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DNP

2,4-Dinitrophenol - the historical mitochondrial uncoupler. Highly effective but with the narrowest safety window in metabolism research.

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At a glance

DNP by the numbers

The key figures from our lexicon.

Full lexicon entry

For research and educational purposes only. Values from the TPD lexicon, sources linked there.

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Knowledge

Everything about DNP

Description

DNP (2,4-Dinitrophenol) is the historical prototype of mitochondrial uncouplers. In the 1930s DNP was briefly marketed as an obesity therapeutic, until high incidence of fatal hyperthermia led to market withdrawal. Since then DNP has remained a standard tool in pharmacological research for investigating oxidative phosphorylation.

In research contexts DNP acts as a protonophoric uncoupler: the lipophilic molecule diffuses into the inner mitochondrial membrane and transports protons along their gradient back to the matrix. This bypasses ATP synthase - the energy from nutrient oxidation is released as heat instead of ATP.

Uncoupling is a real, long-known effect and the reason the substance looked so attractive historically. The problem is the extremely narrow safety window: the desired and the toxic effect lie close together. Serious adverse effects occur at an unacceptably high rate (Grundlingh 2011). Poisoning shows as uncontrollable hyperthermia; body temperature rises faster than the body can dissipate it via sweating.

Described signs are fever, heavy sweating, a racing heart, rapid breathing or shortness of breath. Yellowing of the skin and urine is described as well. They are not something you get used to; they can be the start of poisoning. Medical use in the 1930s also documented cataracts and peripheral nerve inflammation.

Because of its adverse effects, DNP has been banned for human consumption in many countries since 1938 (Sousa 2020). The current toxicology literature reaches the same conclusion.

How long DNP stays in the body has barely been studied in humans; the data come almost entirely from poisoning cases. There, elimination stretched over several days (Zhao 2015, Silvester 2025), so repeated intake can add up.

You can order DNP as oral tablets with 200mg per tablet, 50 tablets per bottle. We deliberately give no dose for DNP: there is no defensible human protocol.

This information is for research and educational purposes only. No medical recommendations.

Risks & Safety

DNP has the narrowest safety margin of any compound in the entire catalog. The substance was pulled from the market for good reason - the toxicology literature is unambiguous and serious.

Documented in the literature:

  • Fatal hyperthermia: the central danger mechanism. The desired and the toxic effect sit extremely close together. Body temperature rises faster than the body can shed it. Documented cases end in death. There is no antidote.
  • Heat and exertion: sauna, intense cardio and warm environments raise the hyperthermia risk massively, because they block the exact route by which the body sheds the extra heat.
  • Fluids and electrolytes: not an add-on but part of the risk. DNP-related hyperthermia is life-threatening without adequate fluid.
  • Accumulation: in poisoning cases elimination stretched over several days, so repeated intake can add up. In the UK case series, repeated intake over days to weeks was more common than a single overdose (Kamour 2014).
  • Warning signs: fever, heavy sweating, a racing heart, shortness of breath and yellowing of the skin and urine are not something you get used to; they can be the start of poisoning.
  • From medical use in the 1930s: cataracts and peripheral nerve inflammation.
  • Emergency: fever, feeling hot, a racing heart or confusion after taking DNP are an emergency. Call emergency services immediately (112 in the EU) and say that DNP is involved.

Risk-Tier 3, top end of the scale. There is no defensible human protocol for DNP, so we give no dose. This classification does not replace medical advice. Risk and responsibility for any actual use lie entirely with the buyer.

Studies

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FAQ

Frequently asked

Sources for every answer: lexicon entry

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Why does this entry give no dose?

There are no modern controlled human trials with the free substance. Almost all data come from poisoning cases in emergency departments. Even in the medical use of the 1930s the desired and the toxic effect were close together. No reliable figure can be derived from that.

How does DNP work?

DNP is a mitochondrial uncoupler. It carries protons back into the mitochondria past ATP synthase. Energy from fat and sugar is then not stored as ATP but released as heat, so the cell burns more for the same result. Exactly how this works at the molecular level is still not fully understood.

How dangerous is DNP?

A 2011 review counted 62 deaths documented in the medical literature. Of 456 cases reported to poisons centres in 38 countries, 11.9 percent were fatal where the outcome was known. In the UK 5 of 30 reported people died, four of them after an acute overdose. In the UK analysis repeated use over days was more common than a single overdose.

What are the warning signs?

In the UK cases fever, racing heart and heavy sweating were the most common, along with nausea, breathing difficulties, skin discolouration, abdominal pain, agitation and headache. The classic picture is overheating with a racing heart, sweating and rapid breathing. These signs are an emergency: call the emergency number straight away and say that DNP is involved.

Is there an antidote?

No. There is no specific antidote for the poisoning, only the consequences such as overheating, circulation and kidneys are treated. Researchers see the reason in the fact that the exact molecular process of uncoupling is not yet understood.

What is HU6?

HU6 is a precursor that the liver converts into DNP, meant to release it in a controlled way. In a phase 2a trial with 80 adults liver fat fell by 26.8 to 35.6 percent in 61 days, on placebo it rose by 5.4 percent. In heart failure with obesity participants lost 2.86 kg more than on placebo over 19 weeks, exercise capacity did not change. This is not comparable with DNP tablets.

How does DNP differ from BAM15?

Both are uncouplers. BAM15 was described in 2014 as a new uncoupler that does not depolarise the outer cell membrane. So far it has only been studied in cells and animals. DNP has been known for almost a hundred years, the human data come from the time before the ban and from poisonings.

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