Why does dnp increased body temperature

Its use for those wishing to lose weight was encouraged by reports of rapid, safe weight loss [ 7 , 8 ]. DNP can cause a significant increase in the basal metabolic rate [ 7 , 8 ]. This leads to weight loss by burning more fat and carbohydrates [ 9 ], and weight loss of up to 1. After , medical prescription of DNP stopped and cases of poisoning due to medical intake were no longer reported, but case reports of deaths associated with the ingestion of DNP still emerged [ 14 , 15 ].

It is anecdotally reported to have been prescribed to the Russian soldiers during World War II to keep them warm [ 16 ]. In , a physician Dr.

It is alleged in subsequent court proceedings that over 14, people were treated by Dr. Individuals using Mitcal started reporting adverse effects, such as fever, shortness of breath and sweating, to the US Food and Drugs Administration in late Following further investigation, Dr.

Bachynsky was convicted in of drug law violations, fined and prohibited from dispensing DNP to any patients. This warning was aimed specifically at bodybuilders, to avoid its use due to significant potential for short-term and long-term harm, following the hospitalisation of a Finish bodybuilder after having taken DNP [ 18 ]. Despite this, DNP remains widely available and as discussed below in more detail, can be purchased over the internet, particularly from online pharmacies.

Additionally, there are instructions for the synthesis of DNP online for self-manufacture. Despite this legislation and warnings of harm associated with its use, reports of deaths due to the use of DNP have increased in the last few years Fig. Summary of previously published fatalities relating to exposure to DNP including basic demographics, amount of exposure and maximal temperature recorded pre-death. 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 or mg capsules. Websites often offer some advice for users around the use of DNP, although this is often targeted towards bodybuilders rather than for generic weight loss. These websites additionally describe the potential toxicity associated with the use of DNP including the potential for hyperthermia and death. They recommend that should body temperature rise above The marketed and desired beneficial effect of weight loss is reportedly not rapid enough for some individuals, and therefore they may take higher and potentially toxic doses in order to hasten the weight loss effects [ 20 , 21 ].

Additionally, there have been a number of recent fatalities due to intentional ingestion of DNP as suicide attempts [ 4 , 22 ]. The classic symptom complex observed by overdose of phenol-based products such as DNP is a combination of hyperthermia, tachycardia, diaphoresis and tachypnoea [ 4 , 21 , 22 ].

There are thought to be several physiological mechanisms involved in the development of toxicity of DNP, which are summarised below. DNP decreases the formation of high-energy phosphate bonds in mitochondria and at the same time stimulates systemic oxygen consumption [ 23 ].

This dissociative effect is known as uncoupling of oxidative phosphorylation. During glycolysis, there is a net production of two ATP molecules, but the majority of energy-rich phosphate bonds 38 in total are produced during the final oxidative phosphorylation process.

During this final phase, ATP synthetase converts adenosinediphosphate to ATP with the addition of an inorganic phosphate molecule. DNP interferes with the final energy production pathway by preventing the uptake of inorganic phosphate molecules into the mitochondria [ 24 , 25 ]. This results in the inhibition of all energy-requiring processes and the extra-mitochondrial accumulation of inorganic phosphate [ 26 ]. This shift in the proton electrochemical gradient then results in potential energy dissipating as heat, instead of being converted to ATP, with rapid consumption of calories [ 27 , 28 ].

The heat production represents a failure in thermoregulatory homeostasis, leading to uncontrolled hyperthermia [ 29 ]. El-Guindy et al. Carbohydrate consumption markedly increases in the presence of dinitrophenol which allows for rapid weight loss when dinitrophenol is taken in small doses [ 26 ]. Pyruvic acid is aerobically metabolised to H 2 O and CO 2 , but results in the production of lactic acid when metabolised anaerobically.

The discrepancy between the stimulation of glycolysis and the inhibition of oxidative phosphorylation results in a rapid rise in the production of pyruvic acid, leading to an increased production of lactic acid [ 24 , 26 , 31 ]. Mudge showed that potassium accumulates in rabbit kidney slices as the concentration of dinitrophenol is increased [ 32 ].

The accumulation of potassium continues even after cellular respiration is inhibited [ 32 ] and hyperkalaemia has contributed to toxicity [ 33 ]. Due to the uncoupling of oxidative phosphorylation, inorganic phosphate is no longer absorbed into the mitochondria and accumulation takes place, but whether this contributes to the clinical presentation is unknown [ 25 , 34 ]. In animal studies, DNP has been shown to be teratogenic, mutagenic and carcinogenic; developmental and reproductive toxicity has also been reported [ 35 ].

The oral route is currently the most common route of therapeutic and suicidal exposure. Dermal exposure can cause yellow staining and may have mild corrosive effects on the skin. Absorption through the skin may lead to systemic effects similar to those seen following ingestion of DNP, although only mild symptoms are usually experienced.

Exposure to the eyes may cause yellow discoloration of the sclera with conjunctival injection and irritation. Dermal exposure is the most common route of unintentional exposure [ 6 , 33 ].

DNP is used in the chemical industry in wood preservatives, herbicides and dyes and may leak onto industrial sites through landfill and storage tanks. Accidental spills during manufacture and transport are possible and exposure is usually through exposure to the water or dirt that it has leaked on. Although there have been no reports of this occurring, there have been two fatalities related to individuals recycling nylon bags that had previously contained DNP [ 33 ]. Inhalational exposure can happen by breathing contaminated air at DNP-containing waste sites or from incineration fumes.

Inhalation of DNP fumes may lead to significant systemic effects, similar to those seen with ingestion. There is a small margin between the beneficial effects and the toxic effects of DNP.

The most common side effect reported with the therapeutic use of DNP is a rash [ 6 , 36 — 38 ]. This rash can be maculo-papular, urticarial, angio-oedematous or a severe exfoliative dermatitis [ 39 — 41 ]. There is often accompanying pruritis and subsequent desquamation [ 39 , 41 , 42 ].

Prolonged peripheral neuritis has been reported, often affecting the hands and feet and associated with skin changes [ 11 , 43 , 44 ]. A common complaint is that of yellow discoloration of the skin, sclera and urine [ 45 — 48 ].

This same yellow discoloration is often seen at autopsy and has been confused with jaundice due to reports of liver damage [ 36 , 45 , 49 — 52 ]. T wave and ST segment abnormalities have been noted and some of the earlier autopsied case reports recorded heart muscle damage [ 46 , 50 , 53 ].

Gastroenteritis and anorexia have been reported in high doses [ 11 , 36 ]. Acute kidney injury, as evidenced by acute tubular necrosis, has been found at autopsy and also reported in two other cases [ 46 , 54 , 55 ].

Confusion, agitation, convulsion and coma are the most common neurological effects reported [ 50 , 56 , 57 ]. Agranulocytosis and neutropaenia have been associated with the therapeutic use of DNP [ 36 , 37 , 45 , 47 , 58 — 61 ]. Cataracts can develop quickly after the use of DNP, usually leading to a permanent decrease in vision to light—dark perception in days to months [ 62 — 65 ]. Permanent deafness has been reported at doses considered to be therapeutic [ 66 ].

The average time to presentation in the reported cases of acute or suicidal overdose is 7—8 h and the average time of death is 14 h [ 4 , 15 , 22 , 51 , 56 , 67 — 69 ]. The onset of symptoms was reported as early as 3 h and 30 min after the overdose [ 56 ]. The usual complaint of the patient is that of profuse sweating [ 46 ].

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 [ 4 , 15 , 22 , 51 , 56 , 67 — 69 ].

However, there has been at least one case of survival following deliberate overdose in an year-old female who developed typical features of DNP toxicity [tachycardia of beats per minute, tachypnoea of 38—40 breaths per minute and hyperthermia of She was managed conservatively with intravenous fluids and ice packs to maintain her temperature below Ingestion of DNP was confirmed by analysis of gastric lavage contents.

Fatalities from the intake of DNP, whether accidental or suicidal, have been reported since the turn of the twentieth century Table 1. To date, there have been 62 published deaths attributed to DNP Fig. The largest publication of 36 deaths due to DNP was published in [ 6 ].

This was a study into the deaths in munition factories in Paris due to occupational exposure to DNP. It highlights the improvements made in the factory to prevent further deaths through simple measures such as ventilation, personal protective equipment and better hygiene. This combined with changes in legislation brought the death rate down from During the s, reported DNP-related fatalities were all individuals who had taken it for weight loss [ 46 , 47 , 51 , 56 , 57 , 61 , 67 , 71 ].

After the s, there have only been two fatalities in the remainder of the twentieth century [ 15 , 68 ]. One related to deliberate ingestion of DNP [ 68 ] and the other was where an individual accidentally ingested a liquid he thought to be grape juice, but in fact contained derivatives of DNP [ 15 ]. Over the last decade, from to , there have been 12 deaths related to exposure to DNP.

These fatalities have been linked to deliberate overdose [ 4 , 22 , 69 ], accidental toxicity associated with use by bodybuilders or for weight loss [ 21 , 28 , 72 — 75 ] and accidental occupational exposure [ 33 ]. This resurgence in reported fatalities may reflect the increased availability of DNP over the internet, marketed particularly towards bodybuilders.

Preceding death, the patient is often profoundly hyperthermic and there may be associated methaemoglobinaemia. Death is usually secondary to massive cardiovascular collapse. There have been frequent reports of a rapid within minutes onset of generalised rigidity after death [ 6 , 11 ]. This profound muscle rigidity has also been seen to happen before death making mechanical ventilation very difficult [ 21 ].

This early onset of generalised rigidity after death has been attributed to the release of calcium from the cytosol due to the depletion of ATP [ 22 ]. Ingestion is currently the most common route of exposure to the drug leading to death. The lowest published lethal human oral dose of DNP is 4. The highest reported dose taken in acute overdose associated with survival was a woman who took 2.

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 [ 46 ]. Patients who have acutely overdosed on DNP in any form should be observed for at least 12 h, as no patient has been recorded to be asymptomatic beyond 10 h after an acute overdose [ 4 ]. During this time, their body temperature, cardiac rhythm, heart rate and oxygen saturation should be carefully monitored.

Previous autopsies have reported a yellow coloured fluid in the intestines of some cases; there is no evidence that this fluid contains DNP rather than staining following ingestion. External decontamination, if appropriate, should be undertaken by washing to reduce dermal exposure. Based on the underlying pathophysiological principles and previous experience, it would be advisable to avoid the use of salicylates as it may worsen the DNP-related toxidrome [ 77 , 78 ]. Aggressive fluid resuscitation should be initiated, using cooled fluids in those with hyperthermia.

Seizures should be controlled with benzodiazepines. These may also be needed to control severely agitated patients, as their agitation will add to the hyperthermic state which may lead to circulatory collapse.

External cooling measures with ice or cooling blankets should be initiated to control hyperpyrexia [ 11 , 70 , 79 — 81 ]. If benzodiazepines do not control agitation or seizures, then paralysis, intubation and ventilation should be considered. Dantrolene and ice baths have been used to control the severe hyperthermic state [ 46 , 82 ]. There is the possibility for the use of external cooling devices, such as those used to induce therapeutic hypothermia following an out of hospital cardiac arrest, to rapidly reduce temperature; however, there have been no previous reports of using these devices in patients with DNP toxicity.

Dantrolene has previously been recommended to manage the hyperthermia associated with the use of DNP. There is no evidence to support this recommendation, but it has been used successfully in a single case report [ 34 , 82 ]. Cardiopulmonary resuscitation was performed in some of the cases of DNP overdose and in one case for up to an hour [ 69 ], but has never led to a return of spontaneous circulation.

I didn't say you did I said: from what I understood If my temp was high and I was loosing a lot of heat; by taking a cold shower I may increase hyperthermia. However, the showers did bring my temp back down. Hyperthermia is HIGH core temperature. So if your temp is high, your losing heat, but your body is creating TOO much heat see.

So taking a cold shower will be effective in lowering your temp slightly. Now by cold shower I mean cool, you don't want to jump into an ice cold shower with a high temp. This can have other complications. But a nice cool shower is absolutley fine. Glad you were pleased with the ol' DNP. I am probably going to start a dnp stretch soon. You must log in or register to reply here. Similar threads I. Starting first HGH cycle tomorrow - some questions.

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These long-term effects were noted back in the s. But in recent years, it's been making a resurgence as a weight-loss drug— thanks in part to a physician named Dr. Nicholas Bachynsky, who, in the 's, began treating people with DNP , re-labeling it "Mitcal," and falsely claimed it to have a multitude of health benefits in addition to weight loss.

He was later imprisoned for fraud— but the ramifications of his actions are still being felt today. Although DNP is banned in both the United States and the United Kingdom, it is still easily available for purchase online— and it's being marketed towards bodybuilders as an easy way to drop body fat, fast. With access to the drug now easier than ever, there has been a marked increase in the number of DNP-attributed deaths since the turn of the century , especially among fit, young people.

A case study from examined the case of a year-old man who died as a result of taking DNP. In a case , a teenage girl also died after purchasing DNP on the internet as a weight-loss supplement. Both people had purchased DNP online thinking it was a "safe" weight-loss aid, despite a nearly year rule that has deemed DNP highly dangerous and unfit for human consumption.