Due to increased concerns of body weight and image, along with the widespread use of the Internet and social media platforms, the already considerable market of weight-loss drugs and supplements grows rapidly. Within this market, various products are available which include substances that could pose health hazards to users.
Like any other market where effective regulatory control is lacking, the supplement market is also open to unethical practice whereby products could contain unlicensed ingredients contaminated with controlled substances and/or deliberately spiked with potent controlled substances to increase effectiveness.
The adulterants in the latter being unconventional and dose set to produce the desired effect, deliberate dietary supplement fraud poses greater health risks than trace contamination from lack of quality control
One example of substances not licensed for human consumption is 2,4-dinitrophenol (2,4-DNP), which is an effective but highly dangerous fat burner. Marketed as a fat burner or weight‐loss supplement, it is particularly popular with younger adults, has no safe dose and is highly toxic. Currently, 2,4-DNP has industrial use but it is not licensed for human consumption and its sale as such is prohibited around the world. Despite the danger, 2,4-DNP has re-emerged within the bodybuilding community and extreme dieters, particularly among young adults.
A precursor for 2,4,6‐trinitrotoluene (TNT), DNP was initially used by the French in First World War munition factories, mainly in manufacturing of explosives.
Since then, it has also been used as a dye, wood preserver, herbicide and photographic developer. It was Maurice Tainter at Stanford University in 1933 who discovered that the human consumption of DNP led to significant weight loss and soon it was popularised as a weight loss drug. It was included in over-the-counter medications and was sold to the public without requiring a prescription.
2,4-DNP was used in diet pills for obesity treatment between 1933 and 1938 under brand names of Dinitriso, Nitromet, Dinitrenal, and Alpha Dinitrophenol. Over 100,000 people were prescribed the drug, with claims of increasing metabolism by up to 50% at a harmless dose.
DNP can cause a significant increase in the basal metabolic rate. This leads to weight loss by burning more fat and carbohydrates. DNP makes energy production in your mitochondria less efficient. This means your body needs to burn more calories to produce the same amount of ATP. In order to increase metabolism, DNP causes potential energy to dissipate as heat, instead of being converted to adenosine triphosphate.
However, the rapid increase in body temperature, consumption of DNP led to patients being “literally cooked to death” from the inside. For those patients who did not die, they either went blind, lost their sense of taste, or experienced an unpleasant rash.
As more side effects, were reported, DNP was labelled as ‘extremely dangerous and not fit for human consumption’ by the Federal Food, Drug and Cosmetic Act of 1938.
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 1981, Dr. Bachynsky processed industrial DNP into tablets which he marketed/dispensed under the trade name ‘Mitcal’ through his private weight loss clinic. He advertised that weight loss occurred using ‘Mitcal’ through a mechanism he called intracellular hyperthermia therapy.
Individuals using Mitcal started reporting adverse effects, such as fever, shortness of breath and sweating, to the US Food and Drugs Administration in late 1982. Additionally, there was a fatality associated with an intentional overdose of ‘Mitcal’ in 1984. Following further investigation, Dr. Bachynsky was convicted in 1986 of drug law violations, fined and prohibited from dispensing DNP to any patients.
Prison should have seen the end of Bachynsky’s influence but when he was incarcerated he met Dan Duchaine. Dubbed the “steroid guru”, Duchaine was notorious as a promoter of steroids for bodybuilding. He had been jailed for illegally selling these drugs and was fascinated to hear Bachynsky’s story of DNP. In the late 1990s, now out of prison, Duchaine promoted DNP to the bodybuilding community as “the king of the fat-loss drugs” and a new era of DNP use began.
However, he continued to use DNP for a variety of different ‘medicinal claims’ and was eventually jailed for fraud in 2008 in the USA in relation to the marketing of a company that was developing DNP being used in Europe as a cancer treatment known as intracellular hyperthermia therapy.
Regular use of 2,4-dinitrophenol (DNP) was reported to cause rapid loss of weight, but unfortunately was associated with an unacceptably high rate of significant side effects As a result, 2,4-DNP was subsequently banned by the Federal Food, Drug, and Cosmetic Act.
Efforts of regulatory bodies to protect the public from harm associated with 2,4-DNP are counterbalanced by the ease of access and availability through Internet retailers, and by a plethora of online discussion forums that share experiences among users and readily offer guidance and advice on what and how to use to chemically boost athletic performance or to achieve the desired appearance.
Adverse side effects ranged from short-term nausea, vomiting, and increased pulse rate, to increasingly severe long-term effects such as cataracts, hepatotoxicity, and death. The issue surrounding DNP is that the adverse side effects may be triggered at various doses, whether considered therapeutic or not. This is because the tolerance to the drug is different for each individual; therefore, doses that may be considered “safe” for some may be lethal to others.
The main symptoms associated with 2,4-DNP intoxication, including hyperthermia (abnormally high body temperature or overheating), tachycardia, decreased blood pressure, and acute renal failure. In animal studies, DNP has been shown to be teratogenic, mutagenic and carcinogenic; developmental and reproductive toxicity has also been reported.
The average time to presentation in the reported cases of acute or suicidal overdose is 7–8h and the average time of death is 14h. The onset of symptoms was reported as early as 3h and 30 min after the overdose. The usual complaint of the patient is that of profuse sweating. The initial fever is not associated with a change in heart rate or blood pressure, but tachycardia, tachypnoea, shock, confusion, convulsions, cardiovascular collapse and pulseless electrical activity are the eventual consequence of the fatal, deliberate overdose, regardless of treatment.
As 2,4-DNP is currently illegal for human consumption, there is concern over those accessing the drug whilst it is unregulated.
2,4-DNP is used knowingly and willingly by obese individuals and those desiring extreme outcomes, such as achieving unnaturally low body fat in bodybuilding, compensating for overeating among bulimia sufferers or motivated by a rapid and effective weight loss and used 2,4-DNP as shortcut. The drug is often taken in cycles, and information regarding dosage and personal programs is readily made available by bodybuilders for others in the industry to follow
Until recently when 2,4-DNP resurfaced in the gym-going population as a potent fat burner and more attention has been drawn to this substance, thanks to numerous media reports of DNP overdose deaths, law enforcement and regulatory bodies were largely unaware that protecting the public by controlling sales and access in the Internet era is an impossible task
Alarmingly, the plethora of personal accounts of successful 2,4-DNP use in bodybuilding websites, discussion boards, and forums gives some the untrue impression that 2,4-DNP is suitable for human consumption and may be considered a “safe” product if used “properly.” Discounting the idea that 2,4-DNP poses danger because it may be disguised within slimming pills.
Nowadays, DNP is sold mostly over the internet under a number of different names such as Aldifen, Chemox, Cawell No.392, Dinofan, Dinosan, Dnoc, DNP steroid, Fenoxyl, Nitro Kleenup, Nitrophen, Osmotox, Sulfo, Solfo Black, Tertosulphur PRB. The chemical is a yellow crystalline powder that has a sweet, musty odour and is soluble in water. The dose of DNP per capsule varies from website to website but it is most commonly sold as either 100- or 200-mg capsules.
Some internet sites have DNP available in bulk quantities, allowing users to purchase kilograms of DNP powder or hundreds/thousands of DNP-containing tablets, as well as offering free anabolic steroids and thyroxine to use in combination with the DNP.
Websites often offer some advice for users around the use of DNP. The informally “recommended” dosage ranges between 200 and 600mg, often recommending that new users start at a lower dosage and increase it gradually if tolerated well. For comparison, 100mg equates to 1.4 mg/kg for healthy average male (70 kg); 1.7 mg/kg for healthy average female (58 kg); 1.2 mg/kg for average bodybuilder male (81.5 kg); 1.6 mg/kg for average bodybuilder female (63.5 kg), based on ideal weight for the average height, with ideal weight adjusted for bodybuilding.
Health warnings are associated with a single dose (i.e., it should not exceed 300–600 mg at any one time) and duration of the DNP regime. The latter varies between recommended cycles (i.e., 8 days on-8 days off; 7–10 day cycle; 2 weeks on–2 weeks off; 20 or 30-day cycle, with shorter cycles tending to be recommended with higher doses) and total duration (i.e., do not exceed 20 days).
These websites additionally describe the potential toxicity associated with the use of DNP including the potential for hyperthermia and death. Advice is provided to users on how to prevent hyperthermia developing, including use of air conditioning/fans and only exercising in cool areas whilst on the DNP phase of a ‘treatment cycle’ and carrying a thermometer to monitor body temperature. They recommend that should body temperature rise above 38.9deg C (102deg F), the user should ‘lower the DNP dose, take a very cold bath and ensure adequate hydration with water and juice-based drinks’.
Preceding death, the patient is often profoundly hyperthermic. Death is usually secondary to massive cardiovascular collapse. There have been frequent reports of a rapid (within minutes) onset of generalised rigidity after death.
However, 2,4-DNP poses serious health risks to new or naïve users who are not experienced with performance- and image-enhancing drugs or conscientious of dosage, and lack of knowledge on the extent of potential harmful effects. This has contributed to an increasing number of mortalities caused by 2,4-DNP.
Fatalities from the intake of DNP, whether accidental or suicidal, have been reported since the turn of the twentieth century. To date, there have been 62 published deaths attributed to DNP. Over the last decade, from 2001 to 2010, there have been 12 deaths related to exposure to DNP. These fatalities have been linked to deliberate overdose, accidental toxicity associated with use by bodybuilders or for weight loss and accidental occupational exposure.
While males continue to make up the majority of users, there is also an increasing proportion of women turning to the drug as a weight loss aid.
What is worse is that, there is no specific antidote for DNP poisoning and all management strategies are based on case reports and expert opinions, but the key to the management of DNP poisoning lies in early recognition and a high index of suspicion.
Patients who have acutely overdosed on DNP in any form should be observed for at least 12h, as no patient has been recorded to be asymptomatic beyond 10h after an acute overdose. During this time, their body temperature, cardiac rhythm, heart rate and oxygen saturation should be carefully monitored.
Death case studies:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131886/
https://www.bjanaesthesia.org/article/S0007-0912(17)34488-4/fulltext
https://pubmed.ncbi.nlm.nih.gov/33706128/
https://www.indiatoday.in/india/story/thane-dancer-dies-hours-after-taking-banned-weight-loss-pill-1645040-2020-02-10
https://pubmed.ncbi.nlm.nih.gov/25367505/
https://www.tandfonline.com/doi/full/10.1081/CLT-58946
https://link.springer.com/article/10.1007/s00414-016-1378-4
https://www.bbc.com/news/uk-england-hereford-worcester-43072003
https://www.theguardian.com/politics/2014/jan/14/dnp-victims-families-fat-burning-drug-reclassify
https://journal.chestnet.org/article/S0012-3692(17)31929-3/fulltext
https://www.sciencedirect.com/science/article/abs/pii/S2352007822002645
https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/pdf/10.21466/ac.ARBDDT2.2013
https://www.kjlm.or.kr/journal/view.php?doi=10.7580/kjlm.2020.44.3.140
https://www.huffingtonpost.co.uk/2015/04/21/eloise-aimee-parry-dead-woman-21-dies-toxic-diet-pills_n_7105938.html?1429605276
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