BIOCHEMISTRY II (BIOL 206)

BY

DOMINIC LOGOSU

Index Number: 0209019016

QUESTION:

How Does Dinitrophenol Help in Reducing Weight as Used as A Diet Drug

LECTURER:

JENNIFER OFORI

DATE: 13TH APRIL, 2018

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INTRODUCTION

2,4-Dinitrophenol (2,4-DNP or simply DNP) is an organic compound with the formula

HOC6H3(NO2)2. It is a yellow, crystalline solid that has a sweet, musty odor. It sublimes, is

volatile with steam, and is soluble in most organic solvents as well as aqueous alkaline

solutions. It is a precursor to other chemicals and is biochemically active, inhibiting energy

(adenosine triphosphate, ATP) production in cells with mitochondria. Its use in high doses as a

dieting aid has been identified with severe side-effects, including a number of deaths.

DNP is produced by hydrolysis of 1-chloro-2,4-dinitrobenzene.

Sample of pure compound

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Although the U.S. Food and Drug Administration banned 2,4-Dinitrophenol, or DNP, in 1938

because of severe adverse health effects, the supplement can still be found online marketed as a

weight-loss aid sold under various names. Avoid this dangerous supplement.

DNP is a substance found in some supplements targeted toward bodybuilders looking to burn fat

while retaining muscle. It's found for sale primarily online and commonly advertised as a safe

weight-loss aid. Despite the advertising claims, DNP is anything but safe, according to the New

York State Department of Health.

DNP causes weight loss by increasing metabolism, or the amount of energy your body uses. In

animals fed a high-fat diet, DNP increased metabolism by 17 percent without a change in food

intake, according to an animal experiment published in the July 2014 edition of "The Journal of

Biological Chemistry." After two months, the mice fed DNP weighed 26 percent less than the

mice not treated with DNP. Researchers found that DNP led to fat loss without a decline in

muscle mass.

DNP can lead to a combination of dangerous side effects such as overheating, rapid heart rate,

profuse sweating and faster than normal breathing, which can eventually lead to death. "The

Journal of Analytical Toxicology" published a report in 2006 of two deaths -- one in Tacoma,

Washington, and the other in San Diego -- caused by DNP. DNP was being used for weight loss

in both cases and caused this dangerous combination of side effects.

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History of Dinitrophenol

The French used DNP in the manufacture of munitions during the First World War. Since then, it

has also been used as a dye, wood preserver, herbicide and photographic developer. It was

Maurice Tainter at Stanford University in 1933 who discovered that the human consumption of

DNP led to significant weight loss and soon it was popularised as a weight loss drug. It was

included in over-the-counter medications and was sold to the public without requiring a

prescription.

Its use for those wishing to lose weight was encouraged by reports of rapid, safe weight loss.

DNP can cause a significant increase in the basal metabolic rate. This leads to weight loss by

burning more fat and carbohydrates, and weight loss of up to 1.5 kg per week is reported without

significant side effects. However, there seems to be significant variation in individual responses

with an average metabolic rate increase of 11% for every 100 mg of DNP when taken regularly.

As more side effects, especially cataracts, were reported, DNP was labelled as ‘extremely

dangerous and not fit for human consumption’ by the Federal Food, Drug and Cosmetic Act of

1938.

After 1938, medical prescription of DNP stopped and cases of poisoning due to medical intake

were no longer reported, but case reports of deaths associated with the ingestion of DNP still

emerged. It is anecdotally reported to have been prescribed to the Russian soldiers during World

War II to keep them warm.

In 1981, a physician (Dr. Bachynsky) in TX, USA processed industrial DNP into tablets which

he marketed/dispensed under the trade name ‘Mitcal’ through his private weight loss clinic. He

advertised that weight loss occurred using ‘Mitcal’ through a mechanism he called intracellular

hyperthermia therapy. It is alleged in subsequent court proceedings that over 14,000 people were

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treated by Dr. Bachynsky. Individuals using Mitcal started reporting adverse effects, such as

fever, shortness of breath and sweating, to the US Food and Drugs Administration in late 1982.

Additionally, there was a fatality associated with an intentional overdose of ‘Mitcal’ in 1984.

Following further investigation, Dr. Bachynsky was convicted in 1986 of drug law violations,

fined and prohibited from dispensing DNP to any patients. However, he continued to use DNP

for a variety of different ‘medicinal claims’ and was eventually jailed for fraud in 2008 in the

USA in relation to the marketing of a company that was developing DNP being used in Europe

as a cancer treatment known as intracellular hyperthermia therapy.

The UK Food Standard Agency issued a warning in 2003, labelling DNP as ‘not fit for human

consumption’. This warning was aimed specifically at bodybuilders, to avoid its use due to

significant potential for short-term and long-term harm, following the hospitalisation of a Finish

bodybuilder after having taken DNP.

Despite this, DNP remains widely available and as discussed below in more detail, can be

purchased over the internet, particularly from online pharmacies. Additionally, there are

instructions for the synthesis of DNP online for self-manufacture. As noted above, DNP has been

banned as a weight loss drug in the USA, and in the UK, it has been labelled as a hazardous

chemical under the Clean Air Act. Despite this legislation and warnings of harm associated with

its use, reports of deaths due to the use of DNP have increased in the last few years (Fig. 1), and

the last decade has seen the highest number of case reports from death due to intentional

dinitrophenol overdose.

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How Dinitrophenol Help in Reducing Weight.

DNP causes weight loss by making cellular respiration less efficient. The majority of ATP

(molecules used for energy) is produced in the mitochondria. Through a series of oxidation-

reduction chemical reactions a higher concentration of protons is built up in the inter-membrane

space of the mitochondria than the proton concentration in the mitochondrial matrix. The inter-

membrane space is separated from the matrix by a membrane that protons can not cross on their

own. Instead they cross through a protein called ATP Synthase which produces ATP as the

protons go through it.

DNP can cross this membrane on it's own. DNP can also grab a proton and carry the proton

across the membrane. When this happens, you have a shortage of protons for ATP synthase

which results in a shortage of ATP. Your body then needs to continue to burn more carbs, fat,

and protein at a higher rate to make up for the shortage of ATP. When DNP transports a proton

across the membrane heat is produced. (When your body oxidizes sugar, fat, or proteins energy

is produced. Your body is designed to use that energy to make ATP, while DNP turns that

energy into heat).

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Side Effects of Dinitrophenol When Used as A Diet Drug to Reducing Weight

2, 4-Dinitrophenol, or DNP is a weight loss drug that has been banned since 1938. Whilst its

effects are fast acting there are a number of serious side effects that occur, ultimately leading to

death. One of the risks of DNP is that it accelerates the metabolism to a dangerously fast level.

Our metabolic system operates at the rate it does for a reason – it is safe. Speeding up the

metabolism may help burn off fat, but it can also trigger a number of potentially dangerous side

effects, such as:

 fever

 dehydration

 nausea

 vomiting

 restlessness

 flushed skin

 excessive sweating

 dizziness

 headaches

 rapid breathing

 rapid or irregular heartbeat

The combination of these side effects can have an extremely damaging effect on the body and

can result in coma and, as we have seen, death.

Long-term use can lead to the development of cataracts and skin lesions and may cause damage

to the heart and nervous system. There is also evidence from animal studies that DNP is

carcinogenic (cancer causing) and increases the risk of birth defects.

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REFERENCE:

1. McFee, RB et al. Dying to be thin: a dinitrophenol related fatality. Vet Huam Toxicol.

2004. 46(5): 251-4

2. Grundlingh, J et al. 2,4-dinitrophenol (DNP): a weight loss agent with significant acute

toxicity and risk of death. J Med Toxicol. 2011; 7(3): 205-12

3. Tainter, ML et al. Use of dinitrophenol in obesity and related conditions. A progress

report. JAMA. 1933;101:1472–1475.

4. Kurt, TL et al. Dinitrophenol in weight loss: the poison center and public health safety .

Vet Hum Toxicol. (1986)

5. Dunlop, DM. The use of 2:4-dinitrophenol as a metabolic stimulant. Br Med J. 1934;

24(1): 524-527

6. Bartlett J et al. Deliberate poisoning with dinitrophenol (DNP): an unlicensed weight loss

pill. Emerg Med J. 2010; 27: 159–160

7. Hsiao, AL et al. Pediatric fatality following ingestion of dinitrophenol: postmortem

identification of a “dietary supplement”. Clin Toxicol (Phila). 2005;43(4):281-5.