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Time-restricted6 human studies cited

18:6 Time-Restricted Eating

18 hours without food · Daily

Written by Reviewed Sep 2026

Also called: 6-hour eating window, 18-hour fast

A 6-hour eating window with an 18-hour fast. It produced the same weight loss as a 4-hour window in a head-to-head trial, and in that same trial its lean mass loss slightly exceeded its fat mass loss.

Overview

18:6 compresses eating into six hours. It has been tested against a 4-hour window in adults with obesity, in women with polycystic ovary syndrome over six months, and under supervised isocaloric feeding in men with prediabetes where the window was placed early and the weight was held constant.

The most useful trial for anyone considering it is Cienfuegos 2020, because it ran a 6-hour window and a 4-hour window side by side in the same trial with the same control. Both lost the same amount of weight. They did not lose the same tissue.

Energy intake fell by roughly 550 kcal/d in both short-window arms without any calorie counting, which is the largest spontaneous reduction measured in the time-restricted eating literature and is the most plausible explanation for the weight result.

How it works

Cienfuegos used fixed windows: 13:00 to 19:00 for the 6-hour arm and 15:00 to 19:00 for the 4-hour arm, in adults with a BMI of 30 to 50, with no restriction on what was eaten inside the window. Corapi used 13:00 to 19:00 for six months in women with PCOS, again with no calorie tracking. Sutton placed the six hours early, with dinner finished before 15:00, and provided every meal.

Compliance in Cienfuegos did not change over the eight weeks (P = 0.76), which is worth noting because the intuition is that a shorter window decays faster.

The practical problem this window creates is arithmetic. A person aiming at 1.6 g/kg/day of protein has six hours in which to eat it, which usually means three substantial protein feedings rather than the four to six the meal-distribution literature is built around.

What 18 hours actually reaches

An 18-hour daily fast has been measured to lower 24-hour glucose and reduce a marker of oxidative damage. Cienfuegos found 8-isoprostane falling 12 pg/mL in the 6-hour arm and 13 pg/mL, a 37% reduction, in the 4-hour arm, significantly different across groups (P = 0.02), with fasting insulin and insulin resistance improving in both while fasting glucose did not differ significantly. The authors noted 8-isoprostane was the only oxidative stress marker they measured. This is also the window length where the only direct human autophagy measurement in a time-restricted protocol sits. In 11 overweight adults doing a four-day crossover of an 08:00 to 14:00 window against 08:00 to 20:00, the early six-hour window raised expression of the autophagy gene LC3A and of SIRT1 in whole blood cells before breakfast (p < 0.04) and raised MTOR expression in the evening (p = 0.007), alongside a 4 mg/dL drop in mean 24-hour glucose. That is gene expression in blood cells over four days, not autophagic flux in muscle or liver, and it was measured with the window placed early. It is the reason this page carries autophagy as a mechanism the window reaches, and it is not the same thing as a threshold hour.

Fig. 1 · what has been measured, hour by hour
  1. 0h to 4h

    Still absorbing

    Burning
    Glucose from the meal just eaten, with insulin high enough to hold fat release down
    • Insulin is at its post-meal peak, and while it is there, adipose tissue lipase stays suppressed and fat is being stored rather than released.
    • The hour count on most fasting charts starts at the last bite. Absorption of a mixed meal is still running here, so the clock and the physiology are not yet the same thing.

    Read the biologyInsulin and insulin sensitivity during a fast

    Measured in people
    The human hour-by-hour fasting series begin later than this. Klein 1993 took its first sample at 12 hours in 6 healthy men, and Rothman 1991 reports its first gluconeogenesis figure as an average across the first 22 hours. This row is the fed state those measurements are compared against, and no extended-fasting measurement exists inside it.

  2. 4h to 12h

    Post-absorptive

    Burning
    A mix of remaining glucose and fatty acids, with the liver covering the brain's glucose demand
    Blood glucose
    5.58 ± 0.08 mmol/L (100.5 mg/dL) at the 12 hour mark, in 6 healthy men
    Ketones (BHB)
    Total ketone bodies around 0.20 mmol/L in overnight-fasted subjects. That figure is acetoacetate plus beta-hydroxybutyrate, not BHB on its own.
    Insulin
    64.6 ± 12.9 pmol/L (9.3 microunits/mL) at 12 hours, in the same 6 men
    • Glycerol release runs at 2.08 ± 0.22 and palmitic acid release at 1.63 ± 0.20 micromol/kg/min at 12 hours. Those are the numbers everything later in the fast is measured against.
    • Gluconeogenesis is already the majority contributor to glucose production rather than a reserve waiting to be called on, which is the first place the popular switch model breaks.

    Read the biologyInsulin and insulin sensitivity during a fastGlycogen depletion and gluconeogenesis

    Measured in people
    Klein 1993 measured glucose, insulin and stable-isotope lipid kinetics at 12 hours in 6 healthy men. Féry 1983 measured total ketone body turnover in overnight-fasted subjects and put the baseline at 0.20 mmol/L. Rothman 1991 measured hepatic glycogen serially by 13C nuclear magnetic resonance through a 68 hour fast in healthy adults and calculated that gluconeogenesis supplied 64 ± 5% of total glucose production across the first 22 hours.

  3. 12h to 18h

    Ketones have not moved yet

    Burning
    Fatty acids rising, with glucose production increasingly made rather than released from store
    Ketones (BHB)
    Median change of 0% between 12 and 18 hours, sampled every 6 hours in 34 adults
    • Beta-hydroxybutyrate does not move in this window. In 34 adults sampled every 6 hours through the standard diagnostic 72 hour fast, the median change from 12 to 18 hours was zero.
    • Gluconeogenesis is supplying 64 ± 5% of glucose production across the first 22 hours, confirmed by an orthogonal method at about 47% by 14 hours. Glucose production does not switch from glycogen to fat at a threshold hour.
    • Whole blood LC3A messenger RNA was 22 ± 5% higher at 18 hours than in a 12 hour control arm in 11 overweight adults (p = 0.001). In the same subjects MTOR expression also rose, by 9 ± 3%.

    Read the biologyGlycogen depletion and gluconeogenesisKetogenesis and beta-hydroxybutyrateAutophagy

    Measured in people
    Service 2005 measured beta-hydroxybutyrate every 6 hours in 34 adults whose 72 hour fasts were negative for insulinoma. Rothman 1991 measured the gluconeogenic share by 13C NMR. Jamshed 2019 measured whole blood messenger RNA in an 11-person 4 day randomised crossover of an 08:00 to 14:00 eating window against 08:00 to 20:00. That is one gene's expression in blood cells, not autophagic flux and not muscle. No study in any species has tested a 16 hour timepoint for autophagy.

  4. 18h to 1d

    The steepest hours for fat release

    past this window
    Burning
    Fatty acids and glycerol, with ketone production starting its climb
    Ketones (BHB)
    Climbing. The median rise from 18 to 36 hours was +333%, the steepest proportional stretch of a 72 hour fast.
    Insulin
    70% of the entire decline seen across a 72 hour fast has already happened by 24 hours
    • The largest single interval increase in lipolysis across a whole 72 hour fast falls between 18 and 24 hours, and 60% of the total rise in lipid kinetics happens between 12 and 24 hours. The authors attribute that to the falling insulin rather than to any change in glucose.
    • Growth hormone was significantly higher after a 24 hour water-only fast than after a fed day in a randomised crossover of 30 healthy adults (p = 1.1 x 10^-4). The size of that rise is not in the accessible record and is not published here.
    • Haemoglobin, red cell count and haematocrit all rose together at 24 hours in the same trial. That combination is the signature of plasma volume contraction, not of new red cells.
    • 24 hour energy expenditure measured in a whole-room calorimeter fell during 24 hour fasting in 20 volunteers, with the size of the fall varying between individuals.

    Read the biologyInsulin and insulin sensitivity during a fastThe growth hormone responseKetogenesis and beta-hydroxybutyrateAutophagy

    Measured in people
    Horne 2013 randomised 30 apparently healthy adults to a 24 hour water-only fast or a day of usual eating in crossover and measured growth hormone, blood counts, cholesterol, triglycerides, bicarbonate and weight. Klein 1993 measured the lipid kinetics by stable isotope tracer. Hollstein 2020 measured 24 hour energy expenditure by whole-room calorimetry in 20 volunteers; the exact percentage decrease is not in the accessible record and is not published here. On autophagy, a 24 hour fast raised p62/SQSTM1 in the vastus lateralis of 50 women, which is movement in the direction of less autophagic degradation rather than more.

  5. 1d to 36h

    Thyroid drops before metabolic rate does

    past this window
    Burning
    Fat, with the remaining glucose built from glycerol, lactate and amino acids
    Ketones (BHB)
    1.308 ± 1.053 mmol/L after day 1 in 13 men beginning a 10 day water fast, from a baseline of 0.177 ± 0.044. The spread on that mean is as wide as the mean.
    • Gluconeogenesis supplies 82 ± 5% of glucose production between 22 and 36 hours.
    • Serum T3 fell from 2.30 ± 0.06 to 1.84 ± 0.03 nmol/L by 30 hours in 8 healthy men (p < 0.01), TSH fell below 1 mU/L and the nocturnal TSH peak was abolished. Serum cortisol did not differ across conditions.
    • Thyroid suppression therefore begins inside the first 30 hours, well before any measurable fall in resting metabolic rate.
    • Sodium excretion has not turned yet. In 9 obese women fasting with pre-fast salt intake maintained, urinary sodium began to rise after roughly 48 hours and then exceeded intake.

    Read the biologyGlycogen depletion and gluconeogenesisKetogenesis and beta-hydroxybutyrateAutophagy

    Measured in people
    Rothman 1991 measured the gluconeogenic share by 13C NMR in healthy adults. Hugues 1984 fasted 8 healthy men for 30 hours with serial thyroid sampling. Dai 2022 measured blood beta-hydroxybutyrate daily in 13 men fasting in a controlled facility. Sigler 1975 collected urine in 3 hour blocks from 9 obese women on a metabolic ward. On autophagy, the only human study with several within-fast timepoints took vastus lateralis biopsies at 2, 12, 24 and 36 hours: LC3I, LC3II and p62 all fell, in untrained subjects only, which the authors summarise as skeletal muscle autophagy being only modestly affected by 36 hours of fasting.

Human evidence

One randomised trial comparing 6-hour and 4-hour windows head to head, one six-month randomised trial in PCOS, and one supervised controlled-feeding crossover where the window was early and weight was held constant.

  • Cienfuegos 2020, 8 weeks, 58 randomised into 6-hour, 4-hour and control arms. Both fasting arms lost 3.2% of body weight against 0.1% in control (both P < 0.001) with no difference between them. Fat mass fell 1.4 kg in the 6-hour arm and 2.8 kg in the 4-hour arm. Energy intake fell about 550 kcal/d in both without calorie counting. Visceral fat did not differ across arms (P = 0.43) (Cell Metabolism, 2020).
  • Corapi 2026, 6 months, 76 women with polycystic ovary syndrome randomised to a 13:00 to 19:00 window with no calorie tracking, 25% daily calorie restriction, or no-intervention control. Weight fell 4.32% versus control (95% CI -6.20 to -2.44; P < 0.01) and 4.66% on calorie restriction, with no difference between them (0.34%; P = 0.79). No serious adverse events (Nature Medicine, 2026).
  • Sutton 2018, a 5-week randomised crossover under isocaloric supervised feeding in men with prediabetes, with the 6-hour window placed early and dinner finished before 15:00. Compliance to provided meals was 100%. Insulin resistance measured by the 3-hour incremental AUC ratio fell 36 U/mg (P = 0.005) and the insulinogenic index rose 14 U/mg (P = 0.05), with morning systolic blood pressure 11 mmHg and diastolic 10 mmHg lower than control (both P = 0.03), all without weight loss. Glucose did not improve, and the authors say so directly. This is 8 completers, screened from 130 men, and should be read as proof of concept (Cell Metabolism, 2018).
  • The autophagy measurement: 11 overweight adults, 4-day randomised crossover of 08:00 to 14:00 versus 08:00 to 20:00. The early six-hour window raised whole blood cell expression of LC3A and SIRT1 before breakfast (p < 0.04) and MTOR in the evening (p = 0.007), and lowered mean 24-hour glucose by 4 mg/dL and glycaemic excursions by 12 mg/dL (Nutrients, 2019).

What this does not tell you: Cienfuegos ran 8 weeks with 16 to 19 completers per arm. Sutton had 8 completers and reported a carryover concern: after a 7-week washout, all but one participant who did the early window first entered the second arm with mean postprandial insulin at least 25% below baseline. The Nutrients autophagy trial measured gene expression in blood cells over four days, which is not the same as autophagic flux and is not muscle or liver. None of these trials measured protein intake in g/kg/day.

Reading the research record

The interesting disagreement at this window is not between research groups, it is inside a single trial. Cienfuegos found the 6-hour and 4-hour arms losing identical weight while splitting that weight very differently, with the 4-hour arm losing twice the fat mass and half the lean mass. If the shorter window were simply a more aggressive version of the longer one, that is not the pattern you would expect.

The second disagreement is between what the supervised and the free-living trials are able to show. Sutton fed participants to hold weight constant and still measured improvements in insulin sensitivity, beta cell responsiveness and blood pressure, which is the strongest existing evidence that something happens beyond calorie reduction. It is also 8 people, with a documented carryover effect, and it used an early window, so its findings cannot be transferred wholesale to the 13:00 to 19:00 window most people actually run.

Against it, Templeman 2021 built a trial specifically to separate fasting from energy deficit and found no fasting-specific effects on metabolic regulation or cardiovascular health once energy was matched, in 36 lean adults over 3 weeks. Both results are in the record and this page does not resolve them.

What happens to muscle

The 6-hour arm of Cienfuegos 2020 is the single most useful body composition result at this window and it deserves reading twice. That arm lost 1.5 kg of lean mass, significantly more than the 4-hour arm at 0.8 kg (P = 0.04) and more than control at 0.3 kg (P = 0.03), against a fat mass loss of 1.4 kg. Lean mass loss slightly exceeded fat mass loss. In the 4-hour arm the split ran the other way, 2.8 kg of fat against 0.8 kg of lean.

That sits at the unfavourable end of the range across the whole literature, which runs from approximately 9% of weight lost as lean in TIMET at a 10-hour window to approximately 65% in TREAT at an 8-hour window, with the 6-hour arm here above both. Neither Cienfuegos arm reported protein intake in g/kg/day, and neither included resistance training.

What the protein research says about that spread is consistent and specific. Trials of compressed windows that ran 1.6 to 2.2 g/kg/day alongside supervised resistance training preserved fat-free mass: Tinsley 2019 at 1.6, Stratton 2020 at 1.83 with an identical prescribed 25% deficit in both arms, Moro 2016 at 1.93. Parr 2023 at 1.0 g/kg/day lost more lean mass than its 12-hour control while integrated daily myofibrillar protein synthesis was identical between arms, 1.28 versus 1.26 %/day (p = 0.82). The variable that tracks lean mass outcomes is protein intake and training, not the number of hours. A six-hour window makes hitting that protein target harder, which is a different problem from the window causing the loss.

Doing it

Protein is the constraint
Six hours means roughly three protein feedings. A 100 g bolus produced a larger and longer anabolic response than 25 g in young men, lasting beyond 12 hours with negligible change in amino acid oxidation, so large single doses are not wasted. The problem is total intake, not per-meal ceiling.
Add resistance training if lean mass matters
The 6-hour arm of Cienfuegos lost more lean mass than fat mass with no training component. Every compressed-window trial that held fat-free mass included supervised resistance training.
Window placement changes what was measured
The insulin sensitivity and blood pressure results at this window come from an early window with dinner before 15:00, and the autophagy gene expression result comes from 08:00 to 14:00. The commonly used 13:00 to 19:00 window has weight and PCOS data behind it, not those measurements.
What breaks the fast
The trials enforced calories rather than intake. No randomised trial at this window tested a threshold below which a small caloric intake is neutral.
Shorter is not automatically more
The 4-hour and 6-hour arms lost the same weight. On the measured record, going shorter than six hours bought a different tissue split rather than more total loss, in one 8-week trial with 16 to 19 completers per arm.

Breaking the fast

No trial at this window prescribed a first meal, and the supervised trial that came closest provided every meal matched to its control arm. The measured physiology worth knowing is that postabsorptive myofibrillar synthesis sits around 0.03 to 0.05 %/h and rises with feeding, that the rise takes at least 90 minutes to begin, and that in young men at rest the anabolic response was identical whether 15 g of essential amino acids arrived as one bolus or in four fractions. Getting the total in matters more than the order it arrives in.

Citations

  1. Human2020
    Effects of 4- and 6-h Time-Restricted Feeding on Weight and Cardiometabolic Health: A Randomized Controlled Trial in Adults with Obesity

    Cell Metabolism

    58 randomised, 8 weeks, adults with obesity. 4-hour and 6-hour arms both lost 3.2% of body weight against 0.1% in control (P < 0.001), with no difference between them. Fat mass -1.4 kg (6-hour) and -2.8 kg (4-hour). Lean mass -1.5 kg in the 6-hour arm, more than the 4-hour arm at -0.8 kg (P = 0.04) and control at -0.3 kg (P = 0.03). Energy intake fell about 550 kcal/d without counting. 8-isoprostane fell 12 to 13 pg/mL across arms (P = 0.02). Visceral fat did not differ (P = 0.43).

  2. Human2026
    Time-restricted eating for body weight management in women with polycystic ovary syndrome: a randomized controlled trial

    Nature Medicine

    76 women with PCOS randomised to a 6-hour window (13:00 to 19:00, no calorie tracking), 25% daily calorie restriction, or control for 6 months. Weight fell 4.32% versus control (95% CI -6.20 to -2.44; P < 0.01) and 4.66% on calorie restriction, with no difference between them (0.34%; 95% CI -2.15 to 2.83; P = 0.79). No serious adverse events. Menstrual cycle outcomes are not in the abstract record.

  3. Human2018
    Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes

    Cell Metabolism

    5-week randomised crossover, isocaloric supervised feeding, 6-hour window with dinner before 15:00 versus 12 hours, in men with prediabetes. 8 completers screened from 130. Insulin resistance by 3-hour incremental AUC ratio -36 U/mg (P = 0.005), insulinogenic index +14 U/mg (P = 0.05), morning systolic -11 mmHg and diastolic -10 mmHg (both P = 0.03), 8-isoprostane -11 pg/mL (P = 0.05) partly driven by worsening in the control arm. Glucose did not improve. No weight change by design. Carryover was observed after a 7-week washout.

  4. Human2019
    Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans

    Nutrients

    11 overweight adults, 4-day randomised crossover of an 08:00 to 14:00 window versus 08:00 to 20:00. The early six-hour window raised whole blood cell expression of the autophagy gene LC3A and of SIRT1 before breakfast (p < 0.04), raised MTOR in the evening (p = 0.007), and lowered mean 24-hour glucose by 4 mg/dL and glycaemic excursions by 12 mg/dL. Gene expression in blood cells over four days, not autophagic flux in muscle or liver.

  5. Human2023
    Eight-hour time-restricted eating does not lower daily myofibrillar protein synthesis rates: A randomized control trial

    Obesity (Silver Spring)

    Cited here for the lean mass mechanism. 18 men at about 1.0 g/kg/day protein, 10 days of a compressed window versus a 12-hour control. Integrated daily myofibrillar protein synthesis was identical (1.28 versus 1.26 %/day, p = 0.82) while lean mass loss was greater in the compressed arm (-1.0 versus -0.2 kg, p = 0.01).

  6. Human2021
    A randomized controlled trial to isolate the effects of fasting and energy restriction on weight loss and metabolic health in lean adults

    Science Translational Medicine

    Cited here as the counterweight to Sutton. 36 lean healthy adults, 3 weeks, three arms designed to separate fasting from energy deficit. No fasting-specific effects on postprandial cardiometabolic indices, gut hormones or adipose gene expression once energy was matched (all P > 0.05).

What people report

These are uncontrolled self-reports, not evidence. They are here because they tell you what to expect and what to watch for, which the trial literature does not. They cannot tell you whether anything works.

  • Reaching the protein target inside six hours is the binding constraint
  • Appetite falling rather than rising after the first weeks
  • Larger, fewer meals, which suits some people and not others
  • Evening social eating becoming the main scheduling problem

Sources: Uncontrolled self-report. These reflect participant-reported experience and measured behaviour inside the trials cited here, including the roughly 550 kcal/d spontaneous intake reduction and the unchanged compliance across 8 weeks in Cienfuegos 2020. A separate review of what fasting communities report is still being compiled and nothing here is drawn from it.

Who this is wrong for

  • Anyone taking an SGLT2 inhibitor without a prescriber stopping it first, because ketoacidosis can develop at a normal-looking blood glucose.
  • Anyone on insulin, a sulfonylurea or a meglitinide without a prescriber adjusting the dose against a six-hour intake window.
  • Pregnancy and breastfeeding.
  • Anyone with a history of an eating disorder or current loss-of-control eating. A six-hour rule is a tighter rule, and the pattern that distinguishes a dietary practice from a disorder is rule-tightening rather than fast duration.
  • Children and adolescents.
  • Anyone with a BMI under 18.5 or meeting the NICE refeeding risk criteria.
  • Older adults at risk of sarcopenia, where each meal has to clear a higher protein dose to raise muscle protein synthesis and a six-hour window offers fewer meals in which to do it. No trial of time-restricted eating in older adults has run with lean mass as the primary outcome.
  • Anyone who cannot reliably reach their protein target inside six hours. That is the situation Parr 2023 measured, and lean mass fell further.

Questions

Is a 6-hour window better than an 8-hour one?
No trial has compared them head to head. What has been compared is 6 hours against 4 hours, in Cienfuegos 2020, and both lost the same weight, 3.2%. The difference between those two arms was what tissue came off: the 6-hour arm lost 1.5 kg of lean mass against 1.4 kg of fat, and the 4-hour arm lost 0.8 kg of lean against 2.8 kg of fat.
Does 18 hours reach autophagy?
One four-day crossover in 11 overweight adults measured raised expression of the autophagy gene LC3A in whole blood cells on an 08:00 to 14:00 window. That is a real human measurement at this window length and it is gene expression in blood cells over four days, not autophagic flux in muscle or liver, and the window was placed early. No study establishes 18 hours, or any hour, as a threshold at which autophagy switches on.
Can I hit my protein target in six hours?
That is the practical question this window raises. The human evidence says large single doses are not wasted: 100 g of protein after whole-body resistance exercise produced a greater and longer response than 25 g, lasting beyond 12 hours. It also says the trials that preserved lean mass on compressed windows ran 1.6 to 2.2 g/kg/day, and the one that ran 1.0 g/kg/day did not.