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  #601  
Unread 10-04-2013, 01:58 AM
MFS MFS is offline
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Forgot to factor in the half, you were right.
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  #602  
Unread 10-04-2013, 08:38 PM
niloluiz niloluiz is offline
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Quote:
Originally Posted by funkypigeon View Post
One thing i have notice though is that if i do my carb refeed on the 9th day instead of the 11th i still have DNP in my system and my muscles feel just as flat as the day before but i feel and visually look fatter and more squishy. I have even carbed up on 6000kcal and still felt flat the next day and look fatter, i was just curious if any of you know is it possible for de novo lipogenesis to occur with depleted glycogen stores, i mean could the carbs be converted to fat without having to replenish glycogen stores?
I understand that any dietary fat consumed could go straight to fat stores, but i make sure my fat is very low during my carb ups, i usually stay around 30-40g.
Have any of you had any other experiences like this?
Or do any of you know of any studies that may answer or even lead me on the right tracks to answering my question?
I have found i quite hard to find any relevant studies on DNP in humans or other animals for that matter using google scholar, i have just started university studying Biochemistry and i am hoping that i will be able to get access of many other studies soon.
Any tips or advice would be GREATLY appreciated.
This was also discussed before in this thread so try catching up with the pages you didn't read yet. There's nothing to support the notion that DNP prevents glycogen refilling, specially in your case after 48h of discontinuing.

DNP tends to cause bloatedness in some people and with a 6k carb refeed.... that alone would cause a nice water retention (unless meticulously done to avoid "spilling"). By my own experience with doing refeeds while on DNP, glycogen will be normally refilled. The performance/muscular throughput is clearly there after the refeed.

The overall fatigue sensation is probably why you feel like no improvement happened... but it's there, even if it's not the same as it would be without DNP. And visually you will look smooth..... only after about 5-10 days discontinuing DNP you will look your best (by then most of excess water you may be carrying will be shed) same goes for scale weight.

Quote:
Originally Posted by Unraveller View Post
...Also, using this math, and I hesitate to say this.... You could front load 600mg (for the very first dose), then switch to 200mg every day after. This will give you an immediate and rather consistent 600mg bloodstream level. This works because the 600mg will breakdown to 420, then get pushed up to 620 by next 200mg dose etc, etc...
24-36h is a rough estimate. Empirically the peak effect for a given dosage is perceived around 3-5 days of steady consumption. I saw topics in other forums with charts using the standard half-life formula to give an idea of accumulation and it's basically what you exemplified above.

However do note that pharmacokinetics of DNP in humans are mostly unknown and as pointed at wikipedia(with references), there's no consensus on research about that:
Oddly, more recent papers give an array of possible half-lives, ranging from 3 hours, to 514 days. Other recent papers maintain that the half-life in humans is unknown.
http://en.wikipedia.org/wiki/2,4-Din...armacokinetics
Quote:
Originally Posted by MFS View Post
I read the thread, I'm not arguing that it cannot cause neuropathy. I'm interested in the conditions under which it causes it. As was pointed out with the 36 hour half-life the serum concentrations are actively increasing as you progress through a cycle up to about day 6-7. Simply because you become resistant to the metabolic effects of the drug does not necessarily imply that you're any more resistant to any potential toxicological effects of the drug so ramping on a constant dosage for long periods of time (say 200mg daily -> 500mg daily) is very different than a 5-7 day cycle where you're running at peak concentration for only 3-4 days before dropping back down.
Like I said in my previous post the cause is unknown with evidence suggesting that either dosage/duration is relevant or that only predisposition is relevant and I believe both may be right. I will get back to that issue soon.
Regarding tolerance to the metabolic effect x tolerance to the potential toxic effects I agree and there's reason to be concerned with that. I think even tolerant people should mind the maximum dosage they would allow, even if the perceived metabolic effects are mild. One major reason is that toxicokinetics / distribution inside the body is not properly researched nor fully understood.
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  #603  
Unread 10-07-2013, 02:30 AM
niloluiz niloluiz is offline
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I mentioned before the ATSDR Toxicological Profile about DNPs and within the context of everything previously discussed in this thread, specially the peripheral neuropathy issue, there's some points worth discussing here.

Also ajntorinj had access to the JAMA article about DNP induced peripheral neuropathy and was kind enough to send a copy my way. The article is short but it also provides data for some important observations as well.

Starting with the ATSDR profile: http://www.atsdr.cdc.gov/toxprofiles...id=729&tid=132

It cover many topics from environmental contamination by dinitrophenols to different exposure routes and the focus of this document is basically to cover all known effects of DNP within the body and how to deal with it or in their own words: "The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects information for the hazardous substance described here."

It relies heavily on existent DNP research, specially from the time when it was being used for weight loss in the 30s so it's a valuable source of information and a good starting point for further research as it provides references for everything.

The biggest caveat is that the purpose being what it is, putting the effective risks into proper context is not the goal of this document and to further compound the distortions they transform useful information (absolute/nominal dosage per day) to the useless notation "mg per kg/lbs" without providing the individual weight or at least an average for the cases mentioned. I'm only mentioning this in case someone decides to read the whole thing since the lethal risks will be grossly exacerbated as the data is taken out of context. They do mention that on a single year over 100,000 people took DNP for weight loss (and DNP was available for over 5 years so it's possible that over a half-million people took it) but don't make the observation that in all those years lethal cases including intentional suicide amounted to a couple dozen or so. And in most cases death if not caused by overdosage (accidental exposure) it happened by the pre-existence of medical conditions like renal/hepatic insufficiency. If they connected these dots, they would be on the odd position to admit "all things considered DNP is relatively safe". But as I said it's not the purpose of this document to provide proper context, it's essentially a "shopping list" of all known symptoms and all things that can go wrong when DNP enters the body.

Most reading this topic already know all that but it's worth mentioning in case someone gets confused/worried with the info presented there. Since major concerns with DNP are proven to be a non-issue (provided that no pre-existing medical condition is present, specially hepatic insufficiency which can lead to death even at small dosages ) what interest most of us is potential secondary side effects. The biggest one would be cataracts which was extensively researched and is proven to be a rare occurrence affecting only genetically predisposed people (and there's some evidence that simple antioxidants like vitamin C would be enough to prevent it - but this is not proven on humans hence why antioxidants are recommended as "insurance"). So for all intents and purposes cataracts can be considered a non-issue (and curiously, in animals the cataracts caused is temporary, the lens get back to normal as soon DNP is discontinued but in humans with the exception of 1 case where cataracts regressed after suspending DNP, all other reported cases the DNP-induced cataract was irreversible).

Next on the list of potential issues that can arise with DNP are immunologic reactions (skin hashes, etc.), peripheral neuritis, arthritis and minor effects which is the sides most folks discuss everywhere: symptoms like nausea, vomiting, diarrhea, water shifting/retention (bloatedness, thirstiness) and the metabolic related sides: increased heat/perspiration, fatigue/tiredness, short-breathness, weight-loss those last being what most people take for granted when taking the DNP ride. There are small weird/bizarre effects like yellow sweats (documented in cases of overdosage by accidental exposure) yellow skin and eyes. Those are not expected common sides but do happen occasionally. Few days ago I saw a report on another forum of a guy who got yellow eyes after just 2 weeks on a small dosage of 200mg/day. While this is not known to be harmful per se, it's a sign things didn't went thru the expected path, prompting discontinuation.

Of all that, the most glaring issue both for the potential harm and incidence rate is peripheral neuropathy, which is mostly unknown and virtually not discussed anywhere, with the exception of occasional reports here and there (some scary by the way). So to bring more context to this issue besides scattered anecdotal reports over the internet I will quote some passages from ATSDR's report and post comments as appropriated (emphasis mine):

Starting from the beginning on page 4:
Most of the ways that DNP can affect your health do not depend on how you are exposed or for how long. Some people who took DNP were harmed, while others were not, even though they took the same or higher doses. Although some people became ill after taking DNP for short periods, other people could take DNP for longer periods before becoming ill. This means that some people are more sensitive to the harmful effects of DNP than others.
...
Some people who took doses of 2 mg/kg/day DNP or more for short or long periods experienced numbness in their hands and feet.
This is an appropriate observation made by the report. Indeed most of the sides including neuropathy do happen regardless of dosage or time taken. All available data suggests it's either a case of predisposition or individual sensitivity/threshold. And right from the beginning they are mentioning numbness in the hands/feets together with all other common symptoms which is an indication that neuritis was present in many of the available research.

Moving on, from page 13:
In the early 1980s, a physician in Texas administered 2,4-DNP to patients at his diet clinic for weight reduction, but was stopped by state authorities (Kurt et al. 1986). Much of the database for animal oral exposure also dates from the 1930s. These human and animal studies have limitations common to studies of the time. For example, none of the human clinical studies includes a concurrent, matched, placebo-treated control group, and statistical analyses generally were not mentioned. Frequently, however, each subject was monitored before and sometimes after treatment as a control measure. Dosages were generally reported as mg/day; for this profile, these were converted to mg/kg/day using average body weight values suggested by the EPA (EPA 1986b).
The 80s texas case is just a curiosity but it shows that there is people from the medical field aware of the potential (and relative safety) of DNP for use as a weight loss agent. In fact there is a patent from 87 that describes a fat-loss product containing DNP and T3. But since DNP status of "banned drug" was never revised, any such attempt fell into a dead end and it's unlikely that this will ever change.

The lack of statistical analyses and limitations of research from that time is a remind that while there is a good deal of information about DNP, the scope of what is covered is somewhat limited and many questions remains unanswered. Finally my previous observation regarding the reported dosages on this paper.... they converted data regarding dosage/day to the standardized format of mg/kg that unfortunately for DNP is not useful. Researches originally used absolute/nominal intakes for a reason, mainly that individual sensitivity/tolerance is the key factor, not relative dosage per body mass.

At pages 64/65:
An increase in basal metabolic rates of 30-70% was seen within the first 24 hours in obese patients who ingested 4.3 mg/kg/day 2,4-DNP for 1-8 weeks and was maintained throughout the treatment period; pretreatment values were not reported (MacBryde and Taussig 1935).
That would be around 400mg/day of actual DNP (non-crystal). Look the reported BMR increases... up to 70% (but also as low as 30%, which is an example of how individual tolerance can interfere).... maintained up to 8 weeks. While it's said that "as seen within the first 24h", I'm pretty sure that the paper demonstrated that metabolic increases were discernible from day 1, but this peak increase of 30-70% certainly wasn't on the first 24h since it takes few days for any given dosage to peak in our bodies.
An 82% increase in basal metabolic rate was measured in a patient who received 3.3 mg/kg/day 2,4-DNP over a period of 182 days (Epstein and Rosenbloom 1935).
A different research.... one guy who took by the looks of it around 400mg of actual DNP daily got a nice BMR boost of 82% for 6 months straight.
In one clinical study in which patients were treated with the sodium salt of 2,4-DNP at an average dose of 4.0 mg/kg/day 2,4-DNP for an average of 88 days, the estimated increase in basal metabolic rate corresponding to this average dose was 38% (Tainter et al. 1935b).
...
These values represent an average increase of ≈11% for each 100 mg
(1.17 mg/kg) increase in dose (Tainter et al. 1935b).
...The data exhibit a dose-severity relationship. Another clinical study also reported an average increase in basal metabolic rate of ≈11% per each 100 mg/day increase in dose in 66 patients given an average dose of 3 mg/kg/day for 22-89 days (Simkins 1937a, 1937b).
The above sum up what we know about average metabolism increase. For the sodium (crystal) version, each 100g daily will raise metabolism by 11%. For the "powder" version (without sodium) this increase is 15%. This is dosage-dependent so the more you take, more your metabolism will be enhanced. All that was mentioned in this thread before many times, with the research graphic and everything. I'm just quoting this passage for completeness and because it demonstrate that those values are averages, as seen above some people get far less and others substantially more (82%@400mg... niiice )

There's more and this post is already extensive so I will resume later.

Last edited by niloluiz : 10-07-2013 at 02:38 AM.
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  #604  
Unread 10-07-2013, 07:16 AM
ajntorinj ajntorinj is offline
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Dumb question, but why is it that 2,4 dinitrophenate is said to be 75% as potent as 2,4 dinitrophenol? The molecular weights are 206.088 and 184.1064, respectively. Shouldn't 1mg 2,4 dinitrophenate be as potent as ~.88mg 2,4 dinitrophenol?

Again, sorry for my ignorance.
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  #605  
Unread 10-07-2013, 07:28 AM
Primalkid Primalkid is offline
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Quote:
Originally Posted by ajntorinj View Post
Dumb question, but why is it that 2,4 dinitrophenate is said to be 75% as potent as 2,4 dinitrophenol? The molecular weights are 206.088 and 184.1064, respectively. Shouldn't 1mg 2,4 dinitrophenate be as potent as ~.88mg 2,4 dinitrophenol?

Again, sorry for my ignorance.
It has a sodium ion attached, so the effective dose of the crystal is only about 75%. Also, read the thread.
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  #606  
Unread 10-07-2013, 08:15 AM
ajntorinj ajntorinj is offline
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Quote:
Originally Posted by Primalkid View Post
It has a sodium ion attached, so the effective dose of the crystal is only about 75%. Also, read the thread.
Your post explained nothing. I have read this thread, but I was hoping someone could spare me from reading all 61 pages again to find out.

Edit: Looking at niloluiz's summary above, although my calculations are correct, it seems the salt is 89% DNP by weight, but only 75% as potent as pure DNP in vivo. I don't think I am going to find the answer as to why that is, though. I guess the reaction in the gut does achieve 100% yield.

Last edited by ajntorinj : 10-07-2013 at 08:33 AM.
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  #607  
Unread 10-07-2013, 09:25 AM
Unraveller Unraveller is offline
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Quote:
Originally Posted by ajntorinj View Post
Your post explained nothing. I have read this thread, but I was hoping someone could spare me from reading all 61 pages again to find out.

Edit: Looking at niloluiz's summary above, although my calculations are correct, it seems the salt is 89% DNP by weight, but only 75% as potent as pure DNP in vivo. I don't think I am going to find the answer as to why that is, though. I guess the reaction in the gut does achieve 100% yield.
His explanation answers your question, and a 10 second search of "molecular" reveals the source material. Which also would have been discovered by reading the thread... Normally I would suggest "read the thread" is a trite answer, but given the gravity of this topic, I believe it's a very legitimate response.

Quote:
Originally Posted by w1cked View Post
he's wrong too then, and I pointed out why 2 posts ago.

"89% comes from comparing their molecular masses."

http://www.ncbi.nlm.nih.gov/pubmed/15058315
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  #608  
Unread 10-07-2013, 11:01 AM
niloluiz niloluiz is offline
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Quote:
Originally Posted by ajntorinj View Post
...it seems the salt is 89% DNP by weight, but only 75% as potent as pure DNP in vivo. I don't think I am going to find the answer as to why that is, though. I guess the reaction in the gut does achieve 100% yield.
Quote:
Originally Posted by Unraveller View Post
His explanation answers your question, and a 10 second search of "molecular" reveals the source material. Which also would have been discovered by reading the thread... Normally I would suggest "read the thread" is a trite answer, but given the gravity of this topic, I believe it's a very legitimate response.
Yes, despite this molecular weight observation the 75% actual DNP content per gram of the phenolate is accurate and still holds and it's not just in-vivo, it actually contains 25% less DNP, gram per gram. The "why" explanation is probably some esoteric techno-chemical stuff, but to my knowledge this fact is not disputed even in more recent research.
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  #609  
Unread 10-07-2013, 12:53 PM
ajntorinj ajntorinj is offline
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Quote:
Originally Posted by Unraveller View Post
His explanation answers your question, and a 10 second search of "molecular" reveals the source material. Which also would have been discovered by reading the thread... Normally I would suggest "read the thread" is a trite answer, but given the gravity of this topic, I believe it's a very legitimate response.
PubMed is down at the moment. And I fail to see how mentioning the attachment of sodium explains the additional 14% decrease in potency than suggested by simply comparing molecular weights. But you are correct; I should be more savvy with searching.
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  #610  
Unread 10-07-2013, 01:53 PM
niloluiz niloluiz is offline
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continuing with the ATSDR report....

there was a typo in the last paragraph of my previous post:
"For the sodium (crystal) version, each 100g daily will raise metabolism by 11%." it's 100mg of course. 100g is enough to "dispatch" an entire football team

On top of page 69, regarding Neurological effects, they list some cases where things went really wrong. They don't mention if there was some underlying medical condition (likely) or if there was any other confounding factors but in all the body of research concerning DNP it's proven beyond any shadow of doubt that such occurrences cannot be attributed to DNP alone since there's no parallel cases to suggest otherwise.

At the end of that page they start to mention the peripheral neuritis cases:
No symptoms of peripheral neuritis were reported by 37 patients who took the sodium salt of 2,4-DNP at an estimated dose of 1.2 mg/kg/day 2,4-DNP for an average of 14 days (Tainter et al. 1935b). However, symptoms of peripheral neuritis occurred in 18 of 170 obese patients who ingested an average of 4 mg/kg/day 2,4-DNP from sodium 2,4-DNP for an average of 88 days (Tainter et al. 1935b).
The above study points out that symptoms of peripheral neuritis didn't develop at low dosages (around 100mg/day of the sodium DNP, which is a very small dosage I should add) for short periods of time. But they did developed for about 10% of patients who took the usual therapeutic dosages (300~400mg/day) for about 3 months. This is very close to my own case, as I reported earlier summing all the days I effectively ingested DNP, it was right about 3 months of ingestion with a similar dosage for peripheral neuritis symptoms to manifest.

Next we have:
The neurological effects occurred only among the 100 patients who took ≥3.5 mg/kg/day for ≥6 weeks and were characterized by abnormal sensations of numbness, pins and needles, heat and cold, and heightened sensation of pain in the extremities, or loss of taste and numbness and tingling of the tongue. In a clinical study of 15 obese women given 4.3 mg/kg/day 2,4-DNP for 1-8 weeks, 1 woman experienced a virtual loss of taste that persisted for several weeks after discontinuation of dosing (MacBryde and Taussig 1935)
Again this suggest that dosage and duration is a key factor. The above symptoms are the usual manifestations of peripheral neuritis. Loss of taste (some people get things like "metalic taste" or messed up taste) is also a form of neuritis, although less common. I saw at least 2 different reports from guys in forums that got this side.
In an extensive clinical study of 159 patients taking 3 mg/kg/day 2,4-DNP as the sodium salt for 22-89 days, 4 frank cases of peripheral neuritis occurred after dosing for 4-10 weeks, persisted for weeks, and gradually abated when dosing was discontinued (Simkins 1937a, 1937b). Five patients lost the sense of taste and developed numbness and tingling of the tongue, usually within the fifth to seventh week of dosing. These symptoms generally persisted for 2 days to several weeks but disappeared spontaneously during the continuation of dosing.
More cases of neuritis in another study. Of a group of 159 patients, 4 got hit by peripheral neuritis with the usual therapeutic dosages (around 300mg/day) but do note the periods: it started as soon as 4 weeks (1 month) up to 10 weeks (2.5 months, close to the observed 3 months from the other studies).
Looks like a pattern to me. Also it persisted for several weeks improving gradually after discontinuing the treatment. More interestingly is the cases of loss of taste. In this particular study more people got hit by this form of neuritis which started sooner (5th to 7th week) and with a difference: It went away spontaneously without interrupting DNP. The same never happened with peripheral neuritis.... once it starts, it only gets worse with time if DNP is not discontinued.
Several individual case reports described symptoms consistent with peripheral neuritis in patients taking 2,4-DNP for weight reduction. In these reports, doses ranged from 1.86 to 3.53 mg/kg/day, and durations ranged from 10 days to several months (Anderson et al. 1933; Bortz 1934; Epstein and Rosenblum 1935; Hitch and Schwartz 1936; Hunt 1934; Nadler 1935).
Looks like peripheral neuritis can start with as little as 10 days of treatment.
That's really fast.

About peripheral neuropathy this is the most relevant passages I took note from the ATSDR's report. There's more about toxicokinetics and assorted subjects that I will get into later. Next post I will quote and comment some passages from that JAMA article about peripheral neuritis that complement the above summary.
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