In order to properly achieve weight loss you ought to maintain disciplined weight loss objectives and keep a sustained degree of determination and persistence to make sure you stand a great chance. Despite the fact that it depends on your initial weight, an idea of a reasonable objective could be to reduce 2 lbs (about 900g) weekly. Otherwise, you might want to establish longer term objectives, for example dropping 20% of your weight or, how about, 30 lbs (about 14 kg) during the following 3 months. Through establishing objectives and retaining a self-disciplined strategy to weight loss, it is possible to attain your required weight loss.

However, there is no way to lose weight without feeling some degree of hunger. Hunger control is obviously the key to successful weight loss. There are many strategies that help reduce hunger: avoiding refined carbohydrates, getting plenty of natural sunlight on your skin, drinking large amounts of water on a regular basis, and getting plenty of fiber in your diet. But there is nothing that absolutely eliminates hunger. Your body’s natural response to calorie deprivation is to increase hunger.

We overeat for lots of reasons, not just because we’re hungry. It is far more complicated than that. A lot of it has to do with hormones secreted by fat cells (leptin) and by stomach and gastrointestinal (GI) tract (Ghrelin, CCK, Neuropeptide YY and others). These hormones interact with central nervous system (brain/hypothalamus) in a way you could describe as turning up the appetite dial a notch. Many of the peptides that are involved in the regulation of food intake in the brain are also found in the enteric nervous system and enteroendocrine cells of the mucosa of the GI tract. Calories go down, appetite goes up, and you go looking for food.

Neuroendocrine control of food intake.

The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis.

Appetite signaling: from gut peptides and enteric nerves to brain.

Gut peptides and the regulation of appetite.

Brain-gut axis and its role in the control of food intake.

People who have tried, but not had success with a number of slimming pills may want to listen up – there’s a new “miracle weight loss solution” and “perfect hunger control solution”. Now imagine if losing weight was this simple and relaxing as well. By fueling your body with the right natural foods and treating your body to comfortable and calming beauty treatments, Herbalzym-Diet.

Herbalzym-Diet provides the perfect solution for anyone who has trouble controlling appetite. It turns off your hunger like a light switch. It is easy, simple, natural ways to curb cravings without adding calories. Perfect late at night or for between-meal cravings no matter what diet plan you’re on. Take 20 ml (about 0.7 fl oz) of Herbalzym-Diet (or mixing it with 1 fl oz or 30 ml cold low fat milk). You’ll probably notice lots of different sensation in your mouth, stomach and gastrointestinal area. So, relax, take a deep breath, and pay attention to everything.

Here are a few methods for teaching yourself to breathe deeply.

• Good breathing posture can help you breathe more efficiently and identify the muscles you engage when inhaling and exhaling (Lie on your back on the floor, and take a deep breath. Feel it growing your lungs. In this placement, you can completely fill your lungs with air. Check out your stomach rise as you inhale completely)
• Beginners sit in a chair with feet flat on the floor or in the lotus position with hands placed on the knees with the palms facing upward, the thumb and index finger together. (Advanced beginners stand up straight with your shoulders back and your pelvis tilted marginally forward. Keep your shoulders, hips, and feet in line with your knees very slightly bent.)
• Bring up your head, but not into an unnatural position. Close your eyes and focus your mind’s eye on your belly button area.
• Breathe through the nose. Do not stop at the top or bottom of your breath. Quiet breathing is especially important.
• Slowly inhale through your nose (8 seconds), drawing the breath toward the abdomen, expanding it, and filling up your belly. Check out your stomach rise as you inhale completely.
• Gently exhale through your nose (8 seconds). Exhale all stale air from lungs, contracting abdominal muscles to squeeze out the last remnants.
• Do this for 20 cycles, and build up to 10 minutes at a sitting.
• Breath in and out several times with precision and attention to detail, then you may arrive at the slight lightness of head – this coming from the oxygen increase

As well as the mental and spiritual benefits, complete breath increases oxygen supply to the blood, bring vitality to all the organs. Complete breath also slows the heart rate. It has a calming effect on central nervous system. The key is to be thorough when you inhale and exhale. Don’t take low depth breaths or release them too fast. You can significantly increase your breath control with this practice method. As you expand your lung capacity, you will have a chance to work at 10 and even 12 second intervals. Notice how powerful this breath feels compared to the breaths you take when you’re leaning over. Feel full… eat well… be slim… be healthy.

What is in Herbalzym-Diet?

Herbalzym-Diet is probiotic-rich fermented liquid formula. Probiotics are live microorganisms that when administered in adequate amounts confer a health benefit on the host. Herbalzym-Diet contains wild-harvested edible mushroom extracts, plant enzymes, herb and vegetable seeds, yucca schidiggera extract, unpasteurized organic wildflower honey, etc.

To create the highest level of concentrated nutrients’ Herbalzym-Diet is fermented naturally. Fermentation is a natural method of concentrating raw food materials, and preserving them. But Herbalzym-Diet uses no ordinary fermentation process. Mushrooms have tough cell walls, which lock health benefits away in indigestible chitin. Fermentation process makes these molecules more available and can help neutralize smaller levels of toxins. Mushrooms really shouldn’t be eaten raw. Fermentation adds new nutrients, and makes the entire symphony of ingredients easy to digest, and more quickly absorbed by your body. Our “unique” fermentation process retains and amplifies the probiotic power of Herbalzym-Diet.

A common misconception about mushrooms is that they are of no nutritional value. However, mushrooms are not only delicious and so versatile, but they are crazy-loaded with nutrition and powerful healing properties. They contain numerous substances including glycoproteins, glyconutrients, etc. Mushrooms are rich in disease-fighting phytochemicals. They are also rich in most vitamins, particularly B and C, and contain practically all the major minerals, particularly potassium, magnesium, phosphorus, iron, copper, zinc and selenium. They supply hard-to-get nutrients.

Mushrooms are low in calories, carbohydrates, fat and sodium. They are very high in water content and fiber which makes them a great diet food. Herbalzym-Diet is made from 4 species of wild-harvested edible mushrooms. These mushrooms have been specifically selected by species and geographical growth area to complement each other in supporting the cell’s metabolism, cell function, immune system, and endurance. This is a powerfully protective tonic and excellent for weight loss.

Here are synergistic superior 4 blends;

• Shitake (Lentinus edodes); Beta-glucans (including Lentinan and the Alpha-glucan KS-2)
• Porcini(Boletus edulis); Beta-glucans, Lectin, Polysaccharides
• Oyster (Pleurotus ostreatus); Lectin, Beta-glucans (Pleuran), Statins (lovastatins)
• Agaricus (Agaricus blazei Murill); Lectin, Agaritine, Beta-glucans (1-3, 1-4, 1-6, D-Beta glucan)

Many species of wild edible mushrooms with medicinal value are widely used for a broad range of diseases. Some species are regarded as therapeutic food for their anti-carcinogenic, anti-cholesteroremic and anti-viral properties. The oyster mushroom contains statins such as lovastatin which work to reduce cholesterol. Most of them possess polysaccharides (complex sugar molecules) called beta-glucans that increase RNA and DNA in bone marrow where immune cells are made. Beta-glucans and other polysaccharides specifically activate the immune system’s cells (such as macrophages, interferon, T cells, and natural killer cells). Beta-glucans are also used to fight high cholesterol by lowering the LDL cholesterol (also known as “bad” cholesterol) levels and raising the HDL cholesterol (also known as “good” cholesterol) levels. They have even been shown to help with diabetes, cancer, allergies, hepatitis, asthma and more. Beta-glucans are also found in yeast, oat bran and other plants

You can literally turn your metabolism into your fat burning slave by ensuring you always have an internal environment primed for burning fat and you do it with your favourite foods. Herbalzym-Diet creates the perfect environment in your body that allows you to burn fat fast, and delivers what your body is hungry for:

• A real aid in achieving your weight loss goals
• A perfect hunger control
• A metabolism support
• A fat flush
• A regular and healthy bowel
• A renovation in the clarity, texture, and tone of your skin
• A new energy — the energy you’ve been missing for years
• A boost in the strength of your body’s immunity

Wild and commercial mushrooms as source of nutrients and nutraceuticals.

Edible mushrooms: role in the prevention of cardiovascular diseases.

Functional properties of edible mushrooms.

Lack of energy compensation over 4 days when white button mushrooms are substituted for beef.

Dietary Shiitake Mushroom (Lentinus edodes) Prevents Fat Deposition and Lowers Triglyceride in Rats Fed a High-Fat Diet.

Pleurotus fruiting bodies contain the inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase-lovastatin.

Fermented mushroom milk-supplemented dietary fibre prevents the onset of obesity and hypertriglyceridaemia in Otsuka Long-Evans Tokushima fatty rats.

Chemical analysis and antioxidant activity in vitro of polysaccharides extracted from Boletus edulis.

Immunological effects of yeast- and mushroom-derived beta-glucans.

Cholesterol-lowering effects of oat β-glucan.

Concentrated oat beta-glucan, a fermentable fiber, lowers serum cholesterol in hypercholesterolemic adults in a randomized controlled trial.

In addition, it’s important to get blood sugar under control to help restore insulin sensitivity through the right nutrition. This means greatly reducing sugars and refined starches in your diet (including fully eliminating any use of harmful high fructose corn syrup), and focusing more of your diet on healthy fats (such as coconut fat, fatty fish and fish oils, avocados, nuts, seeds, olive oil, free-range eggs, etc), as well as increasing protein and fiber intake. The best weight loss tips is following a diet plan without costing your health, without feeling hungry and most importantly without getting the extra weight back once you stop the diet. The way to do this is to increase the pace of your metabolism. And the best way to succeed is to get into the habit of deep breathing exercise. Deep breathing exercise routines are also very effective at increasing your fat-burning hormones and creating a hormonal environment conducive to burning off abdominal fat, including visceral fat. Deep breathing is an essential part of maximizing any form of exercise you do.

Several species of mushrooms have been used as adaptogens (also known as biological response modifiers), or general tonics, to promote overall wellness and vitality. There are many botanicals that act as adaptogens to assist the body in adapting to environmental and psychological stress. Adaptogens, including medicinal mushrooms, benefit all of the important systems of the body, including the nervous, endocrine, adrenal, and immune systems, by increasing or decreasing their function, as needed, for maximum health. A common misconception about mushrooms is that they are of no nutritional value. However, mushrooms are not only delicious and so versatile, but they are loaded with nutrition and powerful healing properties. They contain numerous substances including glycoproteins, glyconutrients, etc. Mushrooms are rich in disease-fighting phytochemicals. They are also rich in most vitamins, particularly B and C, and contain practically all the major minerals, particularly potassium, magnesium, phosphorus, iron, copper, zinc and selenium. They supply hard-to-get nutrients.

All wild edible mushrooms contain medicinal qualities too, as most of them possess polysaccharides (beta glucans). Beta-glucans and other polysaccharides specifically activate the immune system’s cells (such as macrophages, interferon, T cells, and natural killer cells) in order to prevent the multiplication, metastasis, and recurrence of cancer cells. Another function of beta-glucans is to attach to the receptor sites on the immune cells and to activate them, allowing them to recognize the cancer cells as “foreign invaders” and creating a higher state of  immune response. Laboratory experiments have confirmed that several substances in wild edible mushrooms, in addition to the beta-glucans and other polysaccharides, have anti-tumor effects. These include nucleic acids, lectins, sterols, and lipids. The combination of these compounds in mushrooms is believed to enhance the functioning of the immune system. All wild edible mushrooms are probiotic, meaning that they help our body strengthen itself and fight off illness by maintaining physiological homeostasis, restoring our bodies balance and natural resistance to disease.

Immunological effects of yeast- and mushroom-derived beta-glucans.

Functional properties of edible mushrooms.

Chemical analysis and antioxidant activity in vitro of polysaccharides extracted from Boletus edulis.

Oral ingestion of Lentinula edodes mycelia extract can restore the antitumor T cell response of mice inoculated with colon-26 cells into the subserosal space of the cecum.

Characterization and immunomodulating activities of polysaccharide from Lentinus edodes.

Effect of polysaccharide from cultured Cordyceps sinensis on immune function and anti-oxidation activity of mice exposed to 60Co.

Immunostimulating activity of the polysaccharides isolated from Cordyceps militaris.

The Mushroom Agaricus blazei Murill Elicits Medicinal Effects on Tumor, Infection, Allergy, and Inflammation through Its Modulation of Innate Immunity and Amelioration of Th1/Th2 Imbalance and Inflammation.

Potential antitumor activity of a low-molecular-weight protein fraction from Grifola frondosa through enhancement of cytokine production.

Structure of a lectin with antitumoral properties in king bolete (Boletus edulis) mushrooms.

The antineoplastic lectin of the common edible mushroom (Agaricus bisporus) has two binding sites, each specific for a different configuration at a single epimeric hydroxyl.

Anti-inflammatory activity of edible oyster mushroom is mediated through the inhibition of NF-κB and AP-1 signaling.

Immunostimulatory activities of a low molecular weight antitumoral polysaccharide isolated from Agaricus blazei Murill (LMPAB) in Sarcoma 180 ascitic tumor-bearing mice.

Many species of wild edible mushrooms with medicinal value are widely used for a broad range of diseases. Some species are regarded as therapeutic food for their anti-carcinogenic, anti-cholesteroremic and anti-viral properties. Unlike most other complementary or alternative cancer therapies offered in America, the substances in medicinal mushrooms are being used as mainstream therapy in China, Japan and Korea, and have actually been proven (in laboratory, animal, and human studies) to have powerful anti-tumor activity. They have also been shown to significantly enhance the body’s own immune system to eliminate, or stop the spread, of many cancerous tumors. These so called biological response modifiers can be potent antiviral and antitumor agents, not by killing viruses or cancer cells directly but by stimulating the body’s innate ability to marshal cellular defenses. In a recent clinical trial, immune-assist has been shown to significantly reduce the adverse effects of radiation and chemotherapy, including loss of appetite, energy, and hair, as well as reducing the incidence of nausea.

The reality is that this fascination for the medicinal value of wild edible mushrooms is not new. For 3,000 years, the Chinese have looked to mushrooms for their healing powers. The Japanese and Korean have also looked into the healing properties of mushrooms for centuries, so it is fitting that many modern day discoveries regarding the medicinal application of mushrooms have been pioneered by them. In almost all entire laboratory studies published to date, the rate of remission for all types of cancer has been in the high 90% range. While most of these studies have been done with animals, similar results may be shown as clinical studies are conducted on humans. One human study showed that human subjects given wild edible mushrooms in their diet experienced an increase of NK (Natural Killer) cells of 3,000% in 2-4 days.

Oral ingestion of Lentinula edodes mycelia extract inhibits B16 melanoma growth via mitigation of regulatory T cell-mediated immunosuppression.

Anticancer activity of subfractions containing pure compounds of Chaga mushroom (Inonotus obliquus) extract in human cancer cells and in Balbc/c mice bearing Sarcoma-180 cells.

Cancer cell cytotoxicity of extracts and small phenolic compounds from Chaga [Inonotus obliquus (persoon) Pilat].

Natural killer cell activity and quality of life were improved by consumption of a mushroom extract, Agaricus blazei Murill Kyowa, in gynecological cancer patients undergoing chemotherapy.

Agaricus blazei Murill enhances doxorubicin-induced apoptosis in human hepatocellular carcinoma cells by NFκB-mediated increase of intracellular doxorubicin accumulation.

Agaritine from Agaricus blazei Murrill induces apoptosis in the leukemic cell line U937.

Maitake (D fraction) mushroom extract induces apoptosis in breast cancer cells by BAK-1 gene activation.

Characterization and antitumor effect of a novel polysaccharide from Grifola frondosa.

Commonly consumed and specialty dietary mushrooms reduce cellular proliferation in MCF-7 human breast cancer cells.

Pleurotus ostreatus inhibits proliferation of human breast and colon cancer cells through p53-dependent as well as p53-independent pathway.

Inhibitory mechanisms of Agaricus blazei Murill on the growth of prostate cancer in vitro and in vivo.

A low molecular weight polysaccharide isolated from Agaricus blazei suppresses tumor growth and angiogenesis in vivo.

Recent research has indicated that whole mushroom extracts, with concentrations of polysaccharides, are more effective than isolated polysaccharides. Several studies have shown that other components of the mushrooms, besides the polysaccharides, also have anti-cancer and healing properties. The combination of all these elements, as found in whole mushroom extracts, appears to be superior. Hepazym-F is a potent, and very safe, pharmaceutical quality blend of 7 effective mushroom extracts to be used in conjunction with chemotherapy, radiation, or surgery. This formula can also be used by people who have completed conventional cancer treatment, or by people who just want to significantly strengthen their immune systems to aid in warding off illness and disease.

There are over 400 species of wild edible mushrooms. Research proved that all wild edible mushrooms are not equal. The nutritional and therapeutic value of a species of wild edible and medicinal mushrooms varies, depending on the geographical area of growth. Hepazym-F is developed to bring together a mixture of some of the most powerful and research-supported immune modulating mushrooms along with the added benefits of the anticancer, antiviral, antibacterial, antiinflammatory, hepatoprotective, and antioxidant activities. Hepazym-F is made from 7 species of wild-harvested edible mushrooms. These mushrooms have been specifically selected by species and geographical growth area to complement each other in supporting the immune system, cell function and endurance. This is a powerfully protective tonic and excellent for building immune function. Hepazym-F is purified using a specific double-extraction method to concentrate a broad range of medicinal elements. This extraction method keeps the delicate enzymes and other phytonutrients intact. This is the most beneficial extraction method because of its ability to preserve and concentrate all the wonderful things that Hepazym-F has to offer.

To create the highest level of concentrated nutrients, Hepazym-F is fermented naturally. Fermentation is a natural method of concentrating raw food materials, and preserving them. But Hepazym-F uses no ordinary fermentation process. Mushrooms have tough cell walls, which lock health benefits away in indigestible chitin. Fermentation process makes these molecules more available and can help neutralize smaller levels of toxins. Mushrooms really shouldn’t be eaten raw. Fermentation adds new nutrients, and makes the entire symphony of ingredients easy to digest, and more quickly absorbed by your body. Our ”unique” fermentation process retains and amplifies the probiotic power of Hepazym-F. Unlike ordinary food processing, our fermentation system not only improves the overall nutritional value of the phyto-dense formula, it reduces toxins and anti-nutritive by-products. This is the great advantage of its probiotic effect in your body. Hepazym-F creates the perfect environment for your probiotics to thrive, and delivers what your body is hungry for: a regular and healthy bowel, a renovation in the clarity, texture, and tone of your skin, a new energy – the energy you’ve been missing for years, a real aid in achieving your weight loss goals, and a boost in the strength of your body’s anticancer immunity.

Here are synergistic superior 7 blends;

• Shitake (Lentinus edodes); Beta-glucans (including Lentinan and the Alpha-glucan KS-2)
• Chaga (Inonotus obliquus); Beta-glucans , Protein bound polysaccharide (xylogalactoglucose), Triterpenes, Melanin complex, Ergosterols, Betulin and Betulinic acid (concentrated from Birch bark)
• Cordyceps sinensis; Beta-glucans (plus Deoxyadenosine and other nucleosides), Mannitol (Cordicepic acid), Adenosine
• Maitake (Grifola frondosa); Beta-glucans, Protien bound polysaccharide
• Porcini (Boletus edulis); Beta-glucans, Lectin, Polysaccharide (BEPF30, BEPF60 and BEPF80)
• Oyster (Pleurotus ostreatus); Lectin, Beta-glucans (Pleuran), Statins (lovastatins)
• Agaricus (Agaricus blazei Murill); Lectin, Agaritine, Beta-glucans (1-3, 1-4, 1-6, D-Beta glucan)

Extracellular adenosine initiates most of its effects through the activation of adenosine receptors. There are at least four subtypes of the adenosine receptor A1, A2A, A2B and A3 receptors. Adenosine receptors are all coupled to G-proteins and the A1 and A3 subtypes are associated with inhibitory G-proteins. Each of these four cell surface adenosine receptors (ARs) is found to be upregulated in various tumor cells. It is overexpressed in inflammatory and cancer cells, while low expression is found in normal cells. The adenosine receptors are important and ubiquitous mediators of cellular signaling, which play vital roles in protecting tissues and organs from damage. In particular, adenosine triggers tissue protection and repair by different receptor-mediated mechanisms, including an increase of oxygen supply/demand ratio, preconditioning, anti-inflammatory effects, and stimulation of angiogenesis. Activation of the receptors by specific ligands, agonists or antagonists, modulates tumor growth via a range of signaling pathways. At the present time, it can be speculated that adenosine A1, A2A, A2B, and A3 receptor-selective ligands may show utility in the treatment of cancer and other disorders in which inflammation is a feature.

Introduction to adenosine receptors as therapeutic targets.

Adenosine receptors and cancer.

Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review).

Enhancement of tumor immunotherapy by deletion of the A(2A) adenosine receptor.

Adenosine metabolism and cancer. Focus on “Adenosine downregulates DPPIV on HT-29 colon cancer cells by stimulating protein tyrosine phosphatases and reducing ERK1/2 activity via a novel pathway”.

A3 adenosine receptor as a target for cancer therapy.

The A3 adenosine receptor is highly expressed in tumor versus normal cells: potential target for tumor growth inhibition.

Differential effect of adenosine on tumor and normal cell growth: focus on the A3 adenosine receptor.

Elevated expression of A3 adenosine receptors in human colorectal cancer is reflected in peripheral blood cells.

The A3 adenosine receptor as a new target for cancer therapy and chemoprotection.

Induction of apoptosis by A3 adenosine receptor agonist N-(3-iodobenzyl)-adenosine-5′-N-methylcarboxamide in human leukaemia cells: a possible involvement of intracellular mechanism.

Adenosine A2B Receptor Blockade Slows Growth of Bladder and Breast Tumors.

Hypoxia-inducible adenosine A2B receptor modulates proliferation of colon carcinoma cells.

The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-kappaB signal transduction pathways.

CF102 an A3 adenosine receptor agonist mediates anti-tumor and anti-inflammatory effects in the liver.

Adenosine A1 receptor, a target and regulator of estrogen receptoralpha action, mediates the proliferative effects of estradiol in breast cancer.

Methylxanthines, such as caffeine and theophylline, can function as antagonists of adenosine receptors, and their stimulant actions occur primarily through this mechanism. Theophylline is a prescription medication to treat airway spasms in people with asthma or COPD. Caffeine is a mild stimulant. It can be found in many weight loss pills to boost the metabolism. But there are a number of additional situations where caffeine can serve important medical uses. Several studies have found connections between caffeine and cancer. Caffeine is similar in structure to adenosine, and binds to those receptors so that adenosine cannot bind. Caffeine acts mainly via blockade of adenosine receptors. In conclusion, targeting approaches that involve ARs will enhance the possibilities to cure cancer naturally, via the universally consumed substance that is caffeine.

Emerging adenosine receptor agonists – an update.

Methylxanthines, inflammation, and cancer: fundamental mechanisms.

Xanthines as adenosine receptor antagonists.

Caffeine and adenosine.

Analogues of caffeine and theophylline: effect of structural alterations on affinity at adenosine receptors.

Modulation of cellular response to anticancer treatment by caffeine: inhibition of cell cycle checkpoints, DNA repair and more.

Caffeine inhibits adenosine-induced accumulation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and interleukin-8 expression in hypoxic human colon cancer cells.

Caffeine intake induces an alteration in human neutrophil A2A adenosine receptors.

Caffeine is a very common substance that is contained in coffee, tea, chocolate, soft drinks, and can also be purchased as capsules, tablets, or powder. An estimated 80% of the world’s population consumes a caffeine-containing substance daily. A typical 8-ounce (240-ml) cup of instant coffee contains about 100 mg of caffeine — about twice as much as a cup of tea or a 12-ounce (360-ml) can/bottle of soda. A 30-gram chocolate bar might contain as much caffeine as half a cup of tea. Pure caffeine can be obtained in powders, caplets or tablets in products like NoDoz, Stay Awake and Vivarin.

It’s generally agreed that consuming up to 300 mg of caffeine per day is safe. That’s roughly the amount of caffeine you would get from three cups (not mugs or big paper cups) of coffee. Consuming more than 300 mg caffeine per day may give you the “caffeine jitters.” Larger amounts of caffeine may make you irritable, sleepless and may even trigger anxiety and cause diarrhea. Some people are more sensitive to caffeine than are others. So we cannot suggest a universally safe dose. However, it is believed that the expected treatment effect of caffeine is time-dependent and dose-dependent. Some packages will use an age range to figure dose, but it is more effective to dose by weight. So, we recommend you take 4.5 mg per pound of body weight (for metric users, that’s 10mg per kilo). For example: a 133-pound woman would get about 600mg (133 X 4.5 =598) caffeine per day (200mg 3times daily) in combination with 5-LOX inhibitor such as BosturZym. BosturZym has synergistic effect with caffeine against cancer and leukemia. You can take them all together.

Lethal Enzyme 5-LOX and Cancer

Please Note: Caffeine in concentrated forms such as pills or powders can accidentally be taken insufficient quantities to cause nausea, vomiting, stomach upset, trouble sleeping, increased urination, or unconsciousness. If any of these effects persist or worsen, tell your doctor or pharmacist promptly. A single box of Vivarin or No-Doze can be fatal if taken at one time. Although possible with coffee or other strongly caffeinated drink, it generally requires much more awareness of the large dosage before dangerous levels are reached.

        Oral Caffeine Dosages

• Threshold: 10 – 20 mg
• Common: 50 – 150 mg
• Strong: 150 – 400 mg
• Heavy: 400 + mg
• Lethal: 3-20 grams oral (estimated)
• LD50 (Lethal Dose): 192 mg/kg in rats. (LD50 = dose which will kill 50% of the tested animals. It is estimated that fatal doses for humans are between 3 and 20 grams of caffeine taken orally, depending on body weight and tolerance.

       Onset : 5 – 10 minutes
       Duration : 1.5 – 5 hours, Normal After Effects : up to 24 hours

In response to poor dietary choices, our bodies suffer an overload of AA, and the body increases production of enzymes like 5-Lipoxygenase (5-LOX) to remove AA. There are three main LOX enzymes that are known to be involved in the leukotriene pathway, 5-LOX, 12-LOX, and 15-LOX. Most attention has focused on 5-LOX, which appears to be the key enzyme when it comes to blocking leukotriene synthesis. 5-LOX is expressed mainly in leukocytes, dendritic cells and in foam cells of atherosclerotic tissue (in other cells synthesis is blocked by DNA methylation). 5-LOX is a key enzyme in the metabolism of AA to leukotrienes. 5-LOX converts AA to leukotrienes, which are able to enhance proliferation, increase survival, and suppress apoptosis of human cells. Leukotrienes are potent lipid mediators that are significantly involved in immunoregulation, asthma, inflammation and several allergic conditions. Inflammatory mediators such as leukotrienes cause an increased expression and re-distribution of proteins, characteristic of transformed cells, in normal cells. These alterations involve distinct upstream signaling mechanisms and lead to an altered rate of apoptosis and proliferation, changes that could increase the risk for a subsequent tumour development. These mediators could possibly explain the relation between inflammatory conditions and tumour development.

Roles of inflammation in cancer initiation, progression, and metastasis.

Regulation of inflammation in cancer by eicosanoids.

Eicosanoid signalling pathways in the development and progression of colorectal cancer: novel approaches for prevention/intervention.

Beta-adrenergic and arachidonic acid-mediated growth regulation of human breast cancer cell lines.

Structures and mechanisms of enzymes in the leukotriene cascade.

Leukotriene B4 creates a favorable microenvironment for murine melanoma growth.

5-LOX has been implicated in the development and progression of cancers including lung, liver, prostate, pancreatic, colorectal, brain, breast and esophageal cancers. Several pieces of experimental data form the basis for this hypothesis and suggest a correlation between 5-LOX expression and tumor cell viability. First, several independent studies documented an overexpression of 5-LOX in primary tumor cells as well as in established cancer cell lines. Second, addition of 5-LOX products to cultured tumor cells also led to increased cell proliferation and activation of anti-apoptotic signaling pathways. 5-LOX antisense technology approaches demonstrated impaired tumor cell growth due to reduction of 5-LOX expression. Lastly, pharmacological inhibition of 5-LOX potently suppressed tumor cell growth by inducing cell cycle arrest and triggering cell death via the intrinsic apoptotic pathway.

Lipoxygenase metabolism: roles in tumor progression and survival.

5-lipoxygenase: underappreciated role of a pro-inflammatory enzyme in tumorigenesis.

5-Lipoxygenase contributes to the progression of hepatocellular carcinoma.

Lipoxygenase-5 is overexpressed in prostate adenocarcinoma.

5-Lipoxygenase, a marker for early pancreatic intraepithelial neoplastic lesions.

Increased expression of 5-lipoxygenase is common in clear cell renal cell carcinoma.

5-LOX inhibitors induce programmed cell death by an enhanced membrane expression of TRAIL receptors on the membranes of cancer cells, and raise the possibility that the combination of 5-LOX inhibitor and TRAIL is a promising strategy for cancer treatment. In addition, these inhibitors also activate other death signaling pathways in
cancer cells.

Lipoxygenase inhibitors induce death receptor 5/TRAIL-R2 expression and sensitize malignant tumor cells to TRAIL-induced apoptosis.

Overexpression of 5-lipoxygenase in colon polyps and cancer and the effect of 5-LOX inhibitors in vitro and in a murine model.

Inhibition of 5-lipoxygenase triggers apoptosis in prostate cancer cells via down-regulation of protein kinase C-epsilon.

Inhibition of arachidonate 5-lipoxygenase triggers prostate cancer cell death through rapid activation of c-Jun N-terminal kinase.

Inhibition of 5-lipoxygenase pathway suppresses the growth of bladder cancer cells.

5-Lipoxygenase inhibitors attenuate growth of human renal cell carcinoma and induce apoptosis through arachidonic acid pathway.

Increased 5-lipoxygenase expression and induction of apoptosis by its inhibitors in esophageal cancer: a potential target for prevention.

Lipoxygenase inhibitors attenuate growth of human pancreatic cancer xenografts and induce apoptosis through the mitochondrial pathway.

The mechanisms of lipoxygenase inhibitor-induced apoptosis in human breast cancer cells.

Boswellia extracts emerged as the most prominent natural sources of 5-LOX-inhibiting compounds. AKBA (acetyl-keto-beta-boswellic acid), a principal component of boswellia, is a 5-LOX inhibitor. AKBA acts by numerous mechanisms to prevent cancer cells from proliferating. It induces apoptosis by switching on death receptor on cancer cell surfaces by activation of apoptotic pathways inside cancer cells. AKBA also activate the PI3K/Akt pathway and inhibition of the PI3K pathway significantly enhances AKBA-induced apoptosis. AKBA suppresses activity of CXCR4 that cancer cells use to trigger the metastases. AKBA enhances apoptosis induced by cytokines and chemotherapeutic agents, inhibits invasion, and suppresses osteoclastogenesis through inhibition of NF-kappaB-regulated gene expression. And AKBA further inhibits tumor growth by suppressing a growth factor, VEGF (vascular endothelial growth factor), required by cancers to grow necessary new blood vessels. Boswellic acid also blocks important signaling molecules required for cancer cell replication. Boswellia oil extracts can distinguish between healthy and cancerous tissue, suppressing tumor cell viability but sparing normal cells.

Unfortunately dietary boswellia ectracts are characterized by poor solubility and bioavailability, which means that most of what we swallow goes directly into our gastrointestinal area and is expelled.

BosturZym contains an “adaptogenic” mixture of fermented herbal compounds including boswellic acid (AKBA), curcumin and turmerine in a synergistic proprietary formula. BosturZym is the one and only product in the world that has perfect solubility and bioavailability of these compounds enough to induce apoptosis in cancer cells.

Acetyl-11-keto-beta-boswellic acid (AKBA): structure requirements for binding and 5-lipoxygenase inhibitory activity.

Protective effects of nimesulide (COX Inhibitor), AKBA (5-LOX Inhibitor), and their combination in aging-associated abnormalities in mice.

Acetyl-keto-beta-boswellic acid induces apoptosis through a death receptor 5-mediated pathway in prostate cancer cells.

Acetyl-11-keto-beta-boswellic acid induces apoptosis in HL-60 and CCRF-CEM cells and inhibits topoisomerase I.

Acetyl-11-keto-beta-boswellic acid potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis by suppressing NF-kappa B and NF-kappa B-regulated gene expression.

Acetyl-11-keto-beta-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis.

Boswellic acid blocks signal transducers and activators of transcription 3 signaling, proliferation, and survival of multiple myeloma via the protein tyrosine phosphatase SHP-1.

Boswellic acid suppresses growth and metastasis of human pancreatic tumors in an orthotopic nude mouse model through modulation of multiple targets.

Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells.

Frankincense oil derived from Boswellia carteri induces tumor cell specific cytotoxicity.

In addition to the direct inhibition of 5-LOX activity by Boswellia extracts, the sleep hormone melatonin made by body’s pineal gland is able to activate opioid receptors indirectly to inhibit expression of 5-LOX and Cox 2. Melatonin inhibits the synthesis of the 5-LOX via its activation of nuclear receptors.

Melatonin: a hormone that modulates pain.

The nuclear receptor for melatonin represses 5-lipoxygenase gene expression in human B lymphocytes.

Esculetin, a phenolic compound, acts as a 5-LOX inhibitor. Esculetin is reported to display anti-inflammatory and antioxidant properties, as well as induce cell cycle arrest and apoptosis. In the presence of Esculetin and HA14-1 expression of the death receptor DR4 has been observed to be upregulated and extracellular-regulated kinase (ERK) to be activated. Other studies suggest that Esculetin upregulates death receptor DR5 protein expression, and enhances TRAIL-induced apoptosis. Additionally, reports demonstrate that Esculetin also inhibits the activity of 12-LOX, and decreases leukotriene biosynthesis during 5-LOX inhibition.

Binding investigation of human 5-lipoxygenase with its inhibitors by SPR technology correlating with molecular docking simulation.

Intestinal anti-inflammatory activity of esculetin and 4-methylesculetin in the trinitrobenzenesulphonic acid model of rat colitis.

Induction of apoptosis by esculetin in human leukemia U937 cells: roles of Bcl-2 and extracellular-regulated kinase signaling.

Esculetin enhances TRAIL-induced apoptosis through DR5 upregulation in human oral cancer SAS cells.

Caffeic Acid is an endogenous phenolic phytochemical that exists in plants and many foods. A major metabolite product upon hydrolization of chlorogenic acid, caffeic acid inhibits a number of lipoxygenases such as 5-LOX, in a non-competitive manner, and 12-LOX inhibiting leukotriene synthesis resulting in further inhibition of immunoregulation. At high doses Caffeic Acid has also been shown to inhibit arachidonic acid metabolism in platelets, as well as stimulating prostaglandin synthesis.

Caffeic acid derivatives: in vitro and in vivo anti-inflammatory properties.

Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism.

Anti-HIV activities of natural antioxidant caffeic acid derivatives: toward an antiviral supplementation diet.

Analogues of N-hydroxycinnamoylphenalkylamides as inhibitors of human melanocyte-tyrosinase.

Caffeic acid, a phenolic phytochemical in coffee, directly inhibits Fyn kinase activity and UVB-induced COX-2 expression.

Manassantin, a dilignan isolated from Saururus chinensis, has been suggested to exert various biological activities, such as neuroleptic, anti-inflammatory and human acyl-CoA: cholesterol acyltransferase (ACAT) inhibitory activities. Manassantin inhibits 5-LOX translocation and leukotriene biosynthesis.

Methy jasmonate, a plant stress hormone, also specifically inhibits the activity of the 5-LOX. This induces apoptosis in prostate cancer cell lines. Jasmonates act as signal transduction intermediates when plants are subjected to environmental stresses such as UV radiation, osmotic shock and heat.

The prescription drug Zileuton (trade name ZYFLO) is used for the maintenance treatment of asthma. Zileuton is an orally active inhibitor of 5-LOX, and thus inhibits leukotrienes.

Manassantin A isolated from Saururus chinensis inhibits 5-lipoxygenase-dependent leukotriene C4 generation by blocking mitogen-activated protein kinase activation in mast cells.

Methyl jasmonate induced apoptosis in human prostate carcinoma cells via 5-lipoxygenase dependent pathway.

Jasmonates are phytohormones with multiple functions, including plant defense and reproduction.

BIOSYNTHESIS AND ACTION OF JASMONATES IN PLANTS.

The 5-lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages.

Cox-2, the inducible isoform of Cox (cycloxygenase), has emerged as the key enzyme regulating inflammation, and promises to play a considerable role in cancer. The combination of Cox-2 inhibitors and specific 5-LOX inhibitors may be an effective method for controlling cancer development. Some dual COX and 5-LOX inhibitors are chebulagic acid, quercetin, green tea catechins, neem, turmeric (curcumin), milk thistle (silymarin and silibinin), Flavocoxid and BosturZym. Celebrex, generic drug name celecoxib, is the only Cox-2 selective NSAID currently on the market. 5-LOX inhibitors alone or in combination with dual COX /5-LOX inhibitors  and Celebrex could be useful to prevent local recurrence after resection or as palliative option for advanced cancer.

Enhancing antitumor effects in pancreatic cancer cells by combined use of COX-2 and 5-LOX inhibitors.

Simultaneous inhibition of COX-2 and 5-LOX activities augments growth arrest and death of premalignant and malignant human lung cell lines.

Chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits of Terminalia chebula Retz., induces apoptosis in COLO-205 cell line.

Flavocoxid, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, blunts pro-inflammatory phenotype activation in endotoxin-stimulated macrophages.

A medicinal extract of Scutellaria baicalensis and Acacia catechu acts as a dual inhibitor of cyclooxygenase and 5-lipoxygenase to reduce inflammation.

Eicosanoid modulation in advanced lung cancer: cyclooxygenase-2 expression is a positive predictive factor for celecoxib + chemotherapy–Cancer and Leukemia Group B Trial 30203.

Licofelone, a dual COX/5-LOX inhibitor, induces apoptosis in HCA-7 colon cancer cells through the mitochondrial pathway independently from its ability to affect the arachidonic acid cascade.

Regulation of COX and LOX by curcumin.

Evaluation of antioxidant and inhibitory activities for different subclasses flavonoids on enzymes for rheumatoid arthritis. 

Even if drug therapy successfully blocks the Cox-2 and 5-LOX enzyme systems, arachidonic acid can still be converted into other damaging molecules, such as epoxy derivatives. So, another approach to treating the diseases involving eicosanoids seems desirable. Eicosanoids are produced primarily from arachidonic acid that has been released from cell membrane phospholipids. Diets low in arachidonic acid, omega-6 fatty acids, saturated fats, high-glycemic food and overcooked food can suppress inflammatory factors in the body. Not all of the phospholipids in cell membranes include arachidonic acid, only those that were derived from certain dietary fatty acids, mainly linoleic acid. The concept of dietary control over these diseases is based, in part, on starving the eicosanoid system by reducing the fatty acids (specifically, the polyunsaturated fatty acids such as soybean oil, corn oil, safflower oil, grape seed oil, poppy oil and sunflower oil) that can eventually make arachidonic acid, thereby slowing down the production of eicosanoids when a stimulus occurs. Fish oil, flaxseed oil and perilla seed oil help to lower Cox-2 and 5-LOX activity in the body.

In comparison, immunotherapy revolves around bolstering the body’s own defences so that they can mount an effective attack on cancer. Everyone has the power within them to heal cancer and all we have to do is to find a way to unlock our inner potential. Cancer immunotherapy is the stimulation, support, or other assistance of the immune system to help fight cancer. Historical data show that the immune system clearly plays a role in cancer progression. For example, immunosuppression is associated with cancer development. In fact, cancer is more likely to occur in people who take immunosuppressive medications than in people with normal immune function.

Cell death can be achieved by fundamentally different mechanisms, apoptosis, necrosis and autophagy. Through which molecular and cellular mechanisms do cells die in normal tissues? Answering this question is of prime medical importance because homeostatic cell death is an important tumor suppressor mechanism, meaning that a reduced propensity to die is one of the hallmarks of cancer cells. Apoptosis, or programmed cell death, can indeed be considered as a constitutive anti-cancer mechanism that seems to be defective in more than 50% of cancers.When a cancer cell grows it activates two different pathways. The first stimulates cellular growth while the second, acting like a safety net, prevents the activated cells from dying from programmed cell death.

There is a complex interaction between normal cellular growth and cell death if anything goes wrong. The second pathway protects the cells from dying prematurely. If we want to kill cancer cell, we need to inactivate its growth while inhibiting its ability to protect itself from small or large problems in its biochemistry. So, in brief, we need to induce as many problems as we can in its normal growth pathway, while simultaneously blocking its ability to adapt. Major tumor associated genes/pathways such as RAS, PI3K/AKT might not only decrease the overall sensitivity to chemotherapy but also directly effect cell death mechanisms. Hence, the failure to eliminate mutated (or epigenetically modified) cancer cells (or their precursors) by programmed cell death is an obligate step of multi-step carcinogenesis.

Cell death can be induced by a family of death receptors including Fas, TNF (tumor necrosis factor) and TRAIL (Tumor necrosis factor-related apoptosis inducing ligand). One of the main mechanisms by which immune effector cells kill is by induction of apoptosis by Fas/FasL interactions. Fas (CD95 or Apo-1) is a transmembrane protein belonging to the tumor necrosis factor receptor (TNFR) family of cell surface molecules. Its ligation with specific agonistic antibodies or its cognate ligand (FasL or CD95L) induces the activation of a cascade of cysteines proteases, called caspases, and ultimately of nucleases that result in apoptotic cell death in many cell lineages.

The recent identification of the Fas and FasL as a major regulator of both apoptosis and immune function has provided insight into an attractive mechanism of tumor escape from immune clearance. Fas is induced on activated T lymphocytes and targets them for subsequent elimination by FasL-expressing cells. Given the importance of the Fas/FasL system as a major mechanism by which T lymphocytes kill tumor cells, it is not surprising that tumor cells can use this system to evade immune recognition. Tumor cells may acquire resistance to Fas-mediated apoptosis by down-regulating Fas expression, secreting decoy receptors to block FasL on activated T lymphocytes, or by altering intracellular mechanisms mediating Fas-induced apoptosis. There’s another strategy. When some tumor cells encounter activated T cells bearing Fas, FasL/Fas interactions induce apoptosis of the T cell thereby terminating the immune response and providing immune privilege to tumors.

TNF is a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction. It is produced chiefly by activated macrophages, although it can be produced by other cell types as well. The primary role of TNF is in the regulation of immune cells. Unfortunately, two of these pathways, TNF and Fas, are toxic to both cancerous and normal cells. This makes activators of these pathways somewhat dangerous. Under certain circumstances, expression of FasL results in tumor removal, and overexpression of FasL results in an intense inflammatory response in several experimental models.

Life and death by death receptors.

A novel role of microtubular cytoskeleton in the dynamics of caspase-dependent Fas/CD95 death receptor complexes during apoptosis.

The extracellular glycosphingolipid-binding motif of Fas defines its internalization route, mode and outcome of signals upon activation by ligand.

Identification of a lysine-rich region of Fas as a raft nanodomain targeting signal necessary for Fas-mediated cell death.

Involvement of raft aggregates enriched in Fas/CD95 death-inducing signaling complex in the antileukemic action of edelfosine in Jurkat cells.

The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells.

Targeting the Fas/Fas ligand pathway in cancer.

The CD95 receptor: apoptosis revisited.

CD95L/FasL and TRAIL in tumour surveillance and cancer therapy.

TRAIL (Tumor necrosis factor-related apoptosis inducing ligand) is a death pathway. TRAIL is normally expressed in the human immune system and plays a critical role in antitumor immunity. TRAIL was cloned in 1995 and subsequent studies revealed its physiological functions in antitumor innate and adaptive immunity. TRAIL is required for natural killer cell-mediated immunosurveillance against the tumor progression and metastasis. TRAIL interacts with the death receptors, DR4 and DR5, and activates intracellular apoptotic pathway in cancer cells. Interestingly, it is totally non-toxic to normal cells, while retaining its ability to kill highly chemotherapy resistant cancer and leukemia cells. TRAIL can kill any cancer or leukemia cell regardless of their degree of malignancy. The TRAIL death pathway has emerged as an important therapeutic strategy. But activating TRAIL successfully isn’t easy. We need to stimulate TRAIL production and expression of the DR4 and DR5. We also need to overcome all the biochemical pathways that block TRAIL efficacy. Considerable numbers of cancer cells, especially some highly malignant tumors, are resistant to apoptosis induction by TRAIL, and some cancer cells that were originally sensitive to TRAIL-induced apoptosis can become resistant after repeated exposure (acquired resistance).

TNF-related apoptosis-inducing ligand (TRAIL): a new path to anti-cancer therapies.

TRAIL: a sword for killing tumors.

TRAIL death receptors and cancer therapeutics.

TRAIL as a target in anti-cancer therapy.

Mechanisms of resistance to TRAIL-induced apoptosis in cancer.

Biological membranes are sheets of lipids that form barriers between compartments within cells or, in the case of the plasma, between the cell and its external environment. Membrane fluidity is a characteristic of cell membranes that depends on their lipid and protein composition. Membranes of tumor cells have been found to posess higher fluidity than membranes of nontumor cells. The types of lipids in a cell membrane can vary and abruptly form small islands of specific types, known as lipid rafts. Lipids are also linked to many proteins and, once attached, move the protein to specific places in membranes. Localization of the death receptor Fas to specialized membrane microdomains is crucial to Fas-mediated cell death signaling.

Palmitoylation is the posttranslational addition of the 16-carbon palmitate group to specific cysteine residues of proteins via a labile thioester bond. Unlike other forms of lipidation, such as myristoylation and prenylation, palmitoylation is reversible which allows for dynamic regulation of protein-membrane interactions, trafficking between membrane compartments. The attachment of palmitic acid to the amino acid cysteine via thioester linkage (S-palmitoylation) is a reversible post-translational modification that occurs on diverse cellular proteins. Palmitoylation modulates protein function by facilitating targeted membrane association, interaction with other proteins, and determining subcellular localization. Intracellular palmitoylation reactions are mediated by a family of recently identified palmitoyl transferases.

Fas/CD95 death receptor and lipid rafts: new targets for apoptosis-directed cancer therapy.

Lipid rafts and Fas/CD95 signaling in cancer chemotherapy.

Palmitoylation of membrane proteins (Review).

The fat controller: roles of palmitoylation in intracellular protein trafficking and targeting to membrane microdomains (Review).

Palmitoylation of intracellular signaling proteins: regulation and function.

Palmitic acid, also called hexadecanoic acid, is one of the most common saturated fatty acids. It is found in palm oil but also in butter, cheese, milk and meat. Fatty acid synthase (FASN) synthesizes palmitic acid in the body. Palmitic acid is converted to ceramide, the death lipid. Ceramide is made from palmitic acid and the amino acid serine. Neither of these molecules is plentiful in our diets. Ceramide is also used as a building block for the synthesis of other lipids. Since ceramide is a toxic lipid and is involved in the induction of apoptosis (programmed cell death), its synthesis is thghtly controlled in the body.

Fatty acid synthase drives the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains.

Differential regulation of ceramide in lipid-rich microdomains (rafts): antagonistic role of palmitoyl:protein thioesterase and neutral sphingomyelinase 2.

Sphingolipids and cancer: ceramide and sphingosine-1-phosphate in the regulation of cell death and drug resistance.

Metabolism of short-chain ceramide by human cancer cells–implications for therapeutic approaches.

Palmitoylation is required for efficient Fas cell death signaling. S-palmitoylation of Fas in its cytoplasmic domain, which consists of the reversible addition of a palmitic acid to a cysteine, represents an essential signal targeting Fas to rafts. Palmitoylation allows Fas to associate with the cytoskeletal protein ezrin, reported to be critical for Fas mediated cell death. Indeed, the FasL-induced internalization of Fas receptor has been shown to occur in the clathrin-dependent pathway and is a prerequisite for DISC (death-inducing signalling complex) formation, which occurs predominantly in endosomes. Palmitoylation of TRAIL death receptor DR4 is also required for efficient TRAIL-induced cell death signaling. If the TNF, FAS and TRAIL death receptor pathways worked as designed, there would be no cancer, leukemia or autoimmune diseases. These receptors are responsible for killing defective cells by the non-inflammatory process of programmed cell death. However, some other palmitoylated proteins such as Wnt and Hedgehog proteins are involved in cellular differentiation and growth.

Palmitoylation is required for efficient Fas cell death signaling.

Palmitoylation of human FasL modulates its cell death-inducing function.

The extracellular glycosphingolipid-binding motif of Fas defines its internalization route, mode and outcome of signals upon activation by ligand.

Lipid raft localization and palmitoylation: identification of two requirements for cell death induction by the tumor suppressors UNC5H.

Palmitoylation of CD95 facilitates formation of SDS-stable receptor aggregates that initiate apoptosis signaling.

Palmitoylation of the TRAIL receptor DR4 confers an efficient TRAIL-induced cell death signalling.

Overexpression of fatty acid synthase is associated with palmitoylation of Wnt1 and cytoplasmic stabilization of beta-catenin in prostate cancer.

Membrane targeting of palmitoylated Wnt and Hedgehog revealed by chemical probes.

T lymphocytes play an important role in immune surveillance against intracellular pathogens and tumors. Signal transduction through CD90 regulates cytokine production by CD4+ T helper cells, as well as expression of TRAIL, FasL, granzyme B and perforin by CD8+ cytotoxic T cells (CTL), and the induction of CD4+ regulatory T cells. Cytokines, including IL-2, IL-12, and IFN-gamma, are important inducers of the cytotoxic effector molecules that are involved in tumor cell and allograft destruction by the cell-mediated immune response. Granzymes and perforin are known to be important mediators of target cell destruction. TRAIL and FasL expressed by CTL also trigger apoptosis in susceptible target cells. Regulatory T cells are essential for the maintenance of immunologic homeostasis.

Current concepts of tumor-infiltrating lymphocytes in human malignancies.

Signaling defects in anti-tumor T cells.

Antimicrobial and immunoregulatory effector mechanisms in human endothelial cells. Indoleamine 2,3-dioxygenase versus inducible nitric oxide synthase.

Positive and negative consequences of soluble Fas ligand produced by an antigen-specific CD4(+) T cell response in human carcinoma immune interactions.

A critical role for granzymes in antigen cross-presentation through regulating phagocytosis of killed tumor cells.

Reciprocal granzyme/perforin-mediated death of human regulatory and responder T cells is regulated by interleukin-2 (IL-2).

Anticancer properties of the IL-12 family–focus on colorectal cancer.

Active immunity may be the ideal of immunotherapy. Coley’s toxin was the first documented attempt in the U. S. to treat cancer by stimulating the immune system. It was first developed in the 1890s by William B. Coley, MD, who noted that patients who developed bacterial infections after surgery for sarcoma had visible regressions of their cancers. Because using live bacteria was dangerous and because he determined that immune reactions depended upon the toxins of the bacteria rather than the actual bacteria, he eventually mixed toxins of the Streptococcus and Bacillus prodigiosus bacteria. Some regressions of cancer were reported among patients treated with these toxins from the 1890s until the 1950s when the treatment largely fell into disuse with the advent of radiotherapy and chemotherapy. The stimulated human immune system is a whirling tempest of different physiological and biochemical responses, and even now there’s much uncertainty about how Coley’s Toxins modified this complex mechanism to better attack its cancerous target.

We know now that tumors are immunogenic. The question is why, if tumors are immunogenic, do cancers grow? We know an immune response is elicited, yet what prevents the immune response from obliterating the cancer? When cells become cancerous they produce new, unfamiliar antigens. The immune system cells recognize marker proteins (antigens) from the foreign agents and produce proteins (antibodies) that interact with the antigen and ultimately destroy them. Another way the immune system works is by sensitizing a class of immune cells, the T-cells to recognize the foreign agents and destroy them. The immune cells recognize these cells as foreign because of the presence of surface markers. All cells have surface markers. Most tumor antigens are “self” proteins, rendering them weakly immunogenic. Our immune systems tolerate self-proteins, and tolerance is a major mechanism by which cancer can evade immune recognition.

Tumor cells must develop strategies to avoid clearance by the immune system to survive, expand their populations, and metastasize. As tumors grow, they secrete immunosuppressant factors. Thus, tumor cells may escape immune clearance by altering immune recognition or by modulation of the cytotoxic response. This immunomodulatory effect occurs directly, by viral proteins binding to immune receptor molecules and thus preventing their expression on the surface of the virally infected cell, or by tumors secreting factors that downregulate immune activation.

Choosing a conventional cnacer treatment is not easy. Conventional treatments, such as chemotherapy and/or radiation therapy, do nothing to eliminate the cause or prevent recurrence of cancer. But there is hope. With natural phytochemicals and anti-cacer agents, we can now stimulate death receptor pathways, block many of the anti-cell death pathways that inhibit death receptor efficacy and stimulate the anti-cancer immune response. We can also modulate the anti-cancer immune response, thus leading to better immune surveillance.

A number of naturally occurring compounds (phytochemicals) isolated from herbs, fruits and wild mushrooms are able to kill neoplastic cells through a variety of mechanisms. In many cases, the anti-cancer activities of phytochemicals involve inhibitory effects on the activation of transcription factors that promote tumor cell survival, metastasis and resistance to induction of apoptotic cell death.

Induction of apoptotic cell death by ursolic acid through mitochondrial death pathway and extrinsic death receptor pathway in MDA-MB-231 cells.

Ursolic acid induces PC-3 cell apoptosis via activation of JNK and inhibition of Akt pathways in vitro.

Involvement of mitochondria and recruitment of Fas/CD95 signaling in lipid rafts in resveratrol-mediated antimyeloma and antileukemia actions.

Resveratrol enhances the expression of death receptor Fas/CD95 and induces differentiation and apoptosis in anaplastic large-cell lymphoma cells.

Lupulone, a hop bitter acid, activates different death pathways involving apoptotic TRAIL-receptors, in human colon tumor cells and in their derived metastatic cells.

Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts.

Sulforaphane blocks hypoxia-mediated resistance to TRAIL-induced tumor cell death.

Resveratrol induces apoptosis of human nasopharyngeal carcinoma cells via activation of multiple apoptotic pathways.

Induction of apoptosis by rhapontin having stilbene moiety, a component of rhubarb (Rheum officinale Baillon) in human stomach cancer KATO III cells.

Activation of multiple apoptotic pathways in human nasopharyngeal carcinoma cells by the prenylated isoflavone, osajin.

The role of nutraceuticals in the regulation of Wnt and Hedgehog signaling in cancer.

Current findings, future trends, and unsolved problems in studies of medicinal mushrooms.

Mushroom lectins: current status and future perspectives.

The good news is that we are getting close to a true, non-toxic and effective natural anti-cancer/ anti-leukemia formula. Alternative cancer treatments really work. Most of the trials have confirmed the clinical efficacy of Hepazym immunotherapy in patients with lung cancer, liver cancer, colorectal cancer and lymphoma. What we try to achieve with active immunity induced by Hepazym immunotherapy is an endogenous immune response, where the immune system is primed to recognize the tumor as foreign. This approach has been successful in patients with liver cancer, lung cancer, colon cancer and lymphoma, as their immune systems are unable to mount a sufficient response. In the past several years, efforts have focused on using active immune therapies in patients with minimal disease. However, we have seen that the immune system can be quite functional despite advanced stage cancer when the patient has been treated to maximal response.

We have recently shown that Hepazym activates the extrinsic pathway of apoptosis in several different human cancer cells, without harming normal cells. Hepazym shows induction of apoptosis in T leukemia cells. In addition, Hepazym inhibits the proliferation and migration of human endothelial cells, and also inhibits growth factor-stimulated blood vessel development. Hepazym might therefore be able to reduce tumor progression by both a direct cytotoxic effect on the cancer cells and by inhibiting the development of tumor vasculature.  Hepazym offers a number of potential advantages over conventional chemotherapeutic agents. Hepazym immunotherapy is nontoxic and is predicted to be effective against multidrug-resistant variants of cancer cells. Hepazym therefore show potential for the treatment of metastatic cancer.

Our goal is to reduce cancer to the lowest common demoninator so it can be killed with the most basic of weapons. And Hepazym immunotherapy fulfills that goal perfectly. Keep in mind that this immunotherapy applies to all cancers and leukemias. Many people have contacted us after the fact and have told us that they or their loved ones have experienced major benefits, including the reduction in size, or complete disappearance of abnormal growths, when they took enough of Hepazym and Hepazym-F (Fermented Medicinal Mushroom Extracts, Liquid Herbal Minerals) for a long enough period of time.

Case Report: Liver Tumor

A 49-year-old male, South Korean, presented with Stage II hepatocellular carcinoma (liver cancer) caused by HBV. In February 2011, the surgery took place and was a success. In June 2011, cancer has recurred. Serum DCP (PIVKA II) level elevated to 110. He began taking 40 ml (10 ml 4 times) of Hepazym and 20 ml (10 ml twice) of Hepazym-F daily, and the hospital treatment was discontinued. As of September 2011, serum DCP (PIVKA II) level markedly decreased to normal range. The production of Interleukin-2 (IL-2) in his body multiplied because of Hepazym administration. IL-2 has shown antineoplastic activity and has also an antiviral effect. By November 2011 the tumor had disappeared.

Conclusion: The decrease of serum DCP (PIVKA II) level and the elevated serum level of IL-2 during immunotherapy with Hepazym predicts a possible new therapeutic option for HBV and HCV induced liver cancer and chronic viral infections.

With over years of safe use, the effects of the herbs in Hepazym have now been proven to be true. Of course today we know mechanism of the herbal synergy of the Hepazym formula supports the body’s natural healing mechanisms by activating all of the body’s natural healing pathways (immune system, digestive, circulatory, lymphatic, liver, bowels, kidneys, skin, and lungs). The healing synergy of the phytochemicals, super saccharides, immune molecules, antimicrobial peptides, organic plant based enzymes, pre- and probiotics and antioxidants in the herbs comprising Hepazym gently enhances the natural ongoing healing systems of the body, bringing them back to a more optimal state of activity. It does not “force” the body into an unnatural healing mode.  

Hepazym can be used daily as a natural cellular defense, liver cleanse and lung cleanse, gastrointestinal support, immune support and immune modulation for treatment of cancer and chronic infections. Most of the healthy cells in the body can and will regenerate, if there are enough of them and the body is not too exhausted. Hepazym immunotherapy brings the body back into balance, starting a rebuilding and re-education process, so there is the potential for restoration. Keep in mind that Hepazym immunotherapy is an herbal remedy, and as such, although it is very effective, it can take time. So perseverance is needed.

It is difficult to identify how long it will take before you notice a measurable difference in your health after starting on Hepazym immunotherapy. There are many factors involved, but usually some benefits are noticed within two weeks, providing it is taken consistently. It will make your urine more yellow. This is a normal process and is not harmful, so in turn your urine turns the same color. There can be a short period when weakness or nausea may be felt. This is when the body is discharging toxins and poisons that have been gathered, and getting rid of them. Persevere and this will pass shortly. Although everyone responds individually to Hepazym immunotherapy, there are many positive signs of help that encourage:

• Appetite may improve as taste buds, diminished by treatment, are restored.
• The pain level may reduce or disappear altogether.
• Energy may increase, as the detoxifying takes place.
• Bodily functions, such as anti-cancer immune response, may normalize themselves.
• Test results may also show marked improvement.
• Sleep patterns may improve, as it is a natural sedative, and calms the body.
• Outlook in life may become more positive, giving you a sense of well-being.

When doctors prescribe the typical antibiotics for fighting an infection caused by super bacteria, the antibiotics usually fail to eradicate the bacteria. Instead, bacteria may actually thrive despite the medication, sometimes even killing the patient. To fight resistant bacteria, doctors often turn to even stronger antibiotics, but it seems that some super bacteria are developing the ability to thrive despite even the toughest antibiotic treatments.  Bacteria that survive an antibiotic treatment produce new bacteria that may possess genetic structure to survive additional antibiotic treatments. Thus a new strain of the bacteria can be born and passed to other living organisms. Most of the super bacteria types are resistant to several antibiotics and could develop additional resistances in the future.

Unfortunately, much is still unknown about the exact mechanism involved, bacteria become resistant to antibiotics via chromosomal mutations and the incorporation of new genes, sometimes from other bacteria. There are already some super bacteria forms in existence that pose problems. One of the best known of these is methicillin-resistant staphylococcus aureus (MRSA), which has until recently, been mostly noted in hospital and other medical settings. MRSA can cause serious external and internal infections that need specific antibiotic treatment. Generally start as small red bumps that resemble pimples, boils or spider bites. It can quickly turn into deep, painful abscesses that require surgical draining. Sometimes the bacteria remain confined to the skin. But bacteria can also penetrate into the body, potentially causing an infection that threatens the bones, joints, surgical wounds, bloodstream, heart valves and lungs, which in turn threatens a person’s soul. In the recent study, most cases of MRSA were treated with drugs that don’t work against the super bacteria.

Clostridium difficile (C. difficile) is a bacterium that causes mild to severe diarrhea and intestinal conditions like pseudomembranous colitis (or inflammation of the colon). When antibiotics destroy a person’s good bowel bacteria, C. difficile bacteria can grow. When this occurs, the C. difficile bacteria produce toxins, which can damage the bowel and cause diarrhea. However, some people can have C. difficile bacteria present in their bowel and not show symptoms. New data has revealed that infections from C. difficile are surpassing MRSA infections in community hospitals. C. difficile is spreading through hospitals and health care facilities, and it’s proving to be that C. difficile is more aggressive than the MRSA. C. difficile’s resistance to antibiotics allows it to spread easily through hospital. In fact, the drugs can actually increase the risk of getting the bacteria. Those antibiotics for their infection kill the bacteria that are normal in the bowel and C. difficile bacteria starts growing in the bowel.

Because MRSA is a Gram-positive, we don’t talk much here about the Gram-negatives — the two categories of bacteria have different cell-wall structures and thus are treated using different categories of drugs. (That structural difference causes them to react in different ways to a stain invented by a scientist named Gram in the 19th century.) But the resistance situation with Gram-negatives is at least as dire as with MRSA, possible more so, because there are fewer new drugs for Gram-negatives in the pharmacology pipeline.

New Delhi metallo-beta-lactamase-1 (NDM-1) is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. These include the antibiotics of the carbapenem family, which are a mainstay for the treatment of antibiotic-resistant bacterial infections. NDM-1 was first detected in a Klebsiella pneumoniae isolate from a Swedish patient of Indian origin in 2008. Klebsiella pneumoniae can cause different types of healthcare-associated infections, including pneumonia, bloodstream infections, wound or surgical site infections, and catheter-associated bladder infections.

Klebsiella bacteria are normally found in the human intestines (where they do not cause disease) and in human stool (feces). In healthcare settings like hospitals and nursing homes, Klebsiella infections occur most commonly among very sick patients who are receiving treatment for serious conditions. Klebsiella bacteria have developed resistance to antibiotics, most recently to the class of antibiotics known as carbapenems (carbapenem-resistant Klebsiella pneumoniae, or CRKP). CRKP is resistant to nearly all antibiotic options and has been associated with high mortality rates, long hospital stays, and high heathcare costs.

NDM-1 was later detected in bacteria in India, Pakistan, the United Kingdom, the United States, Canada, Japan and Brazil. The most common bacteria that make this enzyme are Gram-negative such as Escherichia coli and Klebsiella pneumoniae, but the gene for NDM-1 can spread from one strain of bacteria to another by horizontal gene transfer. The resistance factor has spread to 14 different species of bacteria, including pathogenic varieties responsible for dysentery and cholera. Most bacteria holding the NDM-1 plasmid are resistant to all but a couple of our most clumsy, brutal antibiotics. One strain is immune to all of them.

Streptococcus pneumoniae is one of the world’s leading causes of death from infectious disease, particularly in children and the elderly. In the late 1970s, strains of pneumococci displaying resistance to penicillin were described in South Africa and Spain. By the early 1990s, penicillin-resistant clones of S. pneumoniae spread rapidly across Europe and globally. S. pneumoniae worldwide are multidrug-resistant (MDR) (i.e., resistant to ≥ 3 classes of antibiotics). The scariest sighting: Nine children in Rochester, N.Y., came down with a strain that shrugs off all 18 antibiotics approved for kids. The Rochester doctors who found the bug beat it into submission with Johnson & Johnson’s Levaquin, a drug for adults, but only after it left one child with permanent hearing loss.

Gonorrhea is a very common infectious bacterium, a Gram negative, fastidious,  diplococci, that can grow and rapidly multiply in the mucous membranes, especially the mouth, throat, and anus of males and females, and the cervix, fallopian tubes, and uterus of the female reproductive tract. Scientists have discovered a new form of gonorrhea in Japan that is resistant to all antibiotics that are used to treat the disease. Known as H041, the disease could become a worldwide epidemic if scientists are unable to find a way to eliminate its resistance to drugs. U.S. government health officials have warned that the sexually transmitted disease gonorrhea is becoming increasingly resistant to the last type of antibiotics left to treat it.

Tuberculosis (TB) is an infectious disease caused by a germ called Mycobacterium tuberculosis. Tuberculosis is spread through the air when a person sneezes, coughs, or breathes. Both “multi-drug resistant (MDR)” and “extensively drug-resistant” forms of TB are now being seen. MDR Tuberculosis is resistant to at least two of the main drugs used to treat TB– isoniazid (INH), and rifampin.

Neisseria meningitidis is a bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia. N. meningitidis is a major cause of morbidity and mortality during childhood in industrialized countries and has been responsible for epidemics in Africa and in Asia. Meningitis is an inflammation of the membranes that cover the brain and spinal cord. People sometimes refer to it as spinal meningitis. Meningitis is usually caused by a viral or bacterial infection. Knowing whether meningitis is caused by a virus or bacterium is important because the severity of illness and the treatment differ depending on the cause. Viral meningitis is generally less severe and clears up without specific treatment. But bacterial meningitis can be quite severe and may result in brain damage, hearing loss, or learning disabilities. Although there have been reports of N. meningitidis with decreased susceptibility to penicillin.

Typhoid fever is a potentially fatal multisystemic illness caused primarily by Salmonella Typhi bacteria which is frequently multidrug resistant with reduced susceptibility to fluoroquinolone-based drugs, the first choice for the treatment of typhoid fever. S.Typhi has been a major human pathogen for thousands of years, thriving in conditions of poor sanitation, crowding, and social chaos. Untreated, typhoid fever is a grueling illness that may progress to delirium, obtundation, intestinal hemorrhage, bowel perforation, and death within one month of onset. Survivors may be left with long-term or permanent neuropsychiatric complications.

Enterococci are bacteria found in the stomach and bowels of about 19 out of every 20 healthy people. Enterococci can get into open wounds and skin ulcers, and cause infection. Less often, they can cause more serious infections of the blood or other body tissues. Vancomycin-Resistant Enterococci (VRE) are enterococci that have become resistant to vancomycin. Vancomycin is an antibiotic medication that is used to treat enterococcal infections. Some antibiotics do not work against some enterococci. Therefore, serious infections caused by VRE may be very hard to treat because they are resistant to vancomycin.

Staphylococcus aureus is a bacterium commonly found on the skin and in the nose of about 30% of individuals. Most of the time, staph does not cause any harm. These infections can look like pimples, boils, or other skin conditions and most are able to be treated. Sometimes staph bacteria can get into the bloodstream and cause serious infections which can be fatal. Vancomycin-intermediate Staphylococcus aureus (VISA) and Vancomycin-resistant Staphylococcus aureus (VRSA) are specific types of antimicrobial-resistant bacteria.

Shigella is the bacterium that causes shigellosis, a diahrreal disease, also known as bacillary dysentery. Shigella is one of the most easily transmitted bacterial diarrheas, since it can occur after fewer than 100 bacteria are ingested. Shigella bacteria are generally transmitted through a fecal-oral route. Foods that come into contact with human or animal waste can transmit Shigella. Thus, handling toddlers’ diapers, eating vegetables from a field contaminated with sewage, or drinking pool water are all activities that can lead to shigellosis. In the developed world, shigellosis typically isn’t considered dangerous. To shorten the length of illness and to reduce potential infection of other people, antibiotics are typically prescribed, usually cotrmoxazole or ampicillin. Over the decades, Shigella isolates resistant to multiple agents, resulting in difficulties in the selection of empirical therapy.

Acinetobacter bacteria are present in water, soil and sewage. Acinetobacter is causing severe bloodstream infection and pneumonia in many hospital patients. Acinetobacter infections are uncommon but, when they occur, usually involve organ systems that have a high fluid content (eg, respiratory tract, CSF, peritoneal fluid, urinary tract), manifesting as nosocomial pneumonia, infections associated with continuous ambulatory peritoneal dialysis (CAPD), or catheter-associated bacteruria. Multi-drug resistant (MDR) Acinetobacter is not a new or emerging phenomenon. Since the 1970s, the spread of MDR Acinetobacter strains among critically ill, hospitalized patients, and subsequent epidemics, have become an increasing cause of concern.

Group B streptococci (GBS) are found commonly in the gastrointestinal tract and have been found to colonize the urethra in both men and women without causing infection. GBS can also colonize the upper respiratory tract. GBS are the leading cause of serious, life-threatening infections  (pneumonia, septicemia, and meningitis) in the newborn. Mortality of GBS sepsis in neonates is over 50% and is particularly high in preterm infants. GBS colonize the vaginal and gastrointestinal tracts in healthy women, with carriage rates ranging from 15%-45%. The absence of antibody to GBS in infants is a risk factor for infection. GBS infection in elderly people (≥70 y) is strongly linked to congestive heart failure and being bedridden, with urinary tract infection, pneumonia, and soft-tissue infection as the most common manifestations of infection. Erythromycin and clindamycin are the drugs of choice for women with serious penicillin allergy who are colonized with GBS. But the prevalence of resistance to clindamycin and erythromycin is high.

What’s the best way to eradicate MDR super bacteria?

When we read or hear the word “bacteria” we often think of getting sick. However, not all bacteria are harmful. Some bacteria are very helpful to humans. Bacteria are involved in the production of fuel, food, and medications. Bacteria are also used in environmental recycling and clean-up. In fact, without certain bacteria, human life would be a lot more difficult. The human body is full of helpful bacteria. The human digestive tract is full of these helpful bacteria. Essentially, these bacteria serve two purposes – they help prevent other harmful bacteria from growing and they help humans digest their food. These bacteria work with the body’s own chemicals in breaking down food, converting it to useful vitamins and minerals, and making sure the intestinal walls can absorb the nutrients for the bloodstream to circulate. Human skin contains many species of harmless bacteria. Their presence prevents harmful bacteria from gaining a foothold on your skin. In fact, if it wasn’t for certain bacteria in your body, you would become ill. Unfortunately most of the people are at war with all bacteria. Keep this in mind. Avoid using any unnecessary antibiotics.

Modern medicine certainly have an important place in treatment. Most Doctors of Medicine, are dedicated, clever people doing wonderful work, but sometimes the treatment is hopeless, or, even worse than the problem. When you get a multi-drug resistant (MDR) strain of super bacteria, what can you do about it? First, stop worrying about it. Our bodies do a great job at fighting the germ war for us! We need some alternate ways to treat these infections. We need to pay attention to our biological design not disease. Drugs override normal immune system cell processes and the problem is not resolved. It is possible to prevent the spread of the MDR super bacteria in the body without the use of typical antibiotics. It is possible to strengthen, balance and boost your immune system with natural non toxic agents and build it up into your body’s best defense mechanism your immune system.

The immune system is an intricate complex of interrelated cellular, molecular, and genetic components that is responsible for protecting us against infections and foreign substances. A healthy immune system can defeat invading super bacteria. Specific nutrients, immune molecules and bio-factors support immune system cell processes and address’s the immune system dysfunctions. Key immune system health supports a cascade of immune responses that begin in the mouth and proceed throughout the body and it optimizes response of natural killer cells, B-cells and T-cells, which seek out and destroy foreign substances. So your body can maximize its immune system functions and eradicate super bacteria. Hepazym may be our best weapon in the fight against MDR super-bacterial infection. It could save your life. Hepazym is much more specific than more antibiotics, so it can be chosen to be harmless not only to the humans, but also to other beneficial bacteria, such as gut flora, reducing the chances of opportunistic infections. It would have a high therapeutic index, that is, Hepazym-therapy would not be expected to give rise to unwanted side effects, as opposed to drugs, and would not stress the liver. It will only kill a harmful bacterium. Hepazym is currently being used therapeutically to treat super-bacterial infections that do not respond to conventional antibiotics. It tend to be more successful than any antibiotics.

The Wnt signaling pathway plays a pivotal role in cellular developmental processes and human carcinogenesis. Inhibition of expression of cyclin D(1) and survivin as well as the Wnt/beta-catenin, p21-RAS signaling pathway could be qualified as promising targets for innovative treatment strategies of colon cancer. Quercetin inhibits these pathways. Moreover, Quercetin activates AMPK (AMP-activated protein kinase), a physiological cellular energy sensor, through ROS generation. Activation of AMPK strongly suppresses cell proliferation in both nonmalignant and tumor cells.

That’s all promising, but it’s too early to recommend quercetin as a supplement. First of all, you have no idea what’s in the bottle you buy. There could be little or no quercetin. Quercetin absorption can vary, depending on its source. Low oral bioavailability of quercetin due to insolubility in water has limited its use as a food additive or dietary supplement. Quercezym™ contains enzymatic fermented high purity quercetin. It has perfect bioavailability and pharmacokinetics of active quercetin. Quercezym™ is the one and only product that has bioavailability of high purity quercetin enough to induce apoptosis in colon cancer cells. Otherwise, quercetin wouldn’t have worked.

Quercetin inhibits human DLD-1 colon cancer cell growth and polyamine biosynthesis.

Quercetin inhibit human SW480 colon cancer growth in association with inhibition of cyclin D1 and survivin expression through Wnt/beta-catenin signaling pathway.

Apoptotic effect of quercetin on HT-29 colon cancer cells via the AMPK signaling pathway.

AMP kinase/cyclooxygenase-2 pathway regulates proliferation and apoptosis of cancer cells treated with quercetin.

Quercetin mediates preferential degradation of oncogenic Ras and causes autophagy in Ha-RAS-transformed human colon cells.

Quercetin inhibits p21-RAS expression in human colon cancer cell lines and in primary colorectal tumors.

Immune system is first line of defence against cancer. Interactions between immune cells and tumor cells involve direct cell-cell physical contact and release of modulator molecules, primarily cytokines and chemokines. In this survival and death battle, on the one hand, the immune cells may prevail and eradicate the tumor cells. On the other hand, tumor cells can counterattack the immune cells by producing inhibitory molecules, activating the immune suppressive cells or acquiring apoptosis-resistant mechanisms to avoid destruction by the immune system. Thus, the anti-tumor immune response can be a two-edged sword and can result in both positive and negative consequences.

 The biologic failure of the immune system to effectively suppress neoplastic disease in immune-competent hosts is not fully understood and has remained a fundamental paradox of tumor immunobiology. Cytotoxic T lymphocytes (CTLs) are the primary effector cells against tumor cells and function primarily through two effector mechanisms. The first cytolytic pathway depends on the polarized secretion of perforin and granzymes. The second effector mechanism involves the interaction of FasL on activated CTLs with its receptor Fas on the target tumor cells. Recent studies have demonstrated that the perforin effector mechanism of tumor-specific CTLs can be selectively suppressed by immune suppressive Treg cells in vivo, whereas acquisition of resistance to Fas-mediated apoptosis is a hallmark of metastatic tumors. Therefore, both the perforin and Fas pathways can be impaired in the tumor microenvironment. Accordingly, suppression of immunosuppression, sensitization of tumor cells to Fas-mediated apoptosis or targeting additional anti-tumor cytotoxic pathways is essential for CTL-based immunotherapy against cancer.

Moreover, a recent study shows that colon cancer cells produce immunoregulatory glucocorticoids and suggests that the synthesis of bioactive glucocorticoids in colon cancer cells may account as a novel mechanism of tumor immune escape. Glucocorticoids (both natural and synthetic) inhibit the immune response, thus preventing inflammation from occurring.

Hepazym™ is an immunomodulator of the potentiator type, which has demonstrated an enhancing effect on the function and number of various cells of the immune system in humans. Hepazym™ is designed to naturally build and provide long term support for healthy immune function and sound immune response, even while suffering from cancer. Hepazym™ has been developed in research on viral pathogenesis and mechanistic insights into viral modulation of immune receptor signaling. Hepazym™ contains the latest research based formula of bio-active fermented 32 naturally-occurring compounds with therapeutic potential for immune system enhancement, modulation or anti-cancer activity.

Hepazym™ helps to maintain resistance to infection and defend against cancer. Hepazym™ has been independently tested in a ground-breaking international clinical trial with excellent results. Hepazym™’s multi strain probiotic formulations are also recommended because each person’s intestinal flora has a unique bacterial community (very similar to fingerprints). Metabolic effects of probiotics on the intestinal epithelium include production of short chain fatty acids which influence epithelial cell metabolism, turnover and apoptosis. Probiotics, through secreted molecules, influence the innate inflammatory response of epithelial cells to stimuli from the gut lumen, and reduce mucosal inflammation. Through effects on dendritic, and possibly epithelial, cells they influence naïve T cells in the lamina propria of the gut and thus influence adaptive immunity.  Hepazym™ the ultimate high potency, broad-spectrum probiotic formula, providing a 16 billion live cell count per day of 17 species of beneficial cultures including soil-based probiotics. Hepazym™ is the most effective supplement for anti-cancer and immune system building. No other supplement shows the quick and consistent benefits that Hepazym™ does.

Role of apoptosis resistance in immune evasion and metastasis of colorectal cancer.

Colon cancer cells produce immunoregulatory glucocorticoids.

Roles for inflammation and regulatory T cells in colon cancer.

Conditional regulatory T-cell depletion releases adaptive immunity preventing carcinogenesis and suppressing established tumor growth.

T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis.

Antitumor activity and immune response induction of a dual agonist of Toll-like receptors 7 and 8.

Two distinct mechanisms of augmented antitumor activity by modulation of immunostimulatory/inhibitory signals.

Fermented wheat aleurone enriched with probiotic strains LGG and Bb12 modulates markers of tumor progression in human colon cells.

The application of probiotic fermented milks in cancer and intestinal inflammation.

The anticancer effect of probiotic Bacillus polyfermenticus on human colon cancer cells is mediated through ErbB2 and ErbB3 inhibition.

Polyamines are involved in cell growth and differentiation. Ornithine decarboxylase (ODC), a key enzyme in mammalian polyamine biosynthesis, has been proposed to be a marker of colonic epithelial cell proliferation and risk for colorectal cancer. ODC regulates cell division by catalysing the first step in polyamine biosynthesis. Apigenin is a nonmutagenic bioflavonoid which is presented in leafy plants and vegetables (e.g., parsley, artichoke, basil, celery) and has significant chemopreventive activity. Apigenin is a major constituent of chamomile. Research shows that it may reduce ODC activity; inhibit cancer cell signal transduction and induce apoptosis. Apigenin is almost insoluble in water (pH = 6.6). Apizym™ is the one and only product that has perfect solubility, bioavailability of high purity apigenin.

Ornithine decarboxylase gene is overexpressed in colorectal carcinoma.

Regulation of ornithine decarboxylase during oncogenic transformation: mechanisms and therapeutic potential.

Effect of dietary apigenin on colonic ornithine decarboxylase activity, aberrant crypt foci formation, and tumorigenesis in different experimental models.

The dietary flavonoid apigenin enhances the activities of the anti-metastatic protein CD26 on human colon carcinoma cells.

Molecular targets of apigenin in colorectal cancer cells: involvement of p21, NAG-1 and p53.

The dietary flavonoid apigenin sensitizes malignant tumor cells to tumor necrosis factor-related apoptosis-inducing ligand.

Apigenin acts on the tumor cell invasion process and regulates protease production.

Eflornithine is a drug which was initially developed as a cancer medication. It is also an effective hair growth inhibiting agent. As a topical application, the drug has been shown to be an effective hair growth retardant in some patients, and is sold under the brand name Vaniqa. Protein polyamines are needed for rapid cell growth and differentiation, and the production of these polyamines depends on the activity of enzyme ornithine decarboxylase (ODC). Eflornithine is believed to block ODC and thereby slow the growth and differentiation of the cells within the hair follicles.

A trial was reported involving combination chemoprevention with eflornithine and NSAID sulindac treatment on colorectal adenoma recurrence. Sulindac, like other NSAIDs, has polyamine-inhibitory properties via induction of spermidine spermine acetyltransferase (SSAT) and resultant cellular polyamine export. Together, eflornithine and sulindac decrease the cellular polyamine pools. Results from a recent trial shows that sulindac combined with eflornithine suppresses colorectal carcinogenesis.

Polyamines as mediators of APC-dependent intestinal carcinogenesis and cancer chemoprevention.

Ornithine decarboxylase-1 polymorphism, chemoprevention with eflornithine and sulindac, and outcomes among colorectal adenoma patients.

Phospho-sulindac (OXT-922) inhibits the growth of human colon cancer cell lines: a redox/polyamine-dependent effect.

Sulindac is a general Cox enzyme inhibitor. It’s an inexpensive prescription drug that has been shown to both prevent and treat colon cancers through Cox-2 dependent and independent mechanisms. Clearly, sulindac has anti-cancer properties that transcend its ability to inhibit the Cox-1 and Cox-2 enzymes.

Phosphodiesterase 5 (PDE5) is an enzyme that accepts cGMP and breaks it down. Sildenafil, vardenafil and tadalafil are inhibitors of this enzyme, which bind to the catalytic site of PDE5. PDE5 is expressed in human colonic cells and in intestinal tissue and its activity is regulated by intracellular cGMP levels in these cells that increase on GCC (guanylyl cyclase C) activation. PDE5 was found to be overexpressed in colon tumor cell lines as well as in colon adenomas and adenocarcinomas compared with normal colonic mucosa. PDE5 inhibition, cGMP elevation, and inhibition of β-catenin transcriptional activity may contribute to the chemopreventive properties of sulindac.

AKT kinases play a key role in proliferation, cell survival, and tumorigenesis. Sulindac can inhibit the AKT kinase. Actually, a metabolite of sulindac, sulindac sulfide, is the AKT inhibitor. It appears that sulindac metabolites inactivate AKT by two different pathways. The first pathway degrades AKT by the caspase-8 enzyme. The second pathway decreases phosphorylation of the AKT kinase. Sulindac also promotes the synthesis of p21Waf1. p21Waf1, P53 and cyclin D1 belong to the cell cycle-regulating family of proteins, and the loss of activity of proteins p21Waf1 and P53 seems to be one of the most important regulatory mechanisms of carcinogenesis in colorectal cancer.  

Colon tumor cell growth-inhibitory activity of sulindac sulfide and other nonsteroidal anti-inflammatory drugs is associated with phosphodiesterase 5 inhibition.

Sulindac suppresses beta-catenin expression in human cancer cells.

NSAID sulindac and its analog bind RXRalpha and inhibit RXRalpha-dependent AKT signaling.

Differential targeting of protein kinase B in cell death induced by sulindac and its metabolite sulindac sulfide.

Sulindac and its metabolites inhibit invasion of glioblastoma cells via down-regulation of Akt/PKB and MMP-2.

Sulindac sulfide and caffeic acid phenethyl ester suppress the motility of lung adenocarcinoma cells promoted by transforming growth factor-beta through Akt inhibition.

p21Waf1/Cip1 is a common target induced by short-chain fatty acid HDAC inhibitors (valproic acid, tributyrin and sodium butyrate) in neuroblastoma cells.

The anti-proliferative effect of sulindac and sulindac sulfide on HT-29 colon cancer cells: alterations in tumor suppressor and cell cycle-regulatory proteins.

Polyethylene glycol (PEG) is a nonabsorbed, nonmetabolized, water-soluble polymer that has been used to treat constipation in France since 1996 and was recently approved for use as a laxative in the US and Canada. Studies demonstrated PEG to be a highly effective chemopreventive agent against colon cancer. PEG induced p21Waf1 levels back to normal. These results demonstrate that PEG is involved in p21 regulation concomitant with G1S phase cell cycle arrest and it is through these effects that it can exert its anti-proliferative and hence chemopreventive role. Moreover, PEG induced expression of pro-apoptotic proteins and there was a dramatic and specific induction of apoptosis.

Involvement of p21cip1/waf1 in the anti-proliferative effects of polyethylene glycol in colon carcinogenesis.

Polyethylene glycol-mediated colorectal cancer chemoprevention: roles of epidermal growth factor receptor and Snail.

Induction of multinucleated cells and apoptosis in the PC-3 prostate cancer cell line by low concentrations of polyethylene glycol 1000.

Polyethylene glycol, unique among laxatives, suppresses aberrant crypt foci, by elimination of cells.

Polyethylene glycol induces apoptosis in HT-29 cells: potential mechanism for chemoprevention of colon cancer.

Cytostatic effect of polyethylene glycol on human colonic adenocarcinoma cells.

Epidemiological and experimental evidence supports the hypothesis that heme iron present in meat promotes colon cancer. Heme iron is found in meat, fish, and poultry in a chemical structure, while nonheme iron can be found in plant sources. This heme iron can be easily absorbed by our body. Heme iron from meat, especially red meat may increase blood pressure and has adverse reaction to health. Another disturbing truth is that when people have this hereditary hemochromatosis, a condition of iron overload, and getting excess iron from meat would affect some vital organs such as the heart, pituary gland, liver, pancreas, and joints. Furthermore, animal fats with high lipids when combined with heme iron can damage cells and generate free radical activity. The analysis of experimental studies in rats with chemically-induced colon cancer showed that dietary hemoglobin and red meat consistently promote aberrant crypt foci, a putative precancer lesion. The mechanism is not known, but heme iron has a catalytic effect on (i) the endogenous formation of carcinogenic N-nitroso compounds and (ii) the formation of cytotoxic and genotoxic aldehydes by lipoperoxidation.

Iron as the most abundant metals on earth are needed by our body to function well by transporting the hemoglobin in the blood. However, people have so many wrong beliefs when it comes to iron consumption. While it is true that iron deficiency is the worlds’ most common dietary disorder, it is also worth noting that iron overload is one of the problems most people are unaware of. You don’t have to give up red meat to be healthy, but the evidence suggests that you’d be wise to limit your consumption.

A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association.

Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved.

Heme of consumed red meat can act as a catalyst of oxidative damage and could initiate colon, breast and prostate cancers, heart disease and other diseases.

Re: Heme iron, zinc, alcohol consumption, and risk of colon cancer.

Red meat and colon cancer: dietary haem, but not fat, has cytotoxic and hyperproliferative effects on rat colonic epithelium. 

Hemoglobin is the protein that makes blood red. It is composed of four protein chains, two alpha chains and two beta chains, each with a ring-like heme group containing an iron atom. Oxygen binds reversibly to these iron atoms and is transported through blood. Heme is oxidized, with the heme ring being opened by the endoplasmic reticulum enzyme, heme oxygenase. Fats (lipids) when in combination with unbound iron can generate free radical activity, which is destructive to cells and can damage DNA. Hemin, added to low-calcium diets, increases colonic proliferation, and hemoglobin, added to high-fat diets, increases the colon tumour incidence in rats, an effect possibly due to peroxyl radicals.

The cells from people eating the high-meat diet contained a large number of cells that had DNA changes; the stools of vegetarians had the lowest number of cells with damaged genetic material, and the people who ate high-meat, high-fiber diets produced intermediate numbers of damaged cells. We thus speculated that heme might be the promoting agent in meat, and that prevention strategies could use calcium and antioxidants. However, it is important to remember that cancer prevention and treatment are 2 distinct phases. What works for one does not necessarily work for the other. Oftentimes, cancer patients turn to guidelines for cancer prevention to help fight their disease. Unfortunately, anti-cancer diet will not cure cancer. Just as quitting smoking will not cure lung cancer after its been diagnosed, neither will taking an antioxidant supplement. Once cancer develops, the role of dietary changes to focus on supporting and managing the side effects of treatment. In this article, we will explore the natural colon cancer treatment options.

Beef meat promotion of dimethylhydrazine-induced colorectal carcinogenesis biomarkers is suppressed by dietary calcium.

Meat and cancer: haemoglobin and haemin in a low-calcium diet promote colorectal carcinogenesis at the aberrant crypt stage in rats.

Red meat and colon cancer: dietary haem-induced colonic cytotoxicity and epithelial hyperproliferation are inhibited by calcium.

Green vegetables, red meat and colon cancer: chlorophyll prevents the cytotoxic and hyperproliferative effects of haem in rat colon.

Natural chlorophyll but not chlorophyllin prevents heme-induced cytotoxic and hyperproliferative effects in rat colon. 

Cellular oxidants, called reactive oxygen species (ROS), are constantly produced in human cells. Excessive ROS can induce oxidative damage in cell constituents and promote a number of degenerative diseases and aging. Cellular antioxidants protect against the damaging effects of ROS. However, in moderate concentrations, ROS are necessary for a number of protective reactions. Thus, ROS are essential mediators of antimicrobial phagocytosis, detoxification reactions and apoptosis which eliminate cancerous cells. Excessive antioxidants could dangerously interfere with these protective functions, while temporary depletion of antioxidants can enhance anti-cancer effects of apoptosis.

Artemisinin is the active compound of the simple plant, Artemisia that grows in Southeast Asia. It has been used for years to treat intestinal parasites. The World Health Organization lauds it as a safe malaria treatment. Cancer cells need irons to enable them to grow aggressively; hence cancer cells typically absorb a significantly larger amount of iron than noraml, healthy cells. When Artemisinin come in contact with these irons in the cancer cells, it would trigger a chemical reaction and stimulate increased generation of reactive oxygen species (ROS) and induce apoptosis. The free radicals attack the cancer cell membranes, breaking them apart and killing them. This is why Artemisinin is highly toxic to cancer cells. Tests have been conducted to show that Artemisinin causes rapid and extensive damage and death in cancer cells and yet has relatively low toxicity to normal cells. Unfortunately dietary Artemisinin in supplement form didn’t help cancers due to low solubility and bioavailability. It is recognized that the therapeutic effectiveness of Artemisinin is limited due to its poor absorption from the GI tract, so the use of the natural fermentation to enhance its uptake is particularly beneficial. Artezym is enzymatic fermented Artemisinin. It has perfect bioavailability and pharmacokinetics of active Artemisinin. Artezym is the one and only product that has perfect bioavailability of Artemisinin enough to induce apoptosis in colon cancer cells. Otherwise, Artemisinin wouldn’t have worked.

Anticancer properties of artemisinin derivatives and their targeted delivery by transferrin conjugation.

Heme synthesis increases artemisinin-induced radical formation and cytotoxicity that can be suppressed by superoxide scavengers.

The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells.

Heme mediates cytotoxicity from artemisinin and serves as a general anti-proliferation target.

Salts and esters of butyric acid are known as butyrates. Butyrate is an important short chain fatty acid that provides fuel for colon cells and may help protect against colon cancer. The most potent dietary source is butter (3%). The membrane of the GI tract undergoes a complete turnover about every three days. Butyric acid is an important inducer of maturation or differetiation of newly growing intestinal cells. Interestingly, so does vitamin D3. Butyrate might be very useful in the treatment of colon, GIST or stomach cancers. Butyrate is a powerful histone deacetylase (HDAC) inhibitor. HDAC is overexpressed in approximately half of all colon cancer. HDAC inhibitors such as butyrate clearly inhibit the growth of colon cancer cells. Scientists have found a human gene that stops the growth of cancer cells when activated by fiber processing in the colon. Although scientists have long linked butyrate to overall reductions in the incidence of colon cancer, the molecular basis of that benefit has remained largely unknown. Butyrate effects a chemical “unloosening” of molecules that otherwise bind and constrict the activity of the p21 gene. This gene is responsible for the manufacture of p21protein, a compound that slows the growth of cancer cells.

HDAC4 promotes growth of colon cancer cells via repression of p21.

HDAC4 represses p21(WAF1/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism.

Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer.

The histone deacetylase inhibitor butyrate downregulates cyclin B1 gene expression via a p21/WAF-1-dependent mechanism in human colon cancer cells.

The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation.

Transient vs. prolonged histone hyperacetylation: effects on colon cancer cell growth, differentiation, and apoptosis.

Butyrate and trichostatin A effects on the proliferation/differentiation of human intestinal epithelial cells: induction of cyclin D3 and p21 expression.

Butyrate inhibits colon carcinoma cell growth through two distinct pathways.

p21(WAF1) is required for butyrate-mediated growth inhibition of human colon cancer cells.

Butyrate, a fatty acid, comes from two dietary sources. First, it is one of the metabolic end products of unabsorbed dietary carbohydrate that has been bacterially fermented in the gut. Butyrate is the single biggest metabolite of fiber. Second, the only direct source in the diet is from butter, which contains 3% butyrate. Adequate amounts of butyrate are necessary for the health of the large intestine cells. Using good ole butter as a concentrated source of butyrate, we can deliver this natural medicine to the cells of the stomach and GI tract. Vitamin D3 is also a differentiation factor for intestinal cells. Vitamin D3 stimulates the synthesis of calcium binding proteins which promote calcium uptake into the blood. As with butyrate, it also stimulates the maturation of growing intestinal cells. And, of course, it is an excellent natural medicine for the treatment of colon cancer.

Butyrate induces the enzyme that converts inactive vitamin D3 to its active form and stimulates the synthesis of the vitamin D3 receptor (VDR). Butyrate and vitamin D3 synergize to induce p21Waf1, a cell cycle inhibitor that is induced by all HDAC (histone deacetylase) inhibitors. In addition to a lack of inactive vitamin D3 in our bodies due to poor sun exposure, the insensitivity to vitamin D3 found in most cancer cells may be due to enhanced HDAC activity. It is clear that HDAC inhibitors increase vitamin D3 sensitivity in cancer cells. Naturally this translates to enhanced apoptosis in a wide diversity of cancer cells. Therefore, butyrate, like vitamin D3_, is a physiological agent that provides an extrinsic signal important in establishing and maintaining colonic mucosal homeostasis. Butyrate decreases cyclin D1 and c-myc expression, each essential for intestinal tumor development, by transcriptional attenuation. Thus, transcriptional attenuation may be a common mechanism involved in normal, well integrated, finely balanced programs of cell maturation in both embryogenesis and in response to physiological inducers of cell maturation in the adult, such as butyrate and vitamin D3 in the intestine.

Transcriptional attenuation in colon carcinoma cells in response to butyrate.

Butyrate and vitamin D3 induce transcriptional attenuation at the cyclin D1 locus in colonic carcinoma cells.

Nutrients regulate the colonic vitamin D system in mice: relevance for human colon malignancy.

Colon-specific regulation of vitamin D hydroxylases–a possible approach for tumor prevention.

Upregulation of 25-hydroxyvitamin D(3)-1(alpha)-hydroxylase by butyrate in Caco-2 cells.

The Vitamin D endocrine system of the gut–its possible role in colorectal cancer prevention.

Vitamin D and colon carcinogenesis.

Gene expression profiles in rat intestine identify pathways for 1,25-dihydroxyvitamin D(3) stimulated calcium absorption and clarify its immunomodulatory properties.

Short-chain fatty acids and colon cancer cells: the vitamin D receptor–butyrate connection.

Butyrate-induced differentiation of Caco-2 cells is mediated by vitamin D receptor.

Tributyrin, a stable and rapidly absorbed prodrug of butyric acid, enhances antiproliferative effects of dihydroxycholecalciferol in human colon cancer cells.

1,25-Dihydroxycholecalciferol enhances butyrate-induced p21(Waf1/Cip1) expression.

Glutamine may actually stimulate growth of tumors.

High concentrations of oral glutamine also produce high amounts of glutamate in the blood, a breakdown product of glutamine. Glutamate is a key molecule in cellular metabolism and is the most common neurotransmitter in the brain. It is particularly abundant in the nervous system. The most common excitatory neurotransmitters are glutamate and aspartate while the primary inhibitory neurotransmitter is GABA. It is necessary for excitatory and inhibitory neurotransmitters to be in balance for proper brain function to occur. Glutamate receptors are responsible for the glutamate-mediated post-synaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation.

Glutamate is also elevated in cancer patients, and several authors have shown that elevated extracellular glutamate levels inhibit competitively the membrane transport of cystine and cause a decrease of intracellular cysteine. A study shows that patients with lung cancer with the lowest glutamate levels had the highest survival rates. They also had the highest cysteine levels. Cysteine – a sulfur containing amino acid – is used to make glutathione as well as taurine – the body’s natural water soluble anti-oxidant. This finding suggests that glutamate may interfere with cysteine and glutathione production in the body.

Glutamate regulates proliferation and migration of neurons during development. Also, glutamate appears to play a central role in the malignant phenotype of glioma via multiple mechanisms. By binding to peritumoral neuronal glutamate receptors, glutamate is responsible for seizure induction and similarly causes excitotoxicity, which aids the expansion of tumor cells into the space vacated by destroyed tissue. Glutamate also activates ionotropic and metabotropic glutamate receptors on glioma cells in a paracrine and autocrine manner.

Glutamate also influences proliferation, migration and invasion of tumor cells. A study demonstrated that glutamate antagonists inhibit tumor growth. Glutamate antagonists apparently also inhibit cancer cell migration and so may be useful in preventing cells from proliferating throughout the body. One has to ask the nagging question, then – If blocking glutamate can cause cancer cells to die and stop migrating, shouldn’t cancer patients stop eating MSG (monosodium glutamate) and aspartame? Unfortunately, patients suffering from cancer are rarely, if ever told this information.

MSG is adding flavor to your food, but if you’re consuming a diet with glutamate in it, particularly high levels, you’re making your cancer grow very rapidly. We refer to it as cancer fertilizer. The cancers of this type include several brain cancers, colon cancer, breast cancer, pancreatic cancer and others as well. When you increase the glutamate level, cancer just grows like wildfire, and then when you block glutamate, it dramatically slows the growth of the cancer. Aspartame is the second most widely used artificial sweetener in the world ans is a multipotential carcinogenic compound. In fact, when cancer cells were exposed to aspartame, they became more mobile, and you see the same effect with MSG.

Glutamine and glutamate–their central role in cell metabolism and function. 

Targeting glutamine metabolism sensitizes melanoma cells to TRAIL-induced death. 

T4+ cell numbers are correlated with plasma glutamate and cystine levels: association of hyperglutamataemia with immunodeficiency in diseases with different aetiologies. 

Glutamate and the biology of gliomas. 

A role for glutamate in growth and invasion of primary brain tumors. 

Glutamate increases pancreatic cancer cell invasion and migration via AMPA receptor activation and Kras-MAPK signaling.

Glutamate receptor-mediated effects on growth and morphology of human histiocytic lymphoma cells. 

Glutamate antagonists limit tumor growth. 

Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice. 

First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats.

In addition to its extracellular roles as a neurotransmitter, glutamate serves important intracellular signaling functions via its metabolism through glutamate dehydrogenase (GDH). GDH is a mitochondrial matrix enzyme that catalyzes the oxidative deamination of glutamate to alpha-ketoglutarate. Glutamate, which already induces insulin release from the pancreas, is turned into GABA in the body. GABA causes the pituitary to release growth hormone – not a good thing if you have cancer. Also, insulin can stimulate the growth of cancer cells as well. Cancer cells actually manufacture and secrete their own insulin. Related to this insulin secretion is the even more interesting fact that cancer cells have ten times more insulin receptors per cell than any of the normal cells in the body. The metabolic modifications by insulin results from the fact that not only can it join up with its own specific receptors on cell membranes, but insulin is also able to join up with the receptors for insulin-like growth-factor, and to communicate messages about growth to these cells.

The growth of blood vessels is the trouble when there is tumor growth. Angiogenesis, the formation of new blood vessels, is a multi-step process regulated by pro- and anti-angiogenic factors. In order to grow and metastasize, tumors need a constant supply of oxygen and nutrients. For their growth beyond the size of 1-2 mm tumors are dependent on angiogenesis. Well – elevated levels of GABA and glutamate are present in people with diabetic retinopathy (damage to the eyes). Vascular endothelial growth factor (VEGF) is at work here too.

Glutaminolysis and insulin secretion: from bedside to bench and back. 

Insulin secretion profiles are modified by overexpression of glutamate dehydrogenase in pancreatic islets. 

Overexpression of constitutively activated glutamate dehydrogenase induces insulin secretion through enhanced glutamate oxidation. 

Expression of the insulin-like growth factors (IGFs) and the IGF-binding proteins (IGFBPs) in human gastric cancer cells. 

Elevated gamma-aminobutyric acid, glutamate, and vascular endothelial growth factor levels in the vitreous of patients with proliferative diabetic retinopathy.

Theanine is an amino acid found in green tea. Theanine is a glutamate receptor antagonist and has been shown to decrease brain norepinephrine (NE) levels secondarily to increasing GABA levels. It is capable of blocking the uptake of the amino acid glutamate into cells. This inhibits something called the glutamate/cystine antiporter (xCT) resulting in a reduction in the reducing agent glutathione in the cancer cells. This makes the cancer cells very sensitive to the waste products they generate. Wolfberries (Lycium barbarum) are also believed to be quite potent as a glutamate antagonist. Wolfberry (Lycium barbarum) is a common ingredient in oriental cuisines.

The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. 

L-theanine protects the APP (Swedish mutation) transgenic SH-SY5Y cell against glutamate-induced excitotoxicity via inhibition of the NMDA receptor pathway. 

Theanine, gamma-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats. 

Theanine, an ingredient of green tea, inhibits [3H]glutamine transport in neurons and astroglia in rat brain. 

l-Theanine, an amino acid in green tea, attenuates beta-amyloid-induced cognitive dysfunction and neurotoxicity: reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-kappaB pathways. 

Polysaccharides from wolfberry antagonizes glutamate excitotoxicity in rat cortical neurons.

Radix Stephaniae tetrandrae, generally known as “Fangji”in Chinese, is the dry root of Stephaniae tetrandra S. Moore (Menispermaceae). This plant is often used in Chinese traditional medicine because its main components fangchinoline and tetrandrine show a lot of pharmacological activities including anti-allergic, anti-inflammatory, anti-hyperglycemic and anti-cancer activities. Fangchinoline has been shown to possess neuroprotective properties. Findings from an animal study suggest that fangchinoline inhibits glutamate release from the cortical synaptosomes through the suppression of voltage-dependent Ca(2+) channel activity and subsequent reduces Ca(2+) entry into nerve terminals, rather than any upstream effect on nerve terminal excitability.

Fangchinoline inhibits glutamate release from rat cerebral cortex nerve terminals (synaptosomes). 

Anti-inflammatory effects of the partially purified extract of radix Stephaniae tetrandrae: comparative studies of its active principles tetrandrine and fangchinoline on human polymorphonuclear leukocyte functions. 

Anti-inflammatory effects of fangchinoline and tetrandrine.

Inhibitory effects of bisbenzylisoquinoline alkaloids on induction of proinflammatory cytokines, interleukin-1 and tumor necrosis factor-alpha. 

Anti-hyperglycemic effect of fangchinoline isolated from Stephania tetrandra Radix in streptozotocin-diabetic mice.

Most immune modulating agents work by improving inter-cellular communication. One way that cells communicate is by presenting on their surface complex, information-rich protein macromolecules linked with molecules of saccharides (polysaccharides). An inter-cell “message” depends on the structure of saccharides. Researchers believe that people with chronic hepatitis B do not produce mature or adequate numbers of dendritic cells and therefore cannot eradicate the viral infection. Hepazym modulates and supports the immune system in a number of ways. It may cause an increase in the number of white blood cells, which are an integral part of the body’s natural immune system.

Combining elements of antiviral and immune modulating natural substances may help rid the body of the hepatitis B virus. Antivirals or nucleoside analogues are designed to deliberately interfere with HBV’s DNA so it can’t reproduce itself. There are 7 approved medications for chronic HBV infection: 5 oral nucleoside/nucleotide analogues (lamivudine, entecavir, telbivudine, adefovir, and tenofovir) and 2 injectable therapies (interferon alfa-2b and pegylated interferon alfa-2a). Baraclude (Entecavir) is an oral prescription antiviral medication used in the treatment of chronic HBV infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases , AST (SGOT) and ALT (SGPT), or histologically active disease, but many patients fail to respond. Currently there is no cure for HBV. Antiviral drugs will not cure HBV. This has prompted a search for effective alternative therapies.

Recently, a patient (male, age 34, South Korean) with chronic hepatitis B treated with 0.5 mg per day of Baraclude (Entecavir) has taken Hepazym 50 ml (10 ml 5 times) a day for 6 weeks to spur the immune system. He was diagnosed with Heptitis B 13 years ago. His ALT (SGPT) levels have been consistently elevated, indicating that the liver is not functioning properly and that the hepatitis viral infection is damaging liver cells.

Blood test results: Oct. 2010

AST (SGOT): 53 (Normal range <40)

ALT (SGPT): 101 (Normal range <45)

HBV DNA: 3350 copies

HbeAg- negative

HbeAb-positive

Blood test results: Nov 19, 2010

AST (SGOT): 40 (Normal range <40)

ALT (SGPT): 119 (Normal range <45)

HBV DNA: 357 copies

HbeAg- negative

HbeAb-positive

Blood test results: Jan 12, 2011

6 weeks after taking Hepazym, this patient responded with significant decreases in ALT (GPT) levels from 119 to 26. He had a rapid increase in WBC (white blood cells) from 4.5 to 7.5. He has always had a low WBC. HBV viral load was undetectable. His chronic fatigue symptoms disappeared within 2 days after being taken Hepazym.

AST (SGOT): 39 (Normal range <40)

ALT (SGPT): 26 (Normal range <45)

HBV DNA: 0.13

HBeAg- negative

HBeAb-positive

WBC (white blood cells): increased from 4.5 to 7.5

HBsAb: 1.00 (HBsAb level was increased to 1.00, but a protective level is more than 10 mIU/ml). This patient will continue Hepazym-immunotherapy for the next 10 weeks.

P.S: Mar 4, 2011 Blood test results

HBsAb (HepB surface antibody) levels elevated to 3. It means the desired immunity (protective antibodies to Hepatitis B) is developing. The development of immunity means that immunological memory has been acquiring. This is the time during which seroconversion occurs. The body is recognizing the HBV virus and producing antibodies to try to fight the infection. Serum HBsAg, AST (GOT) and ALT (GPT) levels showed increase during the period of seroconversion.