Arguably the most dangerous drug used in bodybuilding, 2,4-Dinitrophenol (DNP) is known to have caused deaths via unregulated body temperature increases. DNP is a known toxin, pesticide, and was originally designed as an explosive substitute for TNT… Yet people STILL USE IT!
Why, you ask? Because you can literally burn a pound of fat a day without even exercising!
Related - Fat Loss: How to Lose Belly Fat
In this article, I will explain the chemistry and physiology of the world’s strongest (and most dangerous) fat burner and give my personal thoughts on using it.
Initially used in World War I by French munitions factories, DNP was mixed with picric acid to make explosives. Many of the workers noticed extreme weight loss, fatigue, excessive sweating, and extremely high body temperatures. These observations lead to the first study at Stanford University in 1933 for investigating the use of DNP as a weight loss agent. 
Before I get into the study, I need to give a brief physiology lesson... So bear with me.
Essentially, glycolysis - the breakdown of glucose into pyruvate, the Krebs cycle-a series of reactions that generates the important electron donors NADH, and FADH2 which are then used by the electron transport chain (oxidative phosphorylation) to produce ATP, are all connected or “coupled.” If there is a breakdown of these metabolic pathways, then there is an inefficiency in producing ATP.
The electron carriers NADH and FADH2 generated during the Krebs cycle play an extremely important role for the production of ATP. Through a series of reactions called “redox” (reduction/oxidation) reactions, they help generate the chemical energy needed to drive ATP synthase, the enzyme that turns ADP into ATP. These redox reactions pump protons, which are positively charged to one side of the membrane, which creates a chemical gradient or potential.
Think of this proton pump like a battery that has a positive end and a negative end. The protons are on the positive end and the electrons are on the negative. This allows the flow of charge, or chemical energy which turns ATP synthase, thus creating ATP.
With this in mind, what DNP does is disrupts this proton gradient so that there isn’t enough energy to produce ATP. It does this by binding with the protons and transporting them across the membrane to where the electrons are, thus causing a “leak” in the flow of the proton gradient and releasing this energy as heat.
In order for your body to get the energy that's needed for ATP production, it will break down fatty acids (stored fat) very readily, as the oxidation of fatty acids yields a tremendous amount of energy (and heat). DNP “uncouples” the Krebs cycle from oxidative phosphorylation, hence it’s classified as an uncoupler. 
So back to the 1933 Stanford study, research showed that small doses of DNP increased basal metabolism by 50%. Worth noting, DNP only seems to upregulate carbohydrate and fat metabolism, not protein breakdown. Weight loss of 1.5kg per week without diet restriction was common among subjects taking 3-5mg/kg.
The study did warn about possible fatal overdoses due to overheating, but the overall feel of the study seemed that it was a safe weight loss agent. So much, in fact that within a year of this study being published, 20 different drug companies were marketing DNP as a miracle weight loss OTC supplement, with reports of over 100,000 people using the drug.
However, shortly after this boom the side effects came pouring in. In 1935 there was an inundation of cataracts (DNP depletes antioxidants and vitamin C from cells which may be the reason for the cataracts), mostly in women whom have taken DNP. After further investigation, DNP was listed as “potentially so toxic that they should not be used even under a physician's supervision” in the Federal Food, Drug, and Cosmetic Act of 1938.
Sometimes, truth is stranger than fiction.
DNP made its way into bodybuilding circuits in the 90’s by the “Steroid Guru” Dan Duchaine, who learned about it while in prison from his cellmate (or just an inmate, unclear) Dr. Nicholas Bachynsky. Dr. Bachynsky was a Russian-born doctor who set up weight loss clinics that illegally prescribed DNP. Dr. Bachynsky claims he heard about its weight loss properties from Russian soldiers using it to keep warm during the rough winters.
Duchaine unleashed the magical fat loss of DNP to bodybuilders, and even is on record of having people stack it with insulin, the OTHER most dangerous drug in bodybuilding! To his credit, there is some science behind the theory which I will explain now, but I DO NOT endorse this protocol.
First off, roughly 40% of your body’s energy expenditure is non-usable work energy, meaning thrown off as heat and not used to produce ATP. This is regulated by uncoupling proteins (UPCs) in fat and muscle tissue.
DNP essentially does what these uncoupling proteins do, but without any negative feedback regulation from your body. Herein lies the danger in DNP… You can literally cook your organs by causing your body to release too much heat. There are several reported cases of this happening to bodybuilders. 3
While your mouth temperature may only be elevated 1-2 degrees, this is not an accurate representation of your actual body temperature on DNP. Because of the excess heat produced, your skin will significantly dilate in order to attempt to dissipate the heat. Studies show that a body temperature of 37.7C (100F) has a metabolic rate of nearly twice normal.
Secondly, since DNP is uncoupling ATP production from glucose, the demand for glucose is significantly higher and your body will upregulate glucose transport… By double. 
This happens via a separate signaling transduction pathway, independent of the insulin-stimulated glucose uptake pathway, meaning DNP is actually forcing glucose into your muscle cells. Also noted is the DNP can cause insulin resistance in adipose cells.  This is extremely beneficial for fat loss, as DNP seems to decrease fat cells’ ability to store glucose.
So taking into account that DNP can:
- Double glucose transport into your cells.
- Do this independently of the insulin-stimulated glucose uptake pathway.
- Increase your metabolic rate by 50% so you burn fat like crazy.
It was suggested that you can stack DNP with insulin, which also dramatically increases glucose uptake in muscle cells to create this super anabolic/fat loss environment. To repeat myself, I DO NOT CONDONE OR RECOMMEND THIS COMBINATION. But, there are others who have stacked these compounds with success.
One of the main issues people have with using DNP is that its half-life is 36 hours. This means that if you take 100mg on day one, you still have 50mg left 36 hours later, and 25mg left 36 hours, and so on. It takes 252 hours before it’s all gone.
Most people take the same dose daily, without realizing that it will build up significantly in your body over time and reach much higher levels than you think. If you look at the chart below, if one takes 200mg on day one, the blood concentration of DNP is 325mg on day two, 405mg on day three, and maxes out at around 540mg as your daily blood concentration.
So, even though you’re only taking 200mg/d, your body is getting 2.7X that amount because of the long half-life.
My Final Thoughts
DNP, as I’ve laid out in this article is very dangerous, and as of 2011 there have been 62 known fatalities from DNP. Even though studies suggest 3-5mg/kg is not toxic, people have died from using this amount. 6
Your body cannot regulate the elevation in body temperature and reports of body temperatures of 111F, which causes severe hyperthermia and death have been documented. I have never tried it myself, but it has intrigued me based on how well it can burn fat, increase glycogen and prevent muscle loss all at the same time.
If after reading this article, you feel the need to try DNP, I would firmly suggest the lowest possible dose and very short cycles. Even at 50-100mg/d, you should notice decent fat loss after a 10-15 day cycle.
I would not do low carb, as that would be counterproductive to the benefits of DNP. You must use antioxidants if you decide to engage in DNP use, as tons of free radicals are generated whenever uncoupling processes occur in the body. Lastly, make sure to stay very hydrated and maintain electrolytes as you will be sweating a lot, especially at night.