The Use of 2:4-Dinitrophenol as a Metabolic Stimulant

Dunlop, Derrick

doi:10.1136/bmj.1.3820.524

Cited by 22 publications

(11 citation statements)

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“…When used in a dose of 300 mg/d, weight loss induced by DNP seemed to be well tolerated and associated with an increase in metabolic rate of ;50% (Tainter et al, , 1934Dunlop, 1934). In subsequent clinical studies, metabolic rate was shown to increase in average by 11% per 100 mg DNP (Dunlop, 1934;Tainter, 1935;Harper et al, 2001). In anesthetized dogs, DNP dose-dependently increased oxygen consumption by as much as 12-fold above baseline (Hall et al, 1933).…”

Section: B 24-dinitrophenolmentioning

confidence: 97%

“…The pharmacological effect resided in the ability of DNP to increase metabolic rate via enhanced mitochondrial uncoupling, thus favoring heat production over ATP synthesis Tainter et al, 1933Tainter et al, , 1935. When used in a dose of 300 mg/d, weight loss induced by DNP seemed to be well tolerated and associated with an increase in metabolic rate of ;50% (Tainter et al, , 1934Dunlop, 1934). In subsequent clinical studies, metabolic rate was shown to increase in average by 11% per 100 mg DNP (Dunlop, 1934;Tainter, 1935;Harper et al, 2001).…”

Section: B 24-dinitrophenolmentioning

confidence: 98%

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Anti-Obesity Therapy: from Rainbow Pills to Polyagonists

et al. 2018

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Section: B 24-dinitrophenolmentioning

confidence: 97%

Section: B 24-dinitrophenolmentioning

confidence: 98%

Anti-Obesity Therapy: from Rainbow Pills to Polyagonists

et al. 2018

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“…This leads to weight loss by burning more fat and carbohydrates [9], 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 [10][11][12]. 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 [2,13].…”

Section: History Of Dinitrophenolmentioning

confidence: 99%

2,4-Dinitrophenol (DNP): A Weight Loss Agent with Significant Acute Toxicity and Risk of Death

2011

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2,4-Dinitrophenol (DNP) is reported to cause rapid loss of weight, but unfortunately is associated with an unacceptably high rate of significant adverse effects. DNP is sold mostly over the internet under a number of different names as a weight loss/slimming aid. It causes uncoupling of oxidative phosphorylation; the classic symptom complex associated with toxicity of phenol-based products such as DNP is a combination of hyperthermia, tachycardia, diaphoresis and tachypnoea, eventually leading to death. Fatalities related to exposure to DNP have been reported since the turn of the twentieth century. To date, there have been 62 published deaths in the medical literature attributed to DNP. In this review, we will describe the pattern and pathophysiology of DNP toxicity and summarise the previous fatalities associated with exposure to DNP.

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“…In the 1930s, a compound that relieves the mitochondrial proton gradient called 2,4-dinitrophenol (DNP) was used extensively as a pharmacological stimulator of metabolic rate. Despite the great effectiveness of this compound to increase resting metabolism, use of DNP can result in cataracts and fatal hyperthermia, and therefore, it is no longer considered safe for human use (2). Substantial ongoing work in the field is aimed at understanding the mechanisms of RMR regulation, but useful pharmacological targets remain elusive.…”

mentioning

confidence: 99%

Direct calorimetry identifies deficiencies in respirometry for the determination of resting metabolic rate in C57Bl/6 and FVB mice

Burnett

Grobe

2013

American Journal of Physiology-Endocrinology and Metabolism

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Burnett CM, Grobe JL. Direct calorimetry identifies deficiencies in respirometry for the determination of resting metabolic rate in C57Bl/6 and FVB mice. Am J Physiol Endocrinol Metab 305: E916 -E924, 2013. First published August 20, 2013; doi:10.1152/ajpendo.00387.2013.-Substantial research efforts have been aimed at identifying novel targets to increase resting metabolic rate (RMR) as an adjunct approach to the treatment of obesity. Respirometry (one form of "indirect calorimetry") is unquestionably the dominant technique used in the obesity research field to assess RMR in vivo, although this method relies upon a lengthy list of assumptions that are likely to be violated in pharmacologically or genetically manipulated animals. A "total" calorimeter, including a gradient layer direct calorimeter coupled to a conventional respirometer, was used to test the accuracy of respirometric-based estimations of RMR in laboratory mice (Mus musculus Linnaeus) of the C57Bl/6 and FVB background strains. Using this combined calorimeter, we determined that respirometry underestimates RMR of untreated 9-to 12-wk-old male mice by ϳ10 -12%. Quantitative and qualitative differences resulted between methods for untreated C57Bl/6 and FVB mice, C57Bl/6 mice treated with ketamine-xylazine anesthesia, and FVB mice with genetic deletion of the angiotensin II type 2 receptor. We conclude that respirometric methods underestimate RMR in mice in a magnitude that is similar to or greater than the desired RMR effects of novel therapeutics. Sole reliance upon respirometry to assess RMR in mice may lead to false quantitative and qualitative conclusions regarding the effects of novel interventions. Increased use of direct calorimetry for the assessment of RMR and confirmation of respirometry results and the reexamination of previously discarded potential obesity therapeutics are warranted. metabolic rate; thermogenesis; heat; calorimetry; respirometry CLINICAL TREATMENT OF OBESITY is currently restricted to behavioral modification (e.g., exercise) and a short list of pharmaceutical agents (Orlistat, Qsymia, and Belviq). These three FDA-approved compounds/mixtures all function by reducing caloric intake/uptake. Interestingly, no safe or efficacious pharmaceutical treatments have been developed to increase resting metabolic rate (RMR), which could be used as an adjunct or alternative therapy to the intake-suppressing drugs currently available. In the 1930s, a compound that relieves the mitochondrial proton gradient called 2,4-dinitrophenol (DNP) was used extensively as a pharmacological stimulator of metabolic rate. Despite the great effectiveness of this compound to increase resting metabolism, use of DNP can result in cataracts and fatal hyperthermia, and therefore, it is no longer considered safe for human use (2). Substantial ongoing work in the field is aimed at understanding the mechanisms of RMR regulation, but useful pharmacological targets remain elusive. We hypothesize that a major problem facing the field is an inadequate ability to acc...

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The Use of 2:4-Dinitrophenol as a Metabolic Stimulant

Cited by 22 publications

References 0 publications

Anti-Obesity Therapy: from Rainbow Pills to Polyagonists

Anti-Obesity Therapy: from Rainbow Pills to Polyagonists

2,4-Dinitrophenol (DNP): A Weight Loss Agent with Significant Acute Toxicity and Risk of Death

Direct calorimetry identifies deficiencies in respirometry for the determination of resting metabolic rate in C57Bl/6 and FVB mice

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