source.
StudyModerate
Stimulation of muscle protein synthesis by whey and caseinate ingestion after resistance exercise in elderly individuals.
Dideriksen KJ, Reitelseder S, Petersen SG +4 more · Scand J Med Sci Sports · 2011 · 85 citations
StudyModerate
Effect of high protein vs high carbohydrate intake on insulin sensitivity, body weight, hemoglobin A1c, and blood pressure in patients with type 2 diabetes mellitus
Karin R. Sargrad, Carol J. Homko, Maria Mozzoli +1 more · Journal of the American Dietetic Association · 2005 · 126 citations
Meta-analysisWikiHigh evidence score
Effects of high-protein supplementation during cancer therapy: a systematic review and meta-analysis.
Orsso CE, Caretero A, Poltronieri TS +5 more · Am J Clin Nutr · 2024 · 23 citations
In cancer patients undergoing active treatment, supplementing with additional protein (typically 20–40 g/day above usual intake) led to modest improvements in body weight (mean gain of ~1.2 kg) and lean body mass (mean gain of ~0.8 kg) over 8–12 weeks, but did not significantly improve muscle strength, physical function, or quality of life compared to standard care or low-protein control.
Read the breakdown →Meta-analysisHigh evidence score
The effectiveness of protein supplements on athletic performance and post-exercise recovery - a Bayesian multilevel meta-analysis of randomized controlled trials.
Zhao S, Zhang X, Liang T +3 more · J Int Soc Sports Nutr · 2026 · 0 citations
StudyModerate
Protein timing and its effects on muscular hypertrophy and strength in individuals engaged in weight-training
Matthew Stark, Judith M. Lukaszuk, Aimee D. Prawitz +1 more · Journal of the International Society of Sports Nutrition · 2012 · 81 citations
The purpose of this review was to determine whether past research provides conclusive evidence about the effects of type and timing of ingestion of specific sources of protein by those engaged in resistance weight training. Two essential, nutrition-related, tenets need to be followed by weightlifters to maximize muscle hypertrophy: the consumption of 1.2-2.0 g protein.kg -1 of body weight, and ≥44-50 kcal.kg-1 of body weight. Researchers have tested the effects of timing of protein supplement ingestion on various physical changes in weightlifters. In general, protein supplementation pre- and post-workout increases physical performance, training session recovery, lean body mass, muscle hypertrophy, and strength. Specific gains, differ however based on protein type and amounts. Studies on timing of consumption of milk have indicated that fat-free milk post-workout was effective in promoting increases in lean body mass, strength, muscle hypertrophy and decreases in body fat. The leucine content of a protein source has an impact on protein synthesis, and affects muscle hypertrophy. Consumption of 3-4 g of leucine is needed to promote maximum protein synthesis. An ideal supplement following resistance exercise should contain whey protein that provides at least 3 g of leucine per serving. A combination of a fast-acting carbohydrate source such as maltodextrin or glucose should be consumed with the protein source, as leucine cannot modulate protein synthesis as effectively without the presence of insulin. Such a supplement post-workout would be most effective in increasing muscle protein synthesis, resulting in greater muscle hypertrophy and strength. In contrast, the consumption of essential amino acids and dextrose appears to be most effective at evoking protein synthesis prior to rather than following resistance exercise. To further enhance muscle hypertrophy and strength, a resistance weight- training program of at least 10-12 weeks with compound movements for both upper and lower body exercises should be followed.
StudyModerate
Diet‐induced adiposity alters the serum profile of inflammation in C57BL/6N mice as measured by antibody array
Jenifer I. Fenton, N. Nuñez, Shoshana Yakar +3 more · Diabetes Obesity and Metabolism · 2008 · 89 citations
Morbid obesity is considered a systemic inflammatory state. The objective of this project was to characterize the adipokine, cytokine and chemokine protein profile in serum from control, lean and obese mice. We hypothesized that chemokines and cytokines are altered by caloric restriction and diet-induced obesity as a function of changes in body composition. Six-week-old female C57BL/6N mice (n = 12 per group) were randomized to one of three diets: control (fed ad libitum); lean (30% calorie-restricted regimen relative to control) and diet-induced obese (DIO; high calorie diet, fed ad libitum). Body weight, body composition and food intake were monitored throughout the study. After 10 weeks on the diets, blood samples were collected, and adipokine/cytokine/chemokine serum profiles were measured by antibody array. Lean mice, relative to the control group, displayed increased concentrations of insulin-like growth factor (IGF) binding protein-3, -5 and -6 and adiponectin and decreased IGF-1. These mice also showed increased concentrations of interleukin (IL)-10, IL-12 p40/p70, eotaxin, monocyte chemoattractant protein-5 and SDF-1. In contrast, DIO mice displayed increased leptin, IL-6 and LPS-induced chemokine and decreased concentrations of all chemokines/cytokines measured relative to control mice. As such, these data indicate that DIO may lead to an inflammatory state characterized as a shift towards a T helper lymphocyte type 1-skewed responsiveness. The demonstration of differential adipokine, cytokine and chemokine protein profile in control, lean and DIO mice may have implications for immune responsiveness and risk of disease.
StudyModerate
Protein intake distribution pattern does not affect anabolic response, lean body mass, muscle strength or function over 8 weeks in older adults: A randomized-controlled trial.
Kim IY, Schutzler S, Schrader AM +4 more · Clin Nutr · 2018 · 75 citations
StudyLeading journalModerate
Inadequate protein intake affects skeletal muscle transcript profiles in older humans
Anna Thalacker‐Mercer, James C. Fleet, Bruce Α. Craig +2 more · American Journal of Clinical Nutrition · 2007 · 79 citations
StudyPreliminary
A randomized trial of a hypocaloric high-protein diet, with and without exercise, on weight loss, fitness, and markers of the Metabolic Syndrome in overweight and obese women
Kelly A. Meckling, Rachel Sherfey · Applied Physiology Nutrition and Metabolism · 2007 · 136 citations
The purpose of this study was to examine the effects of 3:1 and 1:1 carbohydrate to protein ratios, hypocaloric diets with and without exercise, and risk factors associated with the Metabolic Syndrome in overweight and obese Canadian women. Groups were designated as control diet (CON), control diet with exercise (CONEx), high-protein (HP), or high-protein with exercise (HPEx). Free-living women from the Guelph community were studied in a university health and fitness facility. The participants were 44 of 60 overweight and obese women who had been randomized to the 4 weight-loss programs. Habitual diets of the subjects were energy restricted and were to contain either a 1:1 or 3:1 ratio of carbohydrate to protein energy. Subjects either exercised 3 times/week or maintained their normal level of activity for 12 weeks. The main outcome measures were weight loss, blood lipids, blood pressure, insulin, body composition, nitrogen balance, fitness, and resting energy expenditure. All groups lost weight over the 12 week period: -2.1 kg for the CON group, -4.0 kg in the CONEx group, -4.6 kg in the HP group, and -7.0 kg in the HPEx. All participants exhibited improved body composition, decreased blood pressure, and decreased waist and hip circumference. Actual diets consumed by the subjects contained ratios of carbohydrate to protein of 3.0:1, 2.7:1, 1.5:1, and 0.96:1 for the CON, CONEx, HP, and HPEx groups, respectively. Cardiovascular fitness improved in both exercise groups. There were no changes in resting energy expenditure. No adverse events were reported. Significant changes in blood lipids included decreased total cholesterol in the HP and CONEx groups, decreased low-density lipoprotein cholesterol in the HP group only, and decreased blood triglycerides in the HPEx group only. High-density lipoprotein cholesterol, fasting blood glucose, and fasting insulin levels were unaltered by diet or exercise. A high-protein diet was superior to a low-fat, high-carbohydrate diet either alone or when combined with an aerobic/resistance-training program in promoting weight loss and nitrogen balance, while similarly improving body composition and risk factors for the Metabolic Syndrome in overweight and obese Canadian women.
Meta-analysisLeading journalHigh evidence score
Animal Protein versus Plant Protein in Supporting Lean Mass and Muscle Strength: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Lim MT, Pan BJ, Toh DWK +2 more · Nutrients · 2021 · 153 citations
Meta-analysisHigh evidence score
Impact of other macronutrient composition within high-protein diet on body composition and cardiometabolic health: a systematic review, pairwise, and network meta-analysis of randomized controlled trials.
Yao Y, Lin S, He Z +1 more · Int J Obes (Lond) · 2025 · 0 citations
Meta-analysisLeading journalWikiHigh evidence score
Effects of Plant-Based Protein Interventions, with and without an Exercise Component, on Body Composition, Strength and Physical Function in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Stoodley IL, Williams LM, Wood LG · Nutrients · 2023 · 24 citations
Plant-based protein supplementation (soy, pea, rice, or blends) in older adults produces small but measurable gains in lean body mass and leg strength, but only when combined with resistance exercise — protein alone, without exercise, shows no significant benefit over placebo for body composition or physical function.
Read the breakdown →Meta-analysisWikiHigh evidence score
Impact of Quantity and Type of Dietary Protein on Cardiovascular Disease Risk Factors Using Standard and Network Meta-analyses of Randomized Controlled Trials.
Yao Y, Huang V, Seah V +1 more · Nutr Rev · 2025 · 12 citations
Replacing 5–10% of daily calories from carbohydrates with protein from any source lowers LDL cholesterol by ~5 mg/dL and triglycerides by ~7 mg/dL, but only plant-based proteins (soy, legumes, nuts) consistently reduce blood pressure (by ~2–3 mmHg systolic), while animal-based proteins show no significant blood pressure benefit.
Read the breakdown →Meta-analysisHigh evidence score
The effects of protein intake higher than the recommended value on body composition changes after bariatric surgery: A meta-analysis of randomized controlled trials.
Golzarand M, Toolabi K, Mirmiran P · Clin Nutr · 2024 · 14 citations
Meta-analysisLeading journalHigh evidence score
Does Beef Protein Supplementation Improve Body Composition and Exercise Performance? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Valenzuela PL, Mata F, Morales JS +2 more · Nutrients · 2019 · 34 citations
StudyModerate
Dietary protein intake affects expression of genes for lipid metabolism in porcine skeletal muscle in a genotype-dependent manner.
Liu Y, Li F, He L +7 more · Br J Nutr · 2015 · 51 citations
Systematic ReviewLeading journalHigh evidence score
High-Protein Dietary Interventions in Heart Failure: A Systematic Review of Clinical and Functional Outcomes.
Evangelista LS, Meraz R, Wierenga KL +3 more · Nutrients · 2025 · 3 citations
Meta-analysisHigh evidence score
The Role of Protein Intake and its Timing on Body Composition and Muscle Function in Healthy Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Wirth J, Hillesheim E, Brennan L · J Nutr · 2020 · 80 citations
Meta-analysisLeading journalHigh evidence score
Are Dietary Proteins the Key to Successful Body Weight Management? A Systematic Review and Meta-Analysis of Studies Assessing Body Weight Outcomes after Interventions with Increased Dietary Protein.
Hansen TT, Astrup A, Sjödin A · Nutrients · 2021 · 70 citations
Meta-analysisHigh evidence score
Effects of dietary protein intake on body composition changes after weight loss in older adults: a systematic review and meta-analysis.
Kim JE, O'Connor LE, Sands LP +2 more · Nutr Rev · 2016 · 220 citations
Meta-analysisHigh evidence score
Effect of short- and long-term protein consumption on appetite and appetite-regulating gastrointestinal hormones, a systematic review and meta-analysis of randomized controlled trials.
Kohanmoo A, Faghih S, Akhlaghi M · Physiol Behav · 2020 · 51 citations
StudyModerate
Regulation of skeletal muscle protein degradation and synthesis by oral administration of lysine in rats.
Sato T, Ito Y, Nagasawa T · J Nutr Sci Vitaminol (Tokyo) · 2013 · 44 citations
Systematic ReviewHigh evidence score
Dietary protein and appetite sensations in individuals with overweight and obesity: a systematic review.
de Carvalho KMB, Pizato N, Botelho PB +2 more · Eur J Nutr · 2020 · 31 citations