2,4-Dinitrophenol (DNP) is an industrial chemical that has gained popularity as a weight-loss aid, particularly among bodybuilders and individuals with eating disorders. While DNP can induce rapid weight loss, its use is associated with significant health risks, including death. This article examines the effectiveness of DNP for weight loss, its mechanism of action, its history, and the dangers associated with its use.
Historical Overview of DNP Use
DNP was first used on an industrial scale in French munitions factories during the First World War, where it was mixed with picric acid to make explosives. Workers exposed to DNP experienced weight loss, fatigue, excessive sweating, and elevated body temperature. Many deaths occurred before safety measures were introduced.
These observations led Maurice Tainter and Windsor Cutting at Stanford University to study the effects of DNP. In 1933, they reported that DNP stimulated metabolism by 50% in patients, leading to the breakdown of fat and carbohydrate stores and weight loss of up to 1.5kg per week without dietary restriction. While recognizing DNP's potential for weight loss, they cautioned about the unknown dangers of prolonged use and the potential for fatal overheating with high doses.
Despite the warnings, DNP was embraced enthusiastically as a weight-loss drug. Within a year, up to 20 wholesale drug firms were marketing DNP, and as many as 100,000 people in the US alone had taken DNP. Many sales occurred through drug stores without prescription or supervision.
Initially, the drug seemed relatively safe, but as more patients took DNP for longer periods, side effects such as skin lesions and "dinitrophenol cataracts" were reported. Some deaths occurred, including one man who overdosed and "literally cooked to death" with a temperature of 43.3°C. In 1938, DNP was designated as "extremely dangerous and not fit for human consumption," and its use ceased.
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Mechanism of Action
In 1948, Harvard biochemists W F Loomis and Fritz Lipmann showed that DNP disrupts energy generation in cells. Normally, the energy required for cellular processes comes from the oxidation of food (fat and carbohydrate). In the presence of DNP, fat and carbohydrate in food are broken down, but the production of useful energy for cells is impaired and is instead released as heat. As a result, body reserves of fat and carbohydrate are mobilized, leading to weight loss.
Resurgence of DNP
In the 1960s, Russian-born doctor Nicholas Bachynsky learned of the effects of DNP while translating Russian medical journals for the US government. The Russians had used DNP to keep soldiers warm in winter, with the main side effect being weight loss. In the early 1980s, Bachynsky used this knowledge to set up clinics across the southern US, promoting a weight loss treatment underpinned by DNP. Weight loss of up to 7kg a week was claimed, with the only side effect being increased body temperature. About 14,000 patients enrolled on the program, and Bachynsky became very rich.
Complaints about the side effects of the treatment started to accumulate at the FDA. Legal action was begun against Bachynsky on the basis that he was using a drug that had not been approved, and in 1986 an injunction was issued preventing him from using DNP. Despite this, he continued treating patients, and it was only when he was convicted of insurance fraud that he ended up in prison.
While incarcerated, Bachynsky met Dan Duchaine, dubbed the "steroid guru," who was notorious as a promoter of steroids for bodybuilding. In the late 1990s, after being released from prison, Duchaine promoted DNP to the bodybuilding community as "the king of the fat-loss drugs," and a new era of DNP use began.
Current Availability and Risks
DNP is now available via the internet and is being used without supervision or regulation. This has some parallels with the situation in the 1930s, with reports of overheating and deaths. Four deaths in the UK and up to 60 worldwide have recently been attributed to DNP.
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Diabetic Neuropathic Cachexia (DNC)
Profound weight loss with painful symmetrical peripheral neuropathy in diabetic patients was first described as diabetic neuropathic cachexia more than 4 decades ago. It is a distinct type of diabetic peripheral neuropathy that occurs in the absence of other microvascular and autonomic complications of diabetes. The mechanism and precipitating cause are unknown. It was reported to have good prognosis with spontaneous recovery within months to 2 years. However, it was frequently missed by clinicians because the profound weight loss is the most outstanding complaint, rather than the pain, numbness, or weakness. This often leads to extensive investigation to exclude more sinister causes of weight loss, particularly malignancy.
DNC is an extremely rare variant with unknown prevalence. It was first described by Ellenberg in 1974 based on a group of six patients with mild diabetes who presented with severe weight loss and symmetrical painful peripheral neuropathy. The combination of these two symptoms was so predominant that the admitting diagnosis in each case was either metastatic carcinoma or carcinomatous neuropathy, yet almost all patients recovered spontaneously within a year despite no specific therapy.
DNC is distinct from other types of diabetic neuropathy as weight loss usually occurs rapidly over a period of 3-6 months and is not related to the severity or duration of DM. Autonomic features other than impotence, and microvascular complications such as retinopathy and nephropathy are usually absent in this syndrome. The pathological basis and ascertainable precipitating cause of DNC have not been determined, but an immune mechanism seems likely.
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DNC can be successfully treated with early and optimal nutritional support, good glycemic control, and pain management.