As always, go very very tiny with them in the beginning…
There are alternatuve mitochondrial uncouplers like that by Equator Therapeutics but they take forever
I would be surprised if this a good idea.
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It isn’t a good idea. In the era of GLP-1’s the risks and misery of DNP is far from worth it.
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It is definitely not. Especially in pill or tablet form where dosing can be all over the place. Oh, and also all the other obvious concerns.
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Seconded…
DNP has a low therapeutic index, meaning that the dosage at which toxicity occurs is not much larger than that required to produce a desired effect.[17] Individual tolerance to DNP’s harmful short- and long-term effects varies greatly.[1] The most common adverse effect reported is a rash, which could be maculopapular, urticarial, angioedema, or an exfoliative dermatitis.[17] Cataracts can form, causing a permanent loss of vision in days to months of usage, and permanent deafness has also been reported.[17][35] Other adverse effects reported include peripheral neuritis, agranulocytosis, and neutropaenia.[17] Negative effects on the central nervous system, cardiovascular system, and bone marrow can occur.[1] In animal studies, DNP acted as a teratogen, mutagen, and carcinogen and caused developmental and reproductive harm.[17] An unusually yellow coloring of the skin, mucous membranes, sclera, urine, stomach contents, and internal organs is an indication of DNP exposure, but does not occur in every case.[36] Contact with skin or inhalation can cause DNP poisoning. Symptoms are typically mild with dermal exposure, but inhalation can lead to systemic effects, the same way as oral exposure.[17]
Overdose
Overdose is extremely dangerous;[17] cases reported to poison control centers had a 11.9 percent fatality rate between 2010 and 2020.[27] Although the largest number of overdose deaths occurred in the 1910s and 1920s when the chemical was in more widespread industrial use,[1] the substance’s use as a dieting aid has caused a number of fatalities in the twenty-first century:[17] at least 50 overdose deaths were reported worldwide between 2010 and 2020.[27] Although the lowest published fatal ingested dose is 4.3 mg/kg,[17][16] a typical overdose death occurs at a higher level of exposure, around 20-50 mg/kg.[1]
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It depends on the purpose of taking it. If the purpose is to take it to lose weight by taking it at doses typically used for that, then yes, it’s not really a good idea. However, if the purpose is to take it for longevity I would say that’s not a bad idea at all. Note that for longevity the dose you would need is about 100-times lower than what is used for weight loss so it’s unlikely that you would notice anything and of course any risks of DNP are practically non-existent at such much lower doses.
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yes exactly, that’s why i created this thread
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Problem is the margin of error is extremely small. DNP is notoriously dosed wrong.
Isn’t BAM15 a newer mitochondrial uncoupler that has far less risk? So I’ve heard anyway, I’ve never used any of them.
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Let’s have some research links as to the merit of these. We have evidence as to harm. PEFM - yes, RIR - yes, Sauna - maybe (I don’t, but it may be worthwhile), mitochondrial toxins - hmmm. Thinking mechanistically there would be a route towards mitophagy, but would it clear the right ones. Maybe if the machinery is stuck, but fixing the machinery seems a lot safer. It has to be an evidence question.
When taken in its pure form where around 1-2 pills daily are ok but 10+ pills daily could be deadly, that is definitely a concern. But for much lower doses it’s not really a problem. You just have to use a very accurate scale and dilute the DNP with something else so you create a powder with 1% DNP and then take maybe 100 mg of that daily. To get to dangerous doses you would have to accidentally take well in excess of 10 g of that mix daily, wich would be hard to do by accident.
The point is it is hard to get a legitimate source of it so you don’t know the strength.
What longevity benefit is there to DNP to warrant the risk?
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This is the key question.
Just because there is a substance is no reason to take it.
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Fixing the machinery is generally safer but not always better. In the case of DNP, it works by inducing mitochondrial uncoupling by causing protons to leak accross the inner mitochondrial membrane which results in generation of more heat and less ATP. So it leads to wasting of energy as heat which has the effect that you can eat a lot of food but you don’t get so many calories out of the food because parts of it are turned to heat. This is noticeable as clearly increased body temperature at effective weight loss doses of DNP, and as death by overheating with toxic doses of DNP.
Thing is, while normally you would assume that increasing the efficiency of ATP production would be beneficial, that’s not always the case. In case of uncoupling, it’s well known to reduce mitochondrial oxidative stress since ATP generation increases oxidative stress, while proton leaking across the inner mitochondrial membrane does not, or does so to a much smaller degree. Also to call this toxic is not necessarily correct. Of course excessive uncoupling such as that experienced by DNP ingestion is toxic, but mild one is not. Your body already has some degree of uncoupling in the cells and it is increased in some states, like in brown adipose tissue for thermogenesis, and also by thyroid hormones. I bet this whole subject is of interest to you because of your interest in mitochondria.
As for evidence. Here is probably the main one that leads people to think about trying DNP for longevity.
Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity
In addition there are lots of studies talking about the beneficial effect of mild mitochondrial uncoupling on mitochondrial oxidative stress. I don’t have these at the top of my head but you can easily find these.
Yes, it’s illegal as a drug/supplement so getting hold of a good source is a problem for those that are curious to try. It’s easy to know if you got the right stuff because you can test gradually higher doses in the range of those used for weight loss and if your body temperature starts increasing ever so slightly you can be pretty confident that you have the right stuff. Another indicator would be that it massively stains everything it comes in contact with. Of course this would just show you if you have DNP or not, but not guarantee it’s purity if the source is dubious, so this is not a recommendation on my behalf.
While it is without doubt very risky at doses used for weight loss, I would say that at the 100 times lower doses potentially beneficial for longevity the risk is very low for obvious reasons. The amount many people have taken without clear harm for a several course for weight loss you would be spreading over several years. The risk would mainly be with respect to long term effect of accumulated doses over years or decades, but as the mouse lifespan study above shows, that risk is likely to be low, or else they wouldn’t have lived longer taking it for
What do you think of BAM15? Also do you know of any other mitochondrial uncouplers?
Why not use something like SGLT2i for this purpose? Pee out excess glucose.
Or acarbose, to stop starch breaking down.
Or use a GLP1RA to make caloric restriction mentally easy.
Except if your illicit source wasn’t accurate in their measurement. Are you going to go back down to the minimum dose every time you by more? Is the bag of powder you get evenly mixed? Are the tablets all equal in strength?
A dangerous game. Scares the crap out of me to be honest. On the same level as caffeine powder but worse.
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I don’t know. I can’t say I have looked into it.
For weight loss these can all be useful but for longevity they don’t replace what DNP does at the extremely low doses. DNP probably hardly causes any weight loss at the very low doses that could be used for longevity. It’s possible its benefits are somewhat additive to calorie restriction.
There are solutions to all of this. Same with caffeine powder. Caffeine powder is only risky if you leave it somewhere in its pure form where someone could accidentally overdose. If you know how to evenly dilute it then the risk drops dramatically. If you’re not highly confident you can do that, then stay away from it.
That study is behind a paywall. It is also a single study.
Yes, AFAIK there are no other lifespan studies on DNP so there is only one. There are however lots of studies that indicate that mild mitochondrial uncoupling may be beneficial for aging but nothing conclusive.
It’s unfortunate that the study is behind a paywall. FWIW I read the full text article many years ago and it got me interested in DNP as a potential longevity treatment. I don’t remember the exact dose used but I remember calculating it and coming to the conclusion that it was very low, somewhere around 100 times lower than what people use for weight loss.
Link the study here.
I linked to it above (the link is titled “Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity” ). If you mean link to the full text, unfortunately I don’t have it because I didn’t save it when I read it long ago.
There are many articles about ways to use DNP to help with various things, but I would most worried about the following:
- There are no regulated API manufacturers for this, even if there were you wouldn’t be able to buy from them.
- You are stuck with the underground, they all over/under dose capsules by huge margins.
- DNP is still used in parts of the world as a pesticide and I would guess that is where the underground sources their raws from.
- There is more than 1 ‘raw’ version of this you will encounter (crystal) as well other excipients or cross contamination that you can’t predict with the underground.
- You would need to lab test your raws (not capsules as each capsule would be different). Jano does DNP HPLC for $120 but I would add heavy metal and microbial.
My other question would be: How would you measure results if any in your N=1 experiment?
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