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2,4-Dinitrophenol

A highly toxic yet effective fat burning compound; DNP works via increasing heat production in cells via a process known as uncoupling (making cells less efficient with energy) and small overdoses have been known to result in death.

Our evidence-based analysis on 2,4-dinitrophenol features 23 unique references to scientific papers.

Kamal Patel
Research analysis led by Kamal Patel.
All content reviewed by the Examine.com Team. Published:
Last Updated:

Summary of 2,4-Dinitrophenol

Primary Information, Benefits, Effects, and Important Facts

Dinitrophenol is an ionophoric compound that short circuits mitochondrial ATP production. This cessation of ATP production via the mitochondria leads to an increase in the metabolic rate (as substrate is utilized at a higher rate so cytosolic ATP can sustain life) and subsequent weight loss.

It is one of the few chemical compounds that is causatively linked to death. Overdosing on Dinitrophenol leads to toxicity via excessive heat production, irregular breathing and heartrate, and mitochondrial dysfunction.

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Things To Know & Note

Is a Form Of

Primary Function:

Also Known As

Dinitrophenol, DNP, 2, 4-DNP, Dinitro, Dinosan, Dnoc, Nitrophen, Chemox, Aldifen, Mitcal

Caution Notice

Examine.com Medical Disclaimer

  • Overdosing of this compound requires a surprisingly small excess

How to Take 2,4-Dinitrophenol

Recommended dosage, active amounts, other details

Standard online protocols advice for titrating up towards a dose of 200-400 mg daily with cessation after 2 weeks of usage.

(NOTE: This dosing information is anecdotal in nature and is based on past human trials that were not conducted in a controlled fashion. No information exists in the scientific literature for the best dosages for weight loss.)

Scientific Research on 2,4-Dinitrophenol

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1Sources and structure

The chemical is a yellow crystalline powder that has a sweet, musty odour and is soluble in water.[1]

2History

It has historically been used as a component of explosives, and as a pesticide and food/clothing dye.[2] It was reported in 1933 that usage of Dinitrophenol led to weight loss and it became popularized as an obesity treatment.[3] It was effective in doing so, and led to a reported loss of 1.5kg per week.[4] Over time, as more side effects manifested, it was deemed ill-fit for human consumption by the Food, Drug, and Cosmetic act of 1938.[1][4]

It had a second resurgence in 1981 when a Physician marketed a product with Dinitrophenol in it (under the name Mitcal) through his private clinic[5] which resulted in one reported death and a large number of reported side effects.[5][4]

Since then it has remained available online through some websites, and toxicity cases arise every now and then from misuse of Dinitrophenol despite the FDA advising for its cessation.[6]

3Mechanisms of Action

4Mitochondrial Interactions

4.1Uncoupling and Metabolic Rate

Dinitrophenol can stimulate oxygen consumption in cells[7] and a general spike in the metabolic rate[2] at around an 11% increase per 100mg Dinitrophenol consumed.[8]

Under normal metabolic conditions, 1 ATP molecules are created during one passing of Acetyl-CoA through the Kreb's Cycle (The TCA) and many energy intermediates are produced in addition to the lone ATP; these energy intermediates go through oxidative phosphorylation in the mitochondria to produce an additional 11 ATP. Dinitrophenol is an oxidative phosphorylation inhibitor, and prevents these 11 additional ATP from being formed by interfering with inorganic phosphorus uptake into the mitochondria (needed for ATP synthesis) and also acting as an ionophore, which drastically hinders the electrochemical gradient in the mitochondria required for ATP synthesis.[9][10][11] It is the shift in the electrochemical gradient that causes the fat loss, as the excess ions that carried potential energy (calories) are dissipated as heat.[12]

4.2Uncoupling and Protection from Excitotoxicity

Dinitrophenol, by mitochondrial uncoupling, is able to protect mitochondria from Reactive-Oxygen Species (ROS) mediated cell death by allowing energy to be lost through uncoupling rather than contained in the mitochondria to exert damage. This was demonstrated in an animal model injected with a toxic dose of quinolinic acid.[13]

5Glycolysis and Lactic Acidosis

The usage of glucose as fuel markedly increases with low doses of Dinitrophenol[14] This increase in glycolysis leads to an increase in pyruvic acid and lactic acid (via anaerobic metabolism) due to the lack of ATP from the oxidative phosphorylation inhibition.[15]

6Electrolyte alterations

It has been reported that supplementation with Dinitrophenol can cause potassium accretion in renal tissue in rabbits[16] and may contribute to toxicity.[17]

Due to the lack of phosphate usage for ATP production in the mitochondria, phosphate also can accumulate in cells.[18]

7Safety and Toxicity

7.1General

In rats given 3-30mg/kg DNP for a period of 46 days (14 days prior to mating) noted that while no significant toxicity occurred to either parent and no differences in implantation rates, that the number of live births and average weight of pup birth were both reduced at 30mg/kg (thought to be indicative of developmental/reproductive toxicity) but failed to find teratogenicity when measuring birth defect rates.[19]

7.2Case Studies

Dinitrophenol has been causatively linked to death in numerous occasions,[20][21][22] with the causes of death usually related to hyperthermia and tachycardia (irregular heartbeat) paired with diaphoresis (excessive and unpredictable sweating and tachypnoea (rapid and irregular breathing).[4][1] 

The lethal dosages are sometimes unknown (ie. not reported in the case study or not otherwise known), but seem to range around 2,500mg or a bit higher for acute death (leading to death in under 24h) or taken over the course of 1-6 days; a death was once reported in a 46 year old woman at 300mg, which is within the recommended dosage range.[23]

As of September 2011, there have been 62 reported deaths from DNP usage; 12 of which were in the last decade and half of which were by bodybuilders[4] with two deliberate suicides.[20][22]

Numerous case studies linking DNP to death, with a fair bit of them placing DNP in a position of 'causative beyond a reasonable doubt'. Although most are associated with overconsumption of DNP (relative to the recommended intake range), at least one case study noted death associated with 300mg

References

  1. ^ a b c Colman E. Dinitrophenol and obesity: an early twentieth-century regulatory dilemma. Regul Toxicol Pharmacol. (2007)
  2. ^ a b Actions and Uses of Dinitrophenol.
  3. ^ Use of Dinitrophenol in Obesity and related conditions.
  4. ^ a b c d e Grundlingh J, et al. 2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death. J Med Toxicol. (2011)
  5. ^ a b Kurt TL, et al. Dinitrophenol in weight loss: the poison center and public health safety. Vet Hum Toxicol. (1986)
  6. ^ Food Standards Agency issues urgent advice on consumption of 'fat burner' capsules containing DNP.
  7. ^ Dinitrohenol and Accelerated Tissue Metabolism.
  8. ^ The use of 2,4-Dinitrophenol as metabolic stimulant.
  9. ^ Harper JA, Dickinson K, Brand MD. Mitochondrial uncoupling as a target for drug development for the treatment of obesity. Obes Rev. (2001)
  10. ^ Mechanisms of Dinitrophenol Toxicity.
  11. ^ Issekutz B Jr. Effect of propranolol in dinitrophenol poisoning. Arch Int Pharmacodyn Ther. (1984)
  12. ^ Wallace KB, Starkov AA. Mitochondrial targets of drug toxicity. Annu Rev Pharmacol Toxicol. (2000)
  13. ^ Korde AS, Sullivan PG, Maragos WF. The uncoupling agent 2,4-dinitrophenol improves mitochondrial homeostasis following striatal quinolinic acid injections. J Neurotrauma. (2005)
  14. ^ Mechanisms of Dinitrophenol toxicity.
  15. ^ Rognstad R, Katz J. The effect of 2,4-dinitrophenol on adipose-tissue metabolism. Biochem J. (1969)
  16. ^ MUDGE GH. Electrolyte and water metabolism of rabbit kidney slices; effect of metabolic inhibitors. Am J Physiol. (1951)
  17. ^ 2, 4-dinitrophenol poisoning caused by non-oral exposure.
  18. ^ Moffatt EJ, Miyamoto MD. Effect of sodium and calcium channel blockade on the increase in spontaneous transmitter release produced by the mitochondrial inhibitor, dinitrophenol. J Pharmacol Exp Ther. (1988)
  19. ^ Takahashi M, et al. Reproductive and developmental toxicity screening study of 2,4-dinitrophenol in rats. Environ Toxicol. (2009)
  20. ^ a b Siegmueller C, Narasimhaiah R. 'Fatal 2,4-dinitrophenol poisoning... coming to a hospital near you'. Emerg Med J. (2010)
  21. ^ Hsiao AL, et al. Pediatric fatality following ingestion of dinitrophenol: postmortem identification of a "dietary supplement". Clin Toxicol (Phila). (2005)
  22. ^ a b Bartlett J, Brunner M, Gough K. Deliberate poisoning with dinitrophenol (DNP): an unlicensed weight loss pill. Emerg Med J. (2010)
  23. ^ Reports of two cases of Agranulocytosis following the use of Dinitrophenol.

This page is regularly updated, to include the most recently available clinical trial evidence.

Each member of our research team is required to have no conflicts of interest, including with supplement manufacturers, food companies, and industry funders. The team includes nutrition researchers, registered dietitians, physicians, and pharmacists. We have a strict editorial process.

This page features 23 references. All factual claims are followed by specifically-applicable references. Click here to see the full set of references for this page.

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