The chemical 2,4-dinitrophenol (DNP) is one of the oldest (and most successful) weight loss drugs. It works by not only increasing respiration but also by uncoupling the reactions in the electron transport chain from ATP generation, so that a higher proportion of the energy we get from food is released as heat. In other words, DNP drastically increases thermogenesis (and metabolic rate/speed), which allows a significant portion of food to be “wasted” as heat instead of stored in the body (mostly as fat). Thus, DNP can not only prevent the weight gain from an obesogenic diet, but also induce weight loss in an already obese person. These effects made DNP a very popular remedy for weight loss in the first half of the 20th century. However, due to a few deaths as a result of heat strokes caused by overdosing DNP, the FDA stepped in and banned the sales and personal use of DNP in the US. To this day, people get aggressively prosecuted if they attempt to sell DNP online or give it to friends/family. Interestingly, the FDA does not seem to be as strict when it comes to pharma companies toying with such “poison”. Despite the ongoing fearmongering that DNP is “deadly”, behind the scenes multiple pharma companies are running clinical trials with DNP for quite a few serious and truly deadly conditions. In order to limit the fallout with the public due to the double-standard, DNP is no longer called DNP in clinical trials since it has now been patented (naive me thought generic compounds in the public domain are unpatentable), as the pro-mitochondrial drug MP-101 (and its close analog MP-201). A quick look at the list of trials with MP-101 shows that pharma companies are banking on MP-101 treating a wide variety of serious chronic issues including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington Diasease (HD), Alzheimer Disease (AD), mental illness, obesity, diabetes, immunodeficiency, congenital disorders, etc (see first two links below). In other words, pretty much all major chronic conditions known to medicine. I guess the good news in this entire charade is that if FDA and pharma companies believe DNP….errr..I mean MP-101….can treat all of these conditions then this is an open admission by those entities that all such diseases are metabolic in origin, since DNP…errr…I mean MP-101…has no known mechanism of action other than its uncoupling/pro-metabolic effects. The bad news is that perhaps millions of people worldwide will get poisoned by the newest pharma fad for weight loss known as GLP-1 agonists (Ozempic, anyone?) before the public wisens up to the fact that there are safer, and truly beneficial pharmacological alternative (e.g. uncouplers) for losing weight. Now, since DNP usage does have risks due to its potency as a thermogenic compound, and it is highly illegal to use therapeutically (unless you are a pharma company, rubbing shoulders with the FDA), one could approximate its effects with other uncouplers such as aspirin, caffeine, progesterone, salt, flavones/flavanones, etc.
https://adisinsight.springer.com/drugs/800050437
https://synapse.patsnap.com/drug/7efa6f9581334bb3b18623859ad7835d
EU agency OKs study of therapy to improve mitochondrial function
“…Mitochon Pharmaceuticals is launching a pilot clinical trial to evaluate MP101, its treatment candidate for improving mitochondrial function, in people with multiple sclerosis (MS) and other neurodegenerative diseases. The announcement follows the trial’s clearance by the European Medicines Agency (EMA), which enables Mitochon to begin enrolling patients with neurodegenerative conditions in the biomarker study. The Phase 1/2a trial will enroll people with MS, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and Huntington’s disease, each of whom will receive the experimental therapy for 14 days. The goal is to demonstrate whether the therapy is safe in these populations and induces relevant changes in disease-related biomarkers. “We are delighted for the opportunity to explore [the] provocative idea that most, if not all neurodegenerative diseases are rooted in mitochondrial dysfunction,” John G. Geisler, PhD, Mitochon’s co-founder and chief scientific officer, said in a company press release.”
“…Mitochondria are small cellular structures that produce most of the energy cells need to function — including the energy required for nerve cells to transmit electrical signals to other cells. They’re also involved in other essential cell functions. However, research has shown that these cellular organelles are dysfunctional, or don’t work properly, in most neurodegenerative conditions, including in multiple sclerosis. Thus, impaired mitochondrial function is thought to play an important role in neuronal damage and disease progression. MP101 is an investigational, brain-penetrant oral therapy that works as a mitochondrial stimulator, improving the function of these organelles across cells in the brain and spinal cord. This increases the amount of energy produced by cells and also induces the production of neuroprotective factors, which help protect cells from neurodegenerative disease processes.”
“…In preclinical studies, researchers showed that MP101 was able to protect nerve cells from the demyelination that occurs in people with MS. It also reduced disease severity and improved mobility in animal models of the disease. Similar results were obtained with MP201, a similar candidate molecule. The upcoming trial is expected to confirm the benefits of MP101 in neurodegenerative conditions. If positive, these findings are expected to support Phase 2b studies in people with primary progressive MS and secondary progressive MS, as well as ALS, Huntington’s, and Alzheimer’s. “We predict that chronic treatment with this unique platform, at micro-doses, will resolve mitochondrial issues and change important disease specific biomarkers in all four indications similarly,” Geisler said.”
