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Protein

Protein intake, timing, and dose for muscle synthesis, body composition, and satiety.

Research synthesis3 min read

What the Protein Research Actually Shows

Protein has the strongest evidence of any macronutrient for body composition, satiety, and healthy ageing. The optimal amount is higher than most people consume — and higher than official guidelines.

Why Protein Gets Special Treatment

Of the three macronutrients, protein is the only one with a clearly defined functional role in tissue maintenance and repair. It's also the most satiating and has the highest thermic effect. The research literature on protein is unusually consistent — the debates that remain are about optimal amounts and timing, not whether it matters.

What Replicates Strongly

Muscle protein synthesis requires approximately 1.6–2.2g of protein per kg of bodyweight per day for active individuals. A landmark 2017 meta-analysis by Morton et al. (49 RCTs, 1,800 participants) found muscle gain from resistance training plateaued above ~1.62g/kg/day, with no benefit from higher intakes. Sedentary older adults show similar thresholds. Official guidelines (0.8g/kg RDA) are set to prevent deficiency, not optimise muscle maintenance or anabolism.

Protein is the most satiating macronutrient per calorie. Multiple RCTs show high-protein conditions produce greater reductions in ad libitum food intake, hunger ratings, and next-meal consumption relative to isocaloric high-carb or high-fat conditions. The mechanism involves GLP-1, PYY, and CCK — hormones that signal satiety to the hypothalamus. Effects are dose-dependent up to approximately 30% of total calories.

Per-meal protein threshold for muscle protein synthesis is approximately 20–40g. Leucine is the key anabolic trigger; a meal needs to clear ~2–3g leucine to maximally stimulate MPS. Amounts above ~40g don't add further acute MPS but contribute to total daily intake. Spreading protein across 3–4 meals outperforms two large meals for MPS over 24 hours.

Protein preserves muscle mass during caloric restriction. When calories are reduced for fat loss, high protein (≥1.8g/kg) consistently preserves lean mass relative to lower-protein diets at equal caloric deficit. This effect is important for ageing: the combination of sarcopenia (muscle loss with age) and insufficient protein intake is a primary driver of functional decline.

Plant proteins are effective when combined to provide complete amino acid profiles. Complete essential amino acid availability is the key variable — not source per se. Leucine content of plant proteins is often lower, so total protein needs may be ~10–20% higher for plant-based diets to achieve equivalent MPS. Soy protein shows the strongest evidence among plant sources.

What the Research Can't Tell You

Protein requirements vary based on age, training status, total caloric intake, and health conditions. Older adults (65+) may need the upper end of the range (2.2g/kg) to overcome anabolic resistance. The most useful personal experiment is tracking protein intake alongside strength, body composition, and satiety for 4–6 weeks to find your effective range.

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The effect of protein timing on muscle strength and hypertrophy: a meta-analysis

Consuming protein specifically around your workout (before, during, or immediately after) does not meaningfully increase muscle growth or strength gains compared to eating the same total amount of protein spread across the day — total daily protein intake is what matters most.

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Evidence base

Min quality:

50 papers

Meta-analysisWikiHigh confidence

The effect of protein timing on muscle strength and hypertrophy: a meta-analysis

Brad J. Schöenfeld, Alan A. Aragon, JAMES KRIEGER · Journal of the International Society of Sports Nutrition · 2013 · 193 citations

Consuming protein specifically around your workout (before, during, or immediately after) does not meaningfully increase muscle growth or strength gains compared to eating the same total amount of protein spread across the day — total daily protein intake is what matters most.

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Systematic ReviewWikiHigh evidence score

Health effects of protein intake in healthy adults: a systematic literature review

Agnes N. Pedersen, Jens Kondrup, Elisabet Børsheim · Food & Nutrition Research · 2013 · 168 citations

This systematic review found that the estimated average protein requirement for healthy adults is 0.66 g per kg of body weight per day (based on nitrogen balance studies), but evidence linking total protein intake to mortality, cardiovascular disease, cancer, bone health, or kidney function was inconclusive or suggestive at best — with the strongest positive signals coming from vegetable protein sources, not animal protein.

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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

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.

RCTWikiHigh 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

Very low birth weight infants fed a high-energy (150 kcal/kg/day) and high-protein (4.2 g/kg/day) diet gained more fat-free mass over 28 days compared to infants on a standard preterm formula (129 kcal/kg/day, 3.7 g/kg/day), with no adverse effects beyond elevated blood urea levels.

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StudyModerate

Protein content and amino acid composition of commercially available plant-based protein isolates

Stefan H. M. Gorissen, Julie J. R. Crombag, Joan M. Senden +4 more · Amino Acids · 2018 · 1,068 citations

The postprandial rise in essential amino acid (EAA) concentrations modulates the increase in muscle protein synthesis rates after protein ingestion. The EAA content and AA composition of the dietary protein source contribute to the differential muscle protein synthetic response to the ingestion of different proteins. Lower EAA contents and specific lack of sufficient leucine, lysine, and/or methionine may be responsible for the lower anabolic capacity of plant-based compared with animal-based proteins. We compared EAA contents and AA composition of a large selection of plant-based protein sources with animal-based proteins and human skeletal muscle protein. AA composition of oat, lupin, wheat, hemp, microalgae, soy, brown rice, pea, corn, potato, milk, whey, caseinate, casein, egg, and human skeletal muscle protein were assessed using UPLC-MS/MS. EAA contents of plant-based protein isolates such as oat (21%), lupin (21%), and wheat (22%) were lower than animal-based proteins (whey 43%, milk 39%, casein 34%, and egg 32%) and muscle protein (38%). AA profiles largely differed among plant-based proteins with leucine contents ranging from 5.1% for hemp to 13.5% for corn protein, compared to 9.0% for milk, 7.0% for egg, and 7.6% for muscle protein. Methionine and lysine were typically lower in plant-based proteins (1.0 ± 0.3 and 3.6 ± 0.6%) compared with animal-based proteins (2.5 ± 0.1 and 7.0 ± 0.6%) and muscle protein (2.0 and 7.8%, respectively). In conclusion, there are large differences in EAA contents and AA composition between various plant-based protein isolates. Combinations of various plant-based protein isolates or blends of animal and plant-based proteins can provide protein characteristics that closely reflect the typical characteristics of animal-based proteins.

StudyModerate

Effects of a Vitamin D and Leucine-Enriched Whey Protein Nutritional Supplement on Measures of Sarcopenia in Older Adults, the PROVIDE Study: A Randomized, Double-Blind, Placebo-Controlled Trial

Jürgen M. Bauer, Sjors Verlaan, Ivan Bautmans +21 more · Journal of the American Medical Directors Association · 2015 · 657 citations

BACKGROUND: Age-related losses of muscle mass, strength, and function (sarcopenia) pose significant threats to physical performance, independence, and quality of life. Nutritional supplementation could positively influence aspects of sarcopenia and thereby prevent mobility disability. OBJECTIVE: To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of sarcopenia. DESIGN: A multicenter, randomized, controlled, double-blind, 2 parallel-group trial among 380 sarcopenic primarily independent-living older adults with Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index. The active group (n = 184) received a vitamin D and leucine-enriched whey protein nutritional supplement to consume twice daily for 13 weeks. The control group (n = 196) received an iso-caloric control product to consume twice daily for 13 weeks. Primary outcomes of handgrip strength and SPPB score, and secondary outcomes of chair-stand test, gait speed, balance score, and appendicular muscle mass (by DXA) were measured at baseline, week 7, and week 13 of the intervention. RESULTS: Handgrip strength and SPPB improved in both groups without significant between-group differences. The active group improved more in the chair-stand test compared with the control group, between-group effect (95% confidence interval): -1.01 seconds (-1.77 to -0.19), P = .018. The active group gained more appendicular muscle mass than the control group, between-group effect: 0.17 kg (0.004-0.338), P = .045. CONCLUSIONS: This 13-week intervention of a vitamin D and leucine-enriched whey protein oral nutritional supplement resulted in improvements in muscle mass and lower-extremity function among sarcopenic older adults. This study shows proof-of-principle that specific nutritional supplementation alone might benefit geriatric patients, especially relevant for those who are unable to exercise. These results warrant further investigations into the role of a specific nutritional supplement as part of a multimodal approach to prevent adverse outcomes among older adults at risk for disability.

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.

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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.

StudyModerate

Skeletal muscle protein metabolism in the elderly: Interventions to counteract the 'anabolic resistance' of ageing

Leigh Breen, Stuart M. Phillips · Nutrition & Metabolism · 2011 · 542 citations

Age-related muscle wasting (sarcopenia) is accompanied by a loss of strength which can compromise the functional abilities of the elderly. Muscle proteins are in a dynamic equilibrium between their respective rates of synthesis and breakdown. It has been suggested that age-related sarcopenia is due to: i) elevated basal-fasted rates of muscle protein breakdown, ii) a reduction in basal muscle protein synthesis (MPS), or iii) a combination of the two factors. However, basal rates of muscle protein synthesis and breakdown are unchanged with advancing healthy age. Instead, it appears that the muscles of the elderly are resistant to normally robust anabolic stimuli such as amino acids and resistance exercise. Ageing muscle is less sensitive to lower doses of amino acids than the young and may require higher quantities of protein to acutely stimulate equivalent muscle protein synthesis above rest and accrue muscle proteins. With regard to dietary protein recommendations, emerging evidence suggests that the elderly may need to distribute protein intake evenly throughout the day, so as to promote an optimal per meal stimulation of MPS. The branched-chain amino acid leucine is thought to play a central role in mediating mRNA translation for MPS, and the elderly should ensure sufficient leucine is provided with dietary protein intake. With regards to physical activity, lower, than previously realized, intensity high-volume resistance exercise can stimulate a robust muscle protein synthetic response similar to traditional high-intensity low volume training, which may be beneficial for older adults. Resistance exercise combined with amino acid ingestion elicits the greatest anabolic response and may assist elderly in producing a 'youthful' muscle protein synthetic response provided sufficient protein is ingested following exercise.

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.

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.

RCTWikiHigh 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

Daily protein supplementation (30g milk protein) combined with twice-weekly resistance exercise for one year increased muscle protein synthesis rates by approximately 18% in healthy older adults, but the effect was driven primarily by exercise rather than protein alone, and the metabolome changes were modest — meaning that for most people, adding protein to an existing exercise routine may not produce additional muscle-building benefits beyond what exercise alone provides.

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StudyModerate

Higher Protein Intake Preserves Lean Mass and Satiety with Weight Loss in Pre‐obese and Obese Women

Heather J. Leidy, Nadine S Carnell, Richard D. Mattes +1 more · Obesity · 2007 · 267 citations

OBJECTIVE: To examine the effects of dietary protein and obesity classification on energy-restriction-induced changes in weight, body composition, appetite, mood, and cardiovascular and kidney health. RESEARCH METHODS AND PROCEDURES: Forty-six women, ages 28 to 80, BMI 26 to 37 kg/m(2), followed a 12-week 750-kcal/d energy-deficit diet containing higher protein (HP, 30% protein) or normal protein (NP, 18% protein) and were retrospectively subgrouped according to obesity classification [pre-obese (POB), BMI = 26 to 29.9 kg/m(2); obese (OB), BMI = 30 to 37 kg/m(2)). RESULTS: All subjects lost weight, fat mass, and lean body mass (LBM; p < 0.001). With comparable weight loss, LBM losses were less in HP vs. NP (-1.5 +/- 0.3 vs. -2.8 +/- 0.5 kg; p < 0.05) and POB vs. OB (-1.2 +/- 0.3 vs. -2.9 +/- 0.4 kg; p < 0.005). The main effects of protein and obesity on LBM changes were independent and additive; POB-HP lost less LBM vs. OB-NP (p < 0.05). The energy-restriction-induced decline in satiety was less pronounced in HP vs. NP (p < 0.005). Perceived pleasure increased with HP and decreased with NP (p < 0.05). Lipid-lipoprotein profile and blood pressure improved and kidney function minimally changed with energy restriction (p < 0.05), independently of protein intake. DISCUSSION: Consuming a higher-protein diet and accomplishing weight loss before becoming obese help women preserve LBM. Use of a higher-protein diet also improves perceptions of satiety and pleasure during energy restriction.

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

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.

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.

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.

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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.

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 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.

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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.

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Systematic ReviewLeading journalWikiHigh 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

A systematic review of 10 trials (1080 patients) found that high-protein diets (1.1–1.5 g/kg/day) in heart failure patients produced modest improvements in walking distance (+32 meters), lean body mass (+1.6 kg), quality of life (+9%), and an 18% reduction in hospital readmissions, but effects on muscle strength were inconsistent and long-term safety data are lacking.

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Meta-analysisWikiHigh 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

Adding extra protein (via supplements or high-protein foods) to your diet increases lean body mass by about half a kilogram on average, but the timing of when you eat that protein — before or after exercise, or spread across the day — does not seem to matter for muscle gain or strength.

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