Dieting aidDNP was used extensively in diet pills from 1933 to 1938 after Cutting and Tainter at Stanford University made their first report on the drug's ability to greatly increase metabolic rate.[3][4] After only its first year on the market Tainter estimated that probably at least 100,000 persons had been treated with DNP in the United States, in addition to many others abroad.[5] DNP acts as a protonophore, allowing protons to leak across the inner mitochondrial membrane and thus bypass ATP synthase. This makes ATP energy production less efficient. In effect, part of the energy that is normally produced from cellular respiration is wasted as heat. The inefficiency is proportional to the dose of DNP that is taken. As the dose increases and energy production is made more inefficient, metabolic rate increases (and more fat is burned) in order to compensate for the inefficiency and meet energy demands. DNP is probably the best known agent for uncoupling oxidative phosphorylation. The production or "phosphorylation" of ATP by ATP synthase gets disconnected or "uncoupled" from oxidation.
The factor that limits ever-increasing doses of DNP is not a lack of ATP energy production, but rather an excessive rise in body temperature due to the heat produced during uncoupling.
Accordingly, DNP overdose will cause fatal hyperthermia. In light of this, when it was used clinically, the dose was slowly titrated according to personal tolerance, which varies greatly.[6]
Case reports have shown that an acute administration of 20–50 mg/kg in humans can be lethal.[7] Concerns about dangerous side-effects and rapidly developing cataracts resulted in DNP being discontinued in the United States by the end of 1938. DNP, however, continues to be used by some bodybuilders and athletes to rapidly lose body fat. Fatal overdoses are rare, but are still reported on occasion. These include cases of accidental exposure,[8] suicide,[7][9][10] and excessive intentional exposure.[9][11][12]
http://en.wikipedia.org/wiki/2,4-Dinitrophenol#Dieting_aid
