All about DNP : Animal's manuel
I found this to be the most informative on DNP.
Dnp Faq
DNP FAQ-also a cut and paste FROM ANIMAL'S MANUAL)
Why you might want to use DNP.
Add some DNP to an animals diet. DNP can get metabolism up at least 50% which is conservative as some say 75% This would mean if the animal eats 3000 calories maintenance they are now at 1500 calories a day with no change in diet! A 2500 calorie a day would leave them with 1250 calories a day. There are 4086 calories in 1lb of fat and at 3000 calories a day your DNP adjusted calories for the day is 1500. Multiply that x 7 days to give you 10500 calorie deficit which is 2.5 lbs of fat loss for the week. At the 2500 calorie you have a 2.14 lb fat loss. These are both below what the BO diets claim and you don't have to stop eating!
If your animals weigh around 200lbs their effective dose is 400mg and the max can be as high as 800mg a day.
High fat diets market on the basis that you are going to be able to lose 1.5?2lbs of fat by just changing your diet!
1 gram of fat is 9 calories. There are 454 grams in a 1 pound. This gives you 4086 calories for 1lb of fat. If you want to lose that 1lb of fat you have to have a 4086 calorie deficit to do it. In other words, you need ?4086 calories in your diet if you want to lose 1 lb of fat. Now, Let's say you are at 3000 cal a day for maintenance. That is 21000 calories a week. You believe the marketing of the post above and think you can lose 1.5lbs of fat. That, my friends, is 6129 calories which you have to subtract from 21000 which leaves you with 14871 calories for the week or 2124 calories a day. You are going from 3000 to 2124 a day. If you want to lose that great sounding 2 pounds you are now at 12828 for the week or 1832 calories a day.
Let's be realistic and put you at 2500 maintenance calories. To lose 1.5lb you now need 11371 calories a week or 1624 calories a day or a nearly 900 calorie a day change. To lose the magical 2lb a week you need 9328 calories for the week or 1333 calories a day or a 1167 calorie change per day! That is rather difficult, but let’s add some DNP which can get you metabolism up at least 50% which would mean you are now at only 1500 calories a day for a 3000 calorie diet with no change in diet! A 2500 calorie a day would leave you with 1250 calories a day.
These are both below what the BO diets claim and you don't have to stop eating!
What you want to keep in mind
Everyone is different.
Don’t take it on an empty stomach or it will feel like you have indigestion for most of the day.
I wanted to stress not to just go balls out (5mg/kg) and you should move up gradually on DNP for your first experience.
If you have an allergic reaction with red spots and itching then stop the DNP and get some Benadryl and then you should be able to start again.
The type of diet will also affect how you feel, as well as the type of workouts you are doing. These are variables you also will have to figure out for yourself. The logic of my dieting regimen follows that while you are DNP all the glycogen/glucose is being scavenged to provide ATP for the mitochondria so you will want to eat a regular diet. High fat BO is not going to help you build muscle even though DNP is anti?proteolytic (protein sparing).. Furthermore, when you eat fat it is more likely to go to fat! That is scientifically proven. So if I'm trying to burn fat, why would I want to eat it right back?
DNP is anti-proteolytic which means it uses carbohydrates or fats exclusively to supply energy for the mitochondria and does not facilitate muscle breakdown, however, this does not therefore mean DNP is positive for muscle building. The cells are running on overdrive and they are not going to be looking to make themselves bigger which requires even more energy.
Everyone is different and other supplements you take will affect your results, but as a whole, most people are not going to do well or feel well on high fat and DNP. I also have found that taking particular supplements helps with how will you feel while on the DNP.
I feel better when I don't do huge carbs, however, when I don't do any as in high fat type diets, my workouts suffer just the same. Each individual has to decide for themselves and put those factors into perspective with what their goals are and how fast they want to accomplish them and how bad they are willing to feel for the desired weight loss.
WARNING: DNP will turn everything and anything yellow including skin, clothes, carpet, and hair. I dropped a capsule in my DNP container and bent over to look for it and my hair touched the edge of the container and my hair got dyed yellow! My hair did not even touch the DNP, but just the side of the container for about 2 seconds! DNP for the most part is not removable or bleachable with normal chemicals. It will also track. By that I mean, you think you have washed it off your hands and you touch something and later you see yellow spots on what you touched. If you are making caps you need 2 pairs of gloves, at least, as the DNP goes through the first pair due to an atrraction it has for moisture. DNP sublimes and floats. Due to this sublimation it will land on EVERYTHING if you leave it out even if there is no air circulation. DNP goes through EVERYTHING including plastic, hdpe plastic, pet plastic, plastic bags, nitrile and latex gloves. It can be washed out of clothing with hot water and detergents that have phenolic compounds in them such as Tide. DNP is not solvated by laquer thinner, acetone, paint thinner, or turpentine or any of the common organic solvents. If you wash your hands immediately after touching DNP with gamma-butyrolactone, otherwise know as GBL and use to make GHB, and then a detergent such as Dawn dishwashing soap, the stain will come out for the most part.
I have to say that a certain guru which some people keep quoting is what I feel to be a very unreliable source. I will give him credit for bringing DNP to the forefront, but I will bet you a million bucks that he has never done it or mixed it. Here is a quote that bears this out; 'I don't see what the worry is about everything turning yellow? I have no problems, I just dry it out and cut it with a credit card and cap it.’
That is total BULLSHIT!. Anyone who has used or mixed DNP powder knows that it will get on EVERYTHING and turn it yellow. It goes through plastic bags. Just today I was sending someone 3g for research and I put it into a ziploc and 2 hours later I came back and the envelope under the bag was YELLOW! It goes through 1 laver of rubber gloves. It turns white HDPE bottles yellow. It floats everywhere. I had to put my stuff in a hood because it got on everything I had sitting out and I had to wash all my glassware and scales before I could use them again. DNP floats by sublimation which would be known just be reading the safety sheet or the Merck Index.. On the basis of that statement alone I have some real problems believing anything he says on the subject, but another famouns quote is, ‘DNP will raise your body temp high enough to kill you!’ This also proves that he has never done it because as you will find, your body temp only goes up about one degree. Ok, enough about the fake guru.
Someone just asked me if the shit I sent them was real. Well, if you want a test then rub it on your hands and throw some on your carpet. When your carpet has to be replaced because NOTHING can remove the yellow and you look like a total ass because your hands are bright yellow, then you can ask me if it is real!
Mostly people are taking DNP for 1 week at a time because it exhausts you and you sweat a lot, usually that is what I do, but due to my ‘work’ with DNP I got a dose while on an ECA week and that combination of DNP-ECA was like methamphetamine. In fact it was better because it had less side affects. I would venture that DNP-PPACA would also have the same methamphetamine effects. At this time I do not know, however, whether PPA works on the same receptor so I would not do them back to back in cycles. ECAY where Y is yohimbine is also a combination that has meth type benefits. Clen-DNP did not exert any magical meth benefits that I noticed.
Have not taken PPACA or PPACA-DNP or PPACAY.
Tyramine and yohimbine are awesome and someone that I hold using it was getting goosebumps and asked a pharmacologist what the goosebumps were about. The pharmacologist told him that it meant he was burning a lot of calories. I love this combination and it is just like meth due to large releases of NA although it only lasts 4 hours or so.
DNP also ‘upgrades’ the effects of clen. If you have used clen before and it had/has stopped working, then DNP will bring back it’s glory.
I like to keep the clen and DNP a week apart due to the affects they have on T3 although they work on different mechanism it is just a precaution to keep from shutting down the T3. You could add Y to it for an added benefit which will not cause downgrade of anything. Reports on DNP-Y indicate a higher rise in body temperature on this combination.
Due to the systemic affects of DNP, it affects EVERY cell in the body that has mitochondria, including smooth (digestive) and muscle and fat as well, you will not see a significant rise in body temp like you see with clen or ECA. Clen and ECA work primarily on muscle cells and that causes a rise in body temp just as if you were working out. I don’t know why this is such a difficult concept for some to understand, but I was sweating like hell recently, and I took my temp and it was 95.8. ON DNP!
Last edited by 1sttimer on 06-09-2002 at 02:04 PM
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05-30-2002 02:49 PM
1sttimer
I pity the Fool!!
Registered: Apr 2002
Location:
Posts: 358
DNP MECHANISMS
The basics first. DNP is a classified as a chemical poison. It’s mode of action is to disrupt the ETC (electron transport chain) and cause uninhibited exchange of protons. This exchange of protons is what is responsible for making ADP into ATP. NOTHING can stop the disruption of this process once it starts. DNP works no matter what! High or low T3 has nothing to do with whether or not DNP affects the mitochondria and burns off extra energy. DNP gets into the cell and into the mitochondria and causes proton release. No other hormones are needed or noted.
Even so, it works in much the same way as clen or ECA or PPACA or thyroid. They ALL cause the metabolism to speed up. These all work via the mitochondria as well, although the non-DNP diet drugs work on the receptors first and DNP goes directly to the mitochondria, the results are the same which is speeding up the metabolism to burn fat.
Some other important facts you should know are how ephedrine and beta-3 activation drugs work.
These both cause uncoupling of the ETC chain just like DNP! Ephedrin works part of its magic via beta-3's and much research has been done looking for a magic beta-3 drug. Why, we have it and it is called DNP! If you are sitting around and something is making you hotter, you are most likely experiencing an uncoupling of the ETC chain. No big deal, but DNP just causes a greater effect.
I knew there was a reason that you CANNOT die from DNP usage, at least the doses many are doing. I talked to a couple people about this but just couldn't find the info to prove it. Ok, so what does DNP do? It uncouples the ETC or oxidative phosphorylation as was elaborate upon above, allowing electron flow to go unchecked at maximal rate and resulting in heat production and ATP depletion.
ATP depletion is the key. What condition exists when you have totally exhausted all ATP and no more is being created? A very good instance we all know about is when you are dead and it is called ‘rigor mortis’. Rigor mortis results because no more ATP is binding to the myosin head of the sarcomere in the muscle fibers.
So what does this have to do with us? No one has ever had rigor mortis on DNP or even severe cramping that has ever been documented. Furthermore, and to be more specific as to the uncoupler DNP, the electron gradient is collapsed and it runs unchecked at maximal as I have explained above, but as the gradient continues to increase electron transport becomes more difficult and the process SLOWS! Additionally, under very large artificially created electrochemical proton gradients, normal electron flow stops and may even result in
REVERSE electron transport flow!
All that was complicated and here is what it means. The respiration chain has a safety mechanism which allows for feedback controls to keep you from killing yourself. This is also another reason you will not want to do DNP for long periods. If you have taken enough as to create a large gradient the flow of electrons your burning of calories might even STOP! This will happen if you don’t eat enough calories and appears to be more detrimental on a high fat type diet because as you will see below, glucose can ameliorate charge differentials in the mitochondria and at the cell surface while on DNP.
DNP works NO MATTER WHAT! It uncouples the electron transport train (ETC) and there is nothing you can do to stop it. Some have said it doesn't work after a small dose or only after taking DNP for 2 days or so. I think they are the same kind of person who would take a drink of beer and say, 'Oh, I'm not drunk so alcohol doesn't work'! Alcohol still affects your brain cells and hormone levels and slows down the metabolism. Just because you didn't drink enough to be drunk doesn't mean nothing happens!
DNP is anti?proteolytic. This means DNP does not break down protein via the mechanism through which DNP works. DNP is actually better for you than cardio because exercise is PROTEOLYTIC which in itself is another reason to not be doing a high fat diet. High fat diets and exercise both lower insulin and raise glucagon levels which cause breakdown of protein. It is a proven fact that 10?20% of energy from exercise comes from AA breakdown as well as release of glutamine from the cells. DNP burns calories and does not affect hormone levels. Someone said something about it causing ketosis which is likely if you don't eat any carbs, but DNP is not, by itself going to affect insulin levels like glucose disposal agents metformin or phenformin.
DNP is not going to be advantageous to muscle building. THIS DOES NOT DISAGREE WITH WHAT I WROTE ABOVE! It is anti?proteolytic via its mode of action, BUT if there is not enough energy in the cells to build muscle it ain't gonna happen. Again, diet is key.
DNP is one of the SAFEST drugs you can take!!!!! Why? Am I nuts?! I am basing this on DNP's mode of action. DNP has one purpose and mechanism and affects nothing else, but the mitochondria. DNP does not affect hormone levels as do clen, ECA, T3, etc. It has no side affects that you don't expect such as shakes or cramping. Compare DNP to some of the Drugs the FDA has approved and look at their side effects and then tell me what is safer! HAHA!
After you read this study you need to ask yourself, need I say more? In the earlier paragraph on the mechanisms of DNP on the mitochondria I explained the safety mechanism which could keep DNP from being totally depleted of ATP. Some were saying ATP depletion would result in cell death. The study below illustrates another mechanism which I didn’t know about. The crux of it can be summarized by this sentence: ‘The failure to find a reduction in ATP concentration in either fibre type during prolonged exercise in the face of a progressive increase in the number of fibers showing little or no glycogen concentration suggests that protective mechanisms exist that prevent an energy crisis. The nature of these protective mechanisms remains to be elucidated. ‘ In other words,
When glycogen is gone there is a mechanism which keeps ATP from being depleted which is unknown at present!
Energy metabolism in human slow and fast twitch fibers during prolonged cycle exercise.
Author Ball?Burnett M; Green HJ; Houston ME
Address Department of Kinesiology, University of Waterloo, Ontario, Canada.
Source J Physiol (Lond), 437():257?67 1991 Jun
Abstract
1. The effects of prolonged exercise on energy metabolism in type I and type II muscle fibers in the vastus lateralis muscle were investigated in six male subjects (20.0 +/? 0.5 years, mean +/? S.E.M.) who performed one?legged cycling at 61% of maximum O2 consumption (VO2,max; determined with one leg) until fatigue or for a maximum of 2 h. 2. Analysis of pools of freeze?dried fibers obtained by needle biopsy and separated into specific types by the myofibrillar ATPase histochemical procedure indicated higher (P less than 0.05) lactate concentrations in type II fibers compared to type I fibers at 15 min (43.9 +/? 9.7 and 51.2 +/? 9.8 mmol (kg dry wt)?1) and at 60 min (18.2 +/? 4.7 and 25.9 +/? 6.5 mmol (kg dry wt)?1). No differences existed in lactate concentration between fibre types for pre?exercise (10.0 +/? 1.6 and 13.3 +/? 2.8 mmol (kg dry wt)?1) or post?exercise. 3. Glycogen degradation was most pronounced in type I fibers. By the end of exercise, glycogen concentration was 82.4 +/? 45 mmol glucosyl units (kg dry wt)?1 in type I fibers and 175 +/? 62 mmol glucosyl units (kg dry wt)?1 in type II fibers. 4. No significant changes in ATP and creatine phosphate (CrP) were found in either fibre type with exercise. 5. It is concluded that, at least for lactate and glycogen, fibre?specific differences are evident in prolonged submaximal exercise. The cause of the difference probably relates both to the unique energy metabolic characteristics of each fibre type and to the manner in which they are utilized during the exercise. 6. The failure to find a reduction in ATP concentration in either fibre type during prolonged exercise in the face of a progressive increase in the number of fibers showing little or no glycogen concentration suggests that protective mechanisms exist that prevent an energy crisis. The nature of these protective mechanisms remains to be elucidated.
DNP will make you breathe harder via a mechanism called cellular hypermetabolism. You aren’t going to die if you are breathing hard! DNP works by increasing ventilation and oxygen consumption via hypermetabolism of the cell. DNP makes you breath hard.
Role of tissue hypermetabolism in stimulation of ventilation by dinitrophenol.
Author Levine S
Source J Appl Physiol, 43(1):72?4 1977 Jul
Abstract
Several authors have hypothesized that tissue hypermetabolism accounts for increases in ventilation (VE) elicited by 2,4?dinitrophenol. However, some data in the literature indicate that stimulation of VE by isomers of dinitrophenol is unrelated to tissue metabolic rate. To test this latter concept, we compared three different isomers of dinitrophenol (i.e., 2,4?dinitrophenol (2,4?DNP), 2,5?dinitrophenol (2,5,?DNP), 2,6?dinitrophenol (2,6?DNP) with respect to stimulation of VE and with respect to stimulation of oxygen consumption (VO2). In all experiments, 3?4 mg/kg of one dinitrophenol isomer was administered to chloralose anesthetized dogs by intra?arterial infusion. 2,4?DNP elicited large increments in both VE and VO2, 2,6?DNP elicited moderate increments in both VE and VO2, whereas 2,5?DNP elicited small increments in both VE and VO2. These observations demonstrate a correlation between ventilatory and metabolic changes affected by isomers of dinitrophenol. Accordingly, these results are consistent with the hypothesis that ventilatory stimulation by congeners of dinitrophenol is related to tissue hypermetabolism.
How to feel good on 600mg of DNP!
This is not an advertisement because I sell more encapsulated DNP for research than I care to spend time making. Note: I sell it for ‘Research’
The longer I took DNP the more I realized those who had originally recommended DNP use were not looking at the big picture, and they had most likely never used it or mixed it themselves, and/or were just complete morons!
Myth #1.
You die on DNP from heat related to overdose.
Wrong!
You die from dehydration resulting in heat exhaustion and then heat stroke.
Myth #2.
You can do it on high fat-low carbohydrate type diets.
NO YOU CAN’T!
High fat-low carbohydrate diets are based on keeping your blood sugar and insulin low. DNP will also drive down your blood sugar, so if you want to have blurry vision due to low blood sugar and feel like hell, you go right ahead.
Glucose also has some beneficial cellular effects when used with DNP..
Myth #3. You will go blind.
Right! If you do high fat-low carbohydrate diets and don’t keep your blood sugar up and/or don’t take pyruvate.
Myth #4.
You can’t work out on DNP.
Yes you can, if you know what you are doing and which I am about to tell you.
As you may already know you, should be taking the following per day.
1200-1500mg magnesium in 2-3 divided doses.
2-3000mg vitamin C.
1200IU of vitamin E
200mcg of selenium.
1000-2000mg of calcium (can’t take it with the magnesium, though. Take it before bed)
Melatonin if you can’t sleep and it is also one of the best and cheapest anti-oxidants.
50mg of zinc a day
one iron tab as hemoglobin is a protein as well.
A potassium gluconate tab or two a day
Taurine at 3g a day.
Glutamine at 15g a day sublingual or with carb/protein drink.
I think taurine will be most beneficial for cramping and holding onto water. I have worked with some mountain bikers that were having trouble with cramps and had tried using the proverbial potassium supplementation cure and it didn’t work. I had them take the taurine and magnesium and the cramping went away. Taurine is also give to people who have leg cramps at night at a dosage of 3-6g a day resulting in total alleviation of the cramps. Clenbuterol depletes the liver of its taurine supply which changes the osmotic pressure and therefore stops T4-T3 conversion. Taking supplemental taurine can alleviate this.
Glutamine also regulates water, but is a bitch to take and unless you want your small intestine to absorb most of it you have to take it sublingual. You can fool the body a bit by putting it into your carb/protein drink after you work out or by taking 2g doses throughout the day. Glutamine ALSO causes a rise in insulin.
IF you are on clenbuterol, pyruvate and glycerol will help you a little, and I don't know why, but I still got some cramping on clen after an event even on P and G. The latest research I have indicates that the reason clen may cause cramping is due to TAURINE depletion so by taking the 3g a day taurine you should be able to ameliorate those effects as well and keep your thyroid levels normal as well.
In addition to the vitamins and minerals you should be taking:
3-6g Pyruvate (P)
3 tablespoons Glycerol (G)
If you can't get the G and P go right to the taurine which may be cheaper as well.
Glycerin (glycerol) is avail in the skin care section of your pharmacy and 4oz is about1?2 dollars or there are larger versions in white bottles and the brand name is H something. Just buy it from a vet and a gallon is around $20!
I felt like shit when I went above 400mg and sweat profusely on single large doses of 600mg and 800mg which lasted for 2 days. I weigh around 95kg (210).
The object of the DNP dosing with the glycerol and pyruvate was to test their benefits on what is considered an overdose of DNP while maintaining my exercise level in the middle of summer.
Here is what I was taking:
600mg of DNP which would be 6mg/kg which is well above the recommended 3-5mg.
DNP is said to have a half life of 36 hours and this is what I have based the following dosing scheme. I also have anecdotal evidence that DNP can last 48 hours or more. When I took an 800mg dose after 3 days on 300mg a day I sweat for 48 hours straight and that 800mg was the last dose I took.
You have to divide the 600mg into two doses of 300mg 12 hours apart.
After you hit your 600mg limit you don’t take the next 300mg for 36 HOURS from the first dose!
So, if I took the first dose at 6AM on Sunday morning and the second 300 mg dose at 6PM Sunday night, the 3rd dose would not be until 6PM on Monday evening. The fourth dose would again follow 12 hours from the 3rd which would be at 6AM on Tuesday morning.
I am also taking EC with this just for fun although at only 2 x a day for the EC to keep energy levels up and lessen the carb craving that goes with DNP.
How am I not sweating all over the place and not feeling like shit and/or dehydrating in the middle of summer while going on hour or longer rides in 85 plus heat?. Let me tell you again that I hated the way DNP made me feel.
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05-30-2002 02:50 PM
1sttimer
I pity the Fool!!
Registered: Apr 2002
Location:
Posts: 358
YOU HAVE TO TAKE GLYCEROL AND PYRUVATE!
I don’t know if you can take one without the other because I was using the glycerol (G) and pyruvate (P) to enhance endurance and stem dehydration which I am very prone to. I think, however, that you will have to do them both as there may be a synergistic benefit. I have taken G alone and while you have more water to hold on to, you just seem to sweat more which is also backed up by the research. The G-P cocktail let me drink ½ my normal volume of water on rides and that is what made me try the DNP-ECA experiment.
Glycerol dose. YOU ONLY NEED 1 TABLESPOON 3 TIMES A DAY! One in the morning, one in the afternoon and one right before bed. Don’t listen to the researchers who tell you to take 1 gram for every kg body weight 1-2 hours before and event. They are idiots and obviously have never taken it or asked the athletes how they feel. Let me tell you, you feel awful taking that much glycerol! You feel bloated and sometimes get a headache and you piss A LOT! 1 tablespoon 3 times a day comes out to ½ what they recommend to take 2 hours before an event. The glycerol keeps your muscles hydrated and limits the sweating. It will fight the dehydrating effects of the ECA. As we know, DNP is carbohydrate/fat specific and glycerol also is a 3 carbon carbohydrate source that can’t go to fat!. Glycerol also increases power output which may be an added benefit of the type of carb source it is. Glycerol is converted to glucose in the liver and in the liver is where it stays for the most part and does not, therefore, raise insulin levels.
Before I explain the pyruvate, let me tell you that glycerol and glycerin are the same thing! A good recipe for taking your glycerol is 1 packet of Kool-aid, 1/8 cup sugar, 1 tablespoon glycerol and 32-oz of water. The glycerol makes the kool-aid taste like OJ because there are alcohols and fermentation products in the OJ which the glycerol mimics.
Pyruvate dose. 2-5grams a day. Start out at 900mg or so 3 times a day and go up from there. I am at 1.5g 2-3 times a day and if you don’t work your way up it will give you gas and the runs. As I mentioned above, I think the P is working synergistically to hold on to the water in your muscles. Additionally, it is another 3 carbon energy source and/or it is manipulating the Krebs Cycle intermediates and allows for a different energy production pathway. Pyruvate changes/manipulates an ATP/energy pathway and decreases lactic acid output and if it ain’t the Krebs cycle I don’t really care. It works.
Some abstracts on the benefits of pyruvate.
Pyruvate and the heart and glucose and insulin.
Cardiac metabolism and electromechanics of human heart.
Author Prasad K
Source Recent Adv Stud Cardiac Struct Metab, 10():119?37 1975
Abstract
The effects of substrates on the metabolic inhibitor?induced changes in the action potential and contraction of papillary muscles obtained from patients undergoing corrective open?heart surgery were studied. Anoxia produced a marked shortening of the action potential duration and a decrease in the resting potential, rate of rise of action potential, effective refractory period, and contractility. In anoxic muscle, although glucose completely restored the action potential duration, effective refractory period, and resting potential to control levels, it was unable to completely restore the contractility to the control level. Substrate depletion and metabolic inhibitors (iodoacetate, dinitrophenol) produced effects similar to that of anoxia, but at a faster rate. Glucose restored the action potential and, to a lesser extent, contractility to the control level in dinitrophenol?treated muscle but was ineffective in so doing the iodoacetate?treated muscle. Pyruvate, however, was effective in restoring the action potential and contracility in iodoacetate?treated muscle. Pretreatment of the muscle with glucose and, particularly, with glucose plus insulin prevented the combined effects of anoxia and lack of glucose on the action potential and contractility for a prolonged period. These results suggest that intravenous infusion of glucose and insulin before and during surgery might prevent or reduced the effect of anoxia on the electrical and mechanical activity of the heart during open?heart surgery.
Pyruvate was able to restore the action potential (charge) of cells treated with DNP! Unfortunately, most of you won’t understand what an AP is even if I explained it, but I will tell you that restoring it is signiificant!
Now you have a recipe on how to feel good on an overdose of DNP! To recap you need:
3 Tablespoons glycerol 3x a day.
1g Pyruvate 3x a day.
Taurine at 3g a day.
DNP at 36 hour intervals.
If you start to feel bad, just drink some sugared pop or take some glucose or maltodextrin with your psuedo-OJ mix. The only drawback is that you will still smell rather bad and will emit a vinegar type odor although you won’t be sweating all over everything. If you notice you are starting to sweat more it is time for another glycerol dose.
Use of AS during DNP
You can use DNP during an AS cycle although the muscle loss from DNP is minimal, if any, so I don’t think this is the best use of your AS. If, however, you have hit a plateau the DNP for a week will help you break through that plateau in the subsequent week off. Now, I have experienced this, as have others, but as to whether or not it is from an upregulation or having a rush of T3 available or a type of overcompensation rebound is unknown, but it is cool and it happens..
Use of AS after DNP or dieting.
DNP and dieting BOTH stop conversion of T3-T4. T3 is responsible for protein synthesis. If you have been on a diet for 2 weeks or more your thyroid will be depressed and so will protein synthesis due to low T3. By adding AS you will be increasing protein synthesis while waiting for your thyroid to come back online so you won’t get fat right after a diet.
Use non-aromatizing AS like equipoise, ganabol, maxigan, trenbolone (finaplix or Anibolan), winny-V. Or you can use testosterone and an anti-aromatase like cytadren or arimidex. If you want to keep the fat off you HAVE TO use those anti-aromatazes with the testosterones and d-bols as they are the only ones that stop conversion of testosterone to estradiol. Estradiol conversion will make you fat, especially around the waist! If you have to use a testosterone and want to lose fat, I would use cytadren because it increase hormones which cause fat loss as well as increasing IGF-1 levels! (Bet you didn’t know that!) I would, however, not stay on cytadren longer than one month and dosage is one tab divided into 4 doses per day.
A line from a study showing that estrogen makes you fatter for the non-believers!
Obes Res 1995 Nov;3 Suppl 4:561S?568S
Topical fat reduction.
Greenway FL, Bray GA, Heber D
Department of Medicine, UCLA School of Medicine, Torrance, CA, USA.
The fat on women's thighs is more difficult to mobilize due to increased alpha?2 adrenergic receptor activity induced by estrogen. Lipolysis can be initiated through adipocyte receptor stimulation (beta adrenergic) or inhibition (adenosine or alpha?2 adrenergic) or by inhibition of
phosphodiesterase.
While yes, they talk about women and estrogen and fat, the mechanism is still absolute and spans the sexes. Estrogen makes fat cells resistant to lipolysis. Still want to take that test without and anti-estrogen?
Get to fat burning faster!
This is something you can try after you have used DNP once and know your tolerance and is a DNP manual exclusive! Your working dose will be around 400mg a day, correct? The first day, however, you are going to take 600mgs in divided doses! It takes DNP a couple days to build up so this won't bother you in the least. On the second day you will start taking 200mg caps every 8 hours until you are sweating or getting the heat you want. Now you are at your tolerance dose and you can space it out to the 36 hour dosing.
NEW!
Use a blood buffer to combat free radicals and lactic acid!
Add up to one tablespoon of baking soda, sodium citrate, or potassium citrate to your drink of choice throughout the day. A mix of the sodium and potassium would be best. Why?
What does DNP and exercise have in common? During high intensity exercise (supramaximal) ATP production is supplied by anaerobic glycolysis. This increases levels of H+ (protons) both inside and outside the cell via lactate and results in the feeling of fatique (Hermansen and Osnes; Sahlin) In the past, the use of sodium bicarbonate (baking soda) has been used and has been shown to decrease acidosis via buffering of the blood. The problem with baking soda is gastric distress and high salt intake with the recommended dosage of 300mg/kg which is around a tablespoon of baking soda for most people. Dosage for sodium citrate is 100mg-500mg per kg and did not give stomach problems to the users. Time to exhaustion was increased 15% which is the same as with baking soda. Alkalosis (making the blood basic) has been found to increase the rate of lactate and proton release from muscle into the blood. An increase in muscle pH causes phosphofructokinase inhibition (PFK) which is the controlling enzyme in glycogen utilization and therefore causes an increase in lactate formation. Those two mechanisms also will hold true for DNP as DNP releases protons which causes the heat. Get it out of the cell with the citrates.
Testomonial:
Hey animal just thought I’d let you know the great results I had with the DNP. I got tested hydrostatically and I'm at 4.8%. DNP is really the shit. Anyway, a buddy of mine is competing in a month and he's currently at 7% bf(he's about 190lbs) and he'd like to do it for two weeks. I understand that the lower one's bodyfat % the greater amount needed (I responded very well to 4mg/kilo but I was also dieting)
Questions I have answered for DNP users
Are all of the losses on DNP fat losses?
You can’t ever say ALL in the scientific world, but it is the best we can get!
Animal, you have been a big help already. I've got some questions for ya. I am 195#, and plan on taking 200 mg in evening and 200mg before bed. I also plan on taking pyruvate and glycerol (via your recommendation). I'll going to use a 8on/8off cycle.
1) Should I attempt to lift while on dnp?
Sure.
2) What dosage glycerol and pyruvate do you reccommend?
3 tablspoons a day on the G and 3g of the P
3) You said that you experienced an anabolic "burst" directly after coming off of dnp. Could this be contributed to your muscles reglycogenating themselves?
No, because I didn’t really get pumped, but strength went up.
or do you feel that this is genuine protein synthesis?
Yes, or nerve excitation/generation or a return of T3. Let me explain the nerve generation in more detail for a moment. When you do strength exercises of 5 reps or less you are training the nerves to fire more muscle cells and to fire those muscle cells in the sequence you want. Now, if we add DNP we are exhausting our muscle cells and they can’t fire as strongly. Result? Your nervous system trains more nerves to fire other muscle cells which had previously gone un or underused when energy stores were high. You are getting a nerve training session due to exhaustion! The more I think about it the more it is like those overtraining programs where you overtrain for a week and you get a rebound. That is what is happening except you are overtraining at the same weights due to the DNP.
Hehe. It is called overcompensation training and I’ll take it!
A user:
Found some info 'bout DNP "With even a low dosage, in the area of 3?5 mg/kg of body weight a day, it will rate your metabolic rate 30%. If this dosage is continued daily, it will raise your metabolism by 50%. At this rate you can burn about 1 lb. of fat a day."
Animal:
Now, let's think about this for a second. If metabolism can go from 30?50% that means there is a residual amount left over from the previous dose and therefore the 36hour clearance dosing schedule which I recommend. Furthermore, when I overdosed on 800mg I sweat for OVER 48 hours so this tells me that the half-life can be even longer in some circumstances. It is, nonetheless, up to you as to how you want to take it. If every 24 hours is tolerable for you, then do it.
A user:
That's not what I've noticed. At present I'v even gained some weight. I'm 98 kg now. I don't look a bit harder but maybe I shouldn't expect that after only 4 days.
You WILL hold onto to water! You WILL be depleting carbs from the muscle that will make you look flat! Most WILL NOT notice the benefits until a week or two later upon cessation of DNP. Some see benefits right away, but they appear to already have a bodyfat below 10%.
A speculator wrote:
For a person that is highly active and on a calorie restricted diet, DNP will deplete ATP within a matter of days. When this happens your body temperature will go back to normal. The only thing you can do at this point is supplement with in the dosage area of about 150 mcg/day."
Animal:
Believe me, you will feel wasted (tired) and LOSE muscle on the regimen and the liver does not control oxidative phosphorylation in every cell. You will still be hot regardless of your T3 levels.
Question:
Won't the conversion of T4-T3 come back and function again after discontinuing DNP administration?
Animal
Yes, and as long as you do some carbs at 600g a day for three days after.
Or do I have to look to get T3 as well?
Animal
Not really, if ATP was being ever totally depleted you would be cramping. Lack of ATP generation happens when you are what? DEAD!!!!!! It is called rigomortis and if people who write right about DNP had an education or an inkling about body chemistry and process they would know this! Total ATP depletion resulting in death of the cell is not possible. There is some safety mechanism and I imagine it is via the fat cells, but you will not deplete your ATP unless you are an anorexic or dead.
User:
And isn't a total lack of ATP what we want, so we can start burning fat instead of ATP?
Animal:
Wrong and this is not your fault, but again those who claim to be experts who are dispensing such disinformation. Once the ATP to ADP and to AMP is changed below a certain amount the cell gets it energy from another source which would be the fat. You are looking to burn the glycogen and then the fat is used. This does not mean ATP is gone!
Why is thermogenesis stopped if there isn't any ATP?
Animal:
Read above and it is never stopped. DNP NEVER stops working unless the proton gradient is severely altered. Even in such a case, parts of the mitochondria can have one direction of proton gradient while another section can have a DIFFERENT proton flow!
User:
Is this why you want a break after one week? To load up with ATP so thermogenesis can start again?
Animal:
No, so you don't feel like shit all the time and so you can get the liver converting T4-T3 again
Is a one?week?break enough? Or maybe too short if I'm in a hurry.
You could do DNP for 2 weeks or more if you want.
Wouldn't it be enough just to discontinue the DNP?cycle to let the liver start converting T4 to T3?
That is why you stop after a week!
Where are ATP?molecules stored?
In and/around the mitochondria and in the cytosol of the cell and ATP is attached to certain enzymes waiting for activation.
How much ATP do we have in storage?
That is a major calculation and I haven't looked for an answer, but I don’t think it is important as you can never get rid of all of it.
A speculator:
"The administration of DNP, at a dose of 3.5 mg per kilo, increases the total production of heat by about 40%, from the 3rd or 4th day. This increase of the metabolism is due MOSTLY to an increase in the combustion of the fat and a LITTLE to combustion of carbohydrates."
Any comments on this?
Animal:
Again, you are seeing a residual affect. The molecules that the mitochondria use for production of ATP can come from carbs or fat, but the important part is that it is not from muscle.
Another fact found in the same report as above:
"In prolonging the administration of the medication, one observes an increase of the tolerance of carbohydrates."
Does this mean we get increased insulin?sensitivity?
That is a weird sentence and I don't know what it means, but I think it means you will be more receptive to carbs. You now have increased your insulin sensitivity and this could explain the DNP users’ craving for carbs while using DNP.
.
So when I eat carbs (I've noticed that I start to sweat then) the body starts burning fat?
No, the body burns excess ATP and food intake itself is thermogenic.
Why simple sugars? That means I should walk around eating candy all day?
Candy is not really a simple sugar as it usually has fat or fructose with it.
You want a simple sugar every so often to get some insulin rise and some fructose will help recarb the liver as fructose is about 4 times better at recarbing the liver than glucose. Glucose is, BTW, 2 times at good at recarbing muscle when compared to fructose.
What happens with the carbs?
They are burned and insulin release and helps change charge on the cells.
Insulin is secreted. I've noticed that. (If it wouldn't I'd go glucose?high?'n?crazy.) Do I store carbs as glycogen?
AHAHA! So much for the speculators that say you have to do insulin!
You won't have time to make glycogen and the glucose will go right to ATP production.
What about cataracts and skin lesions?
That is a long term chronic dose situation and why you take pyruvate.
Have you noticed anything?
Yes, your sweat smells bad, but no lesions. Another reason you want simple sugars or insulin is that DNP starts to make your vision blurry if you are on a low carb diet.
Animals’ Analysis of someone else’s recommendations:
Comment
After 7 days, DNP dislodges T4 off the carrier proteins, allowing the T4 to be excreted rapidly.
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05-30-2002 02:52 PM
1sttimer
I pity the Fool!!
Registered: Apr 2002
Location:
Posts: 358
Animal:
THIS IS A FUNCTION OF THE PRESENCE OF ATP. END OF DISCUSSION! This has been proven with many people who have used pyruvate which provides an easily usable energy source. Most users only stay on it 7 days so the point would be moot. Since you have depleted the carbs from the liver you are changing the ability of the liver to change T4 to T3. This happens with ANY diet within 7 days. With DNP you have inhibition of conversion via heat (small factor I believe) and via glycogen depletion. This loss of water due to glycogen depletion changes the osmolarity of the liver cells and inhibits the conversion of T4-T3. Now, with the concomitant loss of water you have a loss of charge which is what we are trying to control with the taurine dosing..
Comment
I have used T3, and recorded the average elevated body temperature at day 4 on DNP. After 7 days, the temp will decline, so I use T3 2X a day to restore the elevation.
Animal.
Really? Most people, including myself, hardly notice any temperature change. I used T3 at 50mcg up to 100mcg on day 5 and never felt worse or more run down than any other DNP experiments I have done.
Comment:
It really doesn't matter how much or how long for the T3, because though excessive?looking, T3 blood level will be normal.
Animal:
This is NOT true because people have had their thyroid tested while on DNP and their thyroid levels were sky high. Excess thyroid can be responsible for what when calorie deprived? Muscle breakdown. Carbs are gone due to DNP. Your cells are going to be looking to scavenge energy so they are not going to have any protein synthesis because this requires energy. You are going to be in ketosis which is producing glucagon which is responsible for protein breakdown. You will, therefore, have no insulin which is responsible for anabolism of glycogen. You will have no blood sugar or liver glycogen left. Now what is going to happen?! Muscle breakdown. DNP is carb/fat specific and since there is no glycogen/glucose circulating due to high fat-low carbohydrate diet, where is the energy coming from? Ketones can't be made into carbs and about the only source of carbs you are going to have is the glycerol molecule which results from fat breakdown which is minimal. Now throw your excess T3 on there. Hmmm? Sounds like a recipe for muscle breakdown to me.
Comment:
Besdies, you'll get sick before you have to worry of being on T3 so long. Trust me, children: DNP for 7 days, and 7 off. You'll be much healthier.
Reply.
I totally disagree! Many of us have permanently lowered body temps due to clen?T3 usage which many of the same moron gurus recommended even when using clen for 2-3 weeks. The thyroid is going to see excess T3 in the blood and do you think it is going to want to produce more T4 and T3 on its own? This is what I really don't like about doing the T3, here. Yea, it is only for a week, but 2 weeks on clen which is not even T3 has fucked up many of us,. If your theory panned out then why couldn’t we do 1 week AS cycles or why have all the 2x2x2 cycles fallen into the pit of futility? I know we are talking different receptors, but they all still function via the negative feedback system.
Auxillary
(Consultation question)
After this Clen, DNP, and high fat diet experience I'm hoping to be down to around 7%BF. Which would leave me at about 165?170lbs. That is too small for me. I want to go on a cycle after that and try to put on a good 20lbs. I have a great diet for my cycle, so I know if I dont make the 20lbs gain I want its not because of nutrition. ( A problem i seem to always have). I wanted to know your thoughts on a cycle that I could really put on a good 20lbs. I know how much of your gains you keep depends on what you do prevent losses ( example: Clomid, and something to regulate cortisone levels, along with others, I have a gains keeper formula I plan to use). but If I do this I want to keep the majority of my gains. That’s why I wanted to include primo since you usually keep what you gain from primo.
Answer
Yea, but you don’t gain much and Eq or ganabol would be better as would fina.
Can you think of a good combo to add to primo for permanent MASS gains?????
Answer
Test (Tp, Tc, Te) or a trenbolone (fina, anibolan, parabolan). D-bol then fina always works nicely, too.
Maybe deca and sustanon or deca and omandren????
Answer:
Wouldn’t go with deca and sus and omna are more or less the same.
Any other s??? ? I have heard if you want to keep gains tests are not good to use
(enthanate, cyp etc.)
Answer:
BS. You have to know how to come off and not overtrain as you are coming off. Think about it. You have gotten stronger which is a result of nerve training. Now if you lift and let your muscles recover longer when off the AS you won’t lose your size!
. Do I have to take insulin while on DNP if I am taking equipoise and finaplix?
Answer:
No, not really and not if you are going to stay on only for a week at about 400mg or less DNP dose.
Do I have to take cytomel, clen or ECA stack while on DNP?
Answer:
I would take EC, but do the others after being careful to note that Clen and T3 will suppress your natural T3. Would be better to throw in tyramine and yohimbine or mazindol.
I have quite a bit of clen, and cytomel, but no ephedrine.
Answer:
You can sub in PPA or adipokinetix or pyruvate or nicotine or mazindol.
( I have never had a problem doing nicotine as a chew or as cigars and then quitting, but this is obviously not for all)
I didn't understand if you said whether or not to start with a low dosage of DNP or not.
Answer:
I would if you have never done it before just to see what your tolerance is.
Question:
Also, you told me that I should not take cytomel while I am using> the DNP but to use it after the DNP. I was under the impression that DNP suppresses the thyroid and that I should use the cytomel while using the DNP so I will keep burning fat. Would you please explain this to me?
Answer:
DNP alters the blood and liver glucose levels and THIS is what keeps the liver from converting T4?T3. If you eat normally this won't happen so drastically and T3 will return to normal soon after stopping DNP. Now, if you have low Blood sugar levels and you add T3 you are going to lose muscle as well as is seen in people that are on low calorie diets who supplement T3. T3 without the right energy and hormones stores is disastrous to muscle.
Other dieting stuff
ketotifen and upgrade of clen receptors, but you need 10 1mg tabs of ketotifen a day which will make you hungry and sleepy.
I was thinking of the efficacy or more like the ‘sense of adding t3 toDNP.
Well, if you are adding-T3 you are going to have a lot of T4 AND T3 floating around and the thyroid is going to read that as an exess and shut down T3 and T4 production.
Other cycles for DNP use
Why not do DNP in even smaller doses like that of ephedrine up to 100mg or so?. It will speed up the metabolism and cause a loss of weight without all the discomfort and t4-t3 conversion shutdown. Furthermore, by speeding up the metabolism it may help upgrade steriod receptors and clen receptors with much less discomfort for the user.
DNP seems to upgrade clen receptor sites as well as steroid receptor sites.
The rebound for the AS upgrade is only known from anecdotal feedback from myself and others, but if you increase the metabolism of the cell it only stands to reason that you are going to decrease the time it takes to regenerate the receptor sites. The ATP depletion and opening of ATP channels is also likely to be playing a part in these benefits as well, but that is research that probably won’t be done. So the channel part in the upgrade is just speculation.
Some may need to build?up the dose to start. I had to do it for 3 days and then do 800mg before I started to sweat like a pig for 2 days! Now moderate doses of 200mg make me sweat although not to the same extent, but at least I know I’ve taken it. Kinda like bee stings. You don't have any allergic reaction until one sting and then you get the benefits (problems) from one sting. I do know of a case with a women that had similiar results and said it wasn't working and even talked to w8 about it, but then she ordered more so this has to be what the problem was/is.
Response to someone that was throwing up and nauseated from DNP use.
You have low blood sugar!
This is a classic symptom which can occur with diabetics who use too much insulin. When I use too much insulin and then ride too soon after I would see spots. DNP caused me to see spots as well. DNP depletes all your blood sugar and glycogen first and this will give you low blood sugar, nausea, etc. That is why you want to get your insulin up with glucose once or twice a day on DNP and DO NOT do high fat diets on DNP. W8 will disagree with me on this, but when you look at the actions happening at the liver you will realize that high fat diets just extenuates the slowdown of T4 to T3 conversion.
Q: But when I’m off I’m gonna keep carbs almost non-existant to burn more fat, and take Adipokinetix to avoid a rebound off of the DNP.
A: DNP stops conversion of T4-T3 due to carb depletion so you may not want to do that although the Adipo is good. DNP, Adipo, clen, ECA, DNP would be a good way to go or do the clen right before a week of DNP, but only for a week.
Q: IM OFF MY CYCLE IN AWEEK. THEN IM GONNA TAKE CLOMID, PS,NOLVADEX, TO AVOID A LOSS INGAINS. THEN ITS CUTTING TIME.
A: Nolvadex and clomid are redundant, do one or the other. PS sucks, but if you already have it, then use it.
Good things about DNP:
Biological Study of Dinitro Drugs in Humans
By Dr. Jacques Bell
Translation Copyright 1996 Robert Ames
There is a fundamental difference between biological experimentation with dinitrophenol in humans and what was done in the laboratories of physiologists. These last are essentially interested in hyperthermia (Andre Mayer,Leon Binet, etc.). Yet, in medicine, the doses of dinitrophenol employed do not determine any elevation of temperature. The physiological effects, observed in these conditions, differ considerably from those made by the experimenter. It is thus for example that the animal in hyperthermia presents a polypnoea [rapid, shallow breathing], a hyperglycemia, a hypoglobulinemia that one does not observe with therapeutic doses; it is because experimental hyperthermia is essentially a combustion of carbohydrates, while therapeutic hypermetabolism is
mainly a combustion of lipids, as is shown by the lowering of respiratory quotient.
One shouldn't be surprised at these differences. The clinician uses strychnine as a tonic; the experimenter employs it to cause convulsions. The clinician uses adrenaline, at titrated doses, to produce a manageable hypertension; the physiologist, with massive doses causes acute edema of the lung.
Yet, to base the clinical use of adrenaline or of strychnine on acute edema of the lung or experimental convulsions, constitutes an obvious error. It is the same for dinitrophenol.
In France, besides, one uses almost exclusively dinitrophenyl?lysidine, which, according to the same terms of the study made by Professor Pouchet, "is easy to purify by crystallization, to easily modify the first of its components from the point of view of toxicity, dissolves easily in water, and, by addition of the methylglyoxalidine (lysidine)group, favors energetically the elimination of waste."
After Professor Pouchet, we have, in our thesis [1], demonstrated the superiority of this last product; in what follows, it is by comparison with him that we will study the biology of the dinitro drugs.
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05-30-2002 02:52 PM
1sttimer
I pity the Fool!!
Registered: Apr 2002
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We shall see, in order:
I. Their action on the basal metabolism,
II. Their visceral action,
III. Their nutritional action.
I. ACTION ON BASAL METABOLISM
After the experimental research of Magne, Mayer and Plantefol, in animals, the experiments of Cutting and Tainter has confirmed, in humans, that dinitrophenol is a drug which strongly increases the metabolism, exaggerating the oxidation process of the organism by direct action on the cellular metabolism. These authors have observed a rise of close to 20% after one hour, being able to attain 70% in ten hours and a tendency to return to normal at 24 hours if the administration of the medicine is not continued.
This increase is not due to a sympathetic deregulation. The dinitro treatment respects the autonomic nervous system, in an inverse way from thyroxine, which, at slimming doses, determines rapidly some tremors, insomnia, and a mental instability of the type "basedowien." [a thyroid illness where one secretes too much thyroid hormones]
In the thyroid illnesses, or the thyroid treatments, there is an inverse connection between the level of the basal metabolism and that of blood cholesterol, this being as much lower as the metabolism is higher. One doesn't observe similar phenomena in the course of dinitro treatment.
This fact indicates that the changes caused in the blood cholesterol in the course of thyroid treatment are directly linked with the thyroid medication and not at all to do with the elevation of the metabolism which is responsible for the reduction of obesity. Dinitrophenol has almost no action on the blood cholesterol. (Grant and Schube).
An attentive exploration of the nutritional changes in the course of dinitro treatment, in the cases of five obese women, has shown the following facts:
1. The administration of dinitrophenol, at a dose of 3.5 mg per kilo, increases the total production of heat by about 40%, from the 3rd or 4th day.
2. This increase of the metabolism is due mostly to an increase in the combustion of the fat and a little to combustion of carbohydrates.
3. Dinitrophenol does not attack cell tissue albumin and does not determine the fat loss to the expense of the muscles, contrary to thyroxine.
II. VISCERAL ACTION
Dinitro treatment respects the liver, the kidneys, the cardio?vascular system and the blood.
This innocuity for the principal visceral functions is without doubt one of the main reasons for the distribution of this therapy.
Tainter, Stockton and Cutting have reported a series of cases in which one had measured the plasma bile index and determined the test of Van de Bergh. Their analyses demonstrate, beyond a doubt, that the liver does not suffer any damage in the course of dinitro treatment.
Experimental studies on animals do not show toxic effects of dinitrophenol on the kidney (Taitner, Cutting, Woodand Proescher). Anatomical?pathological examinations of animals, even those which died from a massive dose of dinitrophenol, do not reveal any important anatomical changes, except a small degree of cytolysis. Clinical documents are not abundant, but, on the whole, do not seem to demonstrate that dinitrophenol is toxic for the kidneys.
As T.L. Schulte and M.L. Tainter wrote, "it doesn't seem that dinitrophenol at usual clinical doses is likely to harm the kidneys."
Dinitrophenol is remarkable for its absence of effect on the cardio?vascular system. Even when the basal metabolism is found elevated to significant levels, there is no change in the rhythm of the pulse (Rosenblum).
On this point, dinitrophenol differs from all the other metabolic accelerants known. It is an observation that all the clinicians, today, have had occasion to make.
All the clinicians know that, contrary to thyroxine, dinitrophenol is absolutely devoid of toxicity for the heart.
The research of Professor Loeper and of his students has demonstrated the physiological and clinical importance of myocardiac glycogen. Extensive studies by P.N. Taussig have shown that dinitrophenol does not reduce cardiac glycogen at all and that, on this point, it differs completely from thyroxine.
III. ACTION ON NUTRITION
The influence of dinitro therapy on nutrition has been the object of a very important clinical study.
"One does not observe variations in the elimination of chlorine; eliminated phosphorus varies sometimes more, sometimes less, the elimination of sulphur increases slightly, especially in the form of sulphur conjugates, urines show a small increase of total nitrogen and of urea." (Prof. Pouchet).
It is a well known fact that the administration of thyroid extract or hyperthyroidism is accompanied by an increased secretion of calcium and of phosphorus. This calcium and phosphorus in the urine are not due to the acceleration of metabolism, as one does not observe these facts either during fever, nor in the course of leukemias which raise the metabolism (J.C. Aub, N.B. Bauer, C.I. Heath, Alright, Bauer and Aub).
Thyroxine reduces bone density.
With dinitrophenol, nothing of the sort is observed. The experiments of Clarence L. Robbins show that dinitrophenol, in spite of the elevation of the metabolism that it produces, does not cause any increase of the loss of calcium or of phosphorus. An increase of 37% in the basal metabolism, caused by the ingestion of dinitrophenol, does not lead to modification in the excretion of these elements.
In normal individuals, when one administers dinitrophenol during a short period, it produces a small elevation of reduced substances in the blood after fasting (although one would not be able to call this hyperglycemia). When one administers the medication over a longer period, this phenomenon is not produced and there is a marked elevation of the tolerance to carbohydrates.
In diabetics, following treatments of short duration, the results are variable, the tolerance to glucose being as often increased as it is decreased, with parallel changes in the fasting blood sugar level. But, in prolonging the administration of the medication, one observes an increase of the tolerance of carbohydrates. Anyway, in basing himself on the study of 32 cases of diabetes, Simkins concludes that dinitrophenol is not toxic for diabetics. Here marks that this observation goes counter to some assertions that have been a little prematurely advanced.
Dinitrophenyl?lysidine at therapeutic doses therefore has an action on the organism which is completely physiological. This action has been demonstrated in obesity where it has been compared to the actions of thyroid medication and physical exercise.
The existence of obesities of glandular origin, especially by thyroid insufficiency, has resulted in the use of thyroxine in numerous subjects.
"This wasn't without inconveniences, sometimes grave, characterized especially by cardiac and nervous troubles; the effective dose of thyroxine is, in fact, very close to the toxic dose. Further, we has frequently seen these accidents persisting after the administration even of a single dose, which leads to the impossibility of stopping them immediately by a simple suspension of the medication. Yet, from the point of view of its specific action on the basal metabolism, dinitrophenol offers this precious advantage that the cessation of its use at the slightest appearance of signs indicating an imminence of intoxication results immediately in the arrest of those symptoms."
(Professor Pouchet).
Finally, thyroxine causes a nitrogen malnutrition: it burns the muscle and fatigues the heart.
Dinitrophenol?lysidine, to the contrary, causes a lipid?glycemic loss: it is the elimination of reserve materials without attacking visceral and muscle tissue.
As for physical exercise, it seems to act exactly like dinitro therapy. Marcowitz, in his communication to the Academy of Medicine of Toronto on October 9, 1934, based on 90 cases of obesity, having followed this treatment during a period of 16 months, concludes that its action may be succinctly described in saying that the effects on the organism are similar to those of physical exercises.
The fact is besides established by physiologists, since dinitrophenol raises thermogenesis and not the metabolic quotient.
All the clinicians know actually that dinitro medication is irreplaceable in cases of monstrous obesities which prevent all exercise. It can be used in the obese for whom occupations, life style or cardiac troubles do not permit physical exercises. It is indispensible for the grossly obese in cases of abdominal operations and immobilization due to illness (inflammation of fallopian tubes, appendicitis, etc.) for which there is an urgency to obtain a reduction of subcutaneous fat.
But this clinical use has not been able to be extended other than when the experimental research pursued on humans, with a dinitro drug free from impurities, has been able to demonstrate the biological effects of it in a very precise way.
Studies to ponder which helps you see where my answers have come from.
Here is why you need to eat a regular diet:
Subject: DNP, Insulin, and ATP?sensitive Potassium channels
[Some of the following is speculative. Caveat lector.]
Ion channels are membrane proteins that control the flux of ions across an otherwise impermeable cell membrane. Potassium(K) channels were first decribed by Noma [1] in 1983, and later in 1991 the ATP?sensitive K channel (KATP) was described by the same researcher [2]. Potassium channels determine cell membrane potential.
KATP channels exist in most excitable cells. They are regulated by the intracellular level of ATP as well as by various nucleotide diphosphates, pH and lactate concentrations. The activity of KATP channels is inhibited by increasing the intracellular ATP concentration. Closure of these channels in response to glucose metabolism depolarizes the cell, stimulating voltage?dependent electrical activity, and calcium ion (Ca) entry. In the pancreatic beta cells, an increase in blood sugar level leads to an elevated ATP/ADP ratio, which in turn inhibits KATP channels, so as to alter the membrane potential and cause insulin release. It is accompanied by increases in respiratory rate, pyridine and flavin nucleotide reduction state, and intracellular pH [3].
Thus, the KATP channel couples nutrient metabolism to the membrane potential.
o Increase in blood glucose ?> increase in glucose metabolism ?> increase in intracellular ATP ?> inhibition of KATP channel.
o Channel CLOSED: cell depolarized, Ca++ uptake, insulin exocytosis.
KATP channels play an important role in the control of vascular tone [4]. Polarization following potassium channel activation
(opening) results in lessened calcium influx and smooth muscle relaxation.
o KATP channel BLOCKED ?> vascular tone increases.
o KATP channel ACTIVATED ?> vascular tone decreases.
Besides being regulated by intracellular signals, potassium channels may also be regulated by membrane potential. Thus, in excitable cells in the heart, muscle, and nervous system, voltage?gated potassium channels are activated during an action potential; the activities of these potassium channels determine to a large extent the shape of the action potential, hence the
strength of the signaling.
o KATP BLOCKED ?> more strength
o KATP ACTIVATED ?> less strength
Drugs which block KATP channels: tolbutamide, glyburide, glibenclamide.
Drugs which activate KATP channels: Prostaglandin E2 and I2, adenosine,
lemakalim.
Drugs which activate K channels: pinacidil, cromakalim.
Mitochondria also contain a K+ channel that causes rapid K+ uptake when open [5].
DNP
What happens when someone takes the uncoupler dinitrophenol (DNP)? Blood glucose will result in increased metabolism, but the level of ATP in the cell does not increase! In fact, it is depleted. So in this case, the KATP channel is not inhibited, and it stays open. Calcium is not taken into the cell, and insulin is not released. The person taking DNP has in effect given himself temporary diabetes.
(Animal; another study shows that insulin internalization is also affected so taking insulin is useless)
Insulin is needed to facilitate the uptake of glucose into cardiac, skeletal, and adipose tissue, and to convert glucose to glycogen in the liver. It is anti?proteolytic and protects against the various ailments commonly seen in diabetics, such as vision problems and polyneuropathy. Not coincidentally, the same problems can result from ingesting DNP.
This is why, when one takes DNP, one also needs to take exogenous insulin.Since the KATP channel remains open, vascular and muscular tone relax. Probably blood pressure will decrease. Strength will diminish.
It would seem that an antidote for DNP might be anything that causes the KATP channel to close, for example the drug glibenclamide.
Animal;
Why all this is a good story we do have to look at what he said in the beginning as in caveat lector. While his speculation on KATP channels and the need for insulin is understood-, his mechanisms are a bit incorrect. DNP causes an internalization of the receptor so you now have a cell that is desensitized to insulin and all the insulin in the world will not help that. Second, the KATP channels can be controlled with pyruvate.
Studies
DNP causes insulin insensitivity by preventing internalization of the receptor.
Insulin internalization into monocytes is decreased in patients with type II diabetes mellitus.
Author Trischitta V; Gullo D; Squatrito S; Pezzino V; Goldfine ID; Vigneri R
Source J Clin Endocrinol Metab, 62(3):522?8 1986 Mar
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05-30-2002 02:53 PM
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Abstract
We studied the internalization of [125I]insulin into circulating human monocytes, a cell type widely used for insulin binding studies. The internalization of [125I]insulin was assessed by both an acid extraction technique, which removes surface?bound insulin but not intracellular insulin, and by a trypsinization technique, which removes cell surface?bound hormone. After 5 h of incubation at 22 C, over 40% of the total cell?associated [125I]insulin was internalized into monocytes of normal subjects. This internalization was temperature dependent; the fraction of internalized hormone was progressively decreased when the incubation temperature was reduced from 37 to 4 C. Treatment of monocytes with increasing concentrations of 2,4?dinitrophenol also decreased [125I]insulin internalization, whereas dansylcadaverine, an inhibitor of transglutaminase, had no effect. Analysis by gel filtration of the internalized labeled hormone after 4 h of incubation at 22 C indicated that 50?60% of the label was degraded insulin, but detectable intact insulin was still present. Internalization of insulin was then studied in monocytes from eight obese patients (161% of ideal body weight) with type II diabetes mellitus. After 4 h of incubation at 22 C, the specific total monocyte?associated [125I]insulin was decreased compared to that in cells from 7 normal subjects [6.02 +/? 0.38% (+/? SE) vs. 3.91 +/? 0.31% of the total; P less than 0.001]. Moreover, the percentage of hormone that was internalized was also decreased from 41.4 +/? 1.2% of the total to 28.9 +/? 1.8% (P less than 0.001). In 20 nondiabetic obese subjects, specific cell?associated [125I]insulin was reduced to 3.9 +/? 0.3% (P less than 0.001). However, compared to that in normal subjects, the percentage of hormone that was internalized was not decreased (39.7 +/? 3.51% of the total). The present findings indicate that human circulating monocytes internalize [125I]insulin; this process is temperature and energy dependent; and monocytes from obese type II diabetic patients have a significantly decreased ability to internalize insulin. This decreased internalization may play a role in the cellular resistance to insulin that occurs in these patients.
DNP enhances binding of insulin to the receptor, but does not internalized it.
The effect of phenformin and other adenosine triphosphate (ATP)?lowering agents on insulin binding to IM?9 human cultured lymphocytes.
Author Vigneri R; Maddux B; Goldfine ID
Source J Cell Biochem, 24(2):177?86 1984
Abstract
In the present study, we investigated the mechanism by which the antidiabetic drug phenformin increases insulin binding to its receptors in IM?9 human cultured lymphocytes. After a 24?hr preincubation, phenformin induced a twofold increase in specific 125I?insulin binding, and removal of phenformin was followed 6 hr later by a return in binding to control levels. This effect of phenformin on insulin binding was not a consequence of either inhibition of cell growth, changes in cellular cyclic adenosine monophosphate (AMP) levels, or changes in guanosine triphosphate (GTP) content. Since phenformin is known to inhibit various aspects of cellular energy metabolism, the relationship between 125I?insulin binding and energy metabolism in IM?9 cells was investigated. The phenformin?induced increase in insulin binding to IM?9 cells was related to a time? and dose?dependent decrease in ATP levels. Other agents that lowered ATP levels, including antimycin, dinitrophenol, and 2?deoxyglucose, also raised insulin binding. These studies indicated, therefore, that phenformin enhances insulin binding to receptors on IM?9 cells and that this effect on insulin receptors may be related to alterations in metabolic functions that are reflected by a lowering of ATP levels.
DNP blocks all internalization so is more insulin going to help? No.
Evidence for two independent pathways of insulin?receptor internalization in hepatocytes and hepatoma cells.
Author McClain DA; Olefsky JM
Address Department of Medicine, Veterans Administration Medical Center, San Diego 92161.
Source Diabetes, 37(6):806?15 1988 Jun
Abstract
A study of insulin?receptor internalization and recycling was undertaken in primary cultures of rat hepatocytes and a human hepatoma cell line (HepG2). Receptors were quantitated by measuring 125I?insulin binding to partially purified soluble receptor preparations from untreated cells (total receptors) and trypsinized cells (intracellular receptors). In resting HepG2 cells, exposure to insulin results in internalization of insulin receptors, the rate and extent of which is dependent on the insulin concentration. However, receptors do not accumulate inside the cell in proportion to the higher rates of internalization at high concentrations of insulin. This lack of accumulation is explained by much higher recycling rates after exposure to high concentrations of insulin. Similar results were noted for primary cultures of rat hepatocytes. These results imply qualitatively different fates for receptors internalized after exposure to different concentrations of insulin. To further investigate the possibility of different pathways for insulin?receptor internalization and processing, cells in low (1 ng/ml) or high (100 ng/ml) concentrations of insulin were exposed to drugs or treatments known to affect receptor metabolism. Hypotonic shock and hypokalemia, which arrest coated?pit formation, blocked internalization of insulin and insulin receptors at low concentrations of insulin but allowed internalization in response to high concentrations of insulin. The lysosomotropic drugs monensin and chloroquine caused intracellular accumulation of insulin and its receptors internalized at low concentrations of insulin but had a relatively smaller effect on receptors internalized at high concentrations of insulin. All internalization is blocked by 2,4?dinitrophenol. We conclude that high doses of insulin lead to insulin?receptor internalization and recycling through a pathway that is functionally distinct from the pathway taken by receptors internalized by low (physiologic) concentrations of insulin. The pharmacologic experiments raise the possibility that the high?dose pathway, unlike the low?dose pathway, may proceed independently of coated pits and endosomal acidification.
Degradation of insulin by human fibroblasts: effects of inhibitors of pinocytosis and lysosomal activity.
Author Kooistra T; Lloyd JB
Source Int J Biochem, 17(7):805?11 1985
Abstract
The role of the pinosome?lysosome pathway in the degradation of 125I?labelled bovine insulin by cultured human fibroblasts was examined by comparing the effects of various known inhibitors of pinocytosis and lysosomal degradation on the uptake and degradation of 125I?labelled polyvinylpyrrolidone, formaldehyde?denatured bovine serum albumin and bovine insulin by these cells. Fibroblasts incubated with polyvinylpyrrolidone steadily accumulate this substrate, whereas incubations with insulin or denatured albumin led to the progressive appearance in the culture medium of [125I]iodotyrosine. Inhibitors of pinocytosis (bacitracin, colchicine and monensin), metabolic inhibitors (2,4?dinitrophenol and NaF), lysosomotropic agents (chloroquine and NH4Cl) and an inhibitor of cysteine?proteinases (leupeptin) decreased the rate of uptake of polyvinylpyrrolidone and denatured albumin very similarly, but only bacitracin had an effect on the processing of insulin. Chloroquine, NH4Cl and leupeptin strongly inhibited the digestion of denatured albumin, but not of insulin. The different responses to the modifiers, with polyvinylpyrrolidone and denatured albumin on the one hand and insulin on the other, suggest that insulin degradation can occur by a non?lysosomal pathway. The very strong inhibitory effect of bacitracin on insulin processing by fibroblasts may point to an important role of plasma membrane proteinases in insulin degradation.
References:
1. Noma A. 1983. Nature 305: 147.
2. Noma A, Takano M. 1991. The ATP?sensitive K+ channel. Jpn J Physiol 41(1):77?87.
3. Civelek VN, Deeney JT, et al. 1996. Temporal sequence of metabolic and ionic events in glucose?stimulated clonal
pancreatic?cells. Biochem. J. 315: 1015?1019. Boston University Medical Center.
4. Nichols, C.G. and Lederer, W.J. 1991. ATP?sensitive potassium channels in the cardiovascular system. American Journal
of Physiology 261:H1675?H1686.
5. Paucek, P, Mironova, G, et al. 1992 "Reconstitution and partial purification of the glibenclamide?sensitive, ATP?dependent
K+ channel from rat liver and beef heart mitochondria," J. Biol. Chem. 267, 26062.
6. Nakamura S. 1989. Glucose reverses DNP induced changes in action potentials. Cardiovascular Res. 23(4):286?294.
Here is the scare story that is going around on cataract. I raise this because of the connection with this problem and insulin and the previous story. I was starting to see spots and when I took insulin they went away. The myopia stops when DNP is discontinued. Note, that this was a chronic user below.
Subject: DNP and Cataracts
MDGADPC has kindly sent me a photocopy from the French journal Annales des Oculistes, concerning the effects of DNP on the eyes. Since this paper may be of some general interest, I have translated it and attach it below.
For those who may be unaware, DNP or dinitrophenol is a toxic compound which was used for weight loss in the 1930’s. It was withdrawn from the market as a result of severe side effects, including deaths, but recently it has been suggested that it could have a role in the contest preparation of elite bodybuilders.
One point to consider in the text below is that cataracts may develop 6 to 12 months after the DNP treatment is completed.
Note: the intake of DNP was chronic and continuous.
Citation: Sedan, Jean. 1939. A propos de deux cas de cataracte par phenols dinitres. Annales d’Oculistes. 176:191.
Translation Copyright 1996 by Robert Ames. All rights reserved. Concerning Two Cases of Cataract Caused by Dinitrophenol By Jean Sedan (Marseille)
The implementation of the treatment for obesity by dinitrophenol dates only from 1933, the year when it was suddenly and rapidly put in the limelight by the work of the Americans Tainter, Mehrtens and Cutting.
These authors have established that the ingestion of dinitrophenol accelerates metabolism, causing a marked elevation in temperature. It seemed that dinitrophenol was a specially effective treatment for obesity. In 1936, Horner estimated that in the first 15 months following the appearance of the medication in the market, one hundred thousand persons used it to lose weight.
Note: 100,000 people used it.
Incidents and accidents multiplied and appeared sufficiently serious that the American Medical Association warned the public against the dangers of unsupervised treatment.
Here we discuss only the case of cataracts, which Horner had said that it occurs in one case in 1000 treatments. At the end of this report we will note the principle bibliographic references concerning the American literature devoted to the subject and which is of a great value, but we wish to emphasize how the European work and especially French are on the other hand still
rare and even exceptional.
One can say that it is by the work of Onfray and Gilbert Dreyfus presented to the Congress of the S.F.O. [Societe Francaisedes Oculistes?] in 1937 that French opthamologists had their attention drawn to the subject. This remarkably precise work is enriched by two observations of which one is due to Doctor A. Gallois, of Besancon. We frequently reference this, for it contains in addition to minutely observed details, important physio?pathogenic considerations and a complete history of the subject.
Apart from this work, we should also to point out the observations of Van de Hoeve and Polak?Daniels published in Hollandin 1936, as well as the French summaries and reviews of Halbron on cataracts and of Laignel?Lavastine on dinitrophenol intoxication.
Finally, we emphasize the interest of the work of Vogt on the cataracts caused by dinitrophenol in Switzerland and of G.Ciotola of those caused by alpha dinitrophenol in Italy, both published in 1937. The same year, Stein and Crevecoeur pointed out that in their opinion this affectation was, when all is said and done, quite rare if one thinks of the enormous dissemination of
dinitro treatment. This was also the opinion of Andre Mayer, based on the fact that despite the considerable number of intoxications by dintrophenol observed in munitions factories, no cases of cataracts have been noted.
Note: Because they were not intoxicated with it continuously.
Finally, in 1938, Carlotti and Rivoire de Nice presented a case of cataract by dintrophenyl?lysidine which developed "with almost lightning?like rapidity."
It was possible for us to observe two very demonstrative cases. In one there was an arrest of development of opacity after the patient stopped taking dinitrophenol, which is more than a rarity, a real exception in the pathological history of dinitrophenol cataracts.
OBSERVATION I.—Mme. K... Lea, 32 years old presented herself to me in December 1937 with a marked lowering of the vision of both eyes, which began a few weeks earlier, developing extremely fast and was all the more disturbing since she works at a very visual profession in the editing of a newspaper and as she is especially partial to this pleasant and remunerative
position. I noticed a beginning of bilateral cataract appearing striated and fleecy which is found almost constantly in the description of toxic lens opacities of this kind. The opacity is situated mainly at the level of the equator of the lens, but also involves the posterior part of the central mass. The vision is only 4/10 in the right and 5/10 in the left, these two acuities correctable to 7/10 O.D.G. ?? 2.50.
Mme K... thus learned that she was rapidly becoming myopic.
The most minute research were done in view of identifying a possible cause of this bilateral cataract. All the blood and urine tests were negative. Very complete clinical examinations by Doctor P..., referring physician, point to the same conclusion that it is impossible to relieve Mmme. K...’s pathological process at all.
It is then that I thought of asking her about the possibility of a dinitrophenol anti?obesity treatment, even though the corpulence of my client did not seem excessive. She told me then of having taken two pills each day of 0.30 grams of dinitrophenol in series of ten days with a rest of 15 days, for the past year and a half.
Note: That is a long time!
She had, without the least dietary restriction, lost 19 kilograms out of 87 [42 pounds out of 191]. It was at that point that she began complaining about her vision.
Note: She lost a lot of weight, too!
I wasn’t aware of the topic at that time except by the short summaries of American works, but I didn’t hesitate to warn her against what I considered to be the real origin of her sickness. Very anxious about her state, she was easily convinced and stopped that therapy suddenly and definitively.
I had the opportunity to see her in March, July and October 1938 and I noticed with great interest the complete arrest in the development of these cataracts, which accompanied in very precise fashion the progressive and total disappearance of myopia to the extent that although it was possible to note an appreciable modification in the lens opacities, the visual acuity was spontaneously returned to 7/10 (uncorrected) at the end of October 1938.
We add that Mme. K..., doubly happy, very far from regaining weight in spite of the renunciation of dinitrophenol, had lost another 5 kilos by a very strict nutritional discipline complemented with rigorous gymnastic practices and the introduction into her life of a new intoxification, certainly less dangerous than the preceeding—tea.
In this case, the role played by the toxin in the opacification of the lens seems to us demonstrated in an almost experimental fashion by the disappearance of the myopia at the moment of the cessation of the intoxification and even more by the incontestable and enduring stabilization of the state of opacities that maintained itself for six months. In contrast, the development was very sudden in a month before the application of this measure. It is presumed that only the precocity of the requested medical consultation and of the medical diagnostic given, has permitted a stop in the development of this toxic cataract—a completely unusual phenomenon.
We emphasize that the treatment had included plainly excessive doses and that however the opacification only appeared late in the treatment. On this topic remember that in the discussion which followed the expose made to the S.F.O. in 1937 by MM.Onfray and Gilbert Dreyfus?Arruga, who had occasion to observe and operate in America [illegible] ... don’t generally appear except at the end of many months and even sometimes six to twelve months after the cessation of treatment. These late?developing cataracts are almost always bilateral.
OBSERVATION II.
[Not included. Summary: A 32 year old woman weighing 90 kg. (198 pounds) began taking dinitrophenol on February 1st,
1937. She began with 9 to 10 pills daily, each being 30 mg. of DNP. After a week she increased the dose to 12 pills / day
(360 mg.). At this dosage she lost 800 grams per week, or 10 kg. (22 pounds) in three months, without changing her diet. She
stopped taking DNP for four months and then began again. So she took 32.4 grams of DNP in the first 90 days and the same
amount in the second course. American reports indicated that cataracts had resulted from doses as small as 100 mg. per day
for a total of 40 grams.
On June 10th 1938, after several days in a very sunny seaside resort, the patient began to lose vision in her left eye, and on July 12th, the other eye was affected. By August 1st she was unable to see to drive. By September she was blind. Fortunately, surgery produced favorable results.]
It is necessary, indeed, to publicize cases in order to attract the attention of physicians and of the French public to the danger of intoxification by dinitrophenol. The fact that we have been able to stabilize, if not make regress one cataract of this class by stopping all toxic ingestion is but another reason which compels us to make it known.
These arguments and our observations are so needed to challenge the imagination and influence young women against harmful weight loss techniques that the work appears discouraging.
Indeed, in ending, we repeat the unlikely remark that our second patient made to us upon taking leave following the success of her first operation: "And now, Doctor, do not oppose my taking of dinitrophenol since I no longer risk having cataracts."
My contribution to the articles forum....thanks to Animal (I might not like the guy, but he has Mr. O sized brain)
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