#201

Curious if you had any thoughts on GW0742?

#202

Risk of myocardial infarction, heart failure, and cerebrovascular disease with the use of valsartan, losartan, irbesartan, and telmisartan in patients

“The matched cohort analysis showed that the adjusted hazard ratio (aHRs, 95% confidence interval) for MI was higher for valsartan use (1.39, 1.33–1.45) and losartan use (1.10, 1.05–1.15) but lower for irbesartan use (0.90, 0.86–0.94) compared with the reference (telmisartan). The aHRs for HF were not different among these ARBs (angiotensin receptor blockers). The aHR for cerebrovascular disease was lower for valsartan use (0.85, 0.83–0.87) and losartan use (0.80, 0.78–0.82) but higher for irbesartan use (1.11, 1.09–1.13) compared with the reference. We found differences in the risk of MI and cerebrovascular disease with the use of different ARBs compared to telmisartan use. Valsartan, and losartan with a short half-life, which showed a higher risk of MI, had a lower risk of cerebrovascular disease. Conversely, irbesartan with a long half-life, which showed a lower risk of MI, had a higher risk of cerebrovascular disease.”

3 Likes
#203

AI summary of that study in lay terms:

Telmisartan Study Results: Good News for Patients

This large Korean study of nearly 150,000 patients compared cardiovascular risks between different blood pressure medications, including telmisartan.

Key findings for your medication:

Heart attacks: Telmisartan provided good protection - better than valsartan and losartan, slightly less than irbesartan. Overall strong performance.

Strokes: Mixed results - higher risk than valsartan/losartan but lower than irbesartan. Differences were modest.

Heart failure: No meaningful differences between any blood pressure medications.

What this means for you:

  • 40mg daily: Provides effective blood pressure control and cardiovascular protection
  • 80mg daily: Optimal dose for maximum heart protection benefits

Bottom line: Continue your telmisartan as prescribed. This study confirms it’s safe and effective for cardiovascular protection. Telmisartan is the only blood pressure medication in its class specifically approved by regulators for reducing heart attack and stroke risk. The differences between medications were small, and your medication has proven long-term safety. The study found no major concerns - keep taking it and maintain regular doctor visits.

4 Likes
#204

I don’t agree that DNP is necessarily high risk. Yes, for peopel taking typical doses for quick weight loss, doses that are close to dangerous doses, it is very risky, but there is no reason you couldn’t take ten times less and be far below the dangerous doses, assuming you have an accurate scale to measure the powder. Only problem is you would need to be patient because the weight loss would be very slow. If you know what you’re doing, DNP can be very low risk. This is particularly the case because you can feel the effects. You could start at a very low dose and increase it very slowly and when you start feeling just a tiny bit warmer than usually, that would be a sign it’s the low range of an effective dose and that you shouldnt increase it more if you want to stay safe Note that the effects of high doses are very obvious. Many people using it for weight loss report being much warmer than usual and sweating like crazy.

I am not recommending DNP for weight loss though, just to be clear.

#205

High risk to trust the claimed tablet dosing. I’ve seen tested doses to be dramatically off the claim because of lab math errors. Agree that if one has a quality scale and buys powder it can be done.

But why do this at all when we have retatrutide?

3 Likes
#206

When on telmisartan while watching kidney function, it’s usually advised to monitor electrolytes levels on your kidney or metabolic panels. I take 30 mg (have transplanted kidney) and my electrolytes are normal. No kidney duress (stress) noticed, like proteinuria, fluid retention, fatigue, nausea or brain fog.

#207

True that. I wouldn’t trust the claimed tablet dosing. Instead I would assume it’s as strong as possible, meaning 100% pure DNP, and then dose according to that using a highly accurate scale. That would keep you on the safe side. Anyways, if the DNP is strongly yellow you can assume it’s most likely not far from 100% DNP.

I’m not really advocating DNP over retatrutide. I’m just pointing out how it’s not really dangerous if you know what you’re doing. But there could be reasons to favor either of them. After all, they have very different mechanisms of action (one increases energy expenditure, the other decreases appetite) and could be complementary to each other.

1 Like
#208

DNP is extremely dangerous and potentially fatal. This industrial chemical disrupts cellular energy production by “uncoupling” mitochondrial processes, preventing ATP synthesis while releasing deadly amounts of heat. Clinical presentation mirrors cyanide poisoning: uncontrollable hyperthermia, organ failure, seizures, coma, and bleeding. Mortality rate is 12-16% in reported cases. Chronic effects include irreversible nerve damage, cataracts, heart failure, and bone marrow suppression. One documented case required weeks of life support, resulting in permanent kidney damage requiring dialysis. The substance was banned for human use in 1938 after numerous deaths, yet continues appearing in underground markets. Even controlled pharmaceutical derivatives like HU6 remain experimental and unproven. I cannot emphasize enough: this substance can literally cook you alive from the inside. No amount of weight loss is worth risking multi-organ failure and death. Avoid completely.

Based on the peer-reviewed evidence, @Olafurpall’s harm reduction argument contains several fundamental flaws:
Dose-Response Problems: The research shows DNP’s therapeutic window is extremely narrow. The clinical studies we reviewed found effective weight loss doses (150-450mg) are close to toxic doses, and the mitochondrial uncoupling mechanism that causes weight loss is the same mechanism that causes toxicity. There’s no evidence supporting a “safe” low-dose range for chronic use.
“Feeling Effects” as Safety Indicator: This is particularly problematic. The toxicology studies demonstrate that subjective warmth occurs well within the toxic range - it’s a symptom of mitochondrial uncoupling, not a safety boundary. Fatal cases documented hyperthermia as a primary cause of death, and the Potts study identified tachycardia and hyperpyrexia as independent mortality predictors.
Chronic vs. Acute Toxicity: The Singer neuropathy case and historical cataract data show that even “low” chronic exposure causes irreversible damage. The 19-year-old patient developed severe peripheral neuropathy from chronic use, and cataracts historically occurred in workers with industrial exposure levels below acutely toxic doses.
Measurement Accuracy Limitations: While accurate dosing might reduce acute overdose risk, the research shows DNP has unpredictable pharmacokinetics with significant individual variation in absorption, metabolism, and elimination. The Hermetet case documents fatal toxicity despite the user believing they were taking “controlled” doses.
No Safety Studies: Critically, there are no controlled studies establishing safe chronic dosing protocols for DNP. The HU6 research represents attempts to create safer derivatives precisely because DNP itself cannot be made safe through dose modification alone.
The mortality data (11.9-12.5%) represents cases that likely included people attempting “careful” dosing approaches similar to what’s described.​​​​​​​​​​​​​​​​

Ten Peer-Reviewed Citations on 2,4-Dinitrophenol Toxicity and Dangers

1. Mechanisms and Mitochondrial Uncoupling

Žuna, Kristina; Jovanović, Olga; Khailova, Ljudmila S.; Škulj, Sanja; Brkljača, Zlatko; Kreiter, Jürgen; Kotova, Elena A.; Vazdar, Mario; Antonenko, Yuri N.; Pohl, Elena E.

Mitochondrial Uncoupling Proteins (UCP1-UCP3) and Adenine Nucleotide Translocase (ANT1) Enhance the Protonophoric Action of 2,4-Dinitrophenol in Mitochondria and Planar Bilayer Membranes

Biomolecules 2021; 11(8):1178
DOI: 10.3390/biom11081178
PMID: 34439844

This study provides detailed molecular mechanisms of DNP’s uncoupling action, demonstrating that DNP acts as a protonophore by enhancing proton transport through mitochondrial membrane proteins (ANT1, UCP1-UCP3). The research shows DNP increases membrane conductance ~2-fold when proteins are present, disrupting ATP synthesis by collapsing the proton-motive force across the inner mitochondrial membrane.

2. Mortality Rates and Clinical Epidemiology

Thomas, Simon H.L.

International trends in systemic human exposures to 2,4 dinitrophenol reported to poisons centres

Clinical Toxicology 2022; 60(5):628-631
DOI: 10.1080/15563650.2021.2005797
PMID: 34812657

Large international study of 456 DNP cases from 38 countries (2010-2020) documenting mortality rate of 11.9% (95% CI 9.0-15.4), confirming the 12-16% mortality range. Study shows 50 deaths from 422 cases with available mortality data, with no significant difference between male (12.6%) and female (11.3%) mortality rates.

3. Clinical Toxicity Predictors and Acute Symptoms

Potts, Adam J.; Bowman, Nancy J.; Seger, Donna L.; Thomas, Simon H.L.

Toxicoepidemiology and predictors of death in 2,4-dinitrophenol (DNP) toxicity

Clinical Toxicology 2021; 59(6):515-520
DOI: 10.1080/15563650.2020.1826505
PMID: 33021407

Analysis of 204 DNP exposure cases (2007-2018) identifying independent mortality predictors: acidosis (OR=5.4), tachycardia (OR=3.6), agitation/confusion (OR=3.4), and hyperpyrexia (OR=2.8). Additional risk factors include hypoglycemia (OR=17.1), hypertonia (OR=12.9), and organ failure, confirming the classic acute poisoning syndrome.

4. Acute Poisoning Case Series with Mortality Data

Lu, Yuan-qiang; Jiang, Jiu-kun; Huang, Wei-dong

Clinical features and treatment in patients with acute 2,4-dinitrophenol poisoning

Journal of Zhejiang University Science B 2011; 12(3):189-192
DOI: 10.1631/jzus.B1000265
PMID: 21370505

Case series of 16 patients with acute DNP poisoning from occupational exposure showing 12.5% mortality rate (2 deaths), with fatal cases presenting hyperthermia (40.7°C and 39.8°C), convulsions, muscle rigidity, and disturbance of consciousness. Demonstrates rapid progression from exposure to death within hours, confirming severe acute toxicity profile.

5. Chronic Neuropathy Effects

Singer, Michael A.

Peripheral neuropathy due to dinitrophenol used for weight loss: something old, something new

Neurology 2013; 80(8):773-774
DOI: 10.1212/WNL.0b013e3182825367
PMID: 23386843

Case report documenting chronic peripheral neuropathy in a 19-year-old woman who took up to 1g daily DNP for 6 months. Electrophysiologic studies showed primarily axonal sensorimotor polyneuropathy with severely decreased distal peroneal motor amplitude and absent bilateral sural and plantar sensory responses, demonstrating chronic neurological complications.

6. Historical Use and Cataract Outbreak

Margo, Curtis E.; Harman, Lorraine E.

Diet pills and the cataract outbreak of 1935: reflections on the evolution of consumer protection legislation

Survey of Ophthalmology 2014; 59(5):568-573
DOI: 10.1016/j.survophthal.2014.02.005
PMID: 24913328

Historical analysis documenting DNP-induced cataract outbreak in 1935, with an estimated 2,500 American women going blind from DNP use. Documents how this crisis contributed to passage of the Food, Drug, and Cosmetic Act of 1938, when FDA banned DNP as “extremely dangerous and not fit for human consumption.”

7. Contemporary Bodybuilder Fatality Case

Hermetet, Camille; Jourdan, Marion; Baert, Audrey; Gheddar, Laurie; Ameline, Alice; Kintz, Pascal; Bouvet, Richard

Case report: Fatal long-term intoxication by 2,4-dinitrophenol and anabolic steroids in a young bodybuilder with muscle dysmorphia

Frontiers in Public Health 2024; 12:1452196
DOI: 10.3389/fpubh.2024.1452196
PMID: 39659715

Recent case of 21-year-old bodybuilder who died after 6 months of repeated DNP consumption, with final ingestion of 2 grams. Autopsy showed yellowish coloration and visceral congestion. Hair toxicology demonstrated chronic exposure (5.1-25.5 ng/mg) and co-consumption with anabolic steroids, illustrating ongoing mortality in fitness communities.

8. Comprehensive Toxicity Review and Historical Deaths

Grundlingh, Johann; Dargan, Paul I.; El-Zanfaly, Marwa; Wood, David M.

2,4-Dinitrophenol (DNP): A Weight Loss Agent with Significant Acute Toxicity and Risk of Death

Journal of Medical Toxicology 2011; 7(3):205-212
DOI: 10.1007/s13181-011-0162-6
PMID: 21739343

Definitive review documenting 62 published deaths attributed to DNP from early 1900s through 2010, including 36 deaths in Paris munition factories (1919). Reviews chronic effects including cataracts, peripheral neuritis, and agranulocytosis. Confirms no specific antidote exists and describes characteristic toxidrome of hyperthermia, tachycardia, diaphoresis leading to multi-organ failure.

9. Pharmaceutical Derivatives - HU6/RIVUS Clinical Trial

Noureddin, Mazen; Khan, Shaharyar; Portell, Francisco; Jorkasky, Diane; Dennis, Jameel; Khan, Omer; Johansson, Lars; Johansson, Edvin; Sanyal, Arun J.

Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled, phase 2a trial

The Lancet Gastroenterology & Hepatology 2023; 8(12):1094-1105
DOI: 10.1016/S2468-1253(23)00198-X
PMID: 37806314

First successful clinical trial of HU6, a controlled-release DNP prodrug designed to provide wider therapeutic index through liver-specific metabolism. Study of 80 patients showed significant liver fat reduction (-26.8% to -35.6%) with manageable side effects (flushing, diarrhea, palpitations) and no serious adverse events, demonstrating potential for safer pharmaceutical DNP derivatives.

10. Contemporary Toxicology Update

Sousa, Diana; Carmo, Helena; Roque Bravo, Ricardo; Carvalho, Félix; Bastos, Maria de Lourdes; Guedes de Pinho, Paula; Remião, Fernando

Diet aid or aid to die: an update on 2,4-dinitrophenol (2,4-DNP) use as a weight-loss product

Archives of Toxicology 2020; 94(4):1071-1083
DOI: 10.1007/s00204-020-02675-9
PMID: 32080726

Comprehensive modern review covering DNP’s mechanism as mitochondrial uncoupler, chronic effects (cataracts, neuropathy, agranulocytosis, cardiac complications), and contemporary use patterns in bodybuilding communities. Documents ongoing availability through internet sales despite regulatory prohibition, emphasizing continued public health risks.

Key Findings Summary

These peer-reviewed sources establish DNP’s high toxicity profile with 11.9-12.5% mortality rates, characteristic acute syndrome (hyperthermia, organ failure, seizures, coma), and serious chronic effects (neuropathy, cataracts, bone marrow suppression). The mechanism involves mitochondrial uncoupling that disrupts ATP synthesis, functionally different from cyanide’s electron transport chain inhibition. Historical use as 1930s diet pills led to widespread toxicity and 1938 FDA prohibition, yet contemporary case reports document ongoing deaths in bodybuilders accessing DNP through internet sales. Recent pharmaceutical research on controlled-release derivatives like HU6 suggests potential for safer therapeutic applications while maintaining the established dangers of uncontrolled DNP exposure.

1 Like
#209

tl;dr - This industrial chemical uncouples mitochondria, disrupting cellular energy while generating deadly heat. No safe dosing exists—peer-reviewed studies show effective doses overlap toxic ranges. “Feeling effects” indicates toxicity, not safety boundaries. Even chronic low-dose exposure causes irreversible neuropathy and cataracts. The 19-year-old with severe nerve damage and 21-year-old bodybuilder who died after “careful” dosing disprove harm reduction claims. Banned since 1938 after widespread deaths, DNP continues killing fitness enthusiasts believing they can dose safely. No controlled studies establish safe protocols. Narrow therapeutic window and unpredictable pharmacokinetics make “careful” use impossible. Pharmaceutical companies develop derivatives like HU6 precisely because DNP cannot be made safe through dose modification. Avoid completely.

1 Like
#210

Tons and tons of bodybuilders have used DNP safely at low-moderate dosages short term. There is just a small window between lowest effective dose and fatal dose.

However, like others have stated, I don’t see the point in anyone still using it at any dose with GLP1s available.

3 Likes
#211

Your response is a bit of a hyperbole. I mean, it’s not incorrect, it just applies to typical weight loss doses, which I totally agree are very dangerous. When I say DNP isn’t particularly dangerous, I’m referring to when used at much lower doses than people use for weight loss. Of course, if you ask AI about it you’ll get a very negative response warning about its dangers. This is because DNP has been ingested by humans pretty much exclusively as a weight loss drug and the doses typically used for weight loss are dangerous. All the anecdotes and case reports the AI refers to most certainly involve such doses.

The above should be preceded by “at doses typically used for weight loss”. Uncoupling or reduced ATP production is not harmful per se. Neither is the heat created through increased uncoupling. Only if it’s too much. The dose makes the poison as always. Uncoupling and the resulting heat generation is a natural process that is necessary for your body in moderate amounts. It’s actually one of the things that thyroid hormones do to your body.

This is only partially true. Yes, the typical doses used for weight loss are close to toxic and clearly dangerous. That does not necessarily mean the therapeutic window is extremely narrow. It is only narrow if someone wants to experience clear weight loss relatively fast, which is how it’s typically used.

She was taking 1 g daily. That’s a massive dose and obviously dangerous. Your posts refers to various case reports of toxicity. All of these people are taking way too much.

That’s why anyone that would dare to use it should use much lower doses than those typically used for weight loss.

I’ve seen no evidence of this at very low doses. What they are referring to as low above is low in range of what is used for weight loss, which is not low at all IMO. The study referring to neuropathy above was the case report of the 19 year old taking massive doses.

It depends. The therapeutic window is only narrow if you want to experience noticeable weight loss in a relatively short period of time. Since most people taking DNP are expecting noticeable and fast weight loss, and taking it at doses high enough to achieve that, for them the therapeutic window is certainly dangerously narrow. The unpredictable pharacokinetics is exactly one reason why someone thinking of taking it should dose a lot lower than those typical doses, so low that even if they happen to be sensitive to it it they are not at significant risk of toxicity.

I should mention that I have posted before a mouse study where DNP given to mice tended to increase their lifespan without causing toxic effects even when given for much of their life. That shows that the dose makes the poison. The dose used in that study was more than 100-times lower than those often used for weight loss. It’s unfortunate that we don’t have any human evidence of chronic low doses of DNP.

I should probably end by stating that I’m by no means recommending that people use DNP. I’m just having an interesting discussion on it’s potential.

#212

I agree. For most people, appetite suppression is all they need for weight loss, so GLP1s would be great. There may be some odd cases that have no problems with appetite and can eat very low calories but have more of a problem with burning enough calories. Such people might be more tempted by something that increases metabolism like DNP.

#213

FWIW Reta is supposed to increase metabolism via the glucagon action. Not sure how much this applies in the real world though.

1 Like
#214

Appreciate keeping a conversation going about it, but I feel strongly this compound is dangerous and not supported by research. In that spirit:

Accepting some valid points it’s still far too dangerous for considering on my review:

  • Most documented toxicity cases do involve doses in the 150-450mg range used for weight loss.
    However dosing is problematic from current sources because tablet variability is side.
  • The 1g daily dose in the neuropathy case represents an extremely high exposure
  • Natural mitochondrial uncoupling occurs via brown fat and thyroid hormone regulation

Problems with the “Low-Dose Safety” Argument:

1. Absence of Human Safety Data
No controlled studies have established what constitutes a “safe” chronic dose of DNP in humans. The mouse longevity study mentioned is not translatable to human safety—mice have 7-10 times higher metabolic rates and vastly different drug metabolism profiles. Extrapolating rodent dosing to humans has led to numerous clinical trial failures.

2. Individual Pharmacokinetic Variation
The Hermetet and other case studies document that people can experience fatal toxicity even when attempting “controlled” dosing. DNP’s unpredictable absorption, metabolism, and elimination mean individual “safe” doses could vary by orders of magnitude—making any self-dosing approach fundamentally unsafe.

3. Regulatory and Clinical Reality
If chronic low-dose DNP were safe and beneficial, pharmaceutical companies would have developed it as a prescription medication. The fact that companies like RIVUS are investing heavily in controlled-release prodrugs (HU6) rather than simply recommending lower DNP doses indicates that DNP itself cannot be made safe through dose reduction alone.

4. Natural vs. Pharmacological Uncoupling
While mitochondrial uncoupling occurs naturally, it’s tightly regulated by cellular feedback mechanisms. DNP bypasses these regulatory systems entirely, creating uncontrolled uncoupling that can escalate unpredictably.

5. Chronic Effects at Lower Exposures
The historical cataract cases occurred in industrial workers with chronic low-level exposure—not people taking weight-loss doses. This suggests chronic toxicity can occur below acutely toxic ranges.

Bottom Line: Without controlled human studies establishing safe dosing protocols, monitoring parameters, and long-term safety profiles, any DNP use remains fundamentally experimental self-medication with a compound that has killed hundreds of people.​​​​​​​​​​​​​​​​

2 Likes
#215

Assuming you’re using an AI program for all this, you really should state as much. Otherwise it appears that you are claiming that this is all directly coming from you.

2 Likes
#216

I took it three separate times in 2013-2014. I went up to 600mg (10-14 day cycles) and felt miserable. Sweating profusely 24/7, no energy, extreme hunger. I basically locked myself indoors for 10-14 days each time because I valued burning fat that much. My pumps in the gym were non existent. I was very flat.

I was an idiot and would NEVER do that again. That being said, I suffered no long term damage or anything. I was right back to feeling normal when I stopped.

If I HAD to take it again, which I absolutely won’t do, I’d stay at 200mg for longer.

1 Like
#217

The main problem IMO is the lack of long-term safety data in humans. while we can be pretty certain that doses much lower than those used for weight loss won’t cause acute harm, we really don’t know if they cause some harm when used over the long run.

How much weight/fat did you lose? Your symptoms are very typical for high doses according to anecdotes I read long ago. It’s common for people to report being very tired and having no energy in the gym on DNP. I wonder if you would have gotten similar results if you had taken the same dose spread over a much longer time, something like ten times lower dose for ten times longer. Perhaps that would have resulted in no perceptible negatives.

#218

Maybe a separate thread should be made for this topic, because it doesn’t fit BP or telmisartan.

7 Likes
#219

At 40 mg Telmi my BP remains around 120/75, but too often goes over 120. I’d like to get it down slightly, but shifting to 80 mg results in occasional orthostatic hypertension when going from sitting to standing.

Has anyone experimented with or have deep thoughts about whether it would be more appropriate to shift from 40 mg to 60 mg daily or alternate days, 40 mg one day and 80 mg the next? I’m hoping to find a sweet spot where my systolic pressure stays under 120 but avoid the sudden BP drop occasionally.

Trying to get the discussion back to Telmisartan …

#220

How long have you been taking 40 mg?