The Dangers of Dinitrophenol (DNP)

Written by Kelly White, PharmD, CSPI at the Washington Poison Center

Weight loss has and always will be a common New Year’s resolution. While many people start a gym membership or try healthier recipes, others look for supplements to aid in weight loss. There are many weight loss supplements marketed online — some of them can be dangerous, including dinitrophenol (DNP). DNP was one of the earliest attempts at a pharmaceutical treatment for obesity, and was popularized in the 1930s as a weight loss agent. It was banned in 1938, however, after reports of adverse outcomes, including death. In 2002 there was a resurgence of use following online marketing to bodybuilders as a weight loss supplement. The FDA ban was reissued in 2003 noting DNP was “extremely dangerous and not fit for human consumption.” It is still available online despite being banned, with little to no warnings about the risks involved.

DNP uncouples oxidative phosphorylation, leading to loss of energy as heat instead of being converted to ATP. This results in failure of thermoregulatory homeostasis and profound hyperthermia. Patients display sweating, tachypnea, tachycardia, and fever as early as 3 hours from overdose. Many websites advertise a therapeutic DNP dose as 5–8 mg/kg daily, which is approximately ⅓ of the estimated lethal dose of 20–50 mg/kg. This suggests a narrow therapeutic index. Due to its long half-life (5–14 days), accumulation of DNP in the body can occur easily, leading to toxicity with chronic consumption. Symptom onset and decline is rapid and potentially fatal after overdose. Large volume of distribution and mostly intracellular action limits treatment options, as hemodialysis and hemoperfusion are ineffective. Care should emphasis rapid cooling, maintaining airway, and replacement of insensible fluid loss from diaphoresis and fever. The Poison Center is always available for treatment guidance. While DNP is uncommon, healthcare workers should be aware of its risks.