Tests in the Medical Use of Dinitrophenol (DNP)
The title of this article contains an important qualification: today DNP has no registered medical use in humans. Therefore 'tests in medical use' are primarily the examinations that doctors perform when poisoning is suspected, after it, and also in controlled clinical studies of DNP derivatives. The editorial team explains what is measured and why, and why no test makes self-administration safe.
The medical status of DNP: past and present
In 1933–1938 DNP was sold in the USA as a weight-loss agent. Doctors of that time monitored mainly the basal metabolism (basal metabolic rate) — an indicator measured by oxygen consumption. No modern blood tests for the early detection of toxicity existed then, and they would not have been able to predict cataracts or sudden hyperthermia anyway.
After 1938 DNP was not registered anywhere in the world as a medicine for humans. Consequently, there are no official protocols for 'monitoring DNP therapy', and any online advice about 'tests on a cycle' has no medical basis.
The only modern medical dimension is the study of derivative substances. Scientists are developing DNP prodrugs and other mitochondrial uncouplers for the treatment of metabolic diseases, in particular fatty liver disease. The review by Childress et al. (2018) describes this direction. In such studies participants are under strict supervision, and safety is assessed according to a protocol approved by ethics committees.
Therefore, what follows concerns the real clinical situation that doctors face: a patient who has taken DNP and shows signs of toxicity, or a patient who seeks help after such an experience.
Emergency tests when poisoning is suspected
The first 'test' is not the laboratory but the measurement of body temperature, heart rate, respiratory rate, blood pressure and saturation. Toxicology references emphasize: in DNP poisoning the most important thing is to quickly detect and treat hyperthermia.
In parallel, blood is drawn for gas composition and lactate. Metabolic acidosis with high lactate reflects the energy deficit of cells and is a marker of severity. Next — electrolytes: potassium, sodium, calcium, phosphates, magnesium. Hyperkalemia can be a consequence of rhabdomyolysis and kidney damage and threatens arrhythmias.
Creatine phosphokinase (CPK) shows the degree of muscle breakdown. In rhabdomyolysis it can rise very significantly, and it usually reaches its peak not immediately, so it is measured repeatedly. Creatinine and urea assess kidney function; ALT, AST, bilirubin and a coagulogram — liver function.
An ECG is also performed to detect tachyarrhythmias and signs of hyperkalemia, along with blood glucose and a complete blood count. A urinalysis may show myoglobinuria.
| Indicator | What it reflects | Why it matters in DNP |
|---|---|---|
| Body temperature (core) | Degree of hyperthermia | The main predictor of severity |
| Blood gas composition, lactate | Acid-base status | Acidosis due to ATP deficiency |
| Potassium, phosphates, calcium | Electrolyte balance | Risk of arrhythmias |
| CPK, myoglobin | Muscle breakdown | Rhabdomyolysis, risk to the kidneys |
| Creatinine, urea | Kidney function | Acute kidney injury |
| ALT, AST, coagulogram | Liver function | Hepatocellular damage |
| ECG | Rhythm and conduction | Tachyarrhythmias, signs of hyperkalemia |
Toxicological confirmation
The concentration of DNP in blood or urine can be determined by chromatography-mass spectrometry methods in specialized toxicology laboratories. However, such tests are not performed everywhere and not within minutes, so the decision on treatment is made based on the history and clinical picture.
In other words, a doctor will not wait for the result of a toxicological test to begin cooling. That is precisely why it is so important for the patient or their relatives to name the substance immediately.
Researchers have described the determination of DNP in the blood of the deceased during forensic examinations, as well as in samples of products sold online. These data helped confirm that the content of capsules is often unpredictable (Petróczi et al., 2015).
Yellow coloring of the urine and skin may suggest DNP, but is not a reliable diagnostic test. It does not allow the amount of the substance or the severity of the condition to be assessed.
Dynamic monitoring in hospital
DNP poisoning is a dynamic condition. A patient who has moderate abnormalities on admission may deteriorate within a few hours, so tests are repeated at short intervals.
Temperature is monitored continuously, preferably with a core sensor. Blood gas composition and potassium are repeated often, especially during infusion therapy and cooling. CPK, creatinine and liver enzymes are assessed at least daily, until the values begin to steadily decline.
Diuresis is also monitored: a decrease in the amount of urine is an early signal of kidney damage and a possible basis for dialysis. In severe patients the state of consciousness is assessed, and if necessary — brain imaging is performed, if other causes of the disturbances are suspected.
- Temperature — continuously.
- Blood gas composition, potassium, lactate — repeatedly during the first hours.
- CPK, creatinine, liver enzymes — at least daily.
- Diuresis — hourly in severe cases.
Examination after an episode of use
People who have taken DNP and survived poisoning, or simply had a period of use, should undergo a follow-up examination. The goal is to detect consequences that may have gone unnoticed.
The basic set includes a complete blood count (agranulocytosis has been described historically), creatinine and estimated glomerular filtration rate, liver enzymes, CPK and a urinalysis. The doctor may supplement it depending on complaints.
Especially important is an ophthalmologist examination with biomicroscopy of the lens: cataract associated with DNP can develop imperceptibly. It is also worth telling the doctor about peripheral symptoms — numbness, tingling in the limbs.
No 'normal' test result means that DNP can be used again. Tests assess the past but do not predict how the body will react next time.
Editorial conclusions
There is no registered medical use of DNP, so there are no 'cycle monitoring' protocols either. Real medical practice concerns only the diagnosis and treatment of poisoning and the study of derivative substances.
In poisoning, the key indicators are temperature, lactate and blood gas composition, potassium, CPK, kidney and liver function, and the ECG. They are monitored over time, because the condition can deteriorate quickly.
After an episode of use it is worth undergoing an examination by a general practitioner and an ophthalmologist, but safe repeat use does not exist.
We also recommend reading our articles on the signs of a DNP overdose, on its effect on the liver and kidneys, and on the interaction of DNP with other substances.
References
- Grundlingh J, Dargan PI, El-Zanfaly M, Wood DM. 2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death. J Med Toxicol. 2011;7(3):205–212.
- Kamour A, George N, Gwynnette D, et al. Increasing frequency of severe clinical toxicity after use of 2,4-dinitrophenol in the UK: a report from the National Poisons Information Service. Emerg Med J. 2015;32(5):383–386.
- Agency for Toxic Substances and Disease Registry. Toxicological Profile for Dinitrophenols. Atlanta: US Department of Health and Human Services; 1995.
- Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009;361(1):62–72.
- Petróczi A, Ocampo JA, Shah I, et al. Russian roulette with unlicensed fat-burner drug 2,4-dinitrophenol (DNP): evidence from a multidisciplinary study of the internet, bodybuilding supplements and DNP users. Subst Abuse Treat Prev Policy. 2015;10:39.
- Childress ES, Alexopoulos SJ, Hoehn KL, Santos WL. Small molecule mitochondrial uncouplers and their therapeutic potential. J Med Chem. 2018;61(11):4641–4655.
- Nelson LS, Howland MA, Lewin NA, et al (eds). Goldfrank's Toxicologic Emergencies. 11th ed. New York: McGraw-Hill; 2019.
Andriy Melnyk
A strength-sports coach and author of programs for beginner and intermediate levels. Writes about training planning.
