Research into DNP and health

Apologies that some of the links may be defunct now; this is a collection of items I have found through the years and some links are older. I've spent hours for years collecting this, so if you share it, please give credit.

http://news.yale.edu/2015/02/26/yale-researchers-reverse-type-2-diabetes-and-fatty-liver-disease-rats
Yale researchers have found that DNP can reduce fat and inflammation in the liver, and even reverse Type II Diabetes liver disease in rats. Using a low-dose form of DNP "delivered positive results, reversing fatty liver, insulin resistance, and hyperglycemia in rat models of NAFLD and type 2 diabetes, as well as liver inflammation and liver fibrosis...with no adverse effects." See that? WITH NO ADVERSE EFFECTS.

DNP is Ames negative, and does not promote tumors. See for yourself at http://toxnet.nlm.nih.gov/

http://www.epa.gov/ttn/atw/hlthef/dinitrop.html reports on health risks. While there have not been human studies, animal studies found no cancers caused by DNP administration. It is considered a toxin because it causes nausea, sweating, and weight loss.

http://www.cyberiron.com/drugs/dinitrophenol.html reports on health risks from external exposure. In other words, don’t get it in your eyes, or on your skin if you’re allergic. Pretty elementary stuff.

http://www.ebec2000.com/abstracts/056.htm This animal study documents a 64% increase in metabolism. "These findings confirm that DNP effectively increases metabolic rate..." Duh.

http://www.boehringer-ingelheim.es/workshop-methionina/anglesa/cap13.htm  finds that DNP did not activate liver enzymes (MAT) associated with liver damage

http://potency.berkeley.edu/chempages/2,4-DINITROPHENOL.html
A study to determine whether DNP is carcinogenic or tumor-inducing found NEGATIVE results in male and female animal subjects. In other words, they were not able to induce tumors or cancers with DNP when they tried to.

Results from one oral study in mice indicated no tumor formation occurred after six months exposure, and in another study results indicated 2,4-dinitrophenol did not promote tumor development in mice. The International Agency for Research on Cancer and the U.S. EPA have not classified 2,4-dinitrophenol for potential human carcinogenicity (IARC, 1987a; U.S. EPA, 1994a).


 “The Mitochondrial Uncoupling Agent 2,4-Dinitrophenol Improves Mitochondrial Function, Attenuates Oxidative Damage, and Increases White Matter Sparing in the Contused Spinal Cord”
Journal of Neurotrauma Oct 2004, Vol. 21, No. 10 : 1396 -1404 DNP is found to have neuroprotective properties: “pretreatment with DNP significantly increased the amount of remaining white matter at the injury epicenter 6 weeks after injury. These results indicate that treatment with mitochondrial uncoupling agents may provide a novel approach for the treatment of secondary injury following spinal cord contusion.” Not the pgrase "attenuates oxidative damage" In plain English, that means DNP reduces oxidative damage to cells. DNP helps PROTECT against a lot of harm to spinal cord nerves!


DNP helps prevent brain damage and can be GOOD for mitochondrial function: "The Uncoupling Agent 2,4-Dinitrophenol Improves Mitochondrial Homeostasis." Amit S. Korde, Patrick G. Sullivan, and William F. Maragos. Journal of Neurotrauma. October 2005, 22(10): 1142-1149. doi:10.1089/neu.2005.22.1142.
"Animals treated with the classic uncoupling agent 2,4-dinitrophenol (DNP) show significant protection against brain damage...Our findings indicate that DNP may confer protection against acute brain injury involving excitotoxic pathways by mechanisms that maintain mitochondrial function."


“Comparative study of toxicity of 4-nitrophenol and 2,4-dinitrophenol in newborn and young rats.” Koizumi M, Yamamoto Y, Ito Y, Takano M, Enami T, Kamata E, Hasegawa R. Division of Risk Assessment, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. This study found that DNP can induce death in overdosed amounts, but that up to that point no toxicity was evident, nor were there any abnormalities in physical development.


“Phenol toxicity and conjugation in human colonic epithelial cells.” Pedersen G, Brynskov J, Saermark T. Dept of Medical Gastroenterology, Herlev University Hospital, Copenhagen, Denmark.. This study found that DNP has a toxic effect on cells of the colon, with “toxic” defined in two ways: first, it interfered with metabolism (this we know—it’s the intended effect of DNP use!) and second, it interfered with bowel inflammation (not a health risk. This is caused by osmotic effect, with the  worst result being softened stools and gas). This latter effect subsides, of course.


“Mechanisms of bacterial resistance to macrolide antibiotics.” Nakajima Y. Division of Microbiology, Hokkaido College of Pharmacy, 7-1 Katsuraoka-cho, Otaru, Hokkaido 047-0264, Japan. This study found that antibiotic-resistant bacteria could be thwarted with DNP. “the extent of the accumulated drug in a resistant cell increases as much as that in a susceptible cell in the presence of an uncoupling agent such as…2,4-dinitrophenol (DNP).”


“Absence of Crabtree effect in human melanoma cells adapted to growth at low pH: reversal by respiratory inhibitors.” Burd R, Wachsberger PR, Biaglow JE, Wahl ML, Lee I, Leeper DB. Departments of Radiation Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. Check this out—DNP actually helps make melanoma tumors easier to attack by increasing ratio of oxygen consumption to lactic acid production, while glycolysis remains the same. “Therefore, tumor acute acidification and oxygenation can be achieved by exposure…”


“New insights in the cellular processing of platinum antitumor compounds, using fluorophore-labeled platinum complexes and digital fluorescence microscopy.”
Molenaar C, Teuben JM, Heetebrij RJ, Tanke HJ, Reedijk J. Department of Molecular Cell Biology, Leiden University Medical Centre, The Netherlands. DNP is used as a control in tests of antitumor cells because it does NOT bind to cell DNA, nor promote tumors, yet its staining abilities enable tracking of the uptake of antitumor drugs.


Specific inhibition of breast cancer cells by antisense poly-DNP-oligoribonucleotides and targeted apoptosis.” Ru K, Taub ML, Wang JH. Department of Biochemistry, State University of New York, Buffalo 14260-3000, USA  Are you ready for this? DNP actually INHIBITS (!!!) breast cancers! Yes, not only does it NOT promote cancers, it’s being recognized as a cancer-fighter/blocker. “Two membrane-permeable and RNase-resistant antisense poly-2'-O-(2,4-dinitrophenyl)-oligoribonucleotides (poly-DNP-RNAs) have been synthesized as inhibitors of human breast cancer…fluorescence assay indicates that the targeted antisense inhibition by poly-DNP-RNAs leads to apoptosis of SK-Br-3 cells but does not affect nontumorigenic MCF-10A cells. The control poly-DNP-RNAs with random or sense nucleotide sequence are completely inactive.” Plain English? DNP is being synthesized as an anti-cancer compound, because tests show that it blocks mutagens but does NOT affect non-mutagenic (healthy) cells, and has no RNA effects on them.


“Heat shock protein induction by certain chemical stressors is correlated with their cytotoxicity, lipophilicity and protein-denaturing capacity.” Neuhaus-Steinmetz U, Rensing L. Institute of Cell Biology, Biochemistry and Biotechnology, NW II University of Bremen, Germany. The thermic effect of DNP induces protein synthesis (heat shock protein, or HSP, synthesis). In fact, it’s quite GOOD at it: “ASA, DNP and CCCP induced HSP at lower concentrations than substances with a similar lipophilicity…”


“Comparative effects of the metabolic inhibitors 2,4-dinitrophenol and iodoacetate on mouse neuroblastoma cells in vitro.” Andres MI, Repetto G, Sanz P, Repetto M.
National Institute of Toxicology, Seville, Spain.  In this study, DNP’s observed effect was an increase in metabolism (duh!), while the other toxins compared to it had harmful in vitro effects but no increase in metabolism.


“Inhibition of uncoupled respiration in tumor cells. A possible role of mitochondrial Ca2+ efflux.” Gabai VL.Medical Radiology Research Center, Russian Academy of Medical Sciences, Obninsk. DNP not only does not cause tumors, but it inhibited their respiration by 20-25% compared to controls.


“Amsacrine-induced lesions in DNA and their modulation by novobiocin and 2,4-dinitrophenol.” Shibuya ML, Buddenbaum WE, Don AL, Utsumi H, Suciu D, Kosaka T, Elkind MM. Department of Radiology and Radiation Biology, Colorado State University, Fort Collins 80523. In this study, researchers found that DNP abrogates—or disrupts—cytotoxicity in hamsters (using cancerous cells). They expected to find that DNP would interfere with anticancer treatments, but instead found that DNP increased their effects. They state, though, that they cannot claim a proven effect of DNP on anticancer treatments yet, although they do agree that treatment with DNP actually enhanced the effects of the DNA regenerative therapy of anticancer chemotherapy.


“Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs: a cautionary note.” Kaufmann SH. Oncology Center, Johns Hopkins Hospital, Baltimore, Maryland 21205. The authors warn that certain anti-leukemia drugs resulted in “extensive DNA degradation.” BUT(good ol’ DNP to the rescue!), “Preincubation with dinitrophenol abolished the effect…”


“[Dependence of the nature of the action of metabolic inhibitors on ribosomal RNA synthesis in Ehrlich ascites carcinoma cells on cell integrity]” [Article in Russian] Akhlynina TV, Buzhurina IM, Panov MA, Rozovskaia IA, Chernaia NG. DNP actually inhibits the synthesis of RNA in carcinoma cells. In other words, it helps cancerous cells commit suicide. “Ribosomal RNA (rRNA) synthesis in the intact Ehrlich ascite carcinoma cells is selectively inhibited by papaverin (ED50 = 0.01 mM), 2,4-dinitrophenol (DPN; ED50 = 5 microM), and actinomycin D (ED50 = 0.1 microgram/ml).”


“Autocatabolism of surface macromolecules shed by human melanoma cells.”
Bystryn JC, Perlstein J. Cancer Res 1982 Jun;42(6):2232-7. This study finds that DNP helps
melanoma cells die (autocatabolize) while other cells are unaffected.


DNP does not cause liver damage: "Their analyses demonstrate, beyond a doubt, that the liver does not suffer any damage in the course of dinitro treatment." (Biological Study of Dinitro Drugs in Humans By Dr. Jacques Bell. Bell, Jacques. 1939. Etude biologique des produits dinitres chez l'homme. Medecine. 19:749-54. Translation © 1996 Robert Ames)


Also: "Experimental studies on animals do not show toxic effects of dinitrophenol on the kidney. 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."


“Dinitrophenol has almost no action on the blood cholesterol. (Grant and Schube).”

"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...dinitrophenol is absolutely devoid of toxicity for the heart."

“Dinitrophenol does not attack cell tissue albumin and does not determine the fat loss to the expense of the muscles, contrary to thyroxine.”

“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).”

The most notable health hazard that 2,4-dinitrophenol presents is the reason the FDA barred its use as a weight loss agent. During its short stay as the leading weight loss drug offered, less than 1% of the women who consumed this substance developed clouding of the eyes, or cataracts. Consuming quercetin with DNP neutralizes this risk.

Interestingly, one medical theory on a health ADVANTAGE of DNP is that the slight increase in thermogenic temperature simulates the fever a body induces during a viral attack. The body increases its heat to protect organs but kill viruses, and some theorize that DNP can do the same thing, thus killing viruses in the body. In this mechanism, DNP may have an immune-enhancing effect. The next time you see someone repeat that dumb comment about "DNP cooks you from the inside out", remember this. First, the temperature raise is very slight (except when a person overdoses on DNP--don't do that!), and second, the slight increase helps improve resistance to viral and bacterial infection.