Prolonged Fasting (48+ Hours): What Happens

What Counts as a Prolonged Fast

Prolonged fasting usually refers to 48 hours or more without food, water only. This extends past the 24-to-72-hour range covered on water fasting, which is the more commonly attempted entry point, and the broader landscape of fasting types covered on what is fasting; this page picks up where those leave off, focused on what changes as a fast continues well past the point most people stop, and on the risks that become more material the longer a fast runs. Trials of prolonged fasting as a treatment for a specific diagnosed disease are a separate area and are not summarized here.

The Stages of a Prolonged Fast

As a fast lengthens, the body moves through a reasonably well understood metabolic sequence, described in the general fasting-physiology literature rather than measured hour by hour in a single trial that followed people across weeks (Cahill, 2006) [1].

Roughly the First Day: Glycogen Depletion

In the first day without food, the body draws down its stored glycogen, the short-term reserve of glucose held in the liver and muscles. A single 24-hour water-only fast significantly increased human growth hormone, red blood cell count, hematocrit, and total and HDL cholesterol, and decreased triglycerides and weight, compared with a day of normal eating, in a randomized crossover trial of 30 apparently healthy volunteers; in the 16 participants who fasted first, most of these changes, including growth hormone and cholesterol, were back to baseline after a following day of normal eating, except weight, with triglycerides also staying suggestively lower (Horne et al., 2013) [2]. A secondary analysis of the same trial found the growth-hormone rise was independent of weight loss and larger in people who started with lower growth-hormone levels, correlating with changes in glucose, hemoglobin, and IGF-1, a mechanism finding rather than a health outcome on its own (Horne et al., 2025) [3].

Roughly Day 2-3: The Shift to Ketone Metabolism

As glycogen runs out and insulin falls, the body shifts from burning glucose to breaking down fat into ketone bodies, with beta-hydroxybutyrate becoming a major fuel for the brain and sparing muscle protein that would otherwise be broken down for glucose (Cahill, 2006) [1]. That protein sparing is partial, not complete: across human trials of 5- to 20-day water fasts, roughly two-thirds of the weight lost was lean mass (Ezpeleta et al., 2024) [10]. This shift is what makes a multi-day fast physiologically sustainable at all (Rebello et al., 2025) [14]. A 72-hour water-only fast in five healthy adults found a biphasic pattern across several blood markers, cholesterol, an inflammation marker, and thyroid hormones rising or falling by the end of the fast and then moving back toward baseline after 11 days of refeeding, with only minor, reversible change in liver enzymes and electrolytes; insulin and glucose fell without reaching statistical significance in this small, 5-person pilot (Lauc et al., 2026) [4].

Beyond Day 3: Deepening Ketosis

The most detailed day-by-day human data cited here just past this point comes from a 7-day water-only fast in 12 healthy volunteers, which found distinct, body-wide protein changes, flagged by the study's own authors as pointing to both possible benefits and possible harms, appearing only after day three of complete calorie restriction, alongside an average weight loss of 5.7 kilograms (Pietzner et al., 2024) [11]. The kidney also adapts as ketosis deepens: nitrogen loss shifts from urea toward ammonia as the kidney increasingly uses glutamine, conserving muscle protein, while adjustments in urine sodium help limit potassium loss, and changes in urine pH help limit uric acid crystals (Palmer and Clegg, 2021) [6]. That same review names ketoacidosis from SGLT2-inhibitor medication, alongside diabetic and alcoholic ketoacidosis, as a related condition sharing the same underlying chemistry, directly relevant to the medication caution below (Palmer and Clegg, 2021) [6]. For how fasting is thought to trigger autophagy, the cell's internal recycling process, see autophagy and fasting; that mechanism is a separate question from the ketone-metabolism shift described here.

Ending the Fast: The Refeeding Transition

The longer a fast runs, the more deliberately it needs to end. See how to break a fast safely for the full refeeding guidance; in short, reintroducing food too quickly after an extended fast can cause a fall in blood phosphorus, potassium, or magnesium, a condition with a specific clinical definition and severity grading (da Silva et al., 2020) [15].

What Human Studies Show

Short Studies (24 Hours to 7 Days)

The direct human evidence on fasting length comes from a handful of small studies spanning 24 hours to 7 days: a randomized crossover trial of a 24-hour fast in 30 people (Horne et al., 2013) [2], a single-group 72-hour pilot in 5 people (Lauc et al., 2026) [4], and a single-group 7-day fast in 12 people (Pietzner et al., 2024) [11]. These are useful for understanding what happens inside the body over the first week, not for a settled claim about health outcomes at 48 hours and beyond; none followed participants for more than 11 days total, including refeeding.

Longer, Supervised Fasts (4-21 Days)

The key evidence on what a longer, supervised fast does to weight and metabolic markers is a one-year observational study of 1,422 people doing a supervised, modified fast of 4 to 21 days, with a small daily intake of 200 to 250 kilocalories rather than strictly zero calories: it found significant reductions in weight, waist circumference, and blood pressure, with adverse effects in fewer than 1% of participants (Wilhelmi de Toledo et al., 2019) [12]. This study had no control group. A chart review of 768 strictly water-only fasting visits under medical supervision found the highest-grade adverse event was severe (grade 3) in 212 visits and life-threatening (grade 4) in 1 visit, with no deaths, and 2 of 768 visits involved a serious adverse event (Finnell et al., 2018) [13]. A narrative review of human trials of prolonged water-only fasting lasting 5 to 20 days found weight loss of 2% to 10% of body weight, roughly two-thirds of it lean mass and one-third fat mass, which the authors flag as a concern suggesting increased muscle protein breakdown. Blood pressure consistently decreased, lipid effects were inconsistent, and glycemic measures improved in people with normal blood sugar but not in people with type 1 or type 2 diabetes. Reported adverse events included metabolic acidosis, headaches, insomnia, and hunger, and the metabolic improvements were no longer seen 3 to 4 months after the fast, even when the weight loss was maintained (Ezpeleta et al., 2024) [10].

Two Case Reports at the Extreme End (40 and 44 Days)

Two case reports cited here describe what happened at the far end of fasting length; they are case reports, not trials. A 57-year-old woman admitted to hospital after a 40-day water-only fast had low blood sodium on admission, then developed low potassium, phosphate, and magnesium during refeeding (Brett and Nesbit, 2013) [16]. A case report on a 44-day voluntary fast that produced a 25% body-weight loss found that, during early refeeding, despite a cautious start with a low-sodium, low-calorie liquid feed, the person developed marked low blood phosphate, fluid dilution, and mild swelling; vitamins B1, B12, and B6 were depleted; free fatty acids, ketone bodies, and zinc were abnormally high; liver function became abnormal over the first week; and the appetite hormones leptin and ghrelin were very low at the start of refeeding, with hunger rising along with a transient rise in two other hormones, orexin and resistin, as refeeding continued (Korbonits et al., 2007) [5]. Each is one person, not a generalizable finding; together, these are the two documented extreme-length cases cited here, showing what refeeding danger can look like after a very long fast.

Risks That Rise With Length

Almost all of the safety data on fasts of several days or longer come from medically supervised settings: a residential medical facility in the chart review of 768 water-only fasting visits (Finnell et al., 2018) [13], and a specialised fasting clinic in the 1,422-person study (Wilhelmi de Toledo et al., 2019) [12]. Their low rates of serious events describe supervised fasting. They cannot be read as the risk of a multi-day fast done alone at home, and no study cited here measures that risk. Anyone considering a fast longer than 48 hours should ask a clinician whether it should be done under medical supervision.

Refeeding Syndrome

Refeeding syndrome is a fall in blood phosphorus, potassium, or magnesium of 10% or more within five days of reintroducing calories, with severity graded by how far levels drop (da Silva et al., 2020) [15]. The two cases above show directly what that can look like at the extreme end (Brett and Nesbit, 2013 [16]; Korbonits et al., 2007) [5]. For the full risk-factor and incidence picture, see how to break a fast safely; this page states the risk plainly rather than re-deriving that detail.

Electrolyte Problems

Plain water has no electrolytes, and the longer a fast runs, the more the body's sodium, potassium, and magnesium balance can shift as glycogen and its associated water stores deplete. See electrolytes during a fast for the mechanism behind this. In a chart review of 768 medically supervised water-only fasting visits, both serious adverse events were fluid or electrolyte problems: a life-threatening low-sodium event on fasting day 9 and severe dehydration on fasting day 3, each in a different person, both of whom needed hospital care and recovered; the review does not report what caused either event (Finnell et al., 2018) [13]. A separate case report describes a woman admitted to hospital after a 40-day water-only fast with low sodium, who then developed low potassium, phosphate, and magnesium during refeeding (Brett and Nesbit, 2013) [16]. This is a general caution rather than a dosing guide, and nothing here is a substitute for a clinician's guidance on electrolyte replacement during a prolonged fast.

Medication Interactions (Diabetes Medication, SGLT2 Inhibitors)

SGLT2 inhibitors, a class of medicines used for type 2 diabetes and heart failure, can cause euglycemic ketoacidosis, a dangerous build-up of ketones without high blood sugar. A 2025 review describes this as a well-recognized adverse event in people with diabetes taking these medicines, and summarises six published cases in people without diabetes taking one for heart failure; in five of the six, the common risk factor was eating much less than usual because of illness, fasting, or surgery (Garg et al., 2025) [7]. The six cases show that the risk exists in people without diabetes too; they cannot say how often it happens. Anyone taking an SGLT2 inhibitor should talk to the prescribing clinician before any fast, and should not stop or change the medicine without that advice. More broadly, anyone on any diabetes or blood-pressure medication should not start any fast without that conversation first, and the same general caution applies to any other prescription medication, including blood thinners, since no study cited here tests a specific fasting-medication interaction beyond the SGLT2 class.

Who Should Talk to a Clinician Before a Prolonged Fast

Talk to a clinician before any fast, of any length, if you take any regular prescription medication, manage diabetes or blood pressure with medication, have kidney disease or heart failure, take a diuretic, are pregnant, are under 18, or have a history of an eating disorder. On pregnancy specifically: no study cited here tests prolonged water fasting in pregnancy directly. The closest available evidence is a meta-analysis of observational studies of daytime fasting in pregnancy, mostly during Ramadan, with no randomized trials; it found a small reduction in birth weight (about 94 g) without a higher rate of low birth weight (Giorno et al., 2025) [8]. That is a different kind of fasting and cannot show what a fast of 48 hours or longer does in pregnancy; this gap in the evidence is itself a reason for caution, not a basis for a specific claim about prolonged fasting in pregnancy.

How This Differs From a Shorter Water Fast

Water fasting covers the more commonly attempted 24-to-72-hour range: what it is, whether it is reasonably safe to try, and a first-pass safety list. This page covers a different question: what changes in the body as a fast continues well past that range, and the risks, refeeding syndrome, electrolyte shifts, and medication interactions, that become more material the longer a fast runs. The two pages deliberately overlap in the 48-to-72-hour band, since the stages described above genuinely span that window too; see "Where the studies disagree" in the box above for why that overlap is intentional. For related but shorter fasting patterns, see alternate-day fasting and hunger during intermittent fasting.

Authors and Funding of the Cited Studies

• Wilhelmi de Toledo et al., 2019 [12]: the lead author, FWT, is a member of the Directory Board of the Buchinger Wilhelmi Clinic (BWC), where the study was performed, and, as managing director of Amplius GmbH, executes the scientific leadership at BWC; Amplius GmbH "conceives, coordinates and develops fasting research on behalf of BWC." Co-author FG is currently employed, and co-author SD was formerly employed, at BWC. Co-author AM is a consultant at BWC and receives financial compensation for that role from Amplius GmbH.
• Finnell et al., 2018 [13]: "ACG is the director of the TrueNorth Health Center, president of the board of the TrueNorth Health Foundation, and member of the board of the National Health Association. He does not receive financial compensation for these roles. BCS and TRM are paid consultants for the TrueNorth Health Foundation, which is funded in part by the TrueNorth Health Center. JSF received funds from the National Health Association grant."
• Horne et al., 2025 [3]: one author, BH, discloses membership on the advisory board of Unleash Health and past consulting for Pfizer on risk scores, both "outside this work."
• Garg et al., 2025 [7], Giorno et al., 2025 [8], Pietzner et al., 2024 [11], and Rebello et al., 2025 [14]: each paper states the authors declare no competing interests.
• Disclosures are listed where the full text of the paper was available to us; a study not listed here is not a statement that its authors have no ties.

Safety and Cautions

This is general information, not medical advice. The direct human evidence on fasting length specifically is small, short-term-heavy at the controlled-trial end, and largely uncontrolled at the longer end; a systematic review of the broader fasting literature found only three randomized controlled trials in humans through January 2015, though those trials did show improvements in weight and cardiovascular risk markers, and concluded that more research is needed before fasting can be recommended as a health intervention (Horne et al., 2015) [9]. Talk to a clinician before any fast, of any length, if you are pregnant, under 18, have a history of an eating disorder, have kidney disease or heart failure, take a diuretic, take any regular prescription medication, or manage diabetes or blood pressure with medication. SGLT2-inhibitor medication carries a specific, documented ketoacidosis risk when combined with fasting (Garg et al., 2025) [7]. Stop and seek care for any severe or concerning symptom, and refeed gradually; see how to break a fast safely. For the broader pooled evidence on fasting generally, see what the research shows about fasting.