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2,4-Dinitrophenol

  • Withdrawn substance
  • Withdrawn
  • Identity checked
  • Sources last checked 2026-09-04

This page shows what was measured, who it was measured in, and what that does not settle.

What 2,4-Dinitrophenol does in the body

An unapproved weight-loss chemical whose fat-burning action can also kill.

Think of the mitochondrion as a dam. The cell pumps protons uphill behind the wall, and the only way back down is through a turbine that makes ATP. DNP is a molecule that can carry a proton across the wall directly, bypassing the turbine. The energy that would have been captured as ATP is released as heat instead. The cell, sensing that it is short of ATP, burns more fuel — which makes more heat, not more ATP. That is why it causes weight loss, and it is why an overdose produces a body temperature that will not come down. There is no drug that removes DNP or blocks its effect. Everything a hospital can do is supportive.

What happened in people

It forces stored energy to become heat instead of useful cell energy, causing weight loss and dangerous overheating.

Reviewed first-read answer

Where this came from

A person wrote this and a reviewer approved it against this exact record. It carries no effect size.

A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.

No source is stored against this line.

The limit that matters most

No modern study has found a safe dose, and fatal exposures overlap with reportedly ordinary doses.

Where it acts
Inner mitochondrial membrane, in every cell in the body
Kind of result
A number that stands in for health
Supervision
Professional supervision is normally required. It is a prescription or clinician-administered medicine where it is approved.

What the registries record it as

  • The substance registry classes this as chemical.

    FDA substance registry · Q13SKS21MN · read 2026-08-29

  • Its recorded molecular formula is C6H4N2O5, weighing 184.11.

    PubChem record · 1493 · read 2026-08-29

Where each sentence above came from

No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.

Shown as the opening line on this page.

The limit a reviewer approved as the one that matters most here.

The four opening statements run to 147 words.

Words this page uses

Four words worth knowing first

Chosen from what this page shows, with each one explained before the word it depends on.

Biomarker

A biomarker is a number from a test that stands in for something about health.

A picture of it, and where the picture fails

A biomarker is like a fuel gauge.

Where that stops being true. A gauge is wired to the tank. Many biomarkers are only loosely tied to health.

What people get wrong. A better number is read as a better life. Several medicines improved a number and helped nobody.

A measurable indicator used as a substitute for a clinical outcome of interest.

Placebo

A placebo is a dummy treatment given so the real one can be compared with it.

A picture of it, and where the picture fails

A placebo is like a blank control in an experiment.

Where that stops being true. A blank does nothing. People given a placebo often do get better.

What people get wrong. A placebo effect is read as imaginary. The improvement is measured and real.

An inactive intervention matched in appearance to the test intervention, used to control for non-specific effects.

Comparator

A comparator is whatever the treatment was measured against.

A picture of it, and where the picture fails

It is like the other runner in a race.

Where that stops being true. A race has one winner. A study can show both arms improved.

What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.

The control condition against which the experimental intervention is assessed.

What happened in peopleRead from sources, not yet reviewed

What happened in people

Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.

Metabolic rate and weight change during dinitrophenol administration

The study showed what it set out to show

Who was studied
Tainter 1934 critical survey of clinical results
How many people
0
Study design
Clinical case series and survey, pre-regulatory era
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Published in 1934, before randomisation and formal statistical testing were standard; reported as a critical survey of clinical results
Repeated elsewhere
Replicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. Cataract, the chronic toxicity that emerged as an outbreak in 1935, was not apparent in the initial clinical reports.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral capsule or loose yellow powder; also absorbed through skin

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

Uncoupled respiration, gas exchange and ventilatory dynamics through intensive care in one fatal and one surviving poisoning

The study showed what it set out to show

Who was studied
Lindeman 2026 intensive care case pair with serial respirometry
How many people
2
Study design
Clinical case series with mitochondrial respirometry
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Descriptive: functional half-life of uncoupled respiration 4.9 days; fatal case progressed to respiratory acidosis, hyperthermia and severe hyperkalaemia within hours
Repeated elsewhere
Unreplicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. No limitation is recorded for this study.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral capsule or loose yellow powder; also absorbed through skin

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

No randomised trial of DNP has ever been conducted and none would receive ethical approval

The study did not show it

Who was studied
No modern clinical trial exists or could be conducted
How many people
0
Study design
None
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Not applicable
Repeated elsewhere
Unreplicated

What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.

The limits of this study, and where it came from

Main limit. No limitation is recorded for this study.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral capsule or loose yellow powder; also absorbed through skin

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

What we know
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.

What it changes in the bodyRead from sources, not yet reviewed

The path through the body

From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.

  1. Start

    2,4-Dinitrophenol

    What a person takes: Oral capsule or loose yellow powder; also absorbed through skin.

    The measurement behind this step

    Bought as a bright yellow crystalline powder, sometimes encapsulated. Capsule content is not measured by anyone, which matters more here than for any other substance on this site because the interval between an exposure people call ordinary and a published fatal exposure is narrow. It is also absorbed dermally, so handling the powder is itself an exposure route.

  2. Getting in

    Swallowed as a yellow powder

    Absorbed rapidly from the gut. It also passes through skin, which is why industrial handling has caused poisoning too.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Rapid gastrointestinal absorption, with significant dermal absorption as well. It is a small, lipophilic weak acid, so it distributes into every tissue. Elimination is slow relative to the onset of toxicity, and the functional effect on mitochondria in one measured case declined with a half-life of 4.9 days.

  3. Reaching the cell

    Crosses into the mitochondrion

    It slips through the cell membrane and then through the mitochondrial membranes, because both its charged and uncharged forms are greasy enough to pass.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Both the protonated phenol and the deprotonated phenolate partition into lipid bilayers, which is the unusual property that makes protonophoric shuttling possible. Uptake into mitochondria increases as local pH falls, which is the basis of the self-amplifying loop described in the intensive-care cases.

  4. What it acts on

    Short-circuits the proton gradient — no receptor involved

    It carries protons back across the membrane directly, bypassing the ATP-making turbine. There is nothing to bind and therefore nothing to block.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    The protonated form crosses to the matrix side, releases its proton into the alkaline matrix, and the resulting phenolate crosses back to be reprotonated. The cycle dissipates the proton-motive force. Because the target is the membrane rather than a protein, no antagonist is possible and there is no antidote.

  5. The change it makes

    The cell burns more fuel and makes heat instead of ATP

    Sensing a shortage of ATP, the cell accelerates the electron transport chain. That burns substrate faster, produces more heat, and still does not make ATP.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Electron transport accelerates towards maximal uncoupled capacity while ATP synthesis falls. Substrate energy is dissipated as heat, oxygen consumption and CO2 production rise steeply, and glycolysis is driven hard to compensate — which is why glucose supplementation is a supportive measure and why hyperkalaemia develops as cellular ion pumps fail.

  6. What that does for a person

    Weight loss, or hyperthermia and death, by the identical route

    At a low enough exposure the extra heat is just lost and fat is burned. Past a threshold the body cannot shed the heat, the temperature climbs, ATP runs out and the person dies.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    The therapeutic and the lethal effect differ in degree and not in kind. The fatal case in the Swedish series reached respiratory acidosis, hyperthermia, severe hyperkalaemia and peri-mortem rigidity within hours, a picture consistent with catastrophic ATP depletion. Historically, cataract was the chronic toxicity that ended its medical use.

No suggested links are held for this record, so nothing is hidden from this path.

What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.

What is missing or unclearRead from sources, not yet reviewed

Were people like you studied?

RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.

Who was studied

People similar to this profile were included.

  • In the 1930s, an estimated large number of Americans, on prescription. Today, bodybuilders and people seeking rapid fat loss, buying it as a yellow powder online.

Who is missing from the studies

  • Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

Where the result stopped carrying

  • Its medical use ended within about five years of introduction, after an outbreak of cataracts in 1935
  • The historical review concludes that medical opinion, rather than the 1938 Act, principally drove its withdrawal — the regulatory system of the time could not act quickly
  • This is a scope explorer, not a diagnosis engine.
  • It shows who was studied so you can see whether people similar to you were included.

RNAWiki cannot tell whether a study fits you. It can show who was in it.

What it would be like to takeRead from sources, not yet reviewed

Why it might seem to do nothing

A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.

It was studied in different people

The people in the studies were not much like the reader.

On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

The evidence may simply be wrong

Small early studies often do not hold up.

On this record: RNAWiki has not yet published a reviewed conclusion for this use.

Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.

None of these is a reason to take more. Taking more is not a step this page ever suggests.

What it would be like to takeRead from sources, not yet reviewed

What taking it involves

The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.

How it is supplied

Withdrawn

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

Read from the recorded approval status.

No source is stored against this line.

Form and route

Oral capsule or loose yellow powder; also absorbed through skin

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form and route recorded on this substance.

No source is stored against this line.

Who oversees it

Professional supervision is normally required. It is a prescription or clinician-administered medicine where it is approved.

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

A register records the withdrawal of an approval.

No source is stored against this line.

What is in the pack

Bought as a bright yellow crystalline powder, sometimes encapsulated.

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

Recorded notes on how this is sold. The rest of the recorded wording: Capsule content is not measured by anyone, which matters more here than for any other substance on this site because the interval between an exposure people call ordinary and a published fatal exposure is narrow. It is also absorbed dermally, so handling the powder is itself an exposure route.

No source is stored against this line.

Where it is registered

Regulatory records are listed in the technical disclosure at the foot of this page.

Counted from records

Where this came from

A count of rows RNAWiki holds. It describes our records, not your body.

Register entries are stored per jurisdiction and shown with their dates.

No source is stored against this line.

Why people stop

Not recorded.

Nothing recorded

Where this came from

RNAWiki holds nothing here and says so rather than guessing.

No record of why people stopped taking it is stored for this substance.

No source is stored against this line.

What it would be like to takeRead from sources, not yet reviewed

What can go wrong

Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.

Worth asking a clinician aboutWritten into the record from the studies named on this page

The toxidrome is hyperthermia, tachycardia, profuse sweating and tachypnoea, progressing to respiratory acidosis, hyperkalaemia, rigidity and death from catastrophic ATP depletion. There is no antidote and no receptor-level intervention, because the compound acts on a membrane rather than on a protein. Reported management is supportive: aggressive active cooling, high minute ventilation, glucose supplementation and correction of hyperkalaemia. The mitochondrial effect persists after the last dose, with a measured functional half-life of 4.9 days, so a patient who has stopped taking it is not out of danger. Cataract is the documented chronic toxicity from the 1930s.

Nobody counted how many people took this and were fine, so this cannot be turned into a rate.

Where this came from

Reports sent to a regulator

  • These are reports people sent to a regulator. They do not show the medicine caused the reaction.
  • Nobody counted how many people took the medicine and reported nothing.
  • The same event can be reported more than once, and many reports are incomplete.
  • News coverage, lawsuits and new warnings change how often people report.
  • A count is not a rate and not a risk.

2,4-Dinitrophenol appears in spontaneous reports to regulators. Across the 4 most-reported reaction terms, 29 reaction mentions were counted. One report can name several reactions.

The recorded terms (4)
  • hyperthermia — 8 reaction mentions
  • confusional state — 7 reaction mentions
  • hyperhidrosis — 7 reaction mentions
  • tremor — 7 reaction mentions
  • open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot

Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.

Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

What is missing or unclearNothing found in the sources checked

Does the exact form matter?

Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.

The form that was studied

Oral capsule or loose yellow powder; also absorbed through skin

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form used in the studies cited on this page.

No source is stored against this line.

What is sold

A recorded note compares this form with the others that are sold. It is kept below, word for word.

A fixed RNAWiki sentence

Where this came from

Wording RNAWiki always uses, not a finding about this substance.

The recorded note, unchanged: Capsule content is not measured by anyone, which matters more here than for any other substance on this site because the interval between an exposure people call ordinary and a published fatal exposure is narrow. It is also absorbed dermally, so handling the powder is itself an exposure route.

No source is stored against this line.

Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.

What it would be like to takeRead from sources, not yet reviewed

What you could measure

This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.

Self-experiment planning is not offered for a prescription or clinician-supervised medicine, withdrawn medicine. The questions below are for a clinician or pharmacist.

Questions worth asking

  • Which of the trials of 2,4-Dinitrophenol studied people like me?
  • What was measured, and for how long?
  • Was the result a laboratory value or a health outcome?
  • What would we watch for, and when would we stop?

Tracking can show whether something changed for you. It cannot show what caused it.

RNAWiki records evidence. It does not say whether this substance is right for you.

What is missing or unclearRead from sources, not yet reviewed

Claims that go past the evidence

Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.

Goes past the evidence

That there is a safe dose — no modern dose-finding exists, the products are unmeasured, and the published fatal exposures overlap with doses people describe as ordinary

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That the risk can be managed by cooling or by stopping when symptoms appear, when the intensive-care data describe a self-amplifying loop and a mitochondrial effect that persists for days after the last dose

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That a hospital can reverse it — there is no antidote, and every intervention described in the literature is supportive

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

What is missing or unclearRead from sources, not yet reviewed

What nobody knows yet

Open questions, each with why it is open and what would close it.

How fast does the body clear it?

The sources RNAWiki checked hold nothing for this field.

Why it matters. Without this, nothing on this page can say how long anything lasts.

What would answer it

A stored source that records it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing populations

Which groups were under-represented in the studies has not been recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing long-term data

No completed tested study window is recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

No reviewed conclusion

RNAWiki has not yet published a reviewed conclusion for this use.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing interaction studies

No interaction was found in the registers checked. Not finding one is not the same as showing there is none.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Formulation uncertainty

Several salts, forms or products of 2,4-Dinitrophenol are recorded. Results from one form may not transfer to another.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Mechanism not reviewed

No reviewed mechanism story exists for this substance.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

What happened in peopleRead from sources, not yet reviewed

Check any of this yourself

Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.

Every line above can be traced to the study named beside it. Follow the link and read it.

The mechanism is not disputed and has been understood since the 1930s
In plain words
DNP carries protons across the mitochondrial membrane, short-circuiting the process that makes ATP. The energy comes out as heat instead. This is textbook biochemistry, not a hypothesis.
What was measured
Collapse of the proton-motive force and increase in uncoupled oxygen consumption
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
DNP is the archetypal protonophoric uncoupler of oxidative phosphorylation. As a weak acid with a pKa near 4, both its protonated and deprotonated forms partition into the inner mitochondrial membrane, allowing it to shuttle protons down the electrochemical gradient without passing through ATP synthase. The proton-motive force collapses, ATP synthesis falls, and the electron transport chain accelerates to compensate, dissipating substrate energy as heat. Because the compound has no binding site, there is no antagonist and no receptor-level intervention: this is a physical mechanism, and it is the reason DNP is used as the standard positive control for maximal uncoupled respiration in mitochondrial research.
Source
Molecular mechanisms of mitochondrial uncoupling: focus on 2,4-dinitrophenol. Eur Biophys J 2026
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
It works — that was never the problem
In plain words
DNP was introduced as a weight-loss drug in 1933 on the basis that it raised metabolic rate and produced weight loss. It did. The clinical survey published the following year assessed the results critically and the efficacy was not what came into question.
What was measured
Basal metabolic rate and body weight during dinitrophenol administration
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Tainter, Cutting and Stockton published a critical survey of clinical results with dinitrophenol in nutritional disorders in 1934, following its introduction at Stanford the previous year. Contemporary work also measured the metabolic consequences directly, including the relationship between raised metabolism from dinitrophenol and blood cholesterol. The compound raises basal metabolic rate in a dose-dependent way by a mechanism that cannot fail to raise it, and weight loss follows. Every subsequent account, including modern toxicology reviews, accepts this. The distinctive feature of DNP among weight-loss agents is that its efficacy has never been the contested part.
Source
Tainter ML, Cutting WC, Stockton AB. Use of dinitrophenol in nutritional disorders: a critical survey of clinical results. Am J Public Health Nations Health 1934;24:1045-1053
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Sixty-two published deaths by 2011, and a characteristic terminal picture
In plain words
A 2011 review counted 62 deaths in the medical literature attributed to DNP. The pattern is always the same: high temperature, fast heart rate, drenching sweat, rapid breathing, then death.
What was measured
Published fatalities attributed to DNP exposure, and the terminal symptom complex
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Grundlingh et al. reviewed DNP toxicity and counted 62 published deaths attributed to it in the medical literature up to 2011, with fatalities reported since the turn of the twentieth century. The classic symptom complex is hyperthermia, tachycardia, diaphoresis and tachypnoea, progressing to death. The review notes that the compound is sold mostly over the internet under a range of names as a slimming aid. That count is now well over a decade old and further deaths have been published since, including in the two case reports cited on this page; the figure is a floor, not a current total.
Source
Grundlingh J et al., J Med Toxicol 2011;7:205-212
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Runaway uncoupling: the toxicity amplifies itself, and it took hours
In plain words
In two Swedish intensive care cases, the fatal one went from ingestion to respiratory acidosis, hyperthermia, dangerously high potassium and rigidity within hours. The surviving patient stayed hypermetabolic for more than a week.
What was measured
Serial platelet uncoupled respiration, arterial blood gases, temperature and potassium through intensive care
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Lindeman et al. described two cases managed in Swedish intensive care with serial mitochondrial respirometry and gas exchange analysis. The fatal case, after suicidal ingestion, progressed within hours to respiratory acidosis, hyperthermia, severe hyperkalaemia and peri-mortem rigidity consistent with catastrophic ATP depletion. The non-fatal case showed the same physiology reversibly, with sustained but manageable hypermetabolism lasting more than a week. Serial platelet respirometry showed a marked initial rise in uncoupled respiration followed by progressive decline with a functional half-life of 4.9 days. The authors propose a self-amplifying feedback loop: excessive CO2 production from uncoupling causes local acidosis, which increases mitochondrial uptake of DNP, which increases uncoupling. Glucose supplementation and hyperkalaemia management were essential; active cooling and high minute ventilation may blunt the loop.
Source
Lindeman E et al., Toxicol Rep 2026;16:102183
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
A fatal case with the full exposure history recoverable from hair
In plain words
A 21-year-old bodybuilder died of multi-organ failure after taking 2 grams, having used DNP repeatedly for six months. His blood level was 88 mg/L and hair analysis reconstructed the whole six months.
What was measured
Post-mortem blood concentration and segmental hair concentrations across six months
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Hermetet et al. report a 21-year-old bodybuilder, also using anabolic steroids, who died after ingesting 2 grams of 2,4-DNP following six months of repeated consumption. He had shown the triad of tachycardia, tachypnoea and profuse sweating for six months before death and had been hospitalised with multiple organ failure four months earlier, an episode staff attributed to DNP. He denied continuing use to his general practitioner, who investigated endocrine and tumour causes for the persisting triad. Autopsy showed diffuse visceral congestion and yellow discolouration of the integument. Blood DNP was 88 mg/L; segmental hair concentrations ran from 5.1 to 25.5 ng/mg, and anabolic steroids were also identified in hair. The authors frame the case around muscle dysmorphia and around the difficulty primary care has in recognising a toxidrome that mimics thyrotoxicosis or phaeochromocytoma.
Source
Hermetet C et al., Front Public Health 2024;12:1452196
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The cataract outbreak of 1935, and what actually removed it from the market
In plain words
DNP caused an outbreak of cataracts in 1935. The commonly told story is that the 1938 Food, Drug and Cosmetic Act banned it; the historical review says medical opinion probably drove a voluntary withdrawal first.
What was measured
That the 1938 Act banned DNP directly, when the historical review attributes the withdrawal principally to medical opinion and a voluntary market exit
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Margo and Harman reviewed the 1935 cataract outbreak caused by DNP, the active ingredient of popular diet pills, and set it in the context of the fight over consumer protection legislation. Their assessment is that the outbreak was conspicuous in the medical literature during the New Deal but probably had little impact on the eventual passage of the Federal Food, Drug, and Cosmetic Act of 1938, and that medical opinion about DNP's safety may have contributed to a voluntary withdrawal of the drug from the market. Modern toxicology reviews describe it more briskly as banned by the FDA in the 1930s after reports of severe toxicity. Both accounts agree on the outcome. The distinction matters because the neat story — regulator sees harm, regulator bans drug — is the one usually told, and the historical record is messier than that.
Source
Margo CE, Harman LE. Diet pills and the cataract outbreak of 1935. Surv Ophthalmol 2014;59:568-573
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim

Where else this substance is registered

FDA substance identifier (UNII)
Q13SKS21MN
CAS registry number
51-28-5
PubChem compound
1493
ChEBI
39352
EMA substance identifier
100000126132
European Chemicals Agency number
200-087-7
DrugBank
DB04528

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What is missing or unclearRead from sources, not yet reviewed

What to learn next

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What is not here

8 questions this page could not answer

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The older medicine-wide conclusion held in this record

Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.

The clearest case in medicine of a drug whose efficacy and whose lethality are the same fact: it uncouples oxidative phosphorylation, which is why it burns fat and why it kills by hyperthermia, with no antidote and a mitochondrial functional half-life measured at 4.9 days.

Recorded evidence blocks (2)

Mouse studies of 2,4-Dinitrophenol used 3 ppm — over how long?


Mouse studies of 2,4-Dinitrophenol used "3 ppm". jax-mpd-itp · 2026-09-04

Show the evidence
  • mouse 2,4-dinitrophenol C2020
    3 ppm

recorded 2026-09-04 · last checked 2026-09-04

What do 29 spontaneous reports say about 2,4-Dinitrophenol — and not say?


These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.

2,4-Dinitrophenol appears in spontaneous reports to regulators. Across the 4 most-reported reaction terms, 29 reaction mentions were counted: hyperthermia 8; confusional state 7; hyperhidrosis 7; tremor 7. open-targets-adr · CHEMBL273386 · 2026-06-24

Show the evidence
  • hyperthermia
    8
  • confusional state
    7
  • hyperhidrosis
    7
  • tremor
    7

recorded 2026-06-24 · last checked 2026-09-04

Where it is registered
Identifiers, relations and other names

The exact record

ChEMBL id
CHEMBL273386
PubChem CID
1493
CAS number
51-28-5
InChIKey
UFBJCMHMOXMLKC-UHFFFAOYSA-N
Also called
Aldifen, .alpha.-dinitrophenol, Chemox, Dinitrophenol, Dinofan, Fenoxyl carbon n, Mitcal, Mp-101, Nitrophen, Nitrophene, oleoyl-estrone, 2,4-DINITROPHENOL [HSDB]
Development code
NSC-1532, SR-1C5
Trade name
Marketed in the United States from 1933 under many names, including Formula 281 and Nitromet; sold online today as DNP
Sources (4)

Sources

  • this record's own fields 2,3,5 ·
  • jax-mpd-itp ITP_C2020_Lifespan.xlsx ·
  • jax-mpd-itp jax-mpd-itp ·
  • open-targets-adr CHEMBL273386 ·

NIA ITP via the JAX Mouse Phenome Database · Open Targets 26.06 — CC0 · derived from this page's own recorded fields; no external licence

How these records are assembled · Which registers were checked

Index-quality checks
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