Hydrazine sulfate
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Hydrazine sulfate, more properly hydrazinium hydrogensulfate, is a
salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...
of the cation
hydrazinium Hydrazinium is the cation with the formula . This cation has a methylamine-like structure (). It can be derived from hydrazine by protonation (treatment with a strong acid). Hydrazinium is a weak acid with p''K''a = 8.1. Salts of hydrazinium ar ...
and the
anion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...
bisulfate The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many a ...
(hydrogensulfate), with the formula or more properly . It is a white, water-soluble solid at room temperature. Hydrazine sulfate has a number of uses in chemical laboratories and in the chemical industry, including
analytical chemistry Analytical chemistry studies and uses instruments and methods to separate, identify, and quantify matter. In practice, separation, identification or quantification may constitute the entire analysis or be combined with another method. Separati ...
and the synthesis of organic compounds. In those uses it is usually preferred to pure hydrazine, because it is not volatile and is less susceptible to atmospheric oxidation on storage.


Preparation

The compound can be prepared by treating an aqueous solution of hydrazine () with sulfuric acid ().


Laboratory and industrial uses

Besides its general use as a safe source of hydrazine, the compound is used as a
catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
in making fibers out of acetate, in the analysis and synthesis of minerals, and testing for
arsenic Arsenic is a chemical element with the symbol As and atomic number 33. Arsenic occurs in many minerals, usually in combination with sulfur and metals, but also as a pure elemental crystal. Arsenic is a metalloid. It has various allotropes, ...
in metals.


Medical uses

Hydrazine sulfate can be used as a fungicide and
antiseptic An antiseptic (from Greek ἀντί ''anti'', "against" and σηπτικός ''sēptikos'', "putrefactive") is an antimicrobial substance or compound that is applied to living tissue/skin to reduce the possibility of infection, sepsis, or putre ...
. Hydrazine sulfate has been used as an alternative medical treatment for the loss of appetite (
anorexia Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...
) and rapid weight loss (
cachexia Cachexia () is a complex syndrome associated with an underlying illness, causing ongoing muscle loss that is not entirely reversed with nutritional supplementation. A range of diseases can cause cachexia, most commonly cancer, congestive heart ...
), which are often associated with
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
.


Legal status

Although it has been marketed as a dietary supplement, hydrazine sulfate has never been approved in the United States as safe and effective in treating any medical condition.


History

Hydrazine sulfate was first proposed as an anti-cancer agent by U.S. physician Joseph Gold in the mid-1970s. Gold's arguments were based on the fact that cancer cells are often unusually dependent on glycolysis for energy (the Warburg effect). Gold proposed that the body might offset this increased glycolysis using gluconeogenesis, which is the pathway that is the reverse of glycolysis. Since this process would require a great deal of energy, Gold thought that inhibiting gluconeogenesis might reverse this energy requirement and be an effective treatment for cancer cachexia. Hydrazine is a reactive chemical that in the test tube can inactivate one of the enzymes needed for gluconeogenesis,
phosphoenolpyruvate carboxykinase Phosphoenolpyruvate carboxykinase (, PEPCK) is an enzyme in the lyase family used in the metabolic pathway of gluconeogenesis. It converts oxaloacetate into phosphoenolpyruvate and carbon dioxide. It is found in two forms, cytosolic and mitoch ...
(PEP-CK). It was also postulated that if tumor energy gain (glycolysis) and host-energy loss (gluconeogenesis) were functionally interrelated, inhibition of gluconeogenesis at PEP CK could result in actual tumor regression in addition to reversal or arrest of cancer cachexia. In this model, hydrazine sulfate is therefore thought to act by irreversibly inhibiting the enzyme phosphoenolpyruvate carboxykinase. The use of hydrazine sulfate as a cancer remedy was popularized by the magazine ''
Penthouse Penthouse most often refers to: *Penthouse apartment, a special apartment on the top floor of a building *Penthouse (magazine), ''Penthouse'' (magazine), a British-founded men's magazine *Mechanical penthouse, a floor, typically located directly u ...
'' in the mid-1990s, when Kathy Keeton, wife and business partner of the magazine's publisher
Bob Guccione Robert Charles Joseph Edward Sabatini Guccione ( ; December 17, 1930 – October 20, 2010) was an American photographer and publisher. He founded the adult magazine '' Penthouse'' in 1965. This was aimed at competing with Hugh Hefner's ''Playboy' ...
, used it in an attempt to treat her
metastatic Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...
. Alternative medicine nutritionist
Gary Null Gary Michael Null (born January 6, 1945) is an American talk radio host and author who advocates pseudoscientific alternative medicine and produces a line of questionable dietary supplements. Null is hostile to evidence-based medicine and has ...
wrote three of the articles about alternative cancer treatments, including one titled "The Great Cancer Fraud." Keeton (until her death in 1997) and other supporters of hydrazine sulfate treatment accused the U.S.
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
(NCI) of deliberately hiding the beneficial effects of the compound, and threatened to launch a
class action A class action, also known as a class-action lawsuit, class suit, or representative action, is a type of lawsuit where one of the parties is a group of people who are represented collectively by a member or members of that group. The class actio ...
lawsuit.. The NCI denied the claims, and says that there is little to no evidence that hydrazine sulfate has any beneficial effects whatsoever. The position of the NCI was supported by an inquiry held by the
General Accounting Office The U.S. Government Accountability Office (GAO) is a legislative branch government agency that provides auditing, evaluative, and investigative services for the United States Congress. It is the supreme audit institution of the federal gover ...
.


Clinical evaluation

A review of the clinical research concluded that hydrazine sulfate has never been shown to act as an anticancer agent; patients do not experience remissions or regressions of their cancer, and patients do not live longer than non-treated patients.. Some academic reviews of alternative cancer treatments have described the compound as a "disproved and ineffective treatment for cancer". Joseph Gold's claims have been questioned by the American Cancer Society, and other investigators have been unable to repeat or confirm these results. Gold is reported not to trust the motives or results of other investigators, with CNN quoting him as stating that "they've been out to get hydrazine sulfate, and I don't know why". In response to these results, an uncontrolled clinical trial was carried out at the Petrov Research Institute of Oncology in St. Petersburg over a period of 17 years,. and a controlled trial was carried out at the Harbor-UCLA Medical Center in California over period of 10 years, respectively. The Russian trial reported complete tumor regression in about 1% of cases, a partial response in about 3% of cases and some subjective improvement of symptoms in about half of the patients. The National Cancer Institute analysis of this trial notes that interpretation of these data is difficult, due to the absence of controls, the lack of information on prior treatment and the study's reliance on subjective assessments of symptoms (''i.e.'' asking patients if the drug had made them feel any better). Overall, the trials in California saw no statistically significant effect on survival from hydrazine sulfate treatment, but noted increased calorie intake in treated patients versus controls. The authors also performed a
post-hoc analysis In a scientific study, post hoc analysis (from Latin '' post hoc'', "after this") consists of statistical analyses that were specified after the data were seen. They are usually used to uncover specific differences between three or more group mea ...
on one or more subgroups of these patients, which they reported as suggesting a beneficial effect from treatment. The design and interpretation of this trial, and in particular the validity of this subgroup analysis, was criticized in detail in an editorial in the
Journal of Clinical Oncology The ''Journal of Clinical Oncology'' is a peer-reviewed medical journal published 3 times a month by the Lippincott Williams & Wilkins. It covers research on all aspects of clinical oncology. The journal was established in 1983 and the editor-in-c ...
. Later
randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical te ...
s failed to find any improvement in survival, For example, in a trial of the treatment of advanced
lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, malign ...
, with either
cisplatin Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, ...
and
vinblastine Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small cell lung cancer, bladder ca ...
or these drugs plus hydrazine sulfate, saw complete tumor regression in 4% of the hydrazine group, versus 3% in the control group, and tumor progression in 36% of the hydrazine group, versus 30% of the control group; however, none of these differences were statistically significant. Some trials even found both significantly decreased survival and significantly poorer quality of life in those patients receiving hydrazine sulfate. These consistently negative results have resulted in hydrazine sulfate being described as a "disproven cancer therapy" in a recent medical review. Similarly, other reviews have concluded that there is "strong evidence" against the use of hydrazine sulfate to treat anorexia or weight loss in cancer patients.


Side effects

Hydrazine sulfate is toxic and potentially
carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subs ...
ic..Section 9.2.1, . Nevertheless, the short-term side effects reported in various clinical trials are relatively mild:. minor nausea and vomiting, dizziness and excitement,
polyneuritis Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or o ...
(inflammation of the nerves) and difficulties in fine muscle control (such as writing). However, more serious, even fatal side effects have been reported in rare cases: one patient developed fatal liver and kidney failure,. and another developed serious symptoms of neurotoxicity. These side effects and other reports of hydrazine toxicity are consistent with the hypothesis that hydrazine may play a role in the toxicity of the antibiotic
isoniazid Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. For la ...
, which is thought to be metabolized to hydrazine in the body. Hydrazine sulfate is also a monoamine oxidase inhibitor (MAOI), and is incompatible with alcohol, tranquilizers and sleeping pills ( benzodiazepines and barbiturates), and other psycho-active drugs, with
pethidine Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a synthetic opioid pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemist Otto Eis ...
(meperidine, Demerol), and with foods containing significant amounts of the amino acid breakdown product
tyramine Tyramine ( ) (also spelled tyramin), also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood ...
, such as aged cheeses, raisins, avocados, processed and cured fish and meats, fermented products, and others.


References


External links

;Proponents
Syracuse Cancer Research Institute

The Truth About Hydrazine Sulfate - Dr. Gold Speaks
;Critics

Quackwatch
The Penthouse Politics of Cancer: The Promotion of Hydrazine Sulfate and a Medical Conspiracy Theory
American Council on Science and Health ;Governmental and medical

British Columbia Cancer Agency
What is rocket fuel treatment?
Cancer Research UK
Hydrazine Sulfate
American Cancer Society

University of Minnesota, Cancer Information

The University of Texas, M. D. Anderson Cancer Center ;Physical and chemical hazards

Material safety data sheet {{Sulfates Hydrazinium compounds Alternative cancer treatments IARC Group 2B carcinogens Sulfates