When I use a word . . . Dinitrophenol? Don’t take it

A warning

Dinitrophenol, or more accurately 2,4-dinitrophenol, is a poisonous chemical that was originally used as an explosive, a herbicide and pesticide, and a colourant, among other uses. It should not be used medicinally. If you take it orally, in the hope that it will help you to lose weight, it may kill you, as it has others.

The UK’s 1972 Poisons Act

As I have previously described,1 the UK’s 1972 Poisons Act was originally introduced to enable registered pharmacists, under the aegis of the Royal Pharmaceutical Society, to regulate the sale of non-medicinal poisons. Since then, and having terrorism in mind, precursors of explosives have also been included in its remit.

Since it was first promulgated, the act has been amended on several occasions. The latest amendment, which came into force on 1 October 2023,2 includes, among other amendments, the addition of several substances to the lists of regulated and reportable poisons. In particular “2,4-Dinitrophenol and compounds including sodium dinitrophenolate” have been added to the table of regulated poisons.3

Dinitrophenol

Dinitrophenol was first synthesised in the middle of the 19th century. It was originally called nitrophenesic acid4 and was sometimes confused with trinitrophenol, also called nitrophenisic acid or picric acid.

Dinitrophenol and related substances, such as dinitrocresol and dinitronaphthol, was used as a food colorant in the late 19th century and then, because it was an explosive, in munitions factories in France during the first world war.5 Its thermogenic properties were observed at that time, but it was not until later that they were formally studied.

In the early 1930s groups in France and the USA studied the thermogenic effects of dinitrophenol in experimental animals and then in humans.67891011 When dinitrophenol was given to pigeons, rabbits, rats, cats, dogs, and humans, in doses of 3–40 mg/kg, body temperature rose by 4–7°C and there was marked respiratory stimulation. The maximum febrile response occurred at about 1 hour after subcutaneous or intramuscular injection and at about 4 hours after oral administration. The pulse rate rose, but without a change in blood pressure. Basal metabolic rate rose by 20–30% and the effect of a single dose lasted about two days. Its actions were primarily due to uncoupling of oxidative phosphorylation and stimulation of glycolysis.

When patients took daily doses of dinitrophenol 3–5 mg/kg for 1–10 weeks they lost up to 1.7 (mean 0.9) kg/week; the maximum loss in any patient was 9 kg over 10 weeks.8

However, before long a range of adverse outcomes attributable to dinitrophenol emerged, including cataracts, skin reactions, liver damage, and other occasional adverse effects. Even Maurice Tainter and his colleagues, who were advocates of the careful use of dinitrophenol in the management of obesity, admitted that “in some respects this drug is not ideal as a therapeutic agent, since it may cause certain undesired side-actions in a portion of the patients treated.”10 After deaths occurred in people taking dinitrophenol, its use was made illegal by the US Food and Drug Administration (FDA) under the Food, Drug and Cosmetic Act of 1938, which had been introduced in the wake of over 100 deaths due to the use of diethylene glycol as a solvent in formulations of sulfanilamide in 1937.1213

The clinical use of dinitrophenol was undoubtedly problematic. The margin between its effect in reducing weight and its toxic effects was narrow; there was a great deal of variability in individual dosage requirements, making it difficult to find an appropriate dosage regimen in an individual; the long pharmacological half-life, with an action that lasted two days, meant that during daily dosage there would be accumulation of the effect for several days, steady state not being reached for about 10 days; in addition, weight loss meant that if the daily dose was not reduced during long term treatment, the effective dose in mg/kg increased with increasing duration of treatment. In a modern series of 30 individuals who took varying doses of dinitrophenol, reported to the National Poisons Information Service, including four cases of overdose, symptoms in decreasing frequency were fever, tachycardia, sweating, nausea and vomiting, skin discoloration or rash, breathing difficulties, abdominal pain, agitation, and headache; five died.14

However, dinitrophenol continued to be used as a weight loss remedy. In the 1980s, for example, a Russian-born American doctor, Nicholas Bachynsky, marketed a formulation of dinitrophenol he called Mitcal. He advertised it as a weight loss medication from what he called his “Physicians Clinics” in Texas. He reportedly treated about 14 000 individuals, but when one died he was arraigned, convicted, and fined. However, he continued to use dinitrophenol, and in 2008 was jailed for fraud.15 While in prison he is said to have instructed a body builder in the use of dinitrophenol, leading to its use among body builders.16

Legislation

Many deaths have occurred from the use of dinitrophenol as a slimming remedy, in body building, or with suicidal intent. Section 7 of The Food Safety Act 1990 made it an offence to render any food injurious to health by “(a) adding any article or substance to the food; (b) using any article or substance as an ingredient in the preparation of the food; (c) abstracting any constituent from the food; and (d) subjecting the food to any other process or treatment, with intent that it shall be sold for human consumption.”17 This was followed by prosecutions for marketing and selling products containing dinitrophenol.

However, deaths have continued to occur, and hence the most recent legislation, referred to above and discussed elsewhere,2 making it illegal to purchase dinitrophenol for any purpose whatsoever without a licence from a registered pharmacist.

The latest legislation will make it more difficult than before to market or provide dinitrophenol and to purchase it, and it is to be hoped that the barriers that have been erected will persuade individuals from trying to do so in the UK. However, it is still possible to obtain chemicals such as dinitrophenol online from countries outside the UK from unlicensed sources and via the dark web. Further measures will be needed to reduce the ability to do that.