2,4 Dinitrophenol as Medicine - MDPI
"The consequence was that the mice on DNP lived longer than water alone (placebo). A subgroup after 1 or 5 months of DNP treatment was used to possibly reveal the reasons for increased longevity. These mice had significantly lower circulating triglycerides, glucose and insulin, and less oxidized proteins and DNA in the brain, liver and muscle due to lower hydrogen peroxide (H2O2) production. The salient point is, that a little mitochondrial uncoupling under chronic regimens, may have a large effect on wellness and even slow ageing."
"Focusing on the energy-out side of the equation, one other possible approach is to utilize DNP’s pharmacology, or modified forms of DNP, in low doses to increase energy expenditure [2,84]. Although our understanding of diabetes, insulin resistance and fatty liver diseases in the 1930s has greatly improved over 80 years, it was however reported even back then that for patients that did have diabetes and took DNP for long periods of time, that there was a significant improvement in lowering the AUC during an oral glucose tolerance test (OGTT) [162]. It was also reported that there was no improvement in an OGTT for obese individuals taking DNP for short durations. This makes sense now because it takes time to clear away intra-hepatic and intra-skeletal muscle lipids, from these two, key insulin-sensitive tissues needed to restore insulin sensitivity. This approach is completely different than the immediate effects of an insulin injection to drop blood glucose levels, but it has a far more profound long-term effect of potentially eliminating insulin injections altogether or eliminate the portfolio of anti-diabetic drugs taken for non-insulin dependent diabetic patients [2]. It seems surprising today, why in the 1930s the regime was to dose up to ~3 lbs/week, as in theory a much lower dose of ~50 mg/day would result in ~0.5 lbs of weight loss per week, corresponding to a dramatic ~26 lbs per year alone. However, weight loss may not be necessary to significantly improve many of the detrimental effects of the over-nutritional phenotype [2]. For example, in a study conducted in a colony of wildtype mice, provided a very low dose of DNP of ~100 µg/kg/day (HED ~0.5 mg/day) for basically their entire lifespan, resulted in lower circulating glucose, insulin and triglycerides and increased lifespan relative to placebo (water) [40]. The mice also had less ROS production, lower oxidized proteins and DNA damage in the brain, liver and cardiac tissues. Again, this speaks to the possible anti-aging properties of low dose uncouplers over long periods of time."