It seems like everyday there is a new supplement, additive, powdery substance, workout plan or diet regiment that can rival the Hydroxycuts and the "How to Look Sexy in 15 minutes" plans. Apparently there is one product to beat them all though. The product? Dinitrophenol. The only problem is that it is toxic and can kill you. No big deal right?
2, 4-Dinitrophenol (DNP) is a cellular metabolic poison. Commercially it has been used to make dyes, organic synthesis, wood preservatives, photograph development, explosives, and pesticides. It uncouples oxidative phosphorylation by carrying protons across the mitochondrial membrane, leading to the rapid consumption of energy without the generation of ATP. So why would someone put this in their body? DNP acts as a protonophore (a specific type of lipid soluble molecule used to transport ions across the lipid bilayer of a cellular membrane), thereby allowing protons to leak across the inner mitochondrial membrane and thus bypass ATP synthase. So what right? Well as it turns out, these protons that DNP transports are vital for ATP synthesis. A electrochemical gradient is establish through a series of redox reactions in the Electron Transport Chain of cellular respiration. NADH and FADH are oxidized in a series of enzymatic complexes within the mitochondria that transport H+ protons from the mitochrondrial matrix to the inner membrane space. This established gradient later causes the protons to move back into the matrix by way of ATP synthase. This proton movement initiates Oxidative Phosphorylation which generates ATP. Therefore, if a decreased number/no protons are available, no or hardly any ATP will be produced per 1 mol of glucose. This increases the cells metabolic demands as its energy source is being lost as heat instead of being converted to chemical energy and the cell breaks down fat and other energy stores to compensate.
Sounds great right? Well the danger with DNP is that the inefficiency of ATP synthesis is proportional to the dose of DNP taken. Because of this many people (body builders, athletes, those desperate to lose weight quickly and easily)will take too much that leads to an excessive rise in body temperature due to the heat released by the oxidation uncoupling. This is referred to as hyperthermia (body temperature between 99.5-100.9 degree Fahrenheit) and can be life threatening if body temperature increases above 104 degrees. (Note: The difference between fever and hyperthermia is that fever is an increase in temperature that results in a change in the set point of core temperature in the hypothalamus. Hyperthermia occurs without changing this set point.) Reports have been shown that administration of 20-50mg/kg in humans can be lethal (http://www.ncbi.nlm.nih.gov/pubmed/16035205). Yet, DNP, available in diet pills since 1933, still remains on the market, although its sale is mostly regulated and has to be obtained through illegal/underground means. (Please read this, it's hilarious : http://www.steroid.com/DNP.php)
The true controversy is that some evidence exists that DNP elimination from the body appears to be rapid, unless in the case of compromised liver function (Hmmmm, maybe there is a correlation to all this diabetes/obesity stuff we have been discussing). According to Dr. Edsall, DNP can be eliminated from a healthy person in 3-4 days ( http://www.nejm.org/doi/full/10.1056/NEJM193408302110901) with newly emerging ranges from hours to 5-14 days. Obviously there is controversy with the administration and availability of this drug, but as American continues to get larger and weight loss continues to be viewed as a potential quick fix who knows what people will turn to no matter the risks.
Thoughts?
References:
Cutting WC, Mehrtens HG, Tainter ML (1933). "Actions and uses of dinitrophenol: Promising metabolic applications". J Am Med Assoc 101: 193–195.
Tainter ML, Cutting WC, Stockton AB (1934). "Use of dinitrophenol in nutritional disorders: a critical survey of clinical results". Am J Public Health 24 (10): 1045–1053
http://ajph.aphapublications.org/cgi/reprint/24/10/1045
Simkins S. (1937). "Dinitrophenol and desiccated thyroid in the treatment of obesity: a comprehensive clinical and laboratory study". J Am Med Assoc 108: 2110–2117.
Hsiao AL, Santucci KA, Seo-Mayer P, et al. (2005). "Pediatric fatality following ingestion of dinitrophenol: postmortem identification of a "dietary supplement"". Clin Toxicol (Phila) 43 (4): 281–285.
That's certainly very interesting and, from what you've written, 2,4-Dinitrophenol (DNP) seems like a very poor (and dangerous) substitute to dieting and exercise.
ReplyDeleteA quick search for DNP on PubMed finds a review article about DNP arguing how poor of a weight loss agent it is. They say very similar things to you, arguing that it's associated with severe acute toxicity and a risk of death.
I'm going to summarize their main points here:
DNP, which can be purchased online from various vendors, is thought to aid weight loss by uncoupling oxidative phosphorylation. Since this is such a crucial process biologically, however, this is associated with a number of adverse side effects. These include tachycardia, hyperthemia, tachypnoea, and diaphoresis. If prolonged or taken in excess this will cause death. To date, in fact, 62 deaths due to DNP have been recorded.
References:
Grundlingh J, Dargan PI, El-Zanfaly M, Wood DM. 2011. 2,4-Dinitrophenol (DNP): A Weight Loss Agent with Significant Acute Toxicity and Risk of Death. J Med Toxicol. 3: 205-12.
Poor choice yes. Dangerous yes. Poor weight loss drug, I guess that depends on how much you take. The effectiveness (i.e. its ability to uncouple the ETS by redox aided diffusion) is directly proportional to amount taken. If taken in small enough quantities then perhaps the inefficiency of the ETS would be enough to aid in weight loss through increased metabolism. However, if you take to much, as mentioned in my blog, a multitude of symptoms may arise. Therefore, there is and as always may never be a quick fix to obesity.
ReplyDeleteMy wife lost 105lb using 200mg per day of DNP , and 25mcg of cytomel t3. It took almost exactly 1 year.
ReplyDeleteNo issues cropped up other than being warm at night (sleeping with a fan) and some tingling in her toes that is slowly disappearing now. She actually took it after supper each night.
She went from 210lb to 105, she is 42 years old. She had been over weight since she was 9 years old. Dieting off and on since she was 11.
Slim-Fizz is a special appetite suppressant the ground breaking fibre Glucomannan, which is a natural dissolvable fibre extracted from high quality pure Konjac.
ReplyDelete