How DNP (2,4-dinitrophenol) Works

In technical terms, DNP (2,4-dinitrophenol) is a “classical uncoupler of oxidative phosphorylation”.  It works in the mitochondria, the structures that serve as “powerhouses” of all animal cells.


In the presence of oxygen, cells consume glucose.  Within the inner membrane of each mitochondrion, the resulting molecules are processed through a series of reactions known as the Krebs cycle.  The products of this cycle cause protons (H+) to diffuse through the inner membrane of the mitochondrion, from within the membrane out into the “matrix” (outer region) of the mitochondrion.  As a result, a “chemiosmotic gradient”—similar to an electric potential—is produced.  To relieve this gradient, the protons are allowed to drift back through the inner mitochondrial membrane.


Normally, the only re-entry point for these protons is through an enzyme known as ATP synthase.  When a proton passes through ATP synthase, its energy is used to drive the creation of ATP—the “fuel” of all living cells.  Thus, if the membrane is working properly, this drift of protons ensures a steady supply of fuel for the body.


Now, enter 2,4-dinitrophenol (DNP) into the picture.

When DNP is present in the cell, it serves as a “protonophore”: it is able to shuttle protons back into the inner membrane of the mitochondrion.  As a result, the protons are able to bypass the action of ATP synthase and simply diffuse back inside the inner membrane.  Their energy is not tapped to produce ATP, nor is it used to provide energy for the cell in any other way.  It is simply “wasted” as radiated heat.


This heat, incidentally, accounts for the danger posed by acute overdoses of DNP.  The body has no natural feedback cycle by which to counteract it, and it increases in proportion to the dosage of DNP administered.  Therefore, an acute overdose of DNP can cause dangerous hyperthermia.


Although DNP is a synthetic chemical, there are natural molecules that act as uncouplers in essentially the same way.  For instance, the “brown fat” of newborn infants, and the fat of hibernating animals, contain “uncoupling proteins” that produce excess heat in the same way as DNP.  As a result, newborns and hibernating animals are protected from hypothermia, to which both would otherwise be extremely vulnerable.


Importantly, DNP does not disrupt any other step in the process of respiration and oxygen consumption.  By allowing protons to bypass ATP synthase, DNP makes respiration much less efficient; it also increases oxygen consumption, in much the same way as would cardio exercise.  But it leaves the respiratory chain intact.


Dosing for DNP is discussed here.


Information on stacking DNP with other fat burners is here.


Click here to read more about DNP and calorie consumption.


To read more about the effects of DNP on different bodybuilding diets, click here.


Read about workouts to preserve lean mass here.