DNP as nootropic/life extension

[Cracker69]

Oh ok. You're looking for some good ole fashioned confirmation bias.

If I were somehow attached to this concept then that may have been the case, but I am not attached, and instead looking for people that have simply done this with success and without issue. I have no problems scrapping ideas that don't work out or prove wrong. Seems like you and Lion boy just have a hard on for starting shit under my thread. Homie don't play that!lol. Go back to your moms basement and learn some more phrases that you think apply dipshit.

 

[Cracker69]

Do you get sick more often with this dose? I know it's not just me. Lots of guys online have said that they tend to get more colds on DNP. This might not be the best time historically to have a weakened immune system.

I prefer lower doses like 100 - 150 mg/day. It's a nice little boost to a cutting cycle where I'm already in a deficit. The only side effect I get (for a week or two) is feeling warmer and sweating more in the gym. 250 mg/day takes away my energy at the gym and at my job.

I've never gotten sick on DNP. Last time I ran it before my current run was 10 years ago at 400mg per day. Went well, just hot.lol. I'm sure larger doses aren't great and if I were to get sick I would stop and restart later. I'm not worried about the current virus. Most people croaking from this shit are overweight/obese/high bp/diabetic/prediabetic. So like half the population.lol

 

[Cracker69]

Am I reading this correctly, DNP is somehow creating new mitochondria?

Yes. Energy demands are not being met, so aside from pulling from glycogen and fat, new mitochondria are manufactured in an attempt to create adequate ATP.

 

[Cracker69]

Its akin to Olympic athletes training in high altitudes. Less oxygen puts stress on the body because oxygen demands are not being met, so more red blood cells are created in order to carry more oxygen to working muscles. Then when they compete at sea level, they have this sort of upgrade with an enhanced ability to carry more oxygen due to the stressor. Same concept anyway, only the stressor here is the DNP and lack of ATP instead of oxygen, and the calories aren't being used for energy efficiently and instead thrown off as heat. So once DNP is ceased, you have this upgrade with more mitochondria, powerhouse of cells, and improved performance.

 

[Cracker69]

Also, if you look at UnderConstructions prior posts, he mentions that his strength did increase after some time while still ON DNP. Since DNP suppresses mTOR, its not likely that he was gaining much muscle if any, but this is a clue that the adaptations were taking place with the mitochondria. This is why I think that DNP would be ideal for a cruise phase, because you may not be adding muscle, but you are advancing and upgrading at the cellular level with more horsepower in your engine, so the next time you blast, you have more to work with.

 

[IronLion2]

Yes. Energy demands are not being met, so aside from pulling from glycogen and fat, new mitochondria are manufactured in an attempt to create adequate ATP.

Why it may sound semantical mitochondria biogenesis is not the creation of new additional mitochondria it's increasing its size and working capacity.

You actually made my point perfectly, any positive effects you can came up with on DNP are from the adaptation of stimulating energy systems..... Which is easily done without DNP let alone long term use.

I don't use DNP anymore bc there's no way around it destroying my working capacity, both when I'm on it and when I'm coming off it, and at almost any dose. These trendy fat loss methods often lead to poor metabolism in the long term and I can personally attest to that. While DNP may have worked for fat ass house wives in the 20s who's HRs never go past 80, it won't work as well for a 220lb who's working at heart rates of 100+.

 

[IronLion2]

Also, if you look at UnderConstructions prior posts, he mentions that his strength did increase after some time while still ON DNP. Since DNP suppresses mTOR, its not likely that he was gaining much muscle if any, but this is a clue that the adaptations were taking place with the mitochondria. This is why I think that DNP would be ideal for a cruise phase, because you may not be adding muscle, but you are advancing and upgrading at the cellular level with more horsepower in your engine, so the next time you blast, you have more to work with.

I use to do that and it wrecked my constitution and worked awful. Would only cruise on DNP. Check my past logs I talk about it.

 

[Cracker69]

Why it may sound semantical mitochondria biogenesis is not the creation of new additional mitochondria it's increasing its size and working capacity.

You actually made my point perfectly, any positive effects you can came up with on DNP are from the adaptation of stimulating energy systems..... Which is easily done without DNP let alone long term use.

I don't use DNP anymore bc there's no way around it destroying my working capacity, both when I'm on it and when I'm coming off it, and at almost any dose. These trendy fat loss methods often lead to poor metabolism in the long term and I can personally attest to that. While DNP may have worked for fat ass house wives in the 20s who's HRs never go past 80, it won't work as well for a 220lb who's working at heart rates of 100+.

Well, from what I have read it is not increased size it is more mitochondria. Either way, its something to try and I think at low doses its safe enough to do so. I also think that there is merit in it being conducive to life extension. Most people know that calorie restriction extends the life of organisms,, however if you don't want to be in a deficit ALL of the time to achieve that, DNP gives you some wiggle room and creates a similar environment but still allowing you to eat more. If it doesn't work for you or isn't your cup of tea no biggie. Just something new to ponder.

 

[micro2000]

I remember running across this research years ago. As Stewie pointed out to me, the full research papers use very small doses of DNP, much lower than 250mg. So while DNP may have some use, it's likely way below these doses.

 

[pm123]

For everyone shitting on @Cracker69 's post, ie. @IronLion2 @tren_plz

My suggestion is next time something seemingly dissonant with your worldview is brought to your attention, that a little more effort go into exploring and researching it, before casting it off with undue certainty.



From the 2019 study here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468406/

"
Although diet and exercise should always be the first line of defense, DNP appears to mimic in part the neuroprotective and neurorestorative effects of exercise and fasting by increasing BDNF, lowering cellular stress and building cellular resiliency by mild increases in mitochondrial bioenergetics.
...
It is possible that the increase in cAMP is also due to an inactivation of phosphodiesterases (PDEs) that degrades cyclic nucleotides as well. PDE inhibitors have been sought after to improve cognition, reduce episodes of schizophrenia, depression and improve mental stability with the rise of cAMP, which DNP treatment may address as well [181,182]. The collective benefits of DNP driven increases of cAMP, CREB and BDNF may be vast for mental health. Treatment of animals representing a myriad of human neurodegenerative diseases with DNP appears pro-neuroprotective for diseases of known and unknown etiology, and indications of all ages (pediatrics, adult and elderly). It is not a “magical elixir”, but based upon the scientific fact that: 1) all human cells have mitochondria except mature red blood cells, 2) they have a symbiotic relationship within the cell governing cell survival and functions that impact many pathways, and 3) from experimental studies in so many laboratories across the world that have compiled both positive and significant data showing its merit in animal models of Huntington Disease, Parkinson Disease, Alzheimer’s Disease, Multiple Sclerosis, Rett Syndrome (data not shown), epilepsy, hearing loss, vision loss (optic neuritis), traumatic brain injury, and Duchenne Muscular Dystrophy [28,52,85,86]. Others have tested DNP in models of stroke, sciatic nerve injury, TBI, Aβ1-42 inhibition of plaque formation and various metabolic diseases [29,45,87,88,164,167,183]. This spectrum corresponds to diseases of developmental (Rett), neuromuscular (DMD), metabolic (NASH, diabetes, insulin resistance), neurodegeneration (AD, PD, HD, etc.), autoimmune (MS, ON, etc.) and trauma (hearing, stroke, nerve damage, TBI) (Figure 7).
...
DNP (MP101) or the prodrug of DNP (MP201) has been tested in disease models of acute and chronic studies with a known and unknown genetic cause that representing pediatric, adult and elderly indications with statistically positive outcomes. The indications also present diseases of neuromuscular disorders, development, neurodegeneration, autoimmune, metabolic and trauma. The future will help to determine the limitations of the pharmacology, but given the findings, it appears that DNP may be a broad-spectrum treatment to many disorders.
...
Collectively, DNP may be a treatment for an emerging global term called “metabesity” referring to all the co-morbidities associated with the over-nutritional phenotype such an increased incidence of insulin resistance, obesity, type 2 diabetes, sleep apnea, depression, inflammation, cardiovascular disease, hypertension, non-alcoholic fatty liver disease, but includes accelerated aging, neurodegeneration, and cancer. [2,184,185]. Studies are underway to explore an ever-expanding application of low dose mitochondrial uncoupling pharmacology. There are other insidious diseases like Pompe, Wolfram Syndrome, Friedreich ataxia, cardiolipin production, etc., that are associated with mitochondrial dysfunction of Ca2+, ATP and ROS homeostasis, that have no cures, so it is important to understand if DNP or modified versions of DNP may have merit in these diseases as well [15,43,46,186,187,188]. Since DNP was tested in many laboratories, for completely diverse indications, it speaks to the idea that modulating mitochondrial physiology with uncouplers, can enlist cellular resiliency that is global to many diseases. Therefore, when it comes to mulling on whether a particular disease has a mitochondrial component and whether or not DNP could have merit, it is imperative that it just gets tested.
...
The metabolic impact of raising energy expenditure by a small degree to partition fat out of the insulin-sensitive tissues (liver and muscle), could, in fact, emerge as a method of treatment for the intractable over-nutritional phenotype at safe, weight neutral doses (Figure 8) [2,189]. Since weight neutral doses of DNP significantly raises BDNF, which also has anti-diabetic properties in peripheral organs, there may be a synergistic effect of clearing lipids while raising BDNF [70,71,72,73,190]. This approach is significantly safer than the approach in the 1930s, as doses would be at least 10–60× lower [52].
...
The dose window that we have seen with all the animal studies has been between ~0.5–5 mg/kg in mice, which correlates to a HED range between ~2–22 mg/day. If this translates to the human scenario, including the hormetic response, then it would not make sense to push the dose for instance to 22 mg for AD, which corresponds to 5 mg/kg in the mouse model, when it was clearly shown that 0.5 mg/kg or less in the APP/PS1 was optimal, a HED of 2 mg/day or lower.
...
The progress that has been made in the science of mitochondrial bioenergetics has been tremendously important to gain an understanding of the central role in the cell that this organelle governs over so many pathways. The acceleration of mitochondrial research in the last couple of decades and an emerging focus on the legion of diseases is remarkable. With over 80 years since DNP has been in a clinical study, there is also a tremendous opportunity to learn today what merits the pharmacology may provide repositioned for truly insidious diseases using modern day clinical practices. This approach is a much lower hanging fruit than the very high hurdles of gene replacement as a first line of attack. It is possible to wake up redundant cellular compensatory mechanisms by modulating the mitochondria’s entire physiology towards pro-survival of the cell, with a brain penetrant, simple oral dosing of DNP to attenuate disease progression for a broad number of indications, slow aging, and the potential in the future to prophylactically treat patients to entirely prevent the myriad of age-related illnesses. It may sound unorthodox, but it falls within the physiology/pharmacology of the mechanism of action to be plausibly true.
"

 

[pm123]

From the 2016 study here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5337177/

"
The pharmacological uncoupler 2,4-dinitrophenol (DNP), which was once prescribed to over 100,000 people as a treatment for obesity, stimulates several adaptive cellular stress response signaling pathways in neurons including those involving the neurotrophic factor BDNF, the transcription factor CREB, and autophagy. Preclinical data show that low doses of DNP can protect neurons and improve functional outcome in animal models of Alzheimer’s and Parkinson’s diseases, epilepsy and cerebral ischemic stroke. Repurposing of DNP and the development of novel uncoupling agents with hormetic mechanisms of action provide opportunities for new breakthrough therapeutic interventions in a range of acute and chronic insidious neurodegenerative/neuromuscular conditions, all paradoxically at body weight-preserving doses.
...
The development of uncoupling agents with improved safety profiles are being developed for obesity, diabetes and neurodegenerative disorders. For example, a controlled release oral form of DNP that produces mild uncoupling in hepatocytes reduced insulin resistance, hyperlipidemia and hepatic steatosis in a rat model of diabetes [94]. No evidence of toxicity was detected during chronic administration of the controlled release DNP. In another study, a DNP analog (DNP-methyl ether) targeted to liver was shown to reverse insulin resistance and fatty liver in rats fed a high-fat diabetogenic diet [95].
...
As proof-of-concept it was reported that mice chronically treated for ~80 weeks with DNP provided in their drinking water at a dose of ~100 μg/kg lived longer than control mice and had reduced levels of ROS in both liver and brain, lower amounts of oxidized proteins and DNA damage, and lower circulating glucose, lipid and insulin levels [87]. To put this into perspective, this is the equivalent to humans of ~0.5 mg per day or ~600-fold lower dose than what was used in the 1930s for weight loss (300 mg per day). The intermittent drinking of water containing DNP mimicked sustained delivery, and since DNP lacks a methyl-ether that would cause it to be sequestered in the liver, the drug distributes to cells in all organs. The findings in mice suggest that a very low sustained level of DNP can attenuate the age-related accumulation intra-hepatic and intra-muscular lipids, without reducing body weight [96]. It will therefore be of considerable interest to determine whether very low doses of a mitochondrial uncoupling agent such as DNP would ameliorates metabolic morbidities resulting from excessive calorie intake and a sedentary lifestyle in human subjects.

The theme that is building is that low doses of DNP provide broad neuroprotection, perhaps due to its unique mechanism of action initiated as an adaptive stress response, and its specificity to the mitochondria, the only cellular organelle with a basic pH environment. Indeed, the target of chemical uncouplers such as DNP is not a protein, but is instead the mitochondrial membrane where they transfer protons to the matrix [13]. Although DNP’s initial uncoupling action is non-genomic, several prominent signaling cascades involved in adaptive neuroplasticity and stress resistance are activated including those involving calcium and cyclic AMP, and downstream kinases and transcription factors (Figure 2) [56, 97].

During the 80 years after the initial use of DNP in humans at very high doses for inducing weight loss in obese subjects, the knowledge base of mitochondrial bioenergetics and chemical uncoupling has expanded greatly. It was not known until recently, however, that very low doses of uncoupling agents such as DNP are effective in ameliorating disease processes and improving functional outcome in preclinical models of a range of neurological disorders that involve metabolic and oxidative stress including Alzheimer’s, Parkinson’s diseases, epilepsy and ischemic stroke [61, 65, 98] (Figure 4). The emerging findings described in this article suggest that, similar to the broadly beneficial effects of caloric restriction, even very low levels of mitochondrial uncoupling can protect multiple organ systems against dysfunction and degeneration in preclinical models of a wide range of disorders that involve dysregulation of energy metabolism metabolic and oxidative stress. Translation to humans is the next critical step.
"

 

[Cracker69]

Thank you for the articles. Ive found that one to two 250mg capsules are optimal for health without interfering much with performance and appearance. A minimal amount is needed in your system for the health benefits, which I think could be doubly important for gear users. Especially when it comes to the neuroprotective effects, prevention of atherosclerosis, lowers fasting BG, protects internal organs, and can reduce red blood cells to a degree. It helps maintain insulin sensitivity which in the long run will aid in building muscle as long as the dose is kept low, the anabolics will override much of the mTor effects of dnp. Although at my age, I'm more interested in maintaining, longevity and health. But either way, I think its a worthwhile measure, and even at just 250mg once a week, it leaves enough in your system to give you the health benefits all week without hampering your cycle. I think being on gear, its more risky not to be on DNP.

 

[Butters]

i have a friend whose father has alzheimer's on both sides of his family. he is almost 70, and has been on dnp for years.

im not sure how is cognition is, but it doesn't seem to be declining at all. and he's pretty lean.

 

[Cracker69]

i have a friend whose father has alzheimer's on both sides of his family. he is almost 70, and has been on dnp for years.

im not sure how is cognition is, but it doesn't seem to be declining at all. and he's pretty lean.

That's great. Do you know how much he takes?

 

[pm123]

@Cracker69 @Butters

To be clear, the studies clearly state that many of the benefits (that I bolded above) occur along a biphasic dose response curve, and that doses higher than 22mg lose many of the benefits of the lower doses. So, 250mg once or twice a week may be having some of the benefits listed above, but if you want to get the maximum longevity benefits, you want to be dosing somewhere between 2-22mg a day, with 2-5mg as the ideal range.

 

[Cracker69]

@Cracker69 @Butters

To be clear, the studies clearly state that many of the benefits (that I bolded above) occur along a biphasic dose response curve, and that doses higher than 22mg lose many of the benefits of the lower doses. So, 250mg once or twice a week may be having some of the benefits listed above, but if you want to get the maximum longevity benefits, you want to be dosing somewhere between 2-22mg a day, with 2-5mg as the ideal range.

Oh I know, but its nearly impossible to find someone that supplies small doses, so with the half life of 36 hours, with one 250mg dose, you would still have a few milligrams in your system by the end of the week, which still averages out daily, more than the .5 to 5mg per kg of bw on some days, but is still quite tolerable. I'd make my own, but would have no idea where to get the raw material or how to make it, and it sounds like it can be quite messy if I didn't know what I was doing.lol. Maybe someday. If I could, I'd probably make 5 or 10mg caps for daily use. But I don't mind the 250mg dose once or twice a week. I just think of it like hrt. Most inject a bolus once or twice a week of 100 to 200mg of testosterone with peaks and troughs. Same concept I guess. Although I have taken to daily pokes with slin pins for my test cyp these days which is always ideal over the larger less infrequent dosing. They really should put DNP back on the market just like testosterone. It would be so much safer than the black market with accurate dosing and you could be upfront with your doc about your use. Ok im im done babbling.lol

 

[pm123]

Oh I know, but its nearly impossible to find someone that supplies small doses, so with the half life of 36 hours, with one 250mg dose, you would still have a few milligrams in your system by the end of the week, which still averages out daily, more than the .5 to 5mg per kg of bw on some days, but is still quite tolerable. I'd make my own, but would have no idea where to get the raw material or how to make it, and it sounds like it can be quite messy if I didn't know what I was doing.lol. Maybe someday. If I could, I'd probably make 5 or 10mg caps for daily use. But I don't mind the 250mg dose once or twice a week. I just think of it like hrt. Most inject a bolus once or twice a week of 100 to 200mg of testosterone with peaks and troughs. Same concept I guess. Although I have taken to daily pokes with slin pins for my test cyp these days which is always ideal over the larger less infrequent dosing. They really should put DNP back on the market just like testosterone. It would be so much safer than the black market with accurate dosing and you could be upfront with your doc about your use. Ok im im done babbling.lol

If you have, say, 250mg pills, you can make a solution of water+ethanol+dnp and accurately dose lower amounts that way. Also, it's relatively easy to find powder.

 

[Cracker69]

If you have, say, 250mg pills, you can make a solution of water+ethanol+dnp and accurately dose lower amounts that way. Also, it's relatively easy to find powder.

Interesting. Have you tried making a solution like that? I'm open to sourcing powder if you have any insight and feel comfortable, please enlighten me. I'd be weary of overseas shipping though. But feel free to PM me if you have any suggestions.

 

[pm123]

Interesting. Have you tried making a solution like that? I'm open to sourcing powder if you have any insight and feel comfortable, please enlighten me. I'd be weary of overseas shipping though. But feel free to PM me if you have any suggestions.

Personally, I have powder, which I've used to make a solution of 15mL vodka + 15mL water + 90mg DNP. This gives me 3mg/mL, and is dosed with a 1mL oral syringe.

However, this is easily replicated with pills. For instance, if you wanted a 3mg/mL solution, also, you'd simply add the 250mg to 83.3mL of solution (I recommend half ethanol, half water, for anti-bacterial purposes).

 

[Cracker69]

Personally, I have powder, which I've used to make a solution of 15mL vodka + 15mL water + 90mg DNP. This gives me 3mg/mL, and is dosed with a 1mL oral syringe.

However, this is easily replicated with pills. For instance, if you wanted a 3mg/mL solution, also, you'd simply add the 250mg to 83.3mL of solution (I recommend half ethanol, half water, for anti-bacterial purposes).

I may give it a try. Most caps use a starch filler if I remember correctly so I'll see how that works with trying one. Until then, I'll have to keep an eye out for powder. Thanks man, I appreciate it!