Hello and welcome to my blog. Today it is a very long blog, I’m going to tell you about a bright yellow compound called DNP or 2,4 Di-Nitro-Phenol and a bit about another coloured drug ‘Rainbow diet pill’. Both of these colourful compounds have been around for over 70yrs. The media are talking about DNP a lot at the moment and Rainbow pills are also making a comeback. DNP has the reputation of being the most dangerous supplement in the world and Rainbow diet pill are something most people haven’t heard of, both are weight loss drugs. I will be discussing Rainbow pills first, are they as nice as they sound? Then all about how DNP got its reputation, if its deserved, why people are still using DNP over 80 years after it was first used, if DNP has any benefits and how to step safely into the ‘DNP viper nest’. I first came across DNP when I was studying Biochemistry at university 20 years ago.
Most importantly this is not medical advice and this post is for education only, I am not a medical doctor and taking drugs is dangerous.
I am writing from personal experience in some of this blog and I am not saying taking DNP is a good idea, but scaremongering and misinformation can be dangerous too. Some people will have come to this blog because they have decided they want to try DNP or they are already taking it already and are gathering information. Other people will have never heard of Rainbow pills or DNP.
There are lots of weight loss drugs and supplements available , but many have side effects as these drugs basically try to make your body give up its precious fat stores when it wants to keep it, so you have a battle and more often than not the the fat cells win. When it comes to drugs or supplements the ones which produce the best results usually have the most side effects. If you take a gentle herbal supplement the chances are nothing much will happen. If you do extreme calorie restriction you can crash your metabolism, mess up your hormones and gain all the weight plus a bit when you finish the diet. If you exercise to excess then you can damage joints, discs, tendons and muscles get an injury and that’s the end of training meaning Meaning the fat cells win in these scenarios.Not everyone who resort to drugs are lazy people who can’t be bothered to train or diet, sometimes they have genuinely tried, so its better not to judge. I have come across people who are dancers, models, athletes or work in the media and have resorted to weight loss drugs. Some people are lazy and some people just love studying drugs and taking drugs or AKA ‘Biohackers’, again it’s their choice. The odds are stacked in the favour of the fat cells. As much as we like to say that body image or body composition does not matter and its all about personality, in the western / developed countries we are pretty obsessed with how we look. Body composition is one of the most interesting aspects of biochemistry and like love, we can all relate to it or join in as we all own a body. Most people are interested in bodies, theirs or other people’s, even if its just a little bit.
Lets talk about Rainbow pills first
What are Rainbow Pills?
These brightly coloured capsules and tablets, commonly referred to as rainbow diet pills are a mixture of several controlled or pharmaceutical drugs in once brightly coloured tablet which are then sometimes marketed as ‘herbal weight loss’.The recipes of rainbow diet pill vary depending on the manufacturer and they have been around for over 70yrs. These pills contain amphetamines (speed), diuretics, laxatives, fenfluramine (slimming drug) , sibutramine (slimming drug), ephedrine, clenbuterol and thyroid hormones for the weight loss and things like digitalis, benzodiazepines (eg valium), potassium, corticosteroids, propranolol (Beta blocker), barbiturates and antidepressants to suppress the insomnia, palpitations, anxiety, and other common side effects of the weight loss medications.
The pharmaceutical companies marketing rainbow pills used a variety of unconventional promotional techniques to convince many thousands of doctors to prescribe rainbow pills for weight loss to their patients.
Those involved with rainbow pills used unusual marketing methods and fancy coloured tablets to make the rainbow pills stand out from other medications as well as to attract customers by the pills with pretty coats. This was a money spinner and by 1967 over 5000 doctors in the US devoted their time to rainbow pill practices or rainbow pill weight loss clinics. These clinics earned a staggering $250 million annually in patient fees alone! This is 1967! To cap that patients spent an another $120 million on rainbow pills.There were many serious adverse reactions, such as strokes, seizures, cardiac events, mental health issues and deaths relating to rainbow pills. By 1968 the FDA had stepped in and seized 43 million tablets from a dozen manufacturers over about 2 months. As deaths and injuries linked to these pills accumulated over the years, the US Food and Drug Administration (FDA) eventually removed the rainbow pills from the US market. But that was not the end of the rainbow pill!
After the mass seizure of rainbow pills in the United States, Spain and Brazil dived in and took over the rainbow pills market in the 1980s. The Spanish physicians were aware of and inspired by the US rainbow pill practice.By the 1990s, the number of pharmacies specializing in rainbow diet pills increased 5 times, although the pharmacies thrived, sadly the patients suffered. 86% percent of patients got side effects and in one study almost 4% of pill users required hospitalization from adverse effects of the new generation rainbow pills.
The rainbow pills were banned in many countries by 2007, and the industry went quiet for a few years, but rainbow pills began to make a comeback a few years ago and since the 1960s there are lots of new drugs that can go in the rainbow pills of 2017. Rainbow pills might have 4 drugs in them, where as the super potent could have over 10 different drugs. These drugs are made by people who have scientific knowledge, which means the ingredients in new generation rainbow pills are selected, so in theory they work together. However, taking over the counter medications, prescriptions drugs, alcohol or illegal drugs with rainbow pills could easily produce a nasty result. To add to this there are all sorts of ‘legal highs’ and ‘research compounds (drugs in clinical trials that are available to buy)’ like SARMs. These are cleverly designed designer drugs which are popular, yet nobody knows how they will interact with rainbow pills or if these drugs are in some rainbow pills.
Even if all the drugs in the rainbow pill happily work together, how do you know the dose is correct? One batch of rainbow pills caused a few deaths and dozens of hospitalisations as it contained 100X the recommended dose of thyroxine (30 mg rather than 25 μg), this pill also contained sibutramine, aminophylline, caffeine, metformin (diabetes drug) , and valium. It didn’t go through a quality control check so this rainbow pill escaped into circulation.
There are several disturbing issues with rainbow pills or any strong diet pill. First, is the willingness of some health care professionals to abandon what they learned at medical school or university about the pharmacology, safety of the drugs and duty of care to patients. The public trust doctors and clinics, and they don’t trust people who sell ‘interesting compounds’ at the gym or on the internet. Then there is the willingness of rogue pharmaceutical manufacturers to cash in on the public’s desire to lose weight as well as the willingness to the point of desperation of many patients to grasp at anything that promises hope of shifting the pounds. I have worked with the public and its health / pain issues for over 8 years and I know how much people seek out the beach body, even some people in their 60s and 70s who have neurological issues seek weight loss at the expense of their health.
So that’s dangerous drug number one talked about. I have tried many many compounds in my years of ‘biohacking’ even so called dangerous ones like DNP. I know that many useful supplements exist but in order to talk to people about ‘Biohacking’ I feel I need to have experienced using the compounds. However, I would never try a rainbow pill and I would stop a friend from using them too. Rainbow pills are too much even for me.
Ok so back to dangerous drug number 2, DNP or 2,4 Dinitrophenol and the What? When? How? Why? Of DNP.
What is DNP?
DNP was used for wood preservation, in ammunitions factories, in photography and as a dye in the early 20th century. factories during the 1st. It was observed that people working in these places lost weight and it was traced to DNP, which was getting in through the skin and lungs. The problem was traced to DNP, but nobody know how much DNP the workers were being exposed to. Cutting and Tainter were the MDs at Stanford University made their first report on DNP’s ability to greatly increase metabolic rate and how it could be used as a weight loss drug and published several papers on their findings and methods.
DNP was used extensively in diet pills from 1933 to 1938 so before the 2nd World War, this surprised me as I didn’t think there would be a demand for a weight loss drug for over 80yrs ago, however over 100,000 patients in the USA were treated and even more abroad.
“When one considers that some 100,000 patients have been treated with this exceedingly potent therapeutic agent, it is a matter of some gratification to know that fatalities have not been more numerous”. Cutting and Tainter
One of the first reported deaths from DNP was a doctor who took 5 grams or 5000mg of DNP which is a monster dose, for an imaginary syphilis infection, he died in 12hrs, next person was a lady who obtained her own DNP and instead of using 100mg of DNP each day in her first week as suggest by the clinic in in, she took 800mg on the 3rd day, sadly died. The deaths and the possibility DNP could cause cataracts alarmed the medical community and the public so DNP was classed as dangerous and its usage ceased, also a war was about to start so the world was more interested in that issue. There are plenty of other DNP stories around as it was used in Russia to stop soldiers getting cold in the freezing environments, but sadly solders some died, but again the doses used were pretty high sometimes.
In 1981, the notorious Russian born physician Dr. Bachynsky living in the US used industrial DNP, which he marketed/dispensed under the trade name ‘Mitcal’ through his private weight loss clinic calling it “intracellular hyperthermia therapy”. In court proceedings it was found that over 14,000 people had been treated by Dr. Bachynsky. Individuals using Mitcal started reporting adverse effects, such as fever, shortness of breath and sweating, to the FDA in late 1982. In 2003 the FDA declared DNP ‘unfit for human consumption’ However, Dr. Bachynsky continued to use DNP “intracellular hyperthermia therapy” for variety of different ‘medicinal claims’ which run into ethical complications as one of the claims was as an anti-cancer agent. In 2008 Dr. Bachynsky went to prison, but only for insurance fraud, as one death was reported from ‘Mitcal’ but as it was an underground operation there may have been more.
While in prison Dr. Bachynsky he met Dan Duchaine AKA the “steroid guru”, Duchaine was the notorious godfather of steroid promotion for bodybuilding. He was fascinated and in awe to hear Bachynsky’s story of DNP. As soon as Duchaine was released from prison in the 1990s he continued Dr. Bachynsky legacy and revived the ‘new era of DNP” by promoting DNP to the fitness industry as “the emperor of the fat-loss drugs”. Probably making Dr. Bachynsky the most knowledgeable person on DNP if he is still alive today.
Nowadays DNP is occasionally used industrially as herbicide or defoliant and in scientific research.
How does DNP work?
The mitochondria produce ATP in the cells and are called the powerhouse of the cell, which means cells rely on the mitochondria for energy. The process by which cells make ‘energy’ adenosine tri-phosphate (ATP) is called oxidative phosphorylation and it’s a vastly complex topic, so I will keep the description brief.
In living cells, DNP acts as a proton ionophore, this means it carries hydrogen ions / H+ (a proton), which are positively charged across biological membranes in the mitochondria. In lay terms, in the membrane of the mitochondria there are special pumps which push the protons or H+ up into a certain place in the membrane as part of the energy or ATP making process in the cells. This builds up a store of H+ or a potential energy gradient as later all those H+ are going to ‘fall down’ and be used later in other reactions. As an analogy, its like shoving loads of spare stuff up into your attic at home to use later, it requires effort. The cell build up lots of protons / H+ in an attic to use later. The DNP comes along and sneaks, escorts or smuggles the protons back through a different place in the membrane before they have been used to make ATP, like if someone came along and stole your stuff out of the attic out of the roof.
The more DNP that is around the more protons get escorted back across the membrane, making it difficult for the cell to produce energy. This means higher doses of DNP = more inefficient the ATP (energy) production in the cell. Metabolic rate increases, demand for oxygen increases and more body fat and carbohydrate is burned to make up for the inefficiency and to meet energy demands of the cell.
Another consequence of this is result of this causes a release of calcium from mitochondrial stores and stops calcium being taken back in. This escaped calcium and causes muscle contraction and the increase in body temperature or hyperthermia. People who have OD on DNP had temperatures rising high as 44 °C (111 °F), so they cooked themselves from the inside. Another way to consider how DNP works is like an old engine where loads of fuel goes in but the engine doesn’t run that well and produces a load of waste and heat, this is not 100% accurate but you get the idea. Food goes in but the cell can’t use it properly, so when DNP is there the energy is dissipated as heat rather than being stored, but the key point is there is no cut off point as it messes up the bodies thermostat so if you took loads of DNP and ate loads of food particularly carbohydrates the whole lot get incinerated with you being part of this oven.
Plants have chloroplasts instead of mitochondria, which are similar and DNP targets the chloroplasts in weeds and that is how it is used as a herbicide.
DNP is also called an uncoupling agent and there are other uncoupling agents in mammals such as UCP1 (uncoupling protein1) and they play a role in burning fat to produce heat during hibernation. DNP is hacking into our potential hibernation pathway.
The take home message here is the higher the dose of DNP the more uncoupling, so this means you the more heat and less energy you produce, so it will make a person very hot and tired if they take too much.
The side effects depend entirely on the dose as DNP behaves like three different compounds if taken in a large dose, medium dose or very small dose.
Eating DNP results in increased basal metabolic rate, sweating and loss of weight. This is why people take it and it is very good at doing its biochemical job.
Side effects can include dizziness, headache, nausea, vomiting, overheating and death. Chronic long term exposure to DNP can lead to the formation of cataracts and skin lesions and has caused effects on the bone marrow, central nervous system, and cardiovascular system. I will discuss some of these later as it depends on the dose. The main concern is the formation of cataracts as that is a very real adverse effect and was a major reason why DNP ceased being used in 1938.
The scientists who worked on DNP in the 1930s they have data from treating about 4,500 patients per year with DNP and they discuss side effect they observed (see earlier link to Cutting and Tainter paper). Because DNP is a restricted it is not ethical to do human studies on it or even animal studies therefore the largest published human DNP study with known doses is the one in the link above.Dr. Bachynsky will have a large amount of patient data on the use of DNP and a list of adverse effetcs but it is unlikely to be available and its integrity is questionable. Cells and animals can respond slightly differently to humans to drugs so cell and animal data is very useful but not gospel.
However there is enough evidence to say that DNP is quite toxic in large doses or if taken for a long time and will kill you for certain if you over dose. The lethal dose is about 2500mg but like anything that’s an approximate so it could be 1500mg for one person and 4000mg for another. This is a link to a table showing the number of reported deaths from DNP there are 25, excluding those in the ammunitions factories since 1918 from DNP and the dosages, most of which are over 2500mg but not all.
So far we have learned that DNP can or might affect major systems in the body like heart, eyes and skin and it can be fatal. So why do people love it?
This is why “An increase in the metabolic rate of about 50% can be maintained in most patients without difficulty, by proper selection of dosage; in fact, greater increases have been repeatedly produced”. It enhances the metabolic rate but does so without increasing blood pressure, which is common with stimulant based weight loss drugs or thyroid. No other weigh loss drug gets anywhere near DNP in terms of performance.
However, there seems to be significant variation in individual responses with an average metabolic rate increase of 11% for every 100 mg of DNP when taken regularly [3&4]
Why do people overdose on DNP?
Firstly, some people buy a diet pill on the internet or from someone at the gym without knowing it contains DNP and then take too many pills. Most people adhere to instructions but some people have to go to excess and they take too much DNP because they don’t understand how it works and they don’t believe that it can be dangerous. DNP takes “several” hours to get working and this varies from person to person. DNP has a half life of about 36hr but in some people can be shorter or longer, this is partly why people can OD as they think ‘this is not working’ so take more and more, but because it takes 36hrs for half the DNP you took to leave the body it accumulates. This is becasue it builds up faster than it can be removed from the body if it is taken everyday. DNP is not a pharmaceutical like steroids, growth hormone, fenfluramine or thyroid which people like to use for lots of reasons, not just bodybuilding or sports performance . Even though lots of these pharmaceuticals are banned or controlled, they were designed to be used by humans and went through clinical trials. This means these drugs have special characteristics or pharmacokinetics so that they can be absorbed properly and removed safely from the body. DNPs purpose was industrial so people can react very differently to it as it’s not designed as a medication, its was stumbled upon.
It is not possible to guess the DNP dose by bodyweight as one of my friends who is an ex nurse wanted to try DNP and she is 20kg less than me, yet she took 350mg (and built up to it over 5 days) and was a bit warm so I tried some of the same batch and was a sweaty mess with 250mg in 2 days. I know people who take 1000mg and been fine, where as if I took that I would die. This means that if you have decided you are taking DNP and will not be persuaded not to, don’t just take what your friend took or somebody suggests. Like any dangerous or new drug or new hair products the best approach is to take a very small amount to start with to make sure you are not allergic to DNP. DNP is a dye and humans can react in funny ways to dyes and you will know straight away if you are very sensitive. Humans develop sensitivities to all sorts of things like washing powder, eggs, aspirin and the same happens with DNP, where skin rashes appear, but also swelling in the throat. If that happens then stop immediately as you have probably developed an allergy to DNP, this means if you take it again there is good chance you will mount an immune response to it and that can be very dangerous.
I assume the body builds up a tolerance to DNP and its effects as some people take DNP for months at doses between 200 -400mg and have minimal side effects. if I did the maths on how much DNP the person takes in compared to how much is excreted, bearing in mind DNP has a half life of 36hrs then theoretically they would exceed the lethal dose in a few weeks. It would appear that talking a large amount suddenly is dangerous. I do not know the answer to this.
Using medium doses of DNP
When using say a medium dose of DNP 150-300mg per day (this was the dosage used originally in the 1930s), there will be a considerable amount of uncoupling in the mitochondria and when you do this it causes the mitochondria to produce more ‘free radicals’. In lay terms, during the energy making process in the mitochondria the hydrogens ( H+ or proton) are supposed to be pair with some electrons which are highly reactive molecules. In lay terms the DNP moved the hydrogens meaning the electrons can’t find them so the electorns react with other molecules nearby and make reactive oxygen species and other nasties which damage the cells.
Old or deformed mitochondria make free radicals too in the absence of drugs, which is a key factor in many diseases. This means that if you want to use DNP at a medium dose you need to take anti-oxidants too such as Vitamin C, Vitamin E, Glutathione, Astaxanthine, Co-Enzyme Q10 or any other known oxygen scavenger or anti oxidant. Poly phenols which are in pomegranates, grape skins and dark chocolate are also protective to mitochondria. But you will have to accept that some free radical damage will occur and this is a big part in ageing and other illness. Anecdotal evidence suggests that calcium pyruvate and glutathione supplementation may decrease the likelihood of cataracts, when using DNP, which are more common in women. This has not been proved and finding an orally absorbable glutathione is not easy but liposomal glutathione or glutathione force are supposed to be the best brands.
DNP will kill some mitochondria, the old, small or damaged ones will die first which in a way is a good things as they are a pest in the cell. Another use for DNP in research is to make a hypoxic environment for cells, as in low oxygen. Exercise also causes a temporary hypoxic environment, so in some ways stressing or bullying the mitochondria gently for a short period of time can make them stronger, but there is very fine line between helping and harming them. So the take home message is if you use DNP for a long time than the chances are you will harm the healthy mitochondria as they just can’t cope with the prolonged stress. Without its powerhouse the cell will die. Bear in mind that the cells with the most mitochondria in the body are the eyes, heart, nerves and brain so if you abuse DNP and kill these cells and these organs will suffer first.
DNP really does increase body temperature so when people say don’t use saunas, don’t go out in hot weather and drink plenty then it’s a genuine warning, anyone who doesn’t follow this will end up dehydrated and overheated. I live in the UK and I used DNP in the winter, this doesn’t mean its ok, I was taking a risk, when I tried it, but I wouldn’t take it at the moment as its 29C. The reason that DNP can cause cataracts is not known for certain but it is a mixture of heat induced changes in the eye, damage to mitochondria in the eye and excess escaped calcium. So its fair to say that the prolonged use of DNP at a medium to high dose isn’t not good for eyes at all.
Vitamin K2 and Magnesium are very important for calcium partitioning and management, as in keeping calcium out of muscles, kidney or arteries and sending it into bones. Vitamin D3 is more about calcium absorption, but this is another topic. The point being if you use DNP then make sure you aren’t deficient in K2 or magnesium otherwise you will have even more issues with calcium going where it shouldn’t in the body.
Our body temperature is tightly regulated, so when the body temperature increases after taking DNP this will inhibit the thyroid gland, as one the effects of thyroid is an increase in body temperature. So what people like to do is take thyroid hormones T3 or T4 with DNP to counter act this, but this can be dangerous because the mitochondria in the heart cells are already struggling to produce energy and demanding more oxygen so now you add in thyroid hormones which increase heart rate. So this is bullying the heart cells into beating faster when they don’t want to and they are short on available energy, this can harm the heart cells. Taking too much thyroid by itself can have unwanted effects on the heart. A class of smart drug called racetams, Piracetam is the best known and most popular, can offer some protection to cells in ischemic or low oxygen environments, but taking one drug to combat the side effect of another can get very complicated very quickly.
The kind of people who take DNP are often into fitness or bodybuilding, meaning will have training regimes so extra demand on the heart, so these need to be modified when using DNP or even more so if using DNP and thyroid. Forums will suggest using stimulants like modafinil or Adderall but now you have got DNP+Thyroid+stimulants+ exercise so the really is asking for trouble, so another reason DNP gets blamed for harming people. So yes DNP with other drugs at doses which stress the heart are going to be detrimental to the cardiovascular system over time.
If you take hormones then your body will notice and sometimes it stops producing its own, this is called suppression. DNP doesn’t directly switch off thyroid, the regulatory systems in the body do, this means that when the DNP is taken away, the thyroid will usually switch back on by itself when it senses the body temperature is returning to normal, the body tends to over compensate when you fiddle with its biochemistry, so it sometimes produces more thyroid hormone for a bit after using DNP that it did before. If you take lots of thyroid hormone the body switches off the natural production which is suppression and people have found that sometimes its very difficult to get the thyroid to start up again. Thyroid glands and thyroxine are a huge topic so this is just a brief point in relation to DNP.
People who want to lose weight mean they want to reduce body fat but generally keep muscle. This means its popular to take anabolic steroids or SARMs with DNP to ‘keep’ muscle or prevent muscle catabolism. In general DNP spares muscle and uses fat and carbohydrate anyway, meaning it isn’t necessary for everyone and if DNP is liver toxic, then why add in synthetic hormones, like anabolic steroids which are well know to be heavy on the liver? Using testosterone or testosterone mimics have many beneficial uses, which is a whole book chapter or blog and not relevant right now.
I can see that stacking DNP with other drug would accelerate the effects, but if it comes at the expense of health, its better to be patient and not to rush.
DNP on its own is enough of a stressor for the body there is no need to add more drugs in the cocktail
Click here to read more about why people take DNP knowing the risks.
Why do people still use DNP at moderate doses knowing the risks?
DNP doesn’t aggravate possible mental health issues or raise blood pressure like amphetamine derived slimming drugs do. Another issue which makes DNP so attractive is that if used sensibly, people do not gain back the weight they lost straight away, if they are careful. Firstly many people eat a ‘sensible diet’ at a ‘maintenance calorie’ level and use DNP at the same time, which increases the metabolic rate, which leads to fat loss. When they finish the DNP cycle, they just carry on with the ‘sensible diet’ so the weight stays off, unlike what happens after very low calorie diets. Another reason I believe that after using DNP people are less likely to gain weight is because it corrects an issue which caused weight gain the first place, which is insulin resistance.
‘Overeating doesn’t necessarily cause weight gain, but being overweight causes overeating’ I think is the principle Gary Taubes talks about in his books
DNP and insulin sensitivity Rat studies using DNP at 0.8mg/ml (appx 35mg/kg in a mouse and 3mg/kg for a human, so a medium weight reduction dose of 200 -300mg depending on weight [13,14]) for 2 months showed improved fat loss without lean muscle loss, glucose tolerance, reduced hepatic steatosis (fatty liver) without observed toxicity . This study also showed that DNP is more effective if mice are kept in warmer rather than cold housing environments. In other studies uncoupling agents, DNP derivatives  and DNP also showed improvement in glucose metabolism, insulin sensitivity and liver function [6-8]. So this is helpful for people with fatty liver disease and re-sensitises people to insulin, which is massive in weight management, poly cystic ovaries and type 2 diabetes. The bro-scientists,biohackers, bodybuilders and athletes also discovered this useful facet of DNP and its ability to improve insulin sensitivity. This means people who have got very carbohydrate sensitive or have pre type 2 diabetes will find DNP gives them a second chance to reverse the damage they have done to their biochemistry.
We have learned that at a medium dose DNP causes fat loss but spares muscle. DNP at medium doses can be beneficial for improving insulin sensitivity and fatty liver disease, however there are some side effects such as a risk of cataracts. These are doses between about 200 – 350mg for a human.
Very low doses of DNP and uncoupling agents
At very low doses DNP behaves in a completely different way and has benefits and is not known to be toxic compared to being a killer at high doses. Very low and low are between 6 and 45mg per day for a human[13,14] .
Mitochondria make ATP but they also play important roles in synaptic signalling (cells communicating ), plasticity (how cells adapt and learn) and responses to cellular stress. One of the pathways mitochondria are involved in are learning (motor skills and intellect) and memory and ‘Biohackers’ get very excited at mitochondria. I teach movement and I also do many sorts of activities myself and I am always learning new dance moves or gymnastics moves, I remember being puzzled at why I picked up new skills when I used a very low non weight loss dose of DNP as I thought the opposite would happen, that I’d worsen my performance.
Mitochondrial dysfunctions occur in many diseases linked to the systemic inflammatory response syndrome (SIRS). Mild uncoupling of oxidative phosphorylation buy using uncoupling agents including DNP in animal studies is known to prevent disease and damage from mitochondrial dysfunctions and over-production of reactive oxygen species or free radicals . This is counter intuitive as you would think making the mitochondria be inefficient would harm cells. Neurons depend on mitochondria for homeostasis and survival, and thus, mitochondrial dysfunction has been implicated in neurodegenerative diseases, including Parkinson’s disease . Increasing evidence DNP, protects neurons against neurodegeneration and enhances neural plasticity. Mild mitochondrial uncoupling as in a low dose improves neuronal resistance to stress and facilitates neuronal survival. In another study a low dose of DNP (1mg/kg/day) so 0.086mg/kg for a human so about 6-10mg per day[13,14] significantly improved motor function and had a neuroprotective effect in Huntington’s disease model . In another study daily administration of a very low dose of DNP (0.5 mg/kg) for 4 months improved spatial learning and memory in mice, which equates to appx 3-5mg per day in a medium sized human [13,14].
Another study in 2017  looked in more detail at why low doses of DNP were beneficial for the brain or neurodegenerative disorders. The study found DNP increased the production of several protective molecules in the cell which could also help with mental health problems such as depression. The beneficial psychiatric effects of DNP were reported in the 1930’s, but the precises details of what kind of psychiatric conditions were not discussed as the brain was very poorly understood at that time.
This study was in mice for 14 days and the dosages in this study and the picture are for mice. Low was 1mg/kg, 5mg/kg was moderate and 10mg/kg was high. Human equivalents 0.086mg/kg, 0.43mg/kg or 0.86mg/kg. In total dosage. 6-10mg per day low, 30 -43mg medium and 60-100 high. These are approximate doses converted from mouse to human for the sake of explaining the study and what the equivalent dose for a person would be.
Brain-derived neurotrophic factor (BDNF) is key in depression as many selective serotonin re-uptake inhibitors (SSRI) drugs (eg.Prozac and Sertraline) are supposed to work by increasing levels of serotonin is the brain which would mean antidepressants would work in a few hours, but they take several weeks. Many studies on how SSRI antidepressants really work strongly suggests they improve mood or depressive symptoms by increasing levels of BDNF in the brain, rather than serotonin. There are about 2000 papers in Pubmed on SSRIs and BDNF which is why I have not a put a reference as there is so much information. Biohackers are interested in taking low doses of SSRIs as BDNF has many other useful and protective roles in the brain.
Superoxide dismutase 2 (SOD2) is one of the bodies natural antioxidants and is of course a big player in ageing and illness, meaning increasing your body’s natural defences is a good thing. Some studies have suggested that if people take excessive amounts of antioxidants it can make the cells ‘not bother’ to make their own anti-oxidants, which of course is not good.
Cyclic AMP response element-binding protein (CREB) is critical for the plasticity, growth, and survival of neurons . CREB is a transcription factor, which is a special protein which binds to DNA and turns genes on and off. There is a wealth of information on CREB as scientists have know for a long time CREB is important in memory, brain health and neurodegenerative diseases.
Very low dosages of uncoupling agents like DNP have a very similar effect to fasting and calorie restriction which are known to be beneficial on many levels.
DNP anecdotal studies
From anecdotal evidence and discussions. Doses of above 400mg of DNP often result in insomnia but however lower does 50-200mg often result in vivid or even lucid dreams, I don’t know the mechanism why, so people who are prone to insomnia or nightmares should be careful. People who use DNP report they get bitten less by bugs and mosquitos. Some DNP leaves the body via the lungs people who have chronic lung infections or certain lung conditions find that they have a clearer chest and less infections. This doesn’t mean it’s a good idea to use it, it means that even bugs will avoid DNP given the choice.
Does DNP deserve the tilte of the ‘The most dangerous supplement in the world’?
What do you think?
So I personally don’t think DNP is the most dangerous supplement in the world. It is not safe, but then no drug is safe With respect to DNP if you buy it from a reliable source at least you are taking ONE compound which you know or should know the ‘Dos and Don’t of use and abuse’. There are little biochemistry companies popping up now offering confidential HPLC analysis of any supplement or drug you buy for a very reasonable price. If you do have a nasty reaction to DNP, either an allergy or from ignoring the advice and taking too much then you have a few options.
Firstly of drinking plenty of water, sitting in an ice bath, using an oxygen mask or much better going to A&E ASAP and just being honest about what you took. People are afraid to come clean, but it really is a serious issue. Hospitals stock a drug called Dantrolene which is used for malignant hyperthermia, which is when certain people with a genetic fault over heat under anaesthetic, hospitals also have oxygen masks and ways to cool people down. You can also read the papers from 1935 by Dr MTainter ‘Treatment of acute dinitrophenol poisoning’. Google will tell you that ‘there is no anti-dote to DNP that once you overheat you die’ this frightens some people off, but others who do take too much DNP just stay at home and don’t seek medical advice!
If you OD on rainbow pills then nobody knows exactly what is in them so it will be very hard for medics to help you or give an antidote.
DNP has caused deaths, but most were an overdose of DNP as some people just go to excess. In addition, anyone who uses or wants to use DNP know the risks and they know they are taking something which isn’t 100% safe. Much research has shown DNP can reverse insulin sensitivity meaning there are people who will take a low / medium dose in order to save themselves from type 2 diabetes, which is the biggest cost to the NHS in the UK. Very very low doses like 10mg may helpful in inflammation, learning, anti-ageing and neurodegenerative diseases, but without weight loss effects. If you have Parkinsons or Huntingtons, weightloss is the least of your worries
From doing a lot of research in to DNP there is an element of scare mongering and media hype, this in itself causes problems. iIf people take medium dose and have a good experience with DNP, then they will think that it was all bollocks about it being dangerous, then take a mega dose and be ill or die.
Any student even those under 18yrs old who study how cells make energy or ‘oxidative phosphorylation’ as its called, so pretty much anyone who does any biological science, pharmacology, sports science, medical or dentistry will during their course come across uncoupling agents and DNP in the lecture notes. When the students innocently further research uncoupling agents they will of course discover the weight loss benefits. This is the age group who think they are invincible, are most likely to completely ignore the dosage and use it to excess ( I have been to university and I know what students are like when it comes to getting drunk and high) Many people in that age category (teens, 20s) have varying degrees of body image issues, meaning they are vulnerable when it comes to anything offering weighloss, so they need to be protected or correctly informed.
The future of DNP, is an elderly / responsible persons medication or for anyone interested in its neuro protective or anti-inflammatory effects and only of use when used at very low weight preserving dosages. Doctors aren’t allowed to give DNP to patients with neurological issues and there arent any uncoupling agents on prescription yet. If DNP was allowed to be prescribed again, then like the rainbow pills it would only get abused, stolen and over used by unscrupulous health care professionals and desperate patients, resulting in deaths and illness, so it would be banned again in a few months. There is no doubt a new generation of uncoupler will be designed to replace DNP which doesn’t cause the over heating but has all the other protective benefits. The problem will be the new generation DNP wont be as effective as the ‘grandfather’ version of DNP for weight loss, meaning people who want to use an uncoupler as a diet aid alone will still seek out DNP.
It is not unusual for industrial chemicals to become medicines. Warfarin which is a blood thinner wiped out entire herds of cattle after they ate spoiled silage called “sweet clover,”which resulted in uncontrolled bleeding after common procedures. In the 1930s, the evil ingredient causing the bleeding, warfarin, was extracted and used as a rat poison. However, in the 1950s, warfarin was brought forward as a new life saving blood thinner, by just lowering the dose so changing it from a killer to a saviour of life.
Rainbow pills however are different as they are a big cocktail of drugs, which don’t have any useful effects other than weight loss, so they win beat DNP when it comes to dangerous diet drugs. Most people naturally shy away from DNP the industrial weed killer in disgust as to them it’s the equivalent of eating bleach, but could be attracted to and tempted by Rainbow pills as they just sound like a nice herbal drug.
In terms of deaths from pharmaceuticals and deadly drugs, prescription opioid overdoses caused nearly 15,000 deaths in the United States in 2008, so maybe they deserve the title of the most dangerous drug instead.
For more about supplements, plants, interesting pharmaceutical and biochemistry look out for my eBook which is going to be released in July 2017
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- 1.Yuliana ND et at Comprehensive review on herbal medicine for energy intake suppression. Obes Rev. 2011;12:499–514
- 2.Pieter A. Cohen The Return of Rainbow Diet Pills Am J Public Health. 2012 September; 102(9): 1676–1686
- 3.Dunlop DM. The use of 2:4-dinitrophenol as a metabolic stimulant. BMJ. 1934;3820:524. doi:
- 4. Harper JA, Dickinson K, Brand MD. Mitochondrial uncoupling as a target for drug development for the treatment of obesity. Obes Rev. 2001;2:255–265
- 5.Margalit Goldgof et al The Chemical Uncoupler 2,4-Dinitrophenol (DNP) Protects against Diet-induced Obesity and Improves Energy Homeostasis in Mice at Thermoneutrality J Biol Chem. 2014 Jul 11; 289(28):
- 6.Samuel VT, et al. J. Biol. Chem. 2004;279:32345–32353.
- 7.Perry RJ, et al. Cell Metab. 2013;18:740–748. [PMC free article] [PubMed]
- 8.Perry RJ et al Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats.Science. 2015 Mar 13;347(6227)
9. Zakharova VV et al Low concentration of uncouplers of oxidative phosphorylation decreases the TNF-induced endothelial permeability and lethality in mice. Biochim Biophys Acta. 2017 Apr;1863(4):968-977.
10. Lee Y et al Neuroprotective effects of 2,4-dinitrophenol in an acute model of Parkinson’s diseaseBrain Res. 2017 May 15;1663:184-193.
11. Wu B et al 2,4 DNP improves motor function, preserves medium spiny neuronal identity, and reduces oxidative stress in a mouse model of Huntington’s disease. Exp Neurol. 2017 Jul;293:83-90.
12 .Geisler JG et al DNP, mitochondrial uncoupling, and neuroprotection: A little dab’ll do ya. Alzheimers Dement. 2017 May;13(5):582-591.
13. Agency for Toxic Substances and Disease Registry (ATSDR) (1995) Toxicological Profile for Dinitrophenols, ATSDR, Atlanta, GA
14. Food and Drug Administration (2005) Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers, United States Department of Health and Human Services, Rockville, MD
15. Lonze BE, Ginty DD. Neuron. 2002;35:605–623.