Cachexia (ka-kex-e-a), also known as cancer wasting, is an unfortunate yet common complication of cancer progression. The word “cachexia” comes from the Greek words “kakos”, meaning “bad”, and “hexis”, meaning “state or condition”. The Greek physician Hippocrates, known as the Father of Medicine, provided one of the earliest know descriptions of cachexia.
The shoulders, clavicles, chest and thighs melt away. This illness is fatal… —Hippocrates (460–370 BC)
Cachexia is characterized by unintentional weight loss, muscle wasting, decreased fat storage, hypermetabolism, and a loss of appetite. The onset of cachexia and the accompanying loss of energy and strength worsens survival rates, leading to diminished quality of life for sufferers as they are no longer able or interested in participating in activities that would ordinarily be enjoyable.
More than one process contributes to the cancer cachexia cascade in the body. All underlying factors are not yet fully understood, but certain important facts are known. Though ultimately the best way to treat cancer cachexia is to stop cancer growth and metabolism, understanding the underlying processes involved can help us find better ways to mitigate the impacts of cachexia on the body and improve quality of life.
Anaerobic Metabolism and Cancer
Cancer cells, unlike normal healthy cells, have a very inefficient metabolism, which diverts the body’s energy production away from the healthy cells and funnels everything towards cancer cell growth. Glucose is a major resource for cellular energy production. Most cells in the body require oxygen to convert glucose into energy (ATP) through the process of metabolism. Efficient aerobic (with oxygen) metabolism yields 38 moles of ATP per mole of glucose.
The oxygen concentration in cancer tumors, however, is critically low, especially as the tumor cells continue to grow and become cut off from oxygen-carrying blood vessels. In the absence of sufficient oxygen, cells can switch to a form of metabolism that does not rely on oxygen, the glycolytic pathway. Even when access to oxygen is restored, though, cancer cells still continue to use this anaerobic (without oxygen) metabolism. This is known as the Warburg effect, named for Otto Warburg who was awarded the Nobel Prize in 1931 for his research.
Anaerobic metabolism is a fermentation process. Not only is this form of metabolism very inefficient, yielding only 2 moles of ATP per mole of glucose, but it also produces lactate (lactic acid) as a waste by-product. Lactate is carried away by the blood stream to the liver, where it can then be converted back into glucose through the Cori cycle in a process known as gluconeogenesis. Cancer cells produce large amounts lactate, which lowers intracellular pH levels. Oxygen levels are directly related to pH levels, therefore anything that lowers pH levels lowers oxygen availability to the cells, which in turn continues to support anaerobic fermentation metabolism.
Gluconeogenesis and Increased Energy Demands
Glucose created in the liver from excess lactase through the process of gluconeogenesis is then circulated back into the bloodstream where it is made available again to the body’s cells for use. Gluconeogenesis requires much more energy (6 moles of ATP to produce 1 mole of glucose) than normal cellular energy reactions and is therefore much less efficient. The liver gets the required ATP energy through oxidation of amino acids and fatty acids, which may contribute to cancer cachexia weight loss, even when caloric intake is adequate. In addition, the majority of energy used in the process of gluconeogenesis is dissipated as heat, which can contribute to elevated body temperature and sweating. In cancer patients who are experiencing weight loss, a 40% increase in glucose production in the liver has been reported, which can lead to the increased energy expenditure seen during the development of cachexia as the body struggles to meet the cancer cells’ growing metabolic demands.
Cancer cells’ voracious energy requirements divert much needed energy from the rest of the body. Because growing tumor cells must rely solely on anaerobic glucose fermentation for energy, they require almost 40x more glucose than a normal healthy cell requires in the presence of sufficient oxygen. This imbalance between energy intake and energy expenditure eventually depletes the body’s energy reserves. Food intake becomes inadequate to the ongoing energy demands, which leads to the vicious cachexia cycle: loss of weight, loss of muscle mass, loss of energy, and loss of appetite.
Dr. Joseph Gold and Hydrazine Sulfate
Dr. Joseph Gold, founder of the Syracuse Cancer Research Institute (SCRI), researched cancer cachexia. Dr. Gold’s theory was that if the conversion process that cancer cells use to recycle and reuse their own waste products could be interrupted, this altered metabolism could be normalized and cancer cachexia could be reversed. Dr. Gold’s research at SCRI lead to the discovery of the “gluconeogenic blocking agent” Hydrazine Sulfate which could shut down the liver enzyme necessary for gluconeogenesis through the Cori cycle.
Hydrazine Sulfate is a dietary supplement available liquid and capsuleform. Hydrazine Sulfate was first proposed as an anticachexia agent based on its inhibition of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEP CK). In other words, it can inhibit a key enzyme necessary for the production of glucose from lactic acid, thereby potentially short-circuiting the cachexia process. Excess lactic acid that is not being converted to glucose can be excreted by the kidneys.
Tumor energy demands and host energy loss (resulting from cancer-induced excessive gluconeogenesis) are interrelated, therefore Hydrazine Sulfate was proposed as an indirect and non-toxic method for inhibiting tumor growth. A selective block against gluconeogenesis has no effect on glycolysis, which is the process through which normal healthy tissues, in the presence of oxygen, derive a significant portion of their energy supply.
According to the Syracuse Cancer Research Institute (SCRI), which for the past 20 years has collected reports from thousands of doctors, veterinarians, and individuals using hydrazine sulfate, the following results have been observed: 50% measurable symptomatic improvement, 40% tumor stabilization or regression, 5%-10% long term “complete response,” i.e., survival.
Clinical Trials and Research
Clinical trials performed in accordance with internationally accepted criteria and standards of scientific conduct have been published in several peer-reviewed medical journals and have indicated the efficacy and safety of Hydrazine Sulfate. A large-scale nine year study in Russia begun in the 1970s found a 50% subjective anti-cachexia response, 46% anti-tumor response, and the absence of important clinical side effects. In various trials, Hydrazine Sulfate has been shown to improve glucose tolerance, reduce glucose turnover, increase caloric intake, increase or stabilize weight, increase appetite, diminish anorexia, improve performance status, decrease pain, stabilize tumor growth, induce tumor regression, and promote survival.
The only contrary (and controversial) results, according to Dr. Gold, have been from National Cancer Institute sponsored trials which, wittingly or unwittingly, used known incompatible medications while testing Hydrazine Sulfate. Hydrazine Sulfate is a potent monoamine oxidase (MAOI) inhibitor that can have potentially serious interactions with central nervous system depressants such as barbiturates, tranquilizers, and alcohol. It is known that using these incompatible agents together can result in extremely dangerous effects. Yet the National Cancer Institute (NCI), despite being notified of this known clinical hazard, ignored the warnings in their sponsored trials. In a later “retrospective analysis” the NCI stated that even if there were an incompatibility between Hydrazine Sulfate and alcohol, tranquilizers and barbiturates, usage of these substances made no difference anyway to the studies’ outcome.
In an investigation into the incidents, a report titled “NIH Actions Spur Continued Controversy Over Hydrazine Sulfate Therapy” stated that “NCI did not conduct adequate oversight of these trials. It did not take sufficient measures to appropriately address concerns over alleged incompatible agents….The clinical importance of possible interaction between hydrazine sulfate and tranquilizing agents, barbiturates, or alcohol has not been determined and the issue remains unsettled.”
Although Hydrazine Sulfate was shown to be carcinogenic in a study of weanling mice given Hydrazine Sulfate in their drinking water since birth, in over 30 years of use, there are just a handful, if any, cases of cancer in humans reported as a presumed result of Hydrazine Sulfate. and there has only been one presumptive case of fatal Hydrazine Sulfate toxicity. Compare this to routine chemotherapy drugs, which can produce a significant percentage of secondary cancers and cause known fatalities.
Side effects have been minimal, are usually mild and transient in nature, and may only appear after prolonged use. Symptoms include nausea, pruritus (itching), dizziness, drowsiness, excitation, polyneuritis (peripheral neuritis), and euphoria (mood improvement).
How to Use Hydrazine Sulfate
Hydrazine Sulfate is a dietary supplement and is not intended to treat, cure, mitigate or prevent any disease, including cancer. As a dietary supplement, a standard adult serving size is 30 mg. Many times it is recommended to start with one serving per day, then incrementally increase the amount of servings over a period of days. A break may be suggested after 1-2 months. Always consult with someone knowledgeable and experienced with hydrazine sulfate to ensure correct usage. The liquid form of Hydrazine Sulfate is highly recommended, especially for those who have lost their appetite or those for whom swallowing pills is difficult. The liquid is practically tasteless and is readily accessible to the body, being absorbed quickly.
Hydrazine Sulfate is an MAO (monoamine oxidase) inhibitor and does have potential conflicts with certain medications and foods that it is important to be aware of. Central nervous system depressants such as barbiturates, tranquilizers, morphine, alcohol, and certain antihistamines are incompatible with MAO inhibitors and cannot be taken together.
As with any MAO inhibitor, following a low-tyramine diet is important. Eating foods high in tyramine while using MAO inhibitors like Hydrazine Sulfate can cause side effects such as high blood pressure, headaches, heart palpitations, nausea, vomiting, visual disturbances, and confusion. Tyramine is found in fermented, aged, and spoiled foods, or foods that have been stored for a prolonged periods, but the tyramine content of food can vary greatly. Reactions to tyramine are dose-dependent, therefore some tyramine-containing foods may not pose as great of a risk if consumed only in very small quantities. When in doubt, though, you should always go without.
Cachexia in Pets
Cancer wasting is especially difficult in pets. When a pet stops eating, they can quickly lose energy and begin to lose their will to live. Enticing a pet to eat can become ever increasingly more difficult situation. In pets, Hydrazine Sulfate has been used as an appetite stimulant. If you can get a pet to eat, it will greatly help keep up their energy levels and improve their quality of life. Serving size in pets varies greatly by weight. Very large dogs may use a normal adult serving size, but cats and small dogs will use a much smaller serving size. For pets, the liquid form of Hydrazine Sulfate is by far the easiest to use. It is practically tasteless and can be quickly administered with a syringe or a small eyedropper.
Is Hydrazine Sulfate the Answer to Cachexia?
If someone you know is experiencing an increased loss of appetite, energy, muscle mass and weight while dealing with cancer, they may be in cachexia. The diminished quality of life created by cachexia can be improved if the wasting process can be halted. The sooner cachexia is addressed, the better the chance of slowing or even reversing its progress. As with anything, outcomes vary greatly, but Hydrazine Sulfate has exhibited some promising results with a low risk of side effects as long as diet and medication precautions are observed. For these reasons, Hydrazine Sulfate is definitely something worth looking into. Always consult your health care provider before starting any new supplement program.
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