Medical knowledge, especially in toxicology, is built on experimentation and the preciously won experience over time treating the ingestions and poisonings of our patients. Ignoring these hard won lessons, and having additional patients repeat the suffering is a most pitiful waste. This has been the case with 2,4-dinitrophenol (DNP), which despite abundant evidence of its danger, continues to tempt because of its promise of weight loss.
Dinitrophenol Uses, Mechanism, and Effects
DNP is an industrial chemical widely used in manufacturing. Discovered in 1933, it incidentally was identified as promoting weight loss. As much as 2 lbs/week loss could be seen, which drove its use as a diet aid. DNP uncouples mitochondrial oxidative phosphorylation, interfering with the body’s ability to store energy as ATP. This leads to a dramatic increase in the metabolic rate, and hyperthermia to dissipate the heat. A secondary effect of depletion of ATP caused release of calcium from the sarcoplasmic reticulum and intractable muscle contractions which would generate additional thermal heat.
Unfortunately, its narrow therapeutic window, meant that even while taking recommended doses levels could become “toxic”, and severe side effects were seen including blindness (dinitrophenol cataracts) and death. Federal Food, Drug and Cosmetic Act of 1938 called the chemical “extremely dangerous and not fit for human consumption”. Popularity quickly waned and reported complications from the drug nearly disappeared.
Clinical Presentation and Treatment of Dinitrophenol Toxicity
Presenting symptoms usually include hyperthermia, nausea/vomiting, and diaphoresis. Severe neurological effects such as confusion, agitation, convulsions, and coma are common. The severe hyperthermia can be difficult to control, and patients die of hyperpyrexia and multiorgan failure and refractory shock.
Treatment is almost exclusively aggressive support cares.
- Fluid resuscitation
- Cooling for correction of hyperthermia
- Airway control
From a physiology mechanism, treatment with dantrolene would seem to offer benefit. Since dantrolene inhibits release of calcium from the sarcoplasmic reticulum, reduction in muscle contractions and heat generation should be possible. The threshold for treatment is set at 39-40°C by the U.K. National Poison Information Service (NPIS) guidelines.
Is DNP readily available?
Because of its reputation for weight loss the lessons of DNP have been forgotten or ignored, and the use of DNP is increasing along with occurrences of its toxic effects.
While DNP is certainly available over the internet, self-reported ingestions should be investigated closely. For example, on Amazon.com there are a large number of diet aids using the term DNP as a marketing ploy, without actually containing any DNP at all. True sources of DNP come from industrial or shadier sources.