12 replies to this topic

[medicineman]

Some may have heard, or even tried DNP for weight loss. It is a feared substance in the body building world. It uncouples oxidative phosphorylation, making mitochondria less efficient at atp production. It does this by acting as an active proton shuttle, defeating the proton gradient which exists across membranes. Passive diffusion of hydrogen across an electrochemical gradient fuels atp synthase, and dnp defeats that process, and the energy is lost as heat (positive dose response, the more dnp, the less efficient, the hotter you become)

While oxidative phosphorylation is the backbone of cellular energy, it piles up cellular garbage which over time, creates cellular dysfunction. Interestingly, DNP may inhibit that process, and in theory, may delay aging. Here is a nice summary:

2,4-dinitrophenol (DNP) has long been known to be toxic at high concentrations, an effect related to uncoupling of mitochondrial oxidative phosphorylation. Five years ago, however, we reported that low concentrations of DNP protect neurons against the toxicity of the amyloid-β peptide. Since then, a number of other studies have provided evidence of beneficial actions of DNP (at low concentrations), including neuroprotection against different types of insult, blockade of amyloid aggregation, stimulation of neurite outgrowth and neuronal differentiation, and even extension of lifespan in certain organisms. Some of these effects appear due to mild mitochondrial uncoupling and prevention of oxidative stress, whereas other actions are related to activation of additional intracellular signaling pathways. This study discusses the evidence supporting beneficial neuroprotective actions of DNP. DNP and other compounds with similar biological activities may be of interest in the development of novel therapeutic approaches for neurodegenerative diseases and other neurological disorders.

I highly suggest reading "Neuroprotective actions of 2,4-dinitrophenol Friend or foe?"

There are a few other interesting studies showing what seems like potent neurorestorative and neuroprotective activity of subtherapeutic doses of DNP.

Anyways, I think it is an interesting read.

Please, do not take DNP. It may kill you. It has a very narrow therapeutic window. This post is for academic and research purposes only.

Edited by medicineman, 15 September 2014 - 09:13 PM.

[medievil]

Extremely interesting, i might throw it in my stack, id have to be extremely carefull, wich most say im doing the opposite with my usual stacks lol, still im extremely intrigued and the doses will be lower then those needed for extremely fast weightloss which when done carefully is allright, so in lower doses the risk of dying should be really minimal.

[medicineman]

Extremely interesting, i might throw it in my stack, id have to be extremely carefull, wich most say im doing the opposite with my usual stacks lol, still im extremely intrigued and the doses will be lower then those needed for extremely fast weightloss which when done carefully is allright, so in lower doses the risk of dying should be really minimal.

you owe me a pm. please check your messages.

[medicineman]

Extremely interesting, i might throw it in my stack, id have to be extremely carefull, wich most say im doing the opposite with my usual stacks lol, still im extremely intrigued and the doses will be lower then those needed for extremely fast weightloss which when done carefully is allright, so in lower doses the risk of dying should be really minimal.

Be extremely careful. You could seriously injure yourself. Read as much as you can before making this decision. I will repeat, the post is for academic purposes, anything you do will be your responsibility. I would never suggest DNP as a therapeutic agent to anyone. Be informed, then choose.

[medicineman]

teamtlr carry agents/extracts which uncouple oxidative phosphorylation (dcrm-ox).. I am interested in long term supplementation with an uncoupler of oxidative phosphorylation after having explored the topic further (for mitochondrial health, and dnp is apparently not ideal for long term intake). I may email them and ask if this is feasible with their extract, how comparable it is to dnp, and whether their extract carries similar risks. I'd love to know what natural compound uncouples oxidative phosphorylation (maybe a salicylate?)

Edited by medicineman, 16 September 2014 - 04:25 PM.

[datrat]

teamtlr carry agents/extracts which uncouple oxidative phosphorylation (dcrm-ox).. I am interested in long term supplementation with an uncoupler of oxidative phosphorylation after having explored the topic further (for mitochondrial health, and dnp is apparently not ideal for long term intake). I may email them and ask if this is feasible with their extract, how comparable it is to dnp, and whether their extract carries similar risks. I'd love to know what natural compound uncouples oxidative phosphorylation (maybe a salicylate?)

 

Just curious whether you did email teamtlr about dcrm-ox.

[VERITAS INCORRUPTUS]

As to pursuit of research and academic interests, the uncoupling agents that have been created by TeamTLR are devoid of any adverse effect potential and have an extremely high therapeutic index as such.  Within intrinsic ceilings of effect and the pathways of uncoupling activity themselves they are safe and efficacious target agents for the positive effects offered by uncouplers with a negation of any adverse effect potential of any significance.

 

As with all SEP-OX Optimized Xtracts that is the goal, within therapeutic index being the primary factor, and within only to be fostered for further research within achieving the highest standard of TI, the ratio of efficacy to adverse effects and adverse effect potentials.  Uncouplers have been a strong focus for TLR for several years and several optimized uncouplers have been developed, within currently only two of which are within the website at present. The other prior well developed uncouplers may be added in due time.

 

 

[FW900]

This is a good find medicine man, thanks for sharing it.

 

 

Veritas Incorruptus ....... For Christ's sake, can you please just get to the point of what you are trying to say? Every single post. You and TeamTLR's  statements on pretty much everything are littered with verbose wanderings that are entirely unnecessary and ultimately lead to something that could have been said in one sentence. A lot of people are wordier here but the additional wordage, for most posters, usually (usually!) enhances rather than deters from what is being said. You on the other hand, most posts, especially as of late is littered so many things that it disincentivizes most people from even reading it.

[VERITAS INCORRUPTUS]

LMAO...Apologies

 

1- We have two high efficacy, high therapeutic index caloric-restriction mimetics with potent, high efficacy uncoupling activity.  One is a single pure, potent uncoupler [1] and the other is a related uncoupler (analogue of [1]) which as well has potent PPARa agonist activity [2], of which activity also has been demonstrated to entail similar benefits,

2- As with all SEP-OX Optimized Xtracts, therapeutic index is paramount, with indication of a strong degree of efficacy within levels that display no significant adverse effects

3- This class is intended for research into safe and high efficacy agents for caloric restriction mimetic purposes, body fat/weight loss purposes, antioxidant purposes, and so otherwise as per literature denotes for such within this class.

4- We have other promising uncouplers that have value for further research and appear to have synergy with the above agents when administered concomitantly (though we have not as yet made them available on the site)

 

[1] http://teamtlr.com/s...ts=2#/amount-2g

[2] http://teamtlr.com/s...62-dcrm-ox.html

 

Did I do any better?   - hopefully even a little  

 

BTW, I like you FW900, as you do have a strong tendency to get to the point.  Perhaps some assistance as a translator for my meandering ramblings, lol  

 

 

 

[Fernando Laniado]

I remember i saw some posts in bodybuilding/steroids forums about memory and cognitive decline after midterm use.

Maybe due to atp inneficiency?

[sub7]

I remember i saw some posts in bodybuilding/steroids forums about memory and cognitive decline after midterm use.

Maybe due to atp inneficiency?

 

I can somewhat confidently say that I have read almost every single user feedback on bodybuilding forums on DNP over the years. I do not ever recall such feedback -while it might have been very rarely reported, I am sure it isn't common at all.

 

When reviewing user feedback from DNP, one should keep in mind that almost nobody uses it for life extension. Those who use it for weight loss take far higher doses than one would do to enhance health and longevity. With those absurd doses some serious side effects definitely occur. One such side effect is the lack of energy. If the dose is high, one will report being unable to function both physically and mentally, which is not at all surprising, given the ATP depletion from excess use.

 

DNP is among the most misunderstood pharmaceuticals and may -just saying may- hold significant potential. It is not toxic to any tissue at reasonable doses yet works as a very very effective calorie restriction mimetic. The only potential toxicity is to the eyes, with the occasional occurrence of cataracts in some users back in the 1920s and 1930s. The cataract issue remains mostly a mystery however. It is much more often reported in females; some have suggested the lack of Vitamin C supplementation and poor diet during the harsh economic times were responsible also. In the overall population of DNP users, cataract risk was reported at between 1% and 0.1% with reliable estimates being hard to come by.

 

Other than the cataract issue, the substance at low doses is not known to be toxic.

 

One intellectual / procedural problem is that with many substances, toxicologists give animals, or in some cases humans, large doses to assess the worst case scenario. If the large dose causes issues, the substance is sometimes scratched off as problematic and never reconsidered.

With DNP one cannot do that; too high a dose is lethal, period. However, the effects of low doses are dramatically different and one should not go by the simple logic that if a high dose is lethal, a low dose cannot be good either. Sufficiently high doses of many many things -even coffee- are lethal.

 

Now, is the substance dangerous? Well, I am not here to tell people to use or to refrain. However, please correct me if I am wrong: at a dose of 50-100 mg per day, nobody ever got hurt, no? And that is over the many years of use back in the day...

 

I would be really glad to get an intelligent discussion going on DNP.

[Fernando Laniado]

Well.. I don't know a lot about DNP. But this is scary...dementia is a potential side effect

http://forums.lylemc...&postcount=1073

[Darryl]

Perry RJ, Zhang D, Zhang X, Boyer JL, Shulman GI. Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats. Science 2015

 

We developed a controlled-release oral formulation of DNP, called CRMP, that produces mild hepatic mitochondrial uncoupling. In rat models, CRMP reduced hypertriglyceridemia, insulin resistance, hepatic steatosis and diabetes. It also normalized plasma transaminase concentrations, ameliorated liver fibrosis, and improved hepatic protein synthetic function in a methionine/choline deficient rat model of NASH. Chronic treatment with CRMP was not associated with any systemic toxicity.

 

From the Yale PR:

 

Based on their earlier studies, the researchers determined that toxicity associated with the agent — mitochondrial protonophore 2,4-dinitrophenol (DNP) — was related to its peak plasma concentrations. They discovered that DNP’s efficacy in reducing liver fat and liver inflammation could be achieved with plasma concentrations that were more than a 100-fold less than the toxic levels.

 

“Besides reversing fatty liver disease in a rodent model of NALFD, a low-dose intragastric infusion of DNP that was 100-fold lower than toxic levels also significantly reduced blood glucose, triglyceride, and insulin concentrations in a rodent model of NAFLD and type 2 diabetes”, said Shulman, who is also an investigator with the Howard Hughes Medical Institute.

 

In the next phase of the study, Shulman and his team developed a new oral, controlled-release form of DNP, known as CRMP, which maintained the drug at concentrations that were more than a 100-fold lower than the toxic threshold. Administered once daily, CRMP delivered similar positive results, reversing fatty liver, insulin resistance, and hyperglycemia in rat models of NAFLD and type 2 diabetes, as well as liver inflammation and liver fibrosis in a rodent model of NASH, with no adverse effects.

 

 

CRMP is certainly worth watching, given:

 

Caldeira da Silva, CD, Cerqueira, F.M, Barbosa, LF, Medeiros, MH, Kowaltowski, AJ Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity. Aging cell. 2008: 7(4), 552-560.

 

Treatment of mice with low doses of the protonophore 2,4-dinitrophenol promotes enhanced tissue respiratory rates, improved serological glucose, triglyceride and insulin levels, decrease of reactive oxygen species levels and tissue DNA and protein oxidation, as well as reduced body weight. Importantly, 2,4-dinitrophenol-treated animals also presented enhanced longevity.