Biology: Muscle as an Organ

What It Is

Muscle moves you, and it does three other jobs that have nothing to do with how it looks. Those three are why it belongs in a biology library.

It is the body's largest metabolic organ. After a meal, most of the sugar leaving your blood is pulled into skeletal muscle, so how much of it you carry and how well it responds set how the whole body handles food. It is also an endocrine organ: a contracting muscle releases signaling proteins into the bloodstream that act on distant tissue. And it is a store of strength that declines with age, where the loss tracks with falls, dependence and death. Several of the practices in this section, lifting, walking after a meal, eating enough protein, act on this one tissue. This page describes the machinery; the pages that tell you what to do are linked at the bottom.

How It Works

What muscle does beyond movement

1It is the largest glucose sink

When insulin moves sugar out of the blood after a meal, about 80% of it goes into skeletal muscle. Fat tissue takes a small single-digit share and other tissues take very little. Because muscle is also a large fraction of body mass, its insulin sensitivity governs how the whole body handles a meal, which is why impaired glucose uptake into muscle is the earliest defect in type 2 diabetes.

2It secretes myokines when it contracts

A contracting muscle releases proteins into the blood that act on other tissue. These are called myokines, and their discovery established muscle as a secretory organ. The best characterized is interleukin-6, IL-6, produced by working fibers independent of any damage and rising up to about a hundredfold during a long bout of exercise. During exercise it acts as a metabolic messenger, promoting glucose uptake and fat oxidation. The same molecule raised chronically at rest is a pro-inflammatory signal, so IL-6 is not uniformly good.

3It signals to fat, bone, liver and brain

Myokines reach distant organs, which is what makes muscle an endocrine tissue. One example is the muscle-to-brain link: in mice, running raises a muscle protein called cathepsin B that crosses into the brain, raises the growth factor BDNF and new hippocampal neurons, and improves memory, with a small human sample pointing the same way. That pathway is early and mostly from animals. That muscle signals to the body is well established.

The three jobs stand on different amounts of evidence. The glucose-sink role is settled, measured in clamp studies that hold insulin high and track where the sugar goes. The endocrine role is established for IL-6 and still being worked out for the other candidate myokines. That any single myokine explains a particular health outcome is, for now, unsettled.

Irisin shows that gap most plainly. It was announced in 2012 as an exercise hormone that turns white fat into calorie-burning brown-like fat, and the claim spread fast. Some of the antibodies used to measure it turned out to be non-specific, and researchers questioned whether human irisin existed as described. Mass-spectrometry work later showed it does circulate in people, at low levels around 3.6 ng/ml that rise to about 4.3 ng/ml with training. Whether those levels do anything meaningful in the body is unsettled. Irisin sits at the emerging edge of the evidence, and much of the popular claim rests on mouse data and early tests that did not hold up.

What It Does

The findings below span the three jobs. The metabolic ones are well established. The endocrine ones are graded by how far each has been tested in people, with irisin kept at the emerging end. Grip strength, the longevity marker here, reflects muscle across the whole body.

The Research & Studies

Everything here is based on the research we have collected and checked, sorted into groups and ordered with the strongest evidence first. Click any claim to open the studies behind it.

How it works

Muscle takes up about 80% of the glucose insulin clearsStrong

In plain terms

After a meal, most of the sugar that leaves your blood is pulled into muscle. Skeletal muscle takes up about 80% of the glucose that insulin moves, which makes it the body's main sugar sink.

In detail

Euglycemic-hyperinsulinemic clamp studies established skeletal muscle as the principal site of insulin-mediated glucose disposal, taking up on the order of 80% under insulin stimulation, and identified impaired muscle glucose uptake as the earliest and primary defect in type 2 diabetes. Because muscle is such a large fraction of body mass, its insulin sensitivity dominates whole-body glucose handling.

The study · 1

DeFronzo & Tripathy, skeletal muscle insulin resistance is the primary defect in type 2 diabetes · Diabetes Care 2009;32 Suppl 2:S157-63

Resting muscle burns about 13 kcal per kg per dayStrong · mixed

In plain terms

At rest, a kilogram of muscle burns only about 13 calories a day, a few times more than fat but far less than the liver or brain. Gaining a few kilograms of muscle raises resting calorie burn by a modest amount, not the large figure often quoted.

In detail

Elia's classic organ metabolic rates put skeletal muscle at about 13 kcal/kg/day. Wang and colleagues validated those values across adulthood using whole-body resting energy expenditure by indirect calorimetry with organ and tissue masses measured by magnetic resonance imaging in 131 non-obese healthy adults, with age-adjusted muscle values near 12.6 kcal/kg/day in those over 50. Because muscle is a large fraction of body mass it still contributes a sizeable slice of total resting expenditure, but the per-kilogram rate is low, so the claim that gaining muscle greatly raises the metabolism overstates the effect.

Who this may not transfer to:Modelled in non-obese healthy adults; the per-kilogram rate is a tissue property expected to hold broadly, though a person's total contribution scales with how much muscle they carry.

The study · 1

Wang et al., specific metabolic rates of major organs and tissues across adulthood, evaluation by mechanistic model of resting energy expenditure · Am J Clin Nutr 2010;92(6):1369-77

Contracting muscle releases IL-6, rising up to about 100-foldModerate

In plain terms

When muscle contracts, it releases hormone-like proteins into the bloodstream. The clearest example is IL-6, which can climb up to a hundredfold during a long bout of exercise and signals to other organs, behaving as a messenger rather than a sign of injury.

In detail

Pedersen and Febbraio's work reframed muscle as a secretory (endocrine) organ. IL-6 is produced by contracting fibres independent of muscle damage; its release scales with exercise intensity, duration and low muscle glycogen, and in the exercise context it promotes glucose uptake and fat oxidation and drives anti-inflammatory cascades, in contrast to the pro-inflammatory role of chronically elevated resting IL-6. A growing list of other candidate myokines has since been catalogued.

The studies · 2

Pedersen & Febbraio, muscle as an endocrine organ, focus on muscle-derived interleukin-6 · Physiol Rev 2008;88(4):1379-406

Pedersen & Febbraio, muscles, exercise and obesity, skeletal muscle as a secretory organ · Nat Rev Endocrinol 2012;8(8):457-65

Building older muscle took 0.40 g protein per kg per meal, versus 0.24 in the youngModerate · mixed

In plain terms

Older muscle responds less readily to protein. To fully switch on muscle building, older men in these studies needed roughly 0.40 g of protein per kg of body weight in a meal, versus about 0.24 g/kg for young men, so the older body needs a bigger protein dose for the same signal.

In detail

Moore and colleagues retrospectively pooled myofibrillar protein synthesis data measured by primed constant L-[13C6]phenylalanine infusion after boluses of 0-40 g high-quality protein. Basal synthesis did not differ by age, but biphasic breakpoint analysis showed the per-meal protein needed to plateau synthesis was higher in older men (0.40 vs 0.24 g/kg body mass; 0.60 vs 0.25 g/kg lean body mass). This anabolic resistance is a leading reason muscle is harder to hold in later life.

Who this may not transfer to:Measured in men only; the per-meal protein threshold for maximal muscle protein synthesis in women has not been established the same way, so the exact figures should not be assumed identical.

The study · 1

Moore et al., protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in older versus younger men · J Gerontol A Biol Sci Med Sci 2015;70(1):57-62

Irisin circulates in people, its fat-browning role unsettledEmerging · mixed

In plain terms

Irisin is a much-hyped 'exercise hormone' said to turn ordinary fat into calorie-burning fat. The picture is unsettled: early antibody tests were unreliable and some researchers doubted it existed in people, though careful mass-spectrometry work later showed it does circulate, at low levels that rise a little with exercise.

In detail

The 2012 discovery paper described irisin as a PGC1-alpha-dependent myokine that drives brown-fat-like development of white adipose tissue in mice. The claim drew heavy scrutiny: a 2015 analysis argued the commercial ELISA antibodies were non-specific and questioned whether human irisin was real, while a 2015 tandem mass spectrometry study detected and quantified circulating human irisin and found it rose with exercise. The metabolic significance of those low circulating levels in humans is not established.

The studies · 3

Bostrom et al., a PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat (irisin discovery) · Nature 2012;481(7382):463-8

Albrecht et al., irisin, a myth rather than an exercise-inducible myokine · Sci Rep 2015;5:8889

Jedrychowski et al., detection and quantitation of circulating human irisin by tandem mass spectrometry · Cell Metab 2015;22(4):734-40

In mice, muscle-made cathepsin B lifts brain BDNF and memoryPreliminary

In plain terms

Exercising muscle may talk to the brain. In mice, running raises a muscle protein called cathepsin B that increases a growth factor (BDNF) and new hippocampal neurons, improving memory. A small human study found the same protein rose with fitness and tracked with memory, which is an early hint.

In detail

Moon and colleagues showed running increased cathepsin B in mouse muscle and plasma; recombinant cathepsin B raised BDNF and doublecortin in adult hippocampal progenitors, and cathepsin B knockout mice failed to gain neurogenesis and spatial memory from running. In a small cohort of healthy adults, treadmill-associated changes in cathepsin B correlated with fitness and memory. It is one strand of a broader muscle-organ crosstalk literature reviewed as the myokine field expanded.

The studies · 2

Moon et al., running-induced systemic cathepsin B secretion is associated with memory function · Cell Metab 2016;24(2):332-40

Severinsen & Pedersen, muscle-organ crosstalk, the emerging roles of myokines · Endocr Rev 2020;41(4):594-609

Blood Sugar

Each 10% more relative muscle mass, 11% lower insulin resistanceModerate

In plain terms

People carrying more muscle for their body size tend to handle blood sugar better. In a large US survey, each 10% more relative muscle mass came with about 11% lower insulin resistance and 12% less prediabetes.

In detail

Srikanthan and Karlamangla analyzed NHANES III (n=13,644), estimating skeletal muscle index by bioelectrical impedance as muscle mass relative to body weight. Across the full range, higher relative muscle mass was associated with lower HOMA-IR (11% relative reduction per 10% higher index, 95% CI 6-15%) and lower prevalence of prediabetes (12% relative reduction, 95% CI 1-21%), with associations stronger in non-diabetics, after adjustment for age, ethnicity, sex and generalized and central obesity.

The study · 1

Srikanthan & Karlamangla, relative muscle mass is inversely associated with insulin resistance and prediabetes (NHANES III) · J Clin Endocrinol Metab 2011;96(9):2898-903

Progress Markers

Each 11 lb (5 kg) weaker grip, 16% higher risk of deathModerate

In plain terms

How hard you can squeeze is a surprisingly strong marker of health. In a study of nearly 140,000 people, every 11 lb (5 kg) less grip strength went with a 16% higher risk of dying over the next few years, a better predictor of death than blood pressure.

In detail

The Prospective Urban Rural Epidemiology (PURE) cohort measured grip with a Jamar dynamometer. Over median 4.0 years, each 11 lb (5 kg) reduction in grip strength was associated with all-cause mortality HR 1.16 (95% CI 1.13-1.20), cardiovascular mortality 1.17, myocardial infarction 1.07 and stroke 1.09. Grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure.

The study · 1

Leong et al., prognostic value of grip strength, findings from the PURE study · Lancet 2015;386(9990):266-73

Measurement And Diagnosis

The 2019 sarcopenia consensus puts low strength ahead of low massModerate · mixed

In plain terms

For years sarcopenia was defined mainly by how much muscle you had. The updated expert consensus puts strength first, because how strong a person is predicts falls, disability and death better than muscle size does.

In detail

The European Working Group on Sarcopenia in Older People (EWGSOP2, 2019) moved low muscle strength to the front of the definition, with low muscle quantity or quality confirming it and poor physical performance marking severity. The change reflected accumulating evidence that strength is more closely tied to adverse outcomes than mass, and it set operational cut-points for grip strength and chair-rise testing.

The study · 1

Cruz-Jentoft et al., sarcopenia, revised European consensus on definition and diagnosis (EWGSOP2) · Age Ageing 2019;48(1):16-31

Much of the mechanism work is graded mechanistic because you cannot randomize someone to a different myokine system or a different amount of lifelong muscle. The grades are deliberately uneven: the glucose-sink and sarcopenia findings are firm, while the myokine-to-outcome findings, irisin above all, sit at the emerging end.

What It Means For You

Build muscle, then keep it. Muscle does its metabolic and endocrine work in proportion to how much of it there is and how well it functions.

Two levers do most of the work. Resistance training builds and holds the tissue, and its minimum effective dose is less than most people expect. Enough protein supplies the raw material, and it matters more with age. Older muscle shows anabolic resistance: in stable-isotope studies, fully switching on muscle protein synthesis took about 0.40 g of protein per kg per meal in older men against 0.24 g/kg in young men, so the same building signal needs a larger protein dose at seventy than at twenty.

Train for strength ahead of size. The updated definition of sarcopenia leads with low strength because strength predicts falls, disability and the loss of independent living better than muscle bulk does, so it is what protects independence. Holding muscle protects three things at once: glucose control, because a large muscle mass keeps clearing sugar; survival as a marker, because grip strength tracks mortality; and the ability to keep looking after yourself. The numbers here describe physiology, not your own target, which depends on the rest of your health and history, so the next step for anything specific is the person looking after you.

Go Deeper

This page describes the machinery. The pages that act on it, or use it:

• Resistance training, which builds and holds the tissue, and its minimum effective dose, the least work that still maintains it.
• Protein and muscle, the raw material, which matters more with age.
• Walking and insulin and glucose, which use the glucose-sink role directly, and type 2 diabetes, where it all comes together.
• Grip strength, the cheap read on whole-body robustness that this page treats as a marker.

The Chinese Medicine View

Common Questions

Is muscle really an organ?

By the working definition, yes. An organ is a tissue that does a coordinated job, and muscle does three beyond moving you. It is the largest sink for blood glucose, taking up about 80% of what insulin disposes of. It is a secretory tissue that releases signaling proteins called myokines into the blood when it contracts, which act on fat, bone, liver and brain, which is why it is called an endocrine organ. And it is a store of strength whose decline with age tracks with falls and death.

Does muscle burn a lot of calories at rest?

Less than the popular claim suggests. A kilogram of resting muscle burns only about 13 calories a day, a few times more than fat at about 4.5 but far below the liver at about 200 or the brain at about 240. Adding a few kilograms of muscle raises resting burn by a modest amount, not the large figure often quoted. The metabolic case for muscle comes from where a meal's glucose goes and from myokine signaling; resting calorie burn adds little.

Is irisin real?

The molecule exists. Irisin was described in 2012 as an exercise hormone that browns white fat in mice, and the claim spread fast. Early antibody tests were unreliable and some researchers doubted human irisin existed, though mass spectrometry later confirmed it circulates at low levels that rise a little with exercise. Whether those levels produce a meaningful effect in a human is unsettled, so irisin sits at the emerging end of the evidence.

Does muscle protect against diabetes?

It tracks with better glucose handling. Muscle is where most of a meal's sugar goes, so a larger, more responsive store of it means the body clears glucose more easily. In a survey of 13,644 US adults, each 10% more relative muscle mass came with about 11% lower insulin resistance and 12% less prediabetes. That is an association measured at one point in time, and insulin resistance itself drives muscle loss, so cause runs both ways. The direct route from muscle to glucose is covered on insulin and glucose.

Should I train for strength or size?

Strength, if you have to choose. Size and strength usually rise together, but the outcomes that matter with age track strength more closely, which is why the updated sarcopenia definition leads with it. In a study of nearly 140,000 adults, each 11 lb (5 kg) lower grip strength went with a 16% higher risk of dying over the next few years, a better predictor of death than blood pressure. Grip is a marker, not shown here to be a cause, and weakness often reflects underlying illness. The training that builds strength, resistance training, is what to spend the effort on.