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Longevity Library · Lab reference

Written by Daniel Tagge, MD
Updated October 23, 2026
Reviewed October 24, 2026
45 sources · Measured in g per kg of body weight per day

System: Metabolism & Metabolomics

Protein intakeDietary protein · Protein requirement

The US RDA of 0.8 g of protein per kilogram of body weight a day is the 97.5th percentile of nitrogen-balance requirements, a floor set to prevent deficiency rather than a target for muscle; the PROT-AGE and ESPEN expert groups ask at least 1.0 to 1.2 g/kg/day for healthy adults over 65 and 1.2 to 1.5 when ill. Across 49 randomized trials, protein added strength and lean mass to resistance training up to a total intake of about 1.6 g/kg/day and nothing beyond it; across 28 trials, higher-protein diets did not change kidney function in healthy adults; and in the cohorts the source of protein, plant over animal, tracked mortality more than the amount did.

Protein is the one macronutrient the body cannot store, so intake has to match use every day. The RDA is a floor derived from nitrogen balance, the geriatric expert groups set a higher band for older adults, and the trials show protein building muscle only when a muscle is being loaded. The kidney concern does not hold in healthy adults in randomized trials, the bone concern reversed, and the cohorts tie plant protein, not total protein, to lower mortality.

01 · The scale

Where the laboratory range and the evidence sit.

Protein added 2.49 kg to one-repetition strength and 0.30 kg of fat-free mass to resistance training across 49 randomized trials, with no further lean-mass gain above about 1.6 g/kg/day; higher protein did not change kidney function in healthy adults across 28 trials; 1.3 against 0.8 g/kg/day added no lean mass over six months in older men who were not training; and across 31 cohorts, total protein carried 6 percent lower all-cause mortality and plant protein 8 percent, with the source mattering more than the amount.

00.511.522.5

  1. Below the RDA: the lowest fifth of intake lost the most lean mass over three years in adults aged 70 to 79

    0 to 0.8 g per kg of body weight per day · Institute of Medicine 2005; Houston 2008

  2. From the US RDA (0.8) to the usual US adult intake (about 1.1 to 1.3 g per kg of ideal body weight)

    0.8 to 1.3 g per kg of body weight per day · Institute of Medicine 2005; Berryman 2018

  3. Expert groups for adults over 65: at least 1.0 to 1.2 when healthy, 1.2 to 1.5 when ill

    1 to 1.5 g per kg of body weight per day · PROT-AGE 2013; ESPEN 2014

  4. With resistance training, protein adds lean mass and strength up to a total intake of about 1.6

    1.2 to 1.6 g per kg of body weight per day · Morton 2018; Nunes 2022

  5. Above about 1.6: no further lean-mass gain in training trials; kidney function unchanged in healthy adults

    1.6 and above g per kg of body weight per day · Morton 2018; Devries 2018

  6. People with chronic kidney disease G3 to G5 only: 0.8 suggested, and above 1.3 avoided when at risk of progression

    1.3 and above g per kg of body weight per day · KDIGO 2024

  • Laboratory range
  • Evidence supports
  • Guideline goal or unstudied
  • Higher risk in studies
Scale in g per kg of body weight per day. The RDA, the expert groups for older adults and the training trials state intake as grams per kilogram of body weight per day; the mortality cohorts state it as percent of energy, and the muscle-synthesis studies as grams per meal. Each is quoted as its source states it. Bands show where studies found something, not a recommendation for any one person.

02 · What it is

What protein intake does.

Dietary protein supplies the amino acids the body uses to build and repair its own proteins and the nitrogen it cannot get from fat or carbohydrate. The US Recommended Dietary Allowance rests on a meta-analysis of nitrogen-balance studies: data for 235 people, each studied at three or more protein intakes across 19 studies, gave a median requirement of 105 mg of nitrogen per kilogram a day and a 97.5th percentile of 132 mg, which is 0.65 and 0.83 g of good-quality protein per kilogram a day. Requirements did not differ by climate, age class, sex or protein source, though women may need a little less. The Institute of Medicine's 2005 report set the RDA at 0.8 g/kg/day for every adult over 19 and the estimated average requirement at 0.66.1,2,3,4Grade A

Most Americans already eat more than that. Across 57,980 people in the national survey from 2001 to 2014, usual intake ran from 55.3 g a day in children aged 2 to 3 to 88.2 g a day in adults aged 19 to 30, protein made up 14 to 16 percent of energy, and relative intake ran from 1.10 g per kilogram of ideal body weight a day in adults 71 and older to 3.63 in young children, above the estimated average requirement in every demographic group. The groups most often below it were adolescent girls (11 percent) and older non-Hispanic Black men (13 percent), and fewer than 1 percent of any group ate above the acceptable macronutrient range for protein. The group with the lowest relative intake is the group whose muscle is at stake.5Grade C

The reason a physician asks about protein is muscle. In 2,066 community-dwelling adults aged 70 to 79, those in the highest fifth of protein intake lost about 40 percent less lean mass over three years than those in the lowest fifth (0.50 kg against 0.88 kg of total lean mass; 0.40 against 0.66 kg of appendicular lean mass), an association that held after adjustment for change in fat mass. The mechanism has a name, anabolic resistance: in 44 healthy young and old men of similar build, resting rates of muscle protein synthesis were indistinguishable, but older muscle responded less to the same dose of essential amino acids, with reduced expression and activation of the amino-acid sensing proteins mTOR and p70 S6 kinase and higher levels of the inflammation-linked transcription factor NF-kB, with insulin clamped at basal values. Older muscle needs a larger signal to do the same work.6,7Grade B

03 · Origins

Where it came from, and where it sits in the network.

Humans are primates that learned to eat animals. Plant foods make up 87 to more than 99 percent of the annual diet of the great apes, whose gut form and nutrient needs closely match ours; in plant-eating mammals a larger body means a lower-quality diet, and turning to animal-source foods as a routine rather than an occasional part of the diet is what let the human line grow a large brain while staying large, active and social. The ethnographic record of hunter-gatherers points the same way: 73 percent of the hunter-gatherer societies in the worldwide compilation drew more than half their subsistence from animal foods, which puts protein at an estimated 19 to 35 percent of energy, higher than the 14 to 16 percent of the modern US diet. The upper figure is not arbitrary. There is a ceiling on protein, set by the gut's rate of amino-acid absorption (1.3 to 10 g an hour) and the liver's capacity to turn excess nitrogen into urea; above roughly 35 percent of energy, protein brings raised blood amino acids and ammonia, nausea, diarrhea and, in the historical accounts of people living on lean game, death, the condition called rabbit starvation. The compilation's authors show how the fat content of prey decided how close foragers came to that ceiling, and the ceiling is why a diet can be built around protein but not made of it.8,9,10Grade C

The body has no protein store the way it has fat and glycogen, so amino acids beyond what is being built are burned and their nitrogen leaves as urea. The liver's capacity to make urea has been measured: in 10 healthy people it averaged 65 mg of urea nitrogen an hour per kilogram of metabolic body weight (range 55 to 76), against 27 in 34 people with cirrhosis; a large protein dose pushed blood urea nitrogen up by 7 to 20 mg/dL over eight hours, and larger doses did not raise the rate further but prolonged it to 28 hours. The same disposal shows up at the meal: in young men after lifting, 20 g of egg protein maximally stimulated muscle protein synthesis while leucine oxidation rose at 20 and 40 g, and in 48 trained men 40 g of whey added little to the 20-g response while raising phenylalanine oxidation and urea production. This is the biochemical reason the urea nitrogen on a metabolic panel rises on a high-protein diet and the reason protein taken beyond use becomes energy, not muscle. The protein-leverage hypothesis adds a behavioral layer: protein has stayed near 15 percent of energy within and across populations through the whole rise of obesity, and the authors argue that a fixed appetite for protein, diluted by fat and carbohydrate, could drive overeating of everything else.11,12,13,14Grade C

On the shelf, protein sits where the growth and maintenance signals meet. A meal's amino acids, and leucine above all, switch on muscle protein synthesis through the nutrient sensor mTORC1: in eight young adults, 10 g of essential amino acids raised muscle protein synthesis by about 60 percent, and a single prior dose of rapamycin blocked the rise completely without changing amino-acid availability. Older muscle needs more leucine to trip the switch; an essential amino acid mixture with 26 percent leucine failed to raise synthesis in elderly volunteers and one with 41 percent did, while young muscle responded to both. The switch is also time-limited. After 48 g of whey, synthesis rose from 0.03 to 0.10 percent an hour at 45 to 90 minutes and then fell back to baseline even though blood essential amino acids stayed 130 percent above fasting at two hours, the muscle-full effect that makes a meal's dose matter more than the day's. The same amino-acid signal, through the liver, sets insulin-like growth factor 1: in six volunteers practicing calorie restriction, cutting protein from 1.67 to 0.95 g/kg/day for three weeks lowered IGF-1 from 194 to 152 ng/mL, while years of severe calorie restriction without malnutrition had not lowered it at all. IGF-1 builds muscle and bone, and lower IGF-1 signaling lengthens life in several animal models; that tension is the open question the entry returns to below, and it links this page to fasting insulin, albumin, urea nitrogen and the eGFR on the same panel.15,16,17,18Grade C

04 · The usual guidance

What the guidelines say.

US RDA 0.8 g of protein per kilogram of body weight per day for adults of every age (Institute of Medicine 2005); at least 1.0 to 1.2 g/kg/day for healthy adults over 65 and 1.2 to 1.5 for those with acute or chronic illness (PROT-AGE 2013; ESPEN 2014).

The RDA is a statistical floor, not a goal. It is the intake that covers the requirement of 97.5 percent of healthy adults in nitrogen balance, 0.83 g/kg/day in the meta-analysis that underlies it and 0.8 in the Institute of Medicine's report, which set the same figure for every adult over 19 regardless of age. Nitrogen balance measures the point at which intake equals loss; it says nothing about the intake that best preserves muscle, function or appetite control, which is why the expert groups below, working from different methods, arrive higher.1,2,19,4Grade A

For adults over 65, the PROT-AGE study group, appointed by the European Union Geriatric Medicine Society, recommends an average daily intake of at least 1.0 to 1.2 g/kg/day to maintain and regain lean mass and function, 1.2 or more for those who exercise, and 1.2 to 1.5 for most older adults with acute or chronic disease; older people with severe kidney disease (estimated GFR below 30) who are not on dialysis are the exception and may need to limit protein. It found the evidence on protein quality, timing and supplements insufficient for specific recommendations. The ESPEN expert group, after a 2013 workshop, reached the same figures, 1.0 to 1.2 for healthy older people and 1.2 to 1.5 for those malnourished or at risk because of illness, with higher intakes for severe illness or injury, and added that all older people should take daily exercise for as long as possible.20,21Grade A

A newer method puts the requirement itself higher than nitrogen balance did. The indicator amino acid oxidation technique, which finds the intake at which the body stops burning a labeled amino acid for lack of others to build with, gave a mean requirement of 0.93 and a population-safe intake of 1.2 g/kg/day in eight young men, 41 and 50 percent above the estimated average requirement of 0.66 and the RDA of 0.80; reanalyzing the old nitrogen-balance data with the same two-phase regression gave 0.91 and 1.0. In 12 women over 65, across 82 study days, the same method gave 0.96 and 1.29. These are small studies and the method is debated, but they are the reason a review from the same school proposes at least 1.2 g/kg/day for older adults with an emphasis on leucine, while calling for the longer trials that would settle it.3,22,4Grade C

For people who already have chronic kidney disease the guidance runs the other way. The KDIGO 2024 guideline suggests maintaining a protein intake of 0.8 g/kg/day in adults with CKD stages G3 to G5 (a weak recommendation on low-certainty evidence), and as a practice point advises avoiding intakes above 1.3 g/kg/day in adults with CKD at risk of progression; it notes that average intakes in many societies run about 1.2 g/kg/day and that, absent intercurrent illness, the protein requirement of people with CKD is no different from that of healthy adults. The number on this page that decides which guidance applies is the eGFR, read with its own entry's caveats.23Grade A

05 · The evidence

What the studies support.

The best-measured effect of protein is on a muscle that is being trained. Pooling 49 randomized trials with 1,863 healthy adults who lifted for six weeks or more, protein supplementation added 2.49 kg to one-repetition-maximum strength, 0.30 kg to fat-free mass and 310 square micrometers to muscle fiber cross-section. The gain in fat-free mass shrank with age and was larger in people already trained, and a two-phase break-point analysis found that supplementing beyond a total intake of 1.62 g/kg/day produced no further gain, which the authors round to about 1.6. The lead author discloses support from a dairy industry council that had funded some of the trials reviewed.24Grade A

A broader synthesis of 74 randomized trials in healthy, non-obese adults agrees and adds the age split. Raising daily protein improved lean mass in people doing resistance exercise (standardized mean difference 0.22 across 62 studies, moderate certainty); the effect was significant in adults 65 and older eating 1.2 to 1.59 g/kg/day and in younger adults eating 1.6 or more. Lower-body strength rose slightly more with 1.6 g/kg/day or above during training (0.40 across 19 studies, low certainty), bench press strength slightly in the under-65s, the effect on handgrip strength was unclear and the effect on physical function tests marginal. Protein makes a training program work somewhat better; it is not the program.25Grade A

The trials in older adults show the same dependence. In 62 frail adults with a mean age of 78, 24 weeks of twice-weekly resistance training with 15 g of protein twice a day raised lean mass from 47.2 to 48.5 kg while the placebo group did not change (45.7 to 45.4 kg); strength and physical performance improved in both groups alike. In 65 frail adults given the same supplement without training, muscle mass did not change at all (45.8 to 45.8 kg against 46.7 to 46.6), though physical performance scores rose from 8.9 to 10.0 points against no change on placebo and leg extension strength tended to rise more. In the longest controlled feeding trial, 92 functionally limited men aged 65 and over whose usual intake was within the RDA were randomized for six months to 0.8 or 1.3 g/kg/day, each with or without weekly testosterone; the higher intake added no lean mass (difference 0.31 kg, confidence interval minus 0.46 to 1.08), no strength, power, walking speed or well-being, and did not augment the response to testosterone, though fat mass fell by 1.12 kg more. Without a load on the muscle, extra protein in older men went nowhere the DEXA scanner could see.26,27,19Grade B

The dose that matters is the meal's. In six young men after leg exercise, muscle protein synthesis rose with each dose of egg protein up to 20 g and no further, while leucine oxidation rose at 20 and 40 g; in 48 resistance-trained men of about 80 kg, 20 g of whey raised myofibrillar synthesis 49 percent and 40 g raised it 56 percent, with 10 g adding nothing and 40 g raising amino-acid oxidation and urea production. Older muscle needs more: a retrospective analysis of dose-response data put the plateau at 0.40 g of protein per kilogram of body weight in men of about 71 against 0.24 in men of about 22 (0.60 against 0.25 per kilogram of lean mass). How the day is divided matters too: in eight adults fed the same protein either evenly (about 30 g at each of three meals) or skewed toward dinner (about 11, 16 and 63 g), 24-hour muscle protein synthesis was 25 percent higher on the even pattern (0.075 against 0.056 percent an hour), and the difference held after a week on each diet. These are tracer studies of hours, in small numbers, and they explain why the geriatric groups talk about grams per meal.12,13,28,29Grade C

Protein changes appetite and the composition of weight lost. In 19 adults moved from 15 to 30 percent of energy from protein with carbohydrate held constant, satiety rose markedly on the matched-calorie diet, and when the diet was then eaten freely for 12 weeks spontaneous intake fell by 441 kcal a day, body weight by 4.9 kg and fat mass by 3.7 kg, despite a fall in leptin and a rise in ghrelin that should have driven hunger the other way. Across 24 energy-restricted trials with 1,063 participants and a mean duration of 12 weeks, matched-calorie higher-protein low-fat diets beat standard-protein low-fat diets by 0.79 kg of weight and 0.87 kg of fat, lowered triglycerides by 0.23 mmol/L, spared 0.43 kg of fat-free mass and 595 kJ a day of resting energy expenditure, and left fasting glucose, insulin, blood pressure and cholesterol no different; satiety was greater in three of five studies that measured it. The review from the same field reads the whole literature as supporting 1.2 to 1.6 g/kg/day with about 25 to 30 g at each meal for appetite and weight, notes that acute satiety does not reliably cut intake at the next meal, and attributes the weaker long-term results to people not staying on the diet.30,31,32Grade A

During deliberate weight loss the requirement rises. Thirty-nine adults fed protein at the RDA, twice the RDA or three times it (0.8, 1.6 and 2.4 g/kg/day) through ten days of weight maintenance and 21 days of a 40 percent energy deficit all lost 3.2 kg, but the share of that loss that was fat-free mass was lower, and the share that was fat higher, at twice and three times the RDA, and only the RDA group lost its muscle's anabolic response to a protein-rich meal. In 40 young men on a 40 percent deficit who trained six days a week for four weeks, 2.4 against 1.2 g/kg/day gained 1.2 kg of lean mass against 0.1 and lost 4.8 kg of fat against 3.5, with no difference in performance. The deficit is when the floor moves up.33,34Grade B

The kidney concern does not hold in healthy adults in randomized trials. Across 28 trials with 1,358 participants without kidney disease, comparing higher-protein diets (1.5 g/kg/day or more, or 20 percent or more of energy, or 100 g a day or more) with lower, glomerular filtration rate after the intervention was trivially higher on the higher-protein diets (standardized mean difference 0.19) and the change in GFR from before to after did not differ (0.11, confidence interval minus 0.05 to 0.27); the authors flag unclear selection bias in the trials as the main limitation. The worry traces to a 1982 hypothesis that protein-driven increases in glomerular pressure and filtration could injure the kidney over time; the human data behind it come from kidneys that are already damaged. In 1,624 nurses followed 11 years, protein intake had no significant relation to the change in estimated GFR in women with normal function (0.25 mL/min per 1.73 m2 per 10 g a day), while in women who started with mild insufficiency (an estimated GFR between 55 and 80) each 10 g a day was associated with a decline of 1.69 mL/min per 1.73 m2, driven by non-dairy animal protein (1.21 per 10 g). A healthy kidney filters more on more protein and is not harmed by it on the evidence we have; a kidney already losing function is the exception, and the guideline for it is quoted above.35,36,37,23Grade A

Against death, the amount of protein matters less than where it comes from. Across 31 prospective cohorts with 715,128 participants and 113,039 deaths, the highest against the lowest intake of total protein carried 6 percent lower all-cause mortality (pooled estimate 0.94, confidence interval 0.89 to 0.99), plant protein 8 percent lower all-cause and 12 percent lower cardiovascular mortality, and animal protein no significant association with cardiovascular or cancer death; each additional 3 percent of energy from plant protein went with 5 percent lower all-cause mortality. In 131,342 US health professionals, animal protein (median 14 percent of energy) was not associated with all-cause mortality (1.02 per 10 percent of energy) but was with cardiovascular death (1.08), plant protein (median 4 percent) with lower all-cause mortality (0.90 per 3 percent of energy), and the associations appeared only in people with at least one unhealthy lifestyle factor; swapping 3 percent of energy from processed red meat for plant protein carried a hazard ratio of 0.66, from unprocessed red meat 0.88 and from eggs 0.81. In 416,104 adults followed 16 years with 77,614 deaths, each standard deviation more plant protein carried 5 percent lower overall mortality in both sexes, and replacing 3 percent of energy from animal with plant protein 10 percent lower; in 70,696 Japanese adults the top fifth of plant protein carried 0.87 and the same 3 percent swap from red meat 0.66. Food-frequency questionnaires measured every one of these exposures, and the pattern of eating that comes with plant protein is as plausible a cause as the protein.38,39,40,41Grade B

One analysis argues the answer depends on age, and it should be read as a hypothesis. In a US survey cohort, respondents aged 50 to 65 who reported high protein intake had a 75 percent higher overall mortality and a four-fold higher cancer mortality over the following 18 years, associations abolished or weakened when the protein was plant-derived; in respondents over 65 high protein intake went with lower cancer and overall mortality; and high intake went with a five-fold higher diabetes mortality at every age. The authors tie it to IGF-1 and growth hormone receptor signaling, show in mice that high protein and that signaling drive tumor growth and that low protein harms the very old, and suggest low protein in middle age followed by moderate to high protein in old age; the senior author discloses an equity interest in a company that develops medical food. The IGF-1 thread has human support of its own: in 184 people in their nineties, women with IGF-1 at or below the median of 96 ng/mL survived longer, men showed no such advantage, and lower IGF-1 predicted longer survival in both sexes among those with a cancer history. Against this sit the 31-cohort pooled estimate above, in which total protein carried lower mortality, the geriatric consensus that older adults need more, and the absence of any trial. The entry reports the disagreement and does not resolve it.42,43,38,20Grade C

The old bone concern has reversed. The National Osteoporosis Foundation's systematic review of 16 randomized trials and 20 prospective cohorts found moderate evidence that higher protein intake protects lumbar spine bone density compared with lower intake (net difference 0.52 percent across five trials), no effect at the hip, femoral neck or whole body, and no adverse effects of higher protein at any site. The earlier meta-analysis found protein intake positively related to bone density in every cross-sectional survey, explaining 1 to 2 percent of it, a small positive effect of protein supplementation on spine density in trials, and no relation to hip fracture in the cohorts. The effect is small and in the right direction; protein does not leach calcium from bone on the evidence of the trials.44,45Grade A

06 · What moves it

The levers with evidence behind them.

What is listed here has been tested. The size of each effect, and the size of the study, are in the sentence, so a small effect reads as a small effect.

  • Resistance training

    turns protein into muscle; a supplement without training added little in older adults

    Protein supplementation added strength and lean mass to resistance training across 49 trials and 74 trials in two syntheses, and the frail older adults who gained lean mass on a supplement were the ones who trained twice a week; the same supplement without training left muscle mass unchanged, and six months at 1.3 against 0.8 g/kg/day without training added no lean mass in older men. Load comes first; protein feeds the adaptation. The pairing is on its own page.24,25,26,27,19Grade A

  • Age

    raises the dose a meal needs and the daily intake the expert groups advise

    Older muscle is less sensitive to amino acids: the same dose produced less synthesis in older than younger men, with weaker mTOR signaling and more NF-kB, and the per-meal plateau sat at 0.40 g/kg of body weight in men of about 71 against 0.24 in men of about 22. That is the physiology behind the PROT-AGE figure of at least 1.0 to 1.2 g/kg/day after 65 and the proposal of 1.2 or more with attention to leucine, and behind the finding that in older adults the lean-mass effect of extra protein during training appeared at 1.2 to 1.59 g/kg/day.7,28,20,4,25Grade B

  • Leucine content of the meal

    sets the per-meal trigger, more so in older adults

    Essential amino acids switch on muscle protein synthesis through mTORC1, and leucine is the amino acid that does most of the switching: a mixture with 26 percent leucine failed to raise synthesis in elderly volunteers and the same 6.7 g with 41 percent leucine did, while young volunteers responded to both. Protein sources differ in how much leucine a serving carries, so the serving that reaches the trigger differs by food; the expert groups found the evidence on protein quality insufficient for a specific recommendation.15,16,4,20Grade C

  • Distribution across the day

    an even spread raised 24-hour muscle protein synthesis by 25 percent over a dinner-heavy pattern

    Synthesis after a meal is transient, peaking at 45 to 90 minutes and returning to baseline while blood amino acids are still high, so a day's protein does more spread across meals than stacked at dinner: eight adults fed about 30 g at each of three meals synthesized 25 percent more muscle protein over 24 hours than the same people fed 11, 16 and 63 g, and the difference persisted after a week on each pattern. The common US pattern, a carbohydrate breakfast and a protein dinner, is the skewed arm of that study.17,29Grade C

  • Source: plant against animal

    plant protein tracked lower mortality in every large cohort; animal protein tracked higher cardiovascular death in one

    Across 31 cohorts, plant protein carried 8 percent lower all-cause and 12 percent lower cardiovascular mortality and animal protein no significant association with either cause; in the US professional cohorts, swapping 3 percent of energy from processed red meat to plant protein carried a hazard ratio of 0.66 and the animal-protein signal appeared only in people with at least one unhealthy habit; in 416,104 US adults and 70,696 Japanese adults the same 3 percent swap from red meat protein carried about 13 to 34 percent lower mortality. The source carries the rest of the diet with it, and the cohorts cannot separate the protein from its company.38,39,40,41Grade B

  • An energy deficit

    raises the requirement; twice the RDA protected lean mass during weight loss

    On a 40 percent energy deficit, adults at 1.6 and 2.4 g/kg/day lost less lean mass and more fat than those at 0.8 and kept their muscle's response to a meal, and young men training through a deficit at 2.4 against 1.2 gained 1.2 kg of lean mass against 0.1. Across 24 weight-loss trials, higher protein spared 0.43 kg of fat-free mass and 595 kJ a day of resting energy expenditure. Anyone losing weight on purpose, including on a medication that suppresses appetite, is in the condition these trials studied.33,34,31Grade B

  • Appetite

    raising protein from 15 to 30 percent of energy cut spontaneous intake by about 440 kcal a day

    Protein raises satiety in the feeding studies: 19 adults who moved from 15 to 30 percent of energy from protein ate 441 fewer kcal a day when allowed to eat freely and lost 4.9 kg in 12 weeks with no instruction to eat less. The protein-leverage hypothesis proposes that a fixed appetite for protein, diluted by fat and carbohydrate in the modern food supply, drives overeating of everything else, a model with supporting data and open predictions. The reverse lever is the one most people pull by accident: a low-protein breakfast is followed by a hungrier day.30,14,32Grade B

  • Illness and kidney disease

    illness raises the need to 1.2 to 1.5 g/kg/day in the geriatric guidance; chronic kidney disease lowers the ceiling to 0.8

    The PROT-AGE and ESPEN groups put most older adults with acute or chronic disease at 1.2 to 1.5 g/kg/day, higher still with severe illness or injury, because inflammation and catabolism raise the need; the one exception they name is severe kidney disease with an estimated GFR below 30. KDIGO 2024 suggests 0.8 g/kg/day for adults with CKD G3 to G5 and advises avoiding more than 1.3 when the disease is at risk of progressing, while warning against low-protein diets in anyone metabolically unstable. The same person can move from one rule to the other across a hospital stay, which is why protein is prescribed to the situation, not the birthday.20,21,23Grade A

07 · Reading it well

Caveats, and what belongs with a physician.

Nearly every long-term number here is self-reported food. The mortality cohorts measured protein by food-frequency questionnaire, the nurses' kidney study by a semi-quantitative questionnaire filled in twice, and the national survey is a cross-sectional estimate; people misreport what they eat, and a percent-of-energy figure from a questionnaire converts to grams per kilogram only approximately. The trials that weighed and fed the protein ran weeks to months and measured muscle, weight and filtration rate, not death.38,37,5,35Grade B

The muscle-synthesis studies are small and short. Six men, eight men, eight adults, 48 men, measured over four to 24 hours with a tracer; a rate of synthesis after one meal is not muscle on a scanner a year later, and the one six-month feeding trial that fed 1.3 against 0.8 g/kg/day to older men without training found no lean mass at all. The per-meal and per-day figures above are physiology that the longer trials have confirmed only when training was present.12,29,13,19Grade C

Healthy kidneys and damaged kidneys answer protein differently, and the line between them is an estimate. The randomized trials that found no effect on filtration rate enrolled adults without kidney disease; the nurses with an estimated GFR between 55 and 80 lost filtration with higher intake; and KDIGO's 0.8 applies from stage G3. An eGFR is calculated from creatinine, which rises with muscle and with a meat meal, so a well-muscled person on a high-protein diet can print a stage G3 number they do not have, and a person with early disease can print a normal one. The eGFR and UACR entries carry that reading.35,37,23Grade B

The age-dependent mortality finding is one analysis of one survey cohort, with mouse experiments and a model attached, and it conflicts with the pooled estimate from 31 cohorts in which total protein carried lower mortality. Its senior author discloses a commercial interest. The IGF-1 mechanism it rests on is real in the sense that protein sets IGF-1 in humans and low IGF-1 predicted survival in nonagenarian women, and unsettled in the sense that nobody has shown that lowering protein in a healthy middle-aged adult lengthens life.42,38,18,43Grade C

Several of the leading protein researchers disclose support from dairy, beef or nutrition-product industry groups, including the lead authors of the two training meta-analyses and the distribution study, and some of the trials those analyses pool were industry funded. The disclosures are printed in the papers, the pooled designs are randomized and the methods are open to inspection, which is why the claims are graded as they are, but the reader should know who paid for part of the field.24,25,29Grade C

There is a ceiling. The gut absorbs amino acids at 1.3 to 10 g an hour and the liver makes urea at a maximal rate, measured at about 65 mg of urea nitrogen an hour per kilogram of metabolic body weight in healthy people and less than half that in cirrhosis; above roughly 35 percent of energy, protein produces raised blood amino acids and ammonia, nausea and diarrhea, and a review of the question suggests about 25 percent of energy, around 2 to 2.5 g/kg/day, as a practical maximum. Fewer than 1 percent of Americans eat above the acceptable range, so the ceiling is a fact about physiology rather than a common problem, except in liver disease.10,11,5Grade C

See a physician

  • Weight or strength that is falling without trying, clothes loosening at the arms and legs, or a grip that has weakened noticeably in a year, which is a question about muscle and about what is driving its loss, not a reason to buy a powder.
  • A known kidney condition, an eGFR below 60 on more than one test, or protein in the urine, before raising protein intake; the guidance for a kidney that is losing function runs opposite to the guidance for a healthy one.
  • Liver disease, especially cirrhosis or any episode of confusion after a large meal, since the liver's capacity to clear nitrogen is what limits protein in that condition.
  • Difficulty chewing or swallowing, loss of appetite, nausea with food or a shrinking diet in an older adult, which is how protein intake falls in practice and which has causes worth finding.
  • A pattern of restricting food, or of using protein products to replace meals for weight control, which deserves a conversation rather than a target.
  • A rising creatinine, urea nitrogen or eGFR change on a routine panel after starting a high-protein diet or supplement: it may be the diet, and a physician can add cystatin C and time the repeat draw.

This page is education, not individual medical advice, and reading it creates no physician-patient relationship.

08 · Open questions

What the literature does not settle.

  • No trial has fed one protein intake against another for years and counted deaths, fractures, falls or loss of independence. The mortality evidence is cohort data on self-reported food, and the trials measured muscle, weight, filtration rate and appetite over weeks to months.
  • Whether the RDA is too low is a methodological dispute. The indicator amino acid oxidation studies put the requirement 40 to 50 percent higher than nitrogen balance did, the geriatric groups recommend above the RDA on the basis of muscle outcomes, and the one long controlled feeding trial in older men found no lean-mass benefit from 1.3 over 0.8 without training. Which method defines a requirement, and for what endpoint, has not been settled.
  • The age interaction is unresolved: one analysis finds high protein harmful before 65 and protective after, the pooled cohorts find total protein mildly protective overall, and the IGF-1 mechanism that would explain a middle-age cost has been tested in mice and in people with exceptional longevity, not in a trial.
  • Whether the plant-protein advantage in the cohorts belongs to the protein, to the foods that carry it, or to the people who choose them cannot be answered by the cohorts, and no trial has swapped protein sources long enough to find out.
  • The per-meal dose, the leucine threshold and the benefit of an even distribution rest on tracer studies of hours in small groups; whether distributing protein evenly changes muscle, strength or function over months in free-living adults is thinly tested.
  • The kidney trials ran days to months and the longest cohort 11 years; what decades at 1.6 g/kg/day or more do to a healthy kidney, and whether a higher post-intervention filtration rate is adaptation or strain, is not known.
  • How much protein a person on an appetite-suppressing weight-loss medication needs to protect lean mass, and whether the deficit trials at 1.6 to 2.4 g/kg/day transfer to that setting, is an open trial question.

09 · In practice

How Dr. Tagge reads it in his own practice.

I do not have a protein number of my own to give you, and I distrust the ones that get handed out. The RDA of 0.8 g per kilogram is a floor set to prevent deficiency, the geriatric groups ask 1.0 to 1.2 after 65 and more when you are ill, and the training trials stop adding muscle near 1.6; those are the guidelines' numbers, and I quote them as theirs. What I actually do is read protein against the rest of the panel, because one marker is a clue and three are a story. Grip strength and a DEXA lean-mass trend tell me whether the muscle is holding; if both are slipping in someone over 60, the first question is what they ate at breakfast, and the second is whether anything is loading the muscle, because protein without a load went nowhere in every trial that tried it. Albumin and urea nitrogen tell me about intake and about the liver's handling of it, with the caveat that albumin falls with inflammation long before it falls with diet. The eGFR I read as the estimate it is: a muscular person who lifts and eats meat can print a stage 3 number with healthy kidneys, and I will add cystatin C before I tell anyone to eat less protein, while a true loss of filtration changes the advice entirely and I follow KDIGO there. Fasting insulin sits beside all of this because the person who most needs protein at breakfast is usually the person whose insulin is high and whose breakfast is carbohydrate. Before I advise, I ask what someone eats in a day, when, from what source, and whether they are losing weight on purpose, because a deficit raises the need and the people on appetite-suppressing medication are losing muscle I would rather they kept. I will say where I am ahead of the evidence: I lean toward spreading protein across the day and toward plant sources for the cardiovascular signal, and both rest on short tracer studies and questionnaire cohorts, not on trials that counted outcomes. And I will not tell a healthy person their kidneys forbid a higher intake, because the trials say otherwise, or tell a middle-aged person to go low on protein for longevity on the strength of one disputed analysis. I act on the mechanism and the association together, and I say so.

A practice judgment, labeled as one (Grade D): it is how one physician reads the number for the people he cares for, not a recommendation for you.

10

Questions

11 · Sources

45 sources, read in full.

Numbered in the order they appear. Each line says what this page relies on from the paper; the link opens the record at PubMed or the publisher.

  1. 1.

    Rand WM, Pellett PL, Young VR. Meta-analysis of nitrogen balance studies for estimating protein requirements in healthy adults. American Journal of Clinical Nutrition. 2003. PMID 12499330. DOI 10.1093/ajcn/77.1.109.

    Systematic review and meta-analysis · From 235 individuals studied at three or more intakes across 19 nitrogen-balance studies, the median requirement was 105 mg nitrogen/kg/day and the 97.5th percentile 132 mg, equal to 0.65 and 0.83 g of good-quality protein/kg/day; no significant differences by climate, age class, sex or protein source, with an indication that women may need less.

  2. 2.

    Trumbo P, Schlicker S, Yates AA, Poos M; Food and Nutrition Board of the Institute of Medicine. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. Journal of the American Dietetic Association. 2002. PMID 12449285. DOI 10.1016/s0002-8223(02)90346-9.

    Guideline · The Institute of Medicine's published summary of the macronutrient Dietary Reference Intakes, which set the protein RDA at 0.8 g/kg/day and the estimated average requirement at 0.66 for adults of every age; the record carries no abstract, and the figures are quoted here as restated in Humayun 2007, Traylor 2018 and Bhasin 2018.

  3. 3.

    Humayun MA, Elango R, Ball RO, Pencharz PB. Reevaluation of the protein requirement in young men with the indicator amino acid oxidation technique. American Journal of Clinical Nutrition. 2007. PMID 17921376. DOI 10.1093/ajcn/86.4.995.

    Laboratory method study · In eight healthy men given graded intakes of 0.10 to 1.8 g/kg/day, the indicator amino acid oxidation breakpoint gave a mean requirement of 0.93 and a population-safe intake of 1.2 g/kg/day, 41 and 50 percent above the current EAR of 0.66 and RDA of 0.80; biphase reanalysis of nitrogen-balance data gave 0.91 and 1.0.

  4. 4.

    Traylor DA, Gorissen SHM, Phillips SM. Perspective: Protein Requirements and Optimal Intakes in Aging: Are We Ready to Recommend More Than the Recommended Daily Allowance?. Advances in Nutrition. 2018. PMID 29635313. DOI 10.1093/advances/nmy003.

    Review · The Dietary Reference Intakes set the protein RDA at 0.8 g/kg/day for everyone over 19; metabolic and observational evidence suggests it is inadequate for older adults; the authors propose at least 1.2 g/kg/day for older individuals with emphasis on leucine, call for longer trials, and state that the cited renal and bone harms of higher intake lack a scientific foundation in humans.

  5. 5.

    Berryman CE, Lieberman HR, Fulgoni VL 3rd, Pasiakos SM. Protein intake trends and conformity with the Dietary Reference Intakes in the United States: analysis of the National Health and Nutrition Examination Survey, 2001-2014. American Journal of Clinical Nutrition. 2018. PMID 29931213. DOI 10.1093/ajcn/nqy088.

    Cross-sectional study · Among 57,980 Americans aged 2 and over, usual protein intake ran from 55.3 to 88.2 g/day and 14 to 16 percent of energy; relative intake from 1.10 g per kg ideal body weight per day in adults 71 and older to 3.63 in young children, above the EAR in every group; 11 percent of adolescent girls and 13 percent of older non-Hispanic Black men below the EAR; under 1 percent above the acceptable macronutrient range.

  6. 6.

    Houston DK, Nicklas BJ, Ding J, et al.; Health ABC Study. Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) Study. American Journal of Clinical Nutrition. 2008. PMID 18175749. DOI 10.1093/ajcn/87.1.150.

    Prospective cohort · In 2,066 adults aged 70 to 79, the highest fifth of energy-adjusted protein intake lost about 40 percent less lean mass over three years than the lowest fifth (0.501 against 0.883 kg total; 0.400 against 0.661 kg appendicular), an association that survived adjustment for change in fat mass.

  7. 7.

    Cuthbertson D, Smith K, Babraj J, et al.. Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB Journal. 2005. PMID 15596483. DOI 10.1096/fj.04-2640fje.

    Laboratory method study · In 44 healthy young and old men of similar build, basal muscle protein synthesis was indistinguishable, but older muscle showed less sensitivity and responsiveness to essential amino acids with reduced expression and activation of mTOR, p70 S6 kinase, 4E-BP1 and eIF2B and raised NF-kB, with insulin clamped at basal values.

  8. 8.

    Milton K. The critical role played by animal source foods in human (Homo) evolution. Journal of Nutrition. 2003. PMID 14672286. DOI 10.1093/jn/133.11.3886S.

    Review · Plant foods make up 87 to more than 99 percent of great ape diets; in plant-eating mammals larger size means lower diet quality; routine animal-source foods let the evolving human line escape that constraint and grow a large brain while remaining large, active and social.

  9. 9.

    Cordain L, Miller JB, Eaton SB, Mann N, Holt SH, Speth JD. Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets. American Journal of Clinical Nutrition. 2000. PMID 10702160. DOI 10.1093/ajcn/71.3.682.

    Review · From the ethnographic compilation of hunter-gatherer societies, 73 percent drew more than half their subsistence from animal foods and 14 percent from gathered plants; estimated protein intake 19 to 35 percent of energy and carbohydrate 22 to 40 percent, with a maximal protein ceiling shaping the choice of other macronutrients.

  10. 10.

    Bilsborough S, Mann N. A review of issues of dietary protein intake in humans. International Journal of Sport Nutrition and Exercise Metabolism. 2006. PMID 16779921. DOI 10.1123/ijsnem.16.2.129.

    Review · The limits on protein intake are the gut's amino-acid absorption rate (1.3 to 10 g an hour) and the liver's capacity to make urea; above about 35 percent of energy protein causes hyperaminoacidemia, hyperammonemia, nausea, diarrhea and, historically, death (rabbit starvation); the authors suggest a practical maximum near 25 percent of energy, about 2 to 2.5 g/kg/day.

  11. 11.

    Rudman D, DiFulco TJ, Galambos JT, Smith RB 3rd, Salam AA, Warren WD. Maximal rates of excretion and synthesis of urea in normal and cirrhotic subjects. Journal of Clinical Investigation. 1973. PMID 4727456. DOI 10.1172/JCI107410.

    Laboratory method study · Maximal urea synthesis averaged 65 mg urea nitrogen an hour per kg of metabolic body weight in 10 healthy people (range 55 to 76) and 27 in 34 people with cirrhosis; a large protein dose raised blood urea nitrogen 7 to 20 mg/dL over eight hours, and larger doses prolonged rather than raised the maximal rate, to 28 hours.

  12. 12.

    Moore DR, Robinson MJ, Fry JL, et al.. Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. American Journal of Clinical Nutrition. 2009. PMID 19056590. DOI 10.3945/ajcn.2008.26401.

    Laboratory method study · In six young men after leg exercise, muscle and albumin protein synthesis rose with 0, 5, 10, 20 and 40 g of egg protein and plateaued at 20 g; leucine oxidation rose at 20 and 40 g, showing protein beyond the rate of incorporation is irreversibly oxidized.

  13. 13.

    Witard OC, Jackman SR, Breen L, Smith K, Selby A, Tipton KD. Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise. American Journal of Clinical Nutrition. 2014. PMID 24257722. DOI 10.3945/ajcn.112.055517.

    Randomized trial · In 48 resistance-trained young men of about 80 kg, 20 and 40 g of whey after exercise raised myofibrillar protein synthesis 49 and 56 percent above 0 g, 10 g added nothing, and 40 g raised phenylalanine oxidation and urea production.

  14. 14.

    Simpson SJ, Raubenheimer D. Obesity: the protein leverage hypothesis. Obesity Reviews. 2005. PMID 15836464. DOI 10.1111/j.1467-789X.2005.00178.x.

    Review · Protein makes up about 15 percent of dietary energy and has stayed near constant within and across populations through the obesity epidemic; the authors formalize a model in which a tightly regulated protein appetite, diluted by fat and carbohydrate, drives total intake, with supporting data and predictions for testing.

  15. 15.

    Dickinson JM, Fry CS, Drummond MJ, et al.. Mammalian target of rapamycin complex 1 activation is required for the stimulation of human skeletal muscle protein synthesis by essential amino acids. Journal of Nutrition. 2011. PMID 21430254. DOI 10.3945/jn.111.139485.

    Randomized trial · In eight young adults, 10 g of essential amino acids raised muscle protein synthesis about 60 percent with mTOR, S6K1 and 4E-BP1 phosphorylation; a single prior oral dose of rapamycin completely blocked the rise without changing amino-acid availability, establishing mTORC1 activation as required.

  16. 16.

    Katsanos CS, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe RR. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. American Journal of Physiology: Endocrinology and Metabolism. 2006. PMID 16507602. DOI 10.1152/ajpendo.00488.2005.

    Laboratory method study · After 6.7 g of essential amino acids, muscle protein synthesis rose in young volunteers with 26 or 41 percent leucine; in elderly volunteers it did not rise with 26 percent leucine (0.044 to 0.049 percent an hour) but did with 41 percent (0.038 to 0.056), with no further stimulation in the young.

  17. 17.

    Atherton PJ, Etheridge T, Watt PW, et al.. Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling. American Journal of Clinical Nutrition. 2010. PMID 20844073. DOI 10.3945/ajcn.2010.29819.

    Laboratory method study · In eight young men, 48 g of whey raised myofibrillar protein synthesis from 0.03 to 0.10 percent an hour at 45 to 90 minutes, after which it returned to baseline although plasma essential amino acids stayed 130 percent above fasting at 120 minutes and 80 percent at 180; mTORC1 signaling stayed elevated after synthesis fell.

  18. 18.

    Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell. 2008. PMID 18843793. DOI 10.1111/j.1474-9726.2008.00417.x.

    Cross-sectional study · Severe long-term calorie restriction without malnutrition (one and six years) did not lower IGF-1 or the IGF-1 to IGFBP-3 ratio in humans, unlike rodents; reducing protein from 1.67 to 0.95 g/kg/day for three weeks in six volunteers practicing calorie restriction lowered IGF-1 from 194 to 152 ng/mL.

  19. 19.

    Bhasin S, Apovian CM, Travison TG, et al.. Effect of Protein Intake on Lean Body Mass in Functionally Limited Older Men: A Randomized Clinical Trial. JAMA Internal Medicine. 2018. PMID 29532075. DOI 10.1001/jamainternmed.2018.0008.

    Randomized trial · In 92 functionally limited men aged 65 and over with usual intake within the RDA, six months of controlled diets at 1.3 against 0.8 g/kg/day, with or without weekly testosterone, did not differ in lean body mass (0.31 kg, CI minus 0.46 to 1.08), strength, power, physical function or well-being and did not augment the testosterone response; fat mass fell 1.12 kg more on higher protein.

  20. 20.

    Bauer J, Biolo G, Cederholm T, et al.. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. Journal of the American Medical Directors Association. 2013. PMID 23867520. DOI 10.1016/j.jamda.2013.05.021.

    Consensus statement · For adults over 65: average intake at least 1.0 to 1.2 g/kg/day; 1.2 or more for those exercising; 1.2 to 1.5 for most with acute or chronic disease; those with severe kidney disease (eGFR below 30) not on dialysis may need to limit protein; evidence on protein quality, timing and supplements insufficient for specific recommendations.

  21. 21.

    Deutz NE, Bauer JM, Barazzoni R, et al.. Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group. Clinical Nutrition. 2014. PMID 24814383. DOI 10.1016/j.clnu.2014.04.007.

    Consensus statement · After a 2013 workshop: healthy older people should eat at least 1.0 to 1.2 g protein/kg/day; those malnourished or at risk because of acute or chronic illness 1.2 to 1.5, higher with severe illness or injury; all older people should take daily physical activity or exercise for as long as possible.

  22. 22.

    Rafii M, Chapman K, Owens J, et al.. Dietary protein requirement of female adults >65 years determined by the indicator amino acid oxidation technique is higher than current recommendations. Journal of Nutrition. 2015. PMID 25320185. DOI 10.3945/jn.114.197517.

    Laboratory method study · In 12 free-living women over 65 studied across 82 study days at intakes of 0.2 to 2.0 g/kg/day, the mean requirement was 0.96 and the upper 95 percent bound (approximating an RDA) 1.29 g/kg/day, against the current 0.66 and 0.80.

  23. 23.

    Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney International. 2024. PMID 38490803. DOI 10.1016/j.kint.2023.10.018.

    Guideline · Recommendation 3.3.1.1 suggests maintaining protein intake at 0.8 g/kg/day in adults with CKD G3 to G5 (2C); practice points advise avoiding intakes above 1.3 g/kg/day in adults with CKD at risk of progression and against low-protein diets in metabolically unstable people; the text notes average intakes of about 1.2 g/kg/day in many societies and that requirements in CKD do not differ from healthy adults absent intercurrent disease. Read from the guideline PDF; the PubMed record has no abstract.

  24. 24.

    Morton RW, Murphy KT, McKellar SR, et al.. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. British Journal of Sports Medicine. 2018. PMID 28698222. DOI 10.1136/bjsports-2017-097608.

    Systematic review and meta-analysis · Across 49 randomized trials with 1,863 participants training six weeks or more, protein supplementation added 2.49 kg to one-repetition-maximum strength, 0.30 kg to fat-free mass and 310 square micrometers to fiber cross-section; the fat-free mass effect fell with age and rose with training experience; no further gain beyond a total intake of 1.62 g/kg/day; lead author discloses dairy industry support.

  25. 25.

    Nunes EA, Colenso-Semple L, McKellar SR, et al.. Systematic review and meta-analysis of protein intake to support muscle mass and function in healthy adults. Journal of Cachexia, Sarcopenia and Muscle. 2022. PMID 35187864. DOI 10.1002/jcsm.12922.

    Systematic review and meta-analysis · Across 74 randomized trials in healthy non-obese adults, increasing daily protein raised lean body mass with resistance exercise (SMD 0.22, 62 studies, moderate certainty), significant at 1.2 to 1.59 g/kg/day in adults 65 and older and at 1.6 or more in younger adults; lower-body strength SMD 0.40 at 1.6 or more (19 studies, low certainty); handgrip effect unclear; physical function marginal.

  26. 26.

    Tieland M, Dirks ML, van der Zwaluw N, et al.. Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: a randomized, double-blind, placebo-controlled trial. Journal of the American Medical Directors Association. 2012. PMID 22770932. DOI 10.1016/j.jamda.2012.05.020.

    Randomized trial · In 62 frail adults (mean age 78) training twice a week for 24 weeks, 15 g of protein twice a day raised lean body mass from 47.2 to 48.5 kg while placebo did not change it (45.7 to 45.4 kg); strength and physical performance improved in both groups with no supplement effect.

  27. 27.

    Tieland M, van de Rest O, Dirks ML, et al.. Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial. Journal of the American Medical Directors Association. 2012. PMID 22889730. DOI 10.1016/j.jamda.2012.07.005.

    Randomized trial · In 65 frail adults given 15 g of protein at breakfast and lunch or placebo for 24 weeks without training, skeletal muscle mass and fiber size did not change in either group; physical performance improved from 8.9 to 10.0 points on protein against 7.8 to 7.9 on placebo, and leg extension strength tended to rise more on protein.

  28. 28.

    Moore DR, Churchward-Venne TA, Witard O, et al.. Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men. Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2015. PMID 25056502. DOI 10.1093/gerona/glu103.

    Laboratory method study · Retrospective breakpoint analysis of dose-response data: basal synthesis rates did not differ, but myofibrillar protein synthesis plateaued after 0.40 g protein/kg body mass in men of about 71 against 0.24 in men of about 22 (0.60 against 0.25 g/kg lean mass).

  29. 29.

    Mamerow MM, Mettler JA, English KL, et al.. Dietary protein distribution positively influences 24-h muscle protein synthesis in healthy adults. Journal of Nutrition. 2014. PMID 24477298. DOI 10.3945/jn.113.185280.

    Randomized trial · In eight adults (mean age about 37) on a seven-day crossover, protein spread evenly (31.5, 29.9 and 32.7 g at three meals) raised 24-hour mixed muscle protein synthesis 25 percent over the same protein skewed toward dinner (10.7, 16.0 and 63.4 g): 0.075 against 0.056 percent an hour, maintained after seven days; two authors disclose paid speaking for a beef industry association.

  30. 30.

    Weigle DS, Breen PA, Matthys CC, et al.. A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. American Journal of Clinical Nutrition. 2005. PMID 16002798. DOI 10.1093/ajcn.82.1.41.

    Randomized trial · In 19 adults moved from 15 to 30 percent of energy from protein at constant carbohydrate, satiety rose markedly on the matched-calorie diet; on the free-eating diet for 12 weeks spontaneous intake fell 441 kcal a day, weight 4.9 kg and fat mass 3.7 kg despite lower leptin and higher ghrelin.

  31. 31.

    Wycherley TP, Moran LJ, Clifton PM, Noakes M, Brinkworth GD. Effects of energy-restricted high-protein, low-fat compared with standard-protein, low-fat diets: a meta-analysis of randomized controlled trials. American Journal of Clinical Nutrition. 2012. PMID 23097268. DOI 10.3945/ajcn.112.044321.

    Systematic review and meta-analysis · Across 24 trials with 1,063 participants (mean 12.1 weeks), matched-calorie higher-protein low-fat diets produced 0.79 kg more weight loss, 0.87 kg more fat loss and 0.23 mmol/L lower triglycerides than standard-protein diets, spared 0.43 kg of fat-free mass and 595.5 kJ/day of resting energy expenditure, with no difference in fasting glucose, insulin, blood pressure or cholesterol; greater satiety in 3 of 5 studies.

  32. 32.

    Leidy HJ, Clifton PM, Astrup A, et al.. The role of protein in weight loss and maintenance. American Journal of Clinical Nutrition. 2015. PMID 25926512. DOI 10.3945/ajcn.114.084038.

    Review · Meta-analyses of controlled feeding studies show greater weight and fat loss and lean-mass preservation on higher-protein energy restriction; acute trials show a modest satiety effect without reliably lower intake at the next meal; long-term results are limited by compliance; the authors read the evidence as supporting 1.2 to 1.6 g/kg/day with about 25 to 30 g of protein per meal.

  33. 33.

    Pasiakos SM, Cao JJ, Margolis LM, et al.. Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial. FASEB Journal. 2013. PMID 23739654. DOI 10.1096/fj.13-230227.

    Randomized trial · In 39 adults fed 0.8, 1.6 or 2.4 g protein/kg/day through 10 days of maintenance and a 21-day 40 percent energy deficit, all lost 3.2 kg; the proportion lost as fat-free mass was lower and fat loss higher at 1.6 and 2.4, and only the RDA group lost its muscle's anabolic response to a protein-rich meal.

  34. 34.

    Longland TM, Oikawa SY, Mitchell CJ, Devries MC, Phillips SM. Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss: a randomized trial. American Journal of Clinical Nutrition. 2016. PMID 26817506. DOI 10.3945/ajcn.115.119339.

    Randomized trial · In 40 young men on a 40 percent energy deficit training six days a week for four weeks, 2.4 against 1.2 g protein/kg/day gained 1.2 against 0.1 kg of lean mass and lost 4.8 against 3.5 kg of fat, with no difference in exercise performance.

  35. 35.

    Devries MC, Sithamparapillai A, Brimble KS, Banfield L, Morton RW, Phillips SM. Changes in Kidney Function Do Not Differ between Healthy Adults Consuming Higher- Compared with Lower- or Normal-Protein Diets: A Systematic Review and Meta-Analysis. Journal of Nutrition. 2018. PMID 30383278. DOI 10.1093/jn/nxy197.

    Systematic review and meta-analysis · Across 28 randomized trials with 1,358 adults without kidney disease, higher-protein diets (1.5 g/kg/day or more, 20 percent or more of energy, or 100 g/day or more) left the change in GFR no different from lower-protein diets (SMD 0.11, CI minus 0.05 to 0.27); post-intervention GFR was trivially higher (SMD 0.19); unclear selection bias was the main limitation.

  36. 36.

    Brenner BM, Meyer TW, Hostetter TH. Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. New England Journal of Medicine. 1982. PMID 7050706. DOI 10.1056/NEJM198209093071104.

    Review · The hypothesis paper that linked dietary protein to progressive kidney disease through hemodynamically mediated glomerular injury in aging, reduced kidney mass and intrinsic renal disease; the PubMed record carries no abstract and the entry characterizes it from its title only, as the origin of the kidney concern.

  37. 37.

    Knight EL, Stampfer MJ, Hankinson SE, Spiegelman D, Curhan GC. The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency. Annals of Internal Medicine. 2003. PMID 12639078. DOI 10.7326/0003-4819-138-6-200303180-00009.

    Prospective cohort · In 1,624 Nurses' Health Study women followed 11 years, protein intake by food-frequency questionnaire was not associated with change in estimated GFR in women with normal function (0.25 mL/min per 1.73 m2 per 10 g/day); in women with mild insufficiency (eGFR 55 to 80) each 10 g/day went with a 1.69 mL/min per 1.73 m2 decline, 1.21 per 10 g of non-dairy animal protein.

  38. 38.

    Naghshi S, Sadeghi O, Willett WC, Esmaillzadeh A. Dietary intake of total, animal, and plant proteins and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of prospective cohort studies. BMJ. 2020. PMID 32699048. DOI 10.1136/bmj.m2412.

    Systematic review and meta-analysis · Across 31 cohorts with 715,128 participants and 113,039 deaths over 3.5 to 32 years, highest against lowest total protein carried all-cause mortality 0.94 (0.89 to 0.99), plant protein 0.92 for all-cause and 0.88 for cardiovascular mortality, animal protein no significant association with cardiovascular or cancer mortality; each additional 3 percent of energy from plant protein went with 5 percent lower all-cause mortality.

  39. 39.

    Song M, Fung TT, Hu FB, et al.. Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality. JAMA Internal Medicine. 2016. PMID 27479196. DOI 10.1001/jamainternmed.2016.4182.

    Prospective cohort · In 131,342 US health professionals, animal protein (median 14 percent of energy) carried all-cause mortality 1.02 per 10 percent of energy and cardiovascular mortality 1.08; plant protein (median 4 percent) carried 0.90 all-cause and 0.88 cardiovascular per 3 percent; associations confined to those with at least one unhealthy lifestyle factor; substituting plant protein for processed red meat 0.66, unprocessed red meat 0.88, egg 0.81.

  40. 40.

    Huang J, Liao LM, Weinstein SJ, Sinha R, Graubard BI, Albanes D. Association Between Plant and Animal Protein Intake and Overall and Cause-Specific Mortality. JAMA Internal Medicine. 2020. PMID 32658243. DOI 10.1001/jamainternmed.2020.2790.

    Prospective cohort · In 416,104 NIH-AARP adults (77,614 deaths over 6 million person-years), each standard deviation more plant protein carried overall mortality 0.95 in both sexes; replacing 3 percent of energy from animal with plant protein went with 10 percent lower overall and 11 to 12 percent lower cardiovascular mortality, chiefly by substituting for egg (24 and 21 percent) and red meat protein (13 and 15 percent).

  41. 41.

    Budhathoki S, Sawada N, Iwasaki M, et al.; Japan Public Health Center-based Prospective Study Group. Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality in a Japanese Cohort. JAMA Internal Medicine. 2019. PMID 31682257. DOI 10.1001/jamainternmed.2019.2806.

    Prospective cohort · In 70,696 Japanese adults aged 45 to 74 with 12,381 deaths, animal protein showed no clear association with mortality; plant protein quintiles 2 to 5 carried 0.89, 0.88, 0.84 and 0.87 for total mortality; substituting 3 percent of energy from plant protein for red meat protein 0.66 and for processed meat protein 0.54.

  42. 42.

    Levine ME, Suarez JA, Brandhorst S, et al.. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metabolism. 2014. PMID 24606898. DOI 10.1016/j.cmet.2014.02.006.

    Prospective cohort · Survey respondents aged 50 to 65 reporting high protein intake had 75 percent higher overall mortality and four-fold higher cancer mortality over 18 years, abolished or attenuated for plant protein; over 65, high protein went with lower cancer and overall mortality; five-fold higher diabetes mortality at all ages; mouse experiments on GHR-IGF-1 signaling; senior author discloses an equity interest in a medical food company.

  43. 43.

    Milman S, Atzmon G, Huffman DM, et al.. Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity. Aging Cell. 2014. PMID 24618355. DOI 10.1111/acel.12213.

    Prospective cohort · Among 184 nonagenarians, women with IGF-1 at or below the median (96 ng/mL) survived significantly longer than women above it; no such advantage in men; in both sexes with a history of cancer, lower IGF-1 predicted longer survival, holding after multivariable adjustment.

  44. 44.

    Shams-White MM, Chung M, Du M, et al.. Dietary protein and bone health: a systematic review and meta-analysis from the National Osteoporosis Foundation. American Journal of Clinical Nutrition. 2017. PMID 28404575. DOI 10.3945/ajcn.116.145110.

    Systematic review and meta-analysis · Across 16 randomized trials and 20 prospective cohorts, moderate evidence that higher protein intake protects lumbar spine bone density (net 0.52 percent, CI 0.06 to 0.97, five trials), no effect at total hip, femoral neck or total body, and no adverse effects of higher protein intake.

  45. 45.

    Darling AL, Millward DJ, Torgerson DJ, Hewitt CE, Lanham-New SA. Dietary protein and bone health: a systematic review and meta-analysis. American Journal of Clinical Nutrition. 2009. PMID 19889822. DOI 10.3945/ajcn.2009.27799.

    Systematic review and meta-analysis · Protein intake was positively related to bone mineral density in every cross-sectional survey, explaining 1 to 2 percent of it; protein supplementation had a small positive effect on lumbar spine density in randomized trials; cohort studies showed no relation to hip fracture risk; effects small with confidence intervals near zero.

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