2,4-Dinitrophenol (DNP) is an industrial chemical. It has been used to make explosives, dyes, wood preservatives and herbicides. It is not a medicine. For about five years in the 1930s it was sold in the US as a weight-loss drug, until cataracts, deaths and the 1938 Food, Drug, and Cosmetic Act ended that use (Colman, Regul Toxicol Pharmacol 2007).
DNP came back in the 2000s as an illegal “fat burner,” mostly bought online by bodybuilders and people trying to lose weight. The most important fact about it is how often it kills. In poison-center data from the US, UK and 38 countries, about 12–17% of reported systemic exposures ended in death (Potts et al., Clin Toxicol 2021; Gziut & Thomas, Clin Toxicol 2022). There is no antidote.
This page summarizes what the toxicology literature, poison centers and regulators report. It gives no dosing information, because no safe human dose has ever been established. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Nitrophenol industrial chemical; mitochondrial uncoupler |
| Formula / molecular weight | C₆H₄N₂O₅; 184.11 g/mol (PubChem) |
| Medical approval | None. Sold as an over-the-counter slimming drug in the US in the 1930s, then withdrawn |
| Mechanism | Carries protons across the inner mitochondrial membrane, so energy from food is released as heat instead of stored as ATP |
| Main danger | Uncontrolled hyperthermia, with death often within hours of an acute overdose |
| Case fatality (poison centers) | 11.6% (US) and 16.9% (UK), 2007–2018; 11.9% across 38 countries, 2010–2020 |
| Half-life | Not established in controlled studies; poisoning cases give blood estimates of ≈17–89 h |
| US status | Not an approved drug; FDA action and the 1938 Act ended its sale as a medicine |
| UK / Australia | UK regulated poison since October 1, 2023; Australia Schedule 10 (prohibited) since 2017 |
| WADA | Prohibited at all times, class S0 (non-approved substances) |
What it is
DNP is a small aromatic molecule: a phenol ring carrying two nitro groups. It is a yellow crystalline powder that stains skin, eyes and urine yellow (Grundlingh et al., J Med Toxicol 2011). Its CAS number is 51-28-5 (UK SI 2023/810).
History
DNP’s story is one of the earliest cautionary tales in modern drug regulation.
| Period | What happened |
|---|---|
| World War I | French munitions factories used DNP to make explosives. A 1919 report described 36 deaths among exposed workers. Better ventilation, protective equipment and hygiene cut the death rate from 16.3 to 1.2 per 10,000 tonnes handled |
| 1918 | First published death, from occupational exposure |
| 1933 | Maurice Tainter at Stanford reported that DNP raised metabolic rate and caused weight loss. It was soon sold without a prescription in over-the-counter slimming products |
| Mid-1930s | Deaths, rashes, nerve damage and fast-developing cataracts were reported in people taking it for weight loss. One 1936 series summarized 32 cataract cases (Rodin, Cal West Med 1936) |
| 1938 | The Federal Food, Drug, and Cosmetic Act gave FDA the power to stop its sale; DNP was withdrawn from the consumer market under FDA pressure and labeled “extremely dangerous and not fit for human consumption” |
| 1981–1986 | A Texas physician sold DNP tablets (“Mitcal”) through a weight-loss clinic. Court proceedings alleged over 14,000 people were treated. He was convicted in 1986 of drug-law violations |
| 2003 | The UK Food Standards Agency warned that DNP was not fit for human consumption, after a bodybuilder was hospitalized |
| 2000s–2010s | Online sales to bodybuilders and dieters; poison-center calls and deaths rise sharply in the UK, US and Australia |
Sources for this table: Grundlingh et al. 2011, Colman 2007 and Phillips & Singer, Neurology 2013, unless cited in the row.
Colman, writing from FDA’s metabolic drugs division, summarized the episode this way: the drug’s therapeutic index was “razor thin,” and thousands of people suffered irreversible harm before physicians abandoned it (Colman 2007). The therapeutic index is the gap between an effective dose and a toxic one.
Mechanism
Normally, mitochondria (the cell’s power plants) pump protons across their inner membrane. The protons then flow back through ATP synthase, which uses that flow to make ATP, the cell’s energy currency.
DNP is a weak acid that dissolves in membranes. It picks up protons on one side of the membrane and releases them on the other, short-circuiting ATP synthase. This is called uncoupling oxidative phosphorylation. The consequences follow directly (Grundlingh et al. 2011; Phillips & Singer 2013):
- Heat instead of ATP. The energy from burning fat and sugar is lost as heat. The body burns more fuel to meet its energy needs, which is the source of the weight loss.
- Heat production that continues while the drug is present. When sweating and fast breathing cannot shed the extra heat, body temperature climbs.
- Lactic acid build-up. Cells shift to glycolysis (burning sugar without oxygen) to make ATP, producing lactate and acidosis.
- ATP depletion. When ATP runs out, muscles cannot relax. Rigidity has been seen before death, and very rapid stiffening of the body within minutes after death is a repeatedly reported feature.
A 2026 Swedish case report proposed a “runaway uncoupling” loop (Lindeman et al., Toxicol Rep 2026). Uncoupling produces large amounts of CO₂, which makes tissue more acidic. Acidity in turn increases DNP uptake into mitochondria, which deepens uncoupling. This is a hypothesis based on two patients, but it fits the sudden, hard-to-reverse decline seen in many fatal cases.
Pharmacokinetics
No controlled human pharmacokinetic studies exist. What is known comes from poisoning cases.
- Absorption. Swallowing is the most common route. DNP is also absorbed through the skin and by breathing dust or fumes, and occupational skin exposure has caused deaths (Grundlingh et al. 2011).
- Metabolism. The liver reduces DNP to 2-amino-4-nitrophenol and 4-amino-2-nitrophenol, and conjugates DNP and its metabolites with glucuronic acid. In a 2026 fatal case, DNP-glucuronide and 2-amino-4-nitrophenol (plus its glucuronide) were the main urinary metabolites (Vanthourenhout et al., J Anal Toxicol 2026).
- Elimination. Estimates vary widely between patients and studies:
| Source | Patients | Estimated blood or plasma half-life |
|---|---|---|
| Silvester et al., J Med Toxicol 2026 | 1 woman, 18, acute-on-chronic overdose | 18 h (first-order kinetics) |
| Lindeman et al., Toxicol Rep 2026 | 1 survivor | 16.7 h in blood; functional uncoupling in platelets ≈4.9 days |
| Zhao et al., J Zhejiang Univ Sci B 2015 | 14 survivors of occupational poisoning treated with hemoperfusion | 88.8 ± 14.7 h (routine, n = 5); 54.6 ± 12.9 h (intensive, n = 9) |
In the Chinese occupational series, plasma DNP took up to 25 days to clear in most patients. In the Swedish survivor, hypermetabolism lasted more than a week, and the effect on mitochondria outlasted the blood level by days. The practical point from these reports is that toxicity can persist long after the last exposure.
Regulatory status
DNP is not an approved medicine; in the UK, for example, it has never been licensed as one (Kamour et al. 2015). Its legal status is defined by poison and chemical laws rather than drug approvals.
| Jurisdiction | Status |
|---|---|
| United States | Withdrawn from the consumer market in 1938 after the Food, Drug, and Cosmetic Act gave FDA authority over it (Colman 2007; Phillips & Singer 2013). Still made for industrial use. It is not an anabolic steroid and is not listed in Schedule III (21 CFR 1308.13) |
| United Kingdom | Added to the regulated poisons in Schedule 1A of the Poisons Act 1972, effective October 1, 2023 (SI 2023/63; SI 2023/810). Members of the public need a licence to acquire, possess or use it, and suppliers commit an offence if they sell without checking one (Poisons Act 1972, s. 3A) |
| Australia | Moved to Schedule 10 of the Poisons Standard (“substances of such danger to health as to warrant prohibition of sale, supply and use”), implemented February 2017 (Cairns et al., Med J Aust 2020) |
| Sport (WADA) | Named as an example in class S0, non-approved substances, prohibited at all times; a Specified Substance (WADA 2026 Prohibited List) |
Scheduling has not eliminated harm. In Australia, two of four DNP deaths identified in New South Wales poison-center and national coroner data occurred after the 2017 ban (Cairns et al. 2020). The authors noted that DNP is likely often bought online and disguised for shipping.
What the research shows
Toxicity in poison-center data
Poison centers give the best picture of how DNP harms people today. Every large dataset shows rising cases and a high death rate.
| Study | Setting and period | Systemic exposures | Deaths |
|---|---|---|---|
| Kamour et al., Emerg Med J 2015 | UK National Poisons Information Service, 2007–2013 | 30 (27 men; median age 23.5) | 5 (17%; 95% CI 6.9–34%) |
| Potts et al., Clin Toxicol 2021 | US and UK poison centers, 2007–2018 | 204 (86 US, 118 UK) | US 11.6% (95% CI 6.4–20.1%); UK 16.9% (95% CI 11.3–24.7%) |
| Gziut & Thomas, Clin Toxicol 2022 | 38 countries, WHO collaboration, 2010–2020 | 456 (303 male, 125 female) | 11.9% (95% CI 9.0–15.4%) where outcome known |
| Cairns et al., Med J Aust 2020 | New South Wales, Australia, 2004–2018 | 24 | 4 DNP deaths across poison-center and coroner data, all since 2015 |
Key details from these reports:
- Rapid growth. UK telephone cases went from 3 in 2007–2011 combined to 22 in 2013 alone. Worldwide, yearly cases rose from 4 in 2010 to 71 in 2015, then fell to 53 in 2019.
- Young users. In the US–UK study, 86% of patients were under 40 and 71% were male. Reported incidence was higher in the UK than the US (1.78 vs 0.26 cases per million population).
- Women die at the same rate. Across 38 countries, case fatality was 11.3% in women and 12.6% in men, with no significant difference.
- Common symptoms. In the UK series: fever (47%), fast heart rate (43%), sweating (37%), nausea or vomiting (27%), skin discoloration or rash (23%), breathing difficulty (23%) and abdominal pain (23%).
Predictors of death
The US–UK study looked at which findings predicted death (Potts et al. 2021). After adjusting for each other, four features remained independent predictors:
| Feature | Adjusted odds ratio (95% CI) |
|---|---|
| Acidosis | 5.4 (1.8–16.5) |
| Tachycardia (fast heart rate) | 3.6 (1.2–11.0) |
| Agitation or confusion | 3.4 (1.2–9.7) |
| Hyperpyrexia (very high fever) | 2.8 (1.0–7.4) |
On unadjusted analysis, low blood sugar (OR 17.1), muscle hypertonia (OR 12.9) and raised lactate (OR 8.3) were also strongly linked to death.
Published fatalities
A 2011 review counted 62 deaths attributed to DNP in the medical literature since the early 1900s (Grundlingh et al. 2011). Its findings:
- 1930s deaths were in people using it as prescribed for weight loss, not only in overdoses.
- Only two deaths were published for the rest of the 20th century, consistent with the effect of the 1938 restrictions.
- Twelve deaths were published in 2001–2010, from deliberate overdose, use for bodybuilding or weight loss, and occupational skin exposure.
- Acute overdose moves fast. Patients presented on average 7–8 hours after ingestion and died on average at 14 hours. In the cases reviewed, CPR never restored a heartbeat.
Reports since then follow the same pattern in the bodybuilding population. A 17-year-old in France died of hyperthermia after taking DNP with clenbuterol (Dufayet et al., Int J Legal Med 2020). A 21-year-old bodybuilder who also used anabolic steroids had months of fast heart rate, fast breathing and sweating, was hospitalized with multi-organ failure, kept using DNP and later died. Hair testing confirmed months of exposure (Hermetet et al., Front Public Health 2024).
“Safe if you watch your temperature.” Seller websites have long advised users to carry a thermometer and stay cool (Grundlingh et al. 2011). The clinical record does not support this. DNP’s heat is generated inside every cell for as long as the drug is present, and toxicity can last for days after the last dose. The authors of one fatal case report note that even relatively small doses can cause fatal hyperthermia (Dufayet et al. 2020).
Controlled-release DNP derivatives
Because uncoupling burns fat, researchers have tried to make safer, slow-release forms. These are separate investigational products, not DNP itself, and none is approved.
- In rats, a controlled-release oral form designed to produce mild uncoupling in the liver reduced fatty liver, insulin resistance and diabetes without systemic toxicity (Perry et al., Science 2015).
- HU6, a prodrug that the liver converts to DNP, was tested in an 80-person, 61-day randomized placebo-controlled phase 2a trial in adults with fatty liver disease and high BMI. Liver fat fell by 26.8–35.6% across three dose groups versus a 5.4% rise on placebo. Flushing (32% vs 10%), diarrhea (25% vs 0%) and palpitations (12% vs 5%) were more common on HU6; no serious adverse events were reported (Noureddin et al., Lancet Gastroenterol Hepatol 2023).
- In obesity-related heart failure with preserved ejection fraction, a 66-person, 19-week randomized trial found HU6 reduced weight by 2.86 kg more than placebo (95% CI 1.04–4.68 kg) and fat mass by 2.96 kg, with no improvement in exercise capacity (peak VO₂) (Pandey et al., JAMA Cardiol 2025).
These trials used purpose-built formulations under close monitoring. They say nothing about the safety of DNP powder or capsules sold online.
Side effects and risks
Acute poisoning
The classic picture is hyperthermia, fast heart rate, heavy sweating and fast breathing (Grundlingh et al. 2011). It can progress to confusion, seizures, rigidity, shock and cardiac arrest. Other reported features include high potassium, methemoglobinemia (a form of hemoglobin that cannot carry oxygen), acute kidney injury and heart muscle damage. A 2026 case also showed widespread ST depression on the ECG with a raised troponin, a marker of heart injury (Silvester et al. 2026).
There is no specific antidote. Hospital care is supportive: aggressive cooling, fluids, sedation, glucose, and management of high potassium and breathing (Grundlingh et al. 2011; Lindeman et al. 2026).
Effects with repeated use
Reports from the 1930s and recent cases describe harm with ongoing use, not only overdose (Grundlingh et al. 2011):
- Cataracts that can develop within days to months and permanently reduce vision (Rodin 1936).
- Peripheral neuropathy. A 19-year-old woman developed a painful axonal sensorimotor polyneuropathy (nerve damage in the hands and feet). It improved only moderately over two years after she stopped (Phillips & Singer 2013).
- Skin reactions, from rashes and hives to severe exfoliative dermatitis, and yellow staining of skin and eyes.
- Blood disorders, including agranulocytosis (loss of infection-fighting white cells).
- Permanent hearing loss has been reported.
Animal data
In animal studies, DNP has shown developmental and reproductive toxicity and has been reported as teratogenic (causing birth defects), mutagenic and carcinogenic (Grundlingh et al. 2011). These findings are from animals, and human data are lacking.
Hidden exposure
DNP has been found as an undeclared ingredient in supplements sold as fat burners (Cairns et al. 2020). People may be exposed without knowing it.
Key takeaways
- An industrial poison, not a drug. DNP is a chemical used for explosives, dyes and pesticides. Its brief 1930s use as a slimming drug ended after cataracts and deaths.
- One of the first drugs pulled by modern US law. The 1938 Food, Drug, and Cosmetic Act gave FDA the power to stop its sale, and it has never been approved since.
- It works by turning food energy into heat. Uncoupling cannot be switched off once DNP is in the body, which is why hyperthermia can become uncontrollable.
- Very high death rate. About 12–17% of systemic exposures reported to poison centers in the US, UK and worldwide were fatal, mostly in young adults.
- No antidote, long persistence. Treatment is supportive only. Blood half-life estimates range from about 17 to 89 hours, and its effects on mitochondria can last for days.
- Banned or restricted widely. UK regulated poison since 2023, Australian Schedule 10 since 2017, and prohibited at all times by WADA.
Sources
- Grundlingh J, Dargan PI, El-Zanfaly M, Wood DM. 2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death. J Med Toxicol. 2011;7(3):205–212. PubMed.
- Colman E. Dinitrophenol and obesity: an early twentieth-century regulatory dilemma. Regul Toxicol Pharmacol. 2007;48(2):115–117. PubMed.
- Phillips L, Singer MA. Peripheral neuropathy due to dinitrophenol used for weight loss: something old, something new. Neurology. 2013;80(8):773–774. PubMed.
- Rodin FH. Cataracts following the use of dinitrophenol: a summary of thirty-two cases. Cal West Med. 1936;44(4):276–279. PubMed.
- Kamour A, George N, Gwynnette D, et al. Increasing frequency of severe clinical toxicity after use of 2,4-dinitrophenol in the UK: a report from the National Poisons Information Service. Emerg Med J. 2015;32(5):383–386. PubMed.
- Potts AJ, Bowman NJ, Seger DL, Thomas SHL. Toxicoepidemiology and predictors of death in 2,4-dinitrophenol (DNP) toxicity. Clin Toxicol (Phila). 2021;59(6):515–520. PubMed.
- Gziut T, Thomas SHL. International trends in systemic human exposures to 2,4 dinitrophenol reported to poisons centres. Clin Toxicol (Phila). 2022;60(5):628–631. PubMed.
- Cairns R, Raubenheimer J, Brown JA, McArdle K, Buckley NA. 2,4-Dinitrophenol exposures and deaths in Australia after the 2017 up-scheduling. Med J Aust. 2020;212(9):434–434.e1. PubMed.
- Silvester A, Koutsogiannis Z, Richards S, Thomson D, Wong A. Survival of acute-on-chronic 2,4-dinitrophenol overdose with associated pharmacokinetics. J Med Toxicol. 2026;22(1):81–85. PubMed.
- Lindeman E, Sommer T, Leffler M, et al. Runaway uncoupling in 2,4-dinitrophenol poisoning: clinical and mitochondrial observations from two cases. Toxicol Rep. 2026;16:102183. PubMed.
- Zhao XH, Jiang JK, Lu YQ. Evaluation of efficacy of resin hemoperfusion in patients with acute 2,4-dinitrophenol poisoning by dynamic monitoring of plasma toxin concentration. J Zhejiang Univ Sci B. 2015;16(8):720–726. PubMed.
- Vanthourenhout S, Deprez C, Maes P, et al. Further elucidation of the metabolism of 2,4-dinitrophenol in a case of unexpected death. J Anal Toxicol. 2026;50(3):bkag003. PubMed.
- Dufayet L, Gorgiard C, Vayssette F, et al. Death of an apprentice bodybuilder following 2,4-dinitrophenol and clenbuterol intake. Int J Legal Med. 2020;134(3):1003–1006. PubMed.
- Hermetet C, Jourdan M, Baert A, et al. Case report: fatal long-term intoxication by 2,4-dinitrophenol and anabolic steroids in a young bodybuilder with muscle dysmorphia. Front Public Health. 2024;12:1452196. PubMed.
- Perry RJ, Zhang D, Zhang XM, Boyer JL, Shulman GI. Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats. Science. 2015;347(6227):1253–1256. PubMed.
- Noureddin M, Khan S, Portell F, et al. Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled, phase 2a trial. Lancet Gastroenterol Hepatol. 2023;8(12):1094–1105. PubMed.
- Pandey A, Lewis GD, Borlaug BA, et al. Novel controlled metabolic accelerator for obesity-related HFpEF: the HuMAIN-HFpEF randomized clinical trial. JAMA Cardiol. 2025;10(6):609–616. PubMed.
- National Center for Biotechnology Information. PubChem compound summary: 2,4-Dinitrophenol (CID 1493). PubChem.
- The Control of Explosives Precursors and Poisons Regulations 2023 (SI 2023/63); corrected by The Control of Explosives Precursors and Poisons (Amendment) Regulations 2023 (SI 2023/810). In force October 1, 2023. legislation.gov.uk; legislation.gov.uk.
- Poisons Act 1972, section 3A: Supply of regulated substances. legislation.gov.uk.
- World Anti-Doping Agency. The 2026 Prohibited List: International Standard. In effect January 1, 2026. WADA.
- Code of Federal Regulations. 21 CFR 1308.13: Schedule III. eCFR.