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From the Townsend Letter
January 2009

Oral Insulin (Swallowed) and Rectal Insulin Suppository for Diabetics: Panacea or Evolving Future Health Disaster
Part II
by T.R. Shantha, MD, PhD, FACA
and Jessica G. Shantha

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In Part I of this article, we discussed diabetes treatments and the dangers of alternative inhalation insulin delivery systems when used as a replacement for insulin shots.1,2 In recent times, we have seen the research we discussed supported. Pfizer Pharmaceuticals has reported six lung cancer cases resulting from the use of their FDA-approved Exubera, an inhalation insulin product. Pfizer consequently withdrew the drug from the market, taking a 2.5 billion-dollar loss.3,4 The FDA still has not withdrawn their approval. Pharmaceutical giants Amlyin and Eli Lilly have reported six deaths and 30 cases of pancreatitis resulting from the use of the anti-hypoglycemic agent Byetta (Exenatide: oral and injectable forms). These are good examples of the deadly adverse effects of newly introduced, FDA-approved anti-diabetic drugs. Fear of needles and a resistance to the inconvenience of administering insulin injections have created a burgeoning demand for alternative methods of treating diabetes. An apparent breakthrough arrived with the development of insulin inhalation preparations. While the FDA deemed this novel insulin preparation safe and effective, Pfizer, as mentioned, withdrew their inhalation insulin product after publication of our article detailing its dangers.1 Oral and nasal spray insulin preparations are not much different than inhalation insulin, which increases the incidence of cancers and other diseases, hence none of these preparations should be approved for public use.

Given the inhalation insulin debacle, many research centers and pharmaceutical companies are now scrambling to find other alternative methods of delivery to replace painful subcutaneous insulin injections and help make diabetics more compliant. One out of every ten health care dollars spent in the United States goes to treat diabetic patients, and loss of productivity results in a commensurate loss of billions of dollars. It is estimated that the health care costs of US diabetics are three times more than those of healthy individuals. Consequently, besides the obvious health benefits, a safe, effective replacement for subcutaneous insulin injections would save billions in health care costs, given that there are currently more than 180 million diabetics worldwide, a number destined to increase. At present, we have two patents pending for the painless delivery of insulin by time-honored subcutaneous injections and also a new locally applied transmucosal insulin delivery system of existing insulin formulations, which are safe and has been in use for decades. We hope to bring these products to the market to help insulin-dependent diabetics become more treatment-compliant.

In Part I of this article, we described why insulin is carcinogenic in high concentrations. Here, in Part II, we discuss the pros and cons of oral (swallowed) and rectal insulin for diabetics as an alternative treatment to both the standard injectable insulin and the failed inhalation insulin therapy.

Figure 1: Liver Anatomy and Its Function in the Removal of Blood Sugar


To understand how oral insulin works, it is important to have anatomical and histological knowledge of the liver and gastrointestinal tract and also understand how liver function is affected by oral and endogenous insulin. The liver is part of the digestive system. It weighs three pounds and performs about 500 different functions in addition to playing an important role in maintaining blood glucose levels. The liver receives 75% of its blood from the digestive tract (portal veins), which contains nutrients, including sugars, and 100% of insulin from the pancreas, which pours into the liver in response to elevated blood sugar. The liver receives only 25% of its blood supply from the heart (hepatic artery) (see Figure 1), hence only 25% of subcutaneous insulin reaches the liver. The liver removes glucose from the blood with the help of insulin when blood glucose levels are high and stores it as glycogen. When the amount of glucose in the blood falls below the level required to meet the body's needs, the liver reverses this reaction, transforming glycogen into glucose with the help of another pancreatic hormone called glucagon and pouring it into the bloodstream for energy use.

Intestinal Histology and Absorption of Oral Insulin

Figure 2: Cross-section of intestinal villi showing layers of mucous membrane and blood supply
SA402073 LifeART Royalty Free Photograph

Figure 3: Drawings and Diagrams of Intestinal Villi

To understand how the oral and rectal insulin is absorbed into circulation from the digestive track – and the possible adverse effects – knowledge of intestinal histology is needed. Oral insulin and food pass from the stomach after partial digestion by stomach acid to the small intestine. The small intestine has millions of finger-like projections in the lumen called villi (velvety surface), lined by single layer of epithelial enterocele cells. The enterocele have hundreds of additional extensions on their exposed surface towards the lumen called microvilli, which are like tiny hairs ("brush border") coated with glycoprotein layer. These constitute a semi-permeable membrane of the gut interior wall and are the first structures to come in contact with food and oral insulin. These enterocytes on the gut lining live only for three to five days before they are shed into the gut lumen and replaced by new cells from the crypt. The enterocele cells with microvillus and glycoprotein coating are involved in absorbing oral insulin, digested food with sugar, liquids, secretions, etc., and they also act as barrier to prevent unwanted particulate matter from entering the bloodstream. The villi increase the intestinal absorptive surface area 300-fold and themicrovilli 600-fold, providing a massive absorption surface of the gut lumen for oral insulin. The center of the villi contains tiny blood vessels and are lymphatic. They collect the absorbed digested material from the guts, including insulin taken orally, and empty it into the portal vein to the liver and through thoracic lymph duct to heart.

Crypts (of Lieberkuhn) are invaginations of the epithelium at the base and between the villi, like the web of the fingers. The base of the crypts contains stem cells that divide and provide the source of all the epithelial cells in the crypts and the lining of the gut and its secretory cells. Stem cells in the crypts divide to form daughter cells. One daughter cell from each stem cell division is retained as a stem cell. The other becomes committed to differentiate as one of four pathways to become an enterocyte, enteroendocrine cell, goblet cell, or Paneth cell. Cells in the enterocytes lineage divide several more times as they migrate up the crypts, cover the villi, and differentiate into the mature absorptive cells that transport nutrients and enzymes as well as the oral insulin when developed. To put it another way, enterocytes are born at the bottom of the crypts, pass through childhood migrating up the walls of the crypts, then settle down briefly to enjoy an absorptive adulthood on the villi and then die (shed) in less than a week.

Oral Insulin
It is important to note that subcutaneous insulin injection is the only method of insulin delivery at present. The main disadvantage besides pain is that this delivery system does not reproduce the physiological delivery of insulin to the liver – neither do oral insulin preparations, despite claims by their developers and promoters, as we will discuss later. In a normal individual, 100% of insulin from the pancreas is delivered into the portal vein to the liver, the primary site of action. Some of it escapes from the liver to the systemic circulation to act on the muscle, but only after the liver's insulin needs are met. On the other hand, oral insulin enters the portal blood vessel system and the lymphatic system (called lacteal, which carries equal amount to lymphatic sac-chylus sac-thoracic duct) into systemic circulation instead of to the liver. Hence, oral insulin may deliver 30-40 times absorbed insulin into the liver compared to the 25% of the injected insulin. As with injected insulin, orally delivered insulin takes a long time to be absorbed and transported to the liver, which is the primary site of insulin action, and high blood sugar may not play any role in rapid absorption as happens with naturally produced insulin. In theory, oral insulin methods should require less insulin per dose to produce the desired effect on reaching the liver in diabetics. Unfortunately, there is no oral delivery method yet developed in which the amount of insulin equals natural insulin from pancreas, 100% of which is delivered to the liver.

Development and Prerequisites for Oral Insulin Preparation
Many modalities of delivering insulin are in the works from inhaled insulin to sprays to pill forms. From my investigation, the insulin sprays (oral and nasal) and inhalation insulin, discussed in Part I, have no place in insulin delivery system due to the increased incidence of cancers and other diseases.1,2 The development of oral insulin has been in works for decades, and the search for a viable product has intensified since the failure of inhalation insulin drugs. The difficulty is that insulin in pill form is destroyed by digestive juices in the stomach and small intestines. For insulin to escape the destructive action of digestive enzymes and acids, it must be tagged or protected by a coating resistant to the action of digestive juices. The insulin that escapes the onslaught of digestive enzymes must be tagged onto substances that increase absorption and facilitate the transfer of such insulin from the lumen of the gut into circulation. These protective coatings and absorption facilitators should be non-toxic and should not damage the protective lining of the intestines' inner lining even with prolonged use. Further, they should not have any adverse effects on the immune system barrier lining the intestinal interior (villi), which is the first line of defense against all invading infectious and toxic agents. None of the oral insulin delivery methods in development meet these requirements yet.

Some developers of oral insulin claim that three times the amount of orally delivered insulin reaches the liver compared to insulin delivered by subcutaneous injection. Unfortunately, these developers forget that 100% of oral insulin does not enter the portal blood to the liver as does naturally produced pancreatic insulin. Part of the insulin is delivered to the lymphatic duct; part of it reaches the portal circulation; and part of it is lost in the intestinal wall. Thus no more than 30-40% reaches the liver, thus giving a possible 5 to 15% advantage, compared to the injectable form -- not three times as claimed.

Many methods of oral insulin are being developed, including formulations incorporating insulin into vitamin B12; adding a cholera-causing toxin to facilitate transfer; trying gel forms, capsules, liquids, and many other additives. None of these have resulted in much success. Before oral insulin can be guaranteed as safe and market-ready, these products need decades of study. The discovery of new method of delivery may make headlines but, at present, that is all; no reasonably priced, non-carcinogenic oral insulin product is on the horizon.

Oral Insulin Route
The lining epithelium (enterocytes) on the villi of the intestines plays an important role in the digestion and absorption of intestinal contents (food), including oral insulin. Because of the massive amount of fluid (5-7 liters a day, digestive juices and extra fluids intake, with and between meals) and semisolid food turnover, it is likely that oral insulin would have to be taken either some time before food or a long time after meals, making it unsuitable to control a blood sugar level rise after meal. Otherwise, oral insulin would have to be mixed with massive amount of intestinal secretions and food. This, in turn, would result in loss of efficacy of the oral insulin, as only a small amount will be absorbed and available to reduce blood sugar after a meal, as happens with inhaled insulin. To overcome this, the amount of insulin in oral preparations would have to be large, as in inhalation insulin. When oral insulin is taken on an empty stomach, part of the oral insulin can be:

  1. inactivated by digestive enzymes,
  2. diluted with food and many liters of digestive juices,
  3. deposited in the crypts (Crypts of Lieberkuhn) between the villi,
  4. trapped in diverticulas in the intestines and colon,
  5. stuck to mucous lining of the villi for a long period before it is absorbed or mechanically dislodged and evacuated during the next bowel evacuation, or
  6. attached to the glycoprotein lining of the microvilli to be absorbed to the portal blood, lymphatic duct, and intestinal wall.

Once the insulin is absorbed, insulin is distributed in the following ways:

  1. Some insulin passes the lining cells of the villi processes.
  2. Some is deposited inside the villi cells, and part is deposited below these cells
  3. Insulin is also absorbed by the blood vessels in the center of the villi (see Figure 3), which is carried to the portal circulation directly into the liver like natural insulin.
  4. Oral insulin is absorbed by the lymphatic ducts, called lacteals, in the center of the villi and delivered to systemic circulation where it acts like subcutaneous injected insulin (see Figure 3).
  5. Some insulin may be picked up the billions of plasma cells below the villi's mucous membrane lining in the lamina propria of the intestines and get activated.
  6. Some insulin is picked up the muscle layers and fat in the intestinal wall and used to transport the glucose to these cell layers.
  7. Insulin absorbed by the lining of the villi is shed into the lumen of the intestine without entering the circulation. Every hour, 1/120th of the intestinal inner lining wall is shed. Hence, 1/120 of the absorbed insulin inside the lining of villus are shed into the intestinal lumen and mixed with food. Part of it is digested and absorbed; the rest is evacuated as excreta.

Oral Insulin, Insulin Receptors, and Cancer
Though the makers of oral insulin delivery systems may claim advantages, these preparations have a number of deleterious effects on the inner lining cells of the intestines. Such effects can play havoc on patients' health and can be worse than the inconvenience of taking subcutaneous insulin injections. Oral insulin is effective only when the calculated dose is higher than the amount given under the skin by injection, because a large amount is lost, due to reasons detailed above. Oral insulin, then, is not much different than inhaled insulin delivery systems, which make about ten percent of the insulin they deliver bioavailable to enter the bloodstream. The rest is deposited on the tracheo bronchial tree, resulting in untold number adverse effects, including increased development of cancers.1,2 The same result can be seen with the potential use of oral insulin. The only advantage there is that part of the insulin (about 30-40%) is directly absorbed and passed on to the portal veins and reaches the liver where it is needed, instead of circulating all over the body after subcutaneous injections.

Before it is absorbed by the lymph vessels (lacteals) and blood vessels in the villi, oral insulin has to come in contact with the lining cells of intestinal tract. The lining cells are very active; they rapidly divide and are replaced every three to five days, illustrating the dynamic nature of that 30 feet of the gastrointestinal track. Further, to be absorbed, insulin must be tagged to other substances to reach the intestinal surface mucosa. With the chronic use, insulin may adversely affect the intestinal lining cells, increasing cell growth and effecting cancerous changes in actively dividing crypt cells.

Insulin has a more adverse stimulatory effect on dysplasic, precancerous, and cancerous cells, which have up to ten times more insulin receptors (ten more insulin-mediated glucose biochemical entry doors) than normal cells, which each have a single insulin door.
The lining membrane, from the esophagus to the end of colon, is exposed to physical and chemical assaults, as is the respiratory tract, due to various kinds of food, drink, and digestive enzymes with which it comes in contact. Can you imagine adding a cell stimulant to these multiplying dysplasic cells. Even solitary, non-cancerous fibrous tumors, similar to polyps, have more insulin receptors, which facilitate glucose entry into cancer cells in large amounts, promoting their growth, multiplication, and spread.5-17

The adverse effects of oral insulin can be divided into the following routes of administration and their health consequences:

  1. Oral ingestion of insulin, formulated as solid pills, capsules, gels, liquids, phospholipid (liposome) components, tagged on to the vitamins (vitamin B12), and countless other feasible formulations, including a delivery system using nano insulin particles
  2. Rectal insulin suppository formulation

Possible Health Consequences of Oral Insulin
What effect will oral insulin, its preservatives, and absorption enhancers have on the gut wall? Can these enhancers cause exfoliation of the lining cells and the breaking of adhesions between lining cells of the gut, resulting in breaching of the barrier between blood and food? If so, can this result in leaky gut syndrome, which can lead to many gastrointestinal (GI) diseases like irritable bowel syndrome, celiac, Crohn's diseases, IBS, diarrhea, autoimmune diseases, and infections (bacterial, viral, moulds, and fungi) and untold number other diseases? Does anyone know the full effect of oral insulin, which is a powerful growth factor on the intestinal parasites? Many factors need to be considered:

1. All the following concerns need to be addressed by any pharmaceutical or research centers developing oral insulin for diabetics. What will result when oral insulin is taken along with any of the following:

  • Antibiotics, which can to lead to the overgrowth of abnormal flora in the gastrointestinal tract (bacteria, parasites, candida, fungi)
  • Alcohol and caffeine (strong gut irritants)
  • Foods and beverages contaminated by parasites like Giardia lamblia, cryptosporidium, and blastocystis hominis; by bacteria like helicobacter pylori, klebsiella, citrobacter, pseudomonas, and others; mold and fungal mycotoxins in stored grains and fruit and refined carbohydrates.
  • Chemicals in fermented and processed food (dyes, preservatives, peroxidized fats)
  • In those patients with enzyme deficiencies (e.g., celiac disease, lactase deficiency causing lactose intolerance)
  • Non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin, ibuprofen, indomethacin, etc.; corticosteroids, narcotics, blood thinners; hormones (in birth control pills and other medications). Would oral insulin intensify the absorption of hundreds of oral medications, resulting in adverse toxic effects?
  • Chemotherapy and radiation therapy cause immune system destruction and damage to the multiplying crypt cells and enterocytes of the villi, resulting in denudation of the intestinal lining (villi). When we take oral insulin in these situations, what will happen to the oral insulin and what will be its effect on these damaged intestinal lining cells? Will oral insulin help in healing by stimulating cells to multiply and replace the damaged cells? Or will oral insulin aggravate damaged genetic conditions of cells, leading to infections and tumor development? Or will more oral insulin be absorbed in these situations?
  • Diets heavy in highly refined carbohydrates (e.g., white bread, candy bars, cookies, soft drinks)

2. Dysbiosis (also called dysbacteriosis) is a microbial imbalance inside the gut resulting from antibiotic use, chemotherapeutic agents, etc. There are billions of beneficial microbial colonies inside our gut that carry out a series of helpful and necessary functions and protect the body from the penetration of pathogenic microbes. Can the use of oral insulin for long time decrease their ability to check growth, allowing an overgrowth of harmful colonies, with subsequent local (thrush) and systemic damage, including leaky gut syndrome, allergies, and other diseases? Conversely, can oral insulin restore the intestinal flora to homeostatic state?

3. It is estimated that the human gut contains 1000 species of ten trillion bacteria. These play a role in gastric ulcer, autism, cancers, fatty liver, ADHD, leaky gut syndrome, inflammatory bowel diseases, etc.9 According to Dr. J. Nicholson of Imperial College in London, "almost every sort of disease has a gut bug connection somewhere." He says that "if you mess around with gut microbes, you mess around the brain chemistry in major ways. Can you imagine how health will be affected by the changes oral insulin, with its preservatives and absorption enhancers, makes in the gut microbial environment? Before oral insulin methods are approved, their effect on gut flora should be studied to prevent any future diseases comparable to those caused with the use of inhalation insulin.1

4. Destruction of villi and microvilli of the intestines by oral insulin containing biochemical addictives can lead to malabsorption of nutrients and persistent osmotic diarrhea, often accompanied by fever, as seen in celiac disease and microvillus inclusion disease, etc.

5. Insulin-containing particles impacted (stuck) at the crypts are not absorbed into circulation. Crypts of the gut contain the stem cells and are in a dynamic state of cell division to replace the inner lining of the gut. Direct contact with oral insulin will surely enhance the growth and multiplication of these cells, leading to increased incidence of polyps and cancers.

6. Direct contact between oral insulin and precancerous cells in the gut lining and polyps can result in their multiplication and transformation into cancers.

7. When impacted in diverticulas, the insulin-containing oral formulation may enhance the infection of any local cysts (as shown with inhaled insulin) with increased incidence of diverticulitis. This may also stimulate the cell growth, causing cancers in the diverticulas.

8. There are 183,000 plasma cells for each cubic millimeter below the villi cells (in lamina propria). The absorption of insulin through the lining of the intestinal mucosa will stimulate these cells, which will then become over-active and produce large amounts of immune globulins ( IgA, IgG, IgM, and IgG). Patients with inflammatory bowel disease have a higher percentage of some of these immune globulins, which may even increase more due to the supply of oral insulin growth factor. The effect of overstimulation of these plasma cells by oral insulin is unknown.

9. One of the outcomes of inhalation insulin (oral spray and nasal spray insulin) was an increase in the level of insulin antibodies from baseline levels of 6% to 35%. In contrast, there is hardly any change in the patients with subcutaneous insulin therapy.1 Orally administered insulin can result in massive insulin antibody production from plasma cells (in lamina propria). The adverse effects of such antibodies include retarding the action of soluble insulin in the blood and removing this insulin as an immune complex by the immune (reticulo-endothelial) system, making less insulin available to lower the blood sugar.

10. Low doses of orally administered auto-antigens suppress autoimmunity by inducing antigen-specific regulatory T-cells in the gut, which act by releasing inhibitory cytokines at the target organ. Because type 1 diabetes is an autoimmune disease, the studies made on the rats using insulin not only failed to prevent type 1 diabetes, but when insulin was administered with an adjuvant, this actually accelerated the diabetes by destroying insulin-producing cells in the T-cell activated immune system.18 Can you imagine the acceleration and/or complete destruction of insulin-producing cells in the pancreas due to use of oral insulin with adjuvant? Type 2 diabetes may be converted to type 1 diabetes as the result of insulin antibodies and antibody-containing T-cells of the immune system attacking the insulin-producing beta cells in the pancreas. Oral insulin should not be used unless the product is free of these adverse effects as demonstrated through large-scale human studies.

11. Gastrin is a peptide hormone, synthesized and released from stomach (gastric antral G cells). Increased gastrin in the blood (hypergastrinemia) is found in peptic ulcers; treatment of GERD with proton pump inhibitors (PPI); secretion of gastrin from tumor, (gastrinomas- ZES); endocrine neoplasm; atrophic gastropathy; in PPI therapy, and a host of other conditions. High gastrin in the blood causes benign and cancerous tumors in GI tract. Gastrin simulates the growth and proliferation of epithelial cells, the normal mucosa, and the multiplying crypts of the villi, predisposing for colorectal cancer, due to increases in angiogenesis and inhibition of apoptosis by gastrin.19-22 Because insulin stimulates cell multiplication (carcinogenic), taking oral insulin should further increase incidence of gastrointestinal tract cancers, due to synergistic action with gastrin growth factor in the above conditions. Hence, if oral insulin is approved, those with these conditions and those who use PPI should be warned about adverse outcomes.

12. It has been observed that gastric acid suppression, using H2-receptor antagonists (cimetadine) and PPI, is associated with an increased risk of community-acquired pneumonia,19 risk of C. dif infection,20 hip fractures21 due to low calcium absorption, and interference with osteoclasts' acid production.22 What will be the result of H2-receptor antagonists (cimetadine) and PPI use with long-time use of oral insulin on these conditions?

13. In familial polyposis (FAP), an inherited genetic condition of the colon and rectum, adenomatous, swollen, and thickened multiple tumor polyps develop on the inner lining of the bowel. Polyps turning into cancers are a major cause of death in these patients. Can you imagine giving these patients oral or rectal suppository insulin, which promotes cell division, making polyps larger and turning them into cancers? In diabetics with this condition, oral and rectal (suppository) insulin should be contraindicated.

It is only a matter of time before an oral insulin delivery system for diabetics will be formulated and marketed. But we still don't know the full effects of the prolonged use of this form of insulin on our 30-feet-long intestinal lining with its billions of cells and trillions of gut bacteria (flora). The health risk for these treatments may take a long time to unravel as did that with the use of Avandia (oral anti-diabetic agent), Vytorin (anti-cholesterol drug increasing the incidence of cancer) Vioox (used for pain resulting in heart attack deaths), and, more recently, Exubera (lung cancers) and Byetta (pancreatitis).

Rectal Insulin Suppository
The absorption and effect of insulin suppository (rectal) is much different than that of oral insulin due to anatomical differences in blood supply to the rectum. It is important to note that when the insulin is absorbed from the rectal mucosa (mostly from the lower half of the rectum), it won't reach the liver in the same way that oral (25-30-40%) and natural pancreatic insulin (100%) does. It reaches middle and inferior rectal veins, which drain to the systemic circulation (inferior vena cava), then into the heart and on to the liver. Superior rectal veins drain to the portal veins that enter the liver. To reach the superior rectal vein's absorption-draining area, a suppository has to be deposited about four inches from the anus – which is not possible. Hence, the action of insulin suppository when absorbed is similar to subcutaneous injection. Rectal insulin absorption is unpredictable and erratic at best. Besides the social difficulty in inserting the suppository, it can get mixed with fecal remnant if rectum is not completely empty and evacuated with next bowel movement. Like inhalation, sprayed, or oral insulin modes, this method of delivery has a carcinogenic effect on the rectal mucosal cells with which it comes in contact.1

Word of Caution to the FDA and the Pharmaceutical Industry
Oral insulin, if developed and FDA-approved without any health hazards, would be a multibillion-dollar product. One of the developers claims that the oral insulin is a "breakthrough method of delivering insulin orally" that "could bring relief to millions…only an oral capsule mimics the physiological delivery of insulin." These are spurious claims. Such exacerbated claims are not new to this industry when promoting a new product and promoting pharmaceutical company stocks. I recommend that inhalation, oral, and nasal insulin sprays not be FDA-approved. They should not be used by tobacco users, asthmatics, persons with chronic oral-nasal- pharyngeal-esophageal-lung diseases, those with other precancerous lesions (leukoplakia) of the lungs, mouth, and nose. Oral or rectal insulin should never be used by those who have familial polyposis. The FDA must fully investigate the health risks, including the concerns we have enumerated, and mandate post-approval surveillance in addition to pre-approval studies by the developers of these products.

Dr. T.R. Shantha has published more than 125 research papers in distinguished journals such as Nature, Science, New England Journal of Medicine, Journal of Cell Biology, and others. He is the author of six books and the holder of seven patents. In 2005, Dr. T. R. Shantha received the distinguished physician award from the 42,000-member physician organization Association of Physicians from India (AAPI), and he was nominated for the Nobel Prize in physiology and medicine in 2007. Dr. Shantha is also the discoverer of the drug Terbutaline, which is used all over the world for treating priapism. A pioneer in alternative medicine, he has designed many innovative therapies, utilizing both traditional and alternative approaches, for the treatment of cancers and many other incurable diseases. Dr. Shantha has spent 53 years in medical research and in practice, is triple boarded, and is considered by many to be an expert on insulin potential therapy, hyperbaric therapy, and the treatment of both hyperthermia and pain.

Jessica G. Shantha is a medical student at the Morehouse School of Medicine.

1. Shantha TR. Unknown health risks of inhaled insulin. Life Extension. September 2007; 79-82.
2. Pfizer yanks Exubera; Novartis cutting jobs - Oct. 18, 2007; Pfizer warns patients about Exubera lung cancer risk - New Jersey. April 9, 2008. Available at:
3. Li Y, Chang Q, Rubin BP, Fletcher CD, Morgan TW, Mentzer SJ, Sugarbaker DJ, Fletcher JA, Xiao S. Insulin receptor activation in solitary fibrous tumors.
J Pathol. 2007 Apr;211(5):550-4.
4. Ryan CJ, Haqq CM, Simko J, Nonaka DF, Chan JM, Weinberg V, Small EJ, Goldfine ID. Expression of insulin-like growth factor-1 receptor in local and metastatic prostate cancer.
Urol Oncol. 2007 Mar-Apr;25(2):134-40.
5.Mallikarjuna K, Pushparaj V, Biswas J, Krishnakumar S. Expression of insulin-like growth factor receptor (IGF-1R), c-Fos, and c-Jun in uveal melanoma: An immunohistochemical study.
Curr Eye Res. 2006 Oct;31(10):875-83.
6. Dearth RK, Cui X, Kim HJ, Kuiatse I, Lawrence NA, Zhang X, Divisova J, Britton OL, Mohsin S, Allred DC, Hadsell DL, Lee AV. Mammary tumorigenesis and metastasis caused by overexpression of insulin receptor substrate 1 (IRS-1) or IRS-2.
Mol Cell Biol. 2006 Dec;26(24):9302-14. Epub 2006 Oct 9.
7. Shen MR, Hsu YM, Hsu KF, Chen YF, Tang MJ, Chou CY. Insulin-like growth factor 1 is a potent stimulator of cervical cancer cell invasiveness and proliferation that is modulated by alphavbeta3 integrin signaling.
Carcinogenesis. 2006 May;27(5):962-71. Epub 2006 Jan 7.
8. Belfiore A. The role of insulin receptor isoforms and hybrid insulin/IGF-I receptors in human cancer. C
urr Pharm Des. 2007;13(7):671-86.
9. Köhler D. Aerosols for systemic treatment. Lung. 1990;14(suppl.):677-84.
10. Himmelmann A, Jendle J, Mellen A, Petersen AH, Dahl UL, Wollmer P. The impact of smoking on inhaled insulin.
Diabetes Care. 2003;26:677-82.
11. Heise T, Rave K, Bott S, et al. Time-action profile of an inhaled insulin preparation in comparison to insulin lispro and regular insulin.
Diabetes. 2000;49:A10.
12. Inhalation insulin therapy. Available at: (
1/09 Editor note: Use the link at your own risk. It tried to install MS Office components and would only allow me to escape by turning the power off. There is a site, perhaps the "real" site.)
13. Mather LE, Clauson P, Uy C, Kam P, McElduff A. Pharmacokinetics and pharmacodynamics of pulmonary insulin using the AERx insulin diabetes management system during and after an upper tract respiratory tract infection. An open labelled crossover study in healthy subjects.
Diabetologia. 2002;45(suppl 2):A261.
14. Aye M, Sheedy W, Harrison R, Thompson JS, Morice AH, Masson EA. Pulmonary vasodilation in the rat by insulin in vitro could indicate potential hazard for inhaled insulin.
Diabetologia. 2003;46:1199-202.
15. Henry RR, Mudaliar SR, Howland WC, et al. Inhaled insulin using the AERx Insulin Diabetes Management System in healthy and asthmatic subjects.
Diabetes Care. 2003;26:764-769.
16. Weinner M. Going with his gut bacteria.
Scientific American. July 2008; 90-92.
17. Crabbe PA, Heremans IF. The distribution of immunoglobulin-containing cells along the human gastrointestinal tract. Oar.
Woenserotogy. 1966;51:305-16; Crabbe PA, Carbonara AO, Heremans IF. The normal human intestinal mucosa as a major source of plasma cells containing 7A immunoglobulin. Lab invest. l963;14:235-48.
18. Hermansen K, Ronnemaa T, Petersen AH, Bellaire S, Adamson U. Intensive therapy with inhaled insulin via the AERx insulin diabetes management system: a 12-week proof-of-concept trial in patients with type 2 diabetes.
Diabetes Care 2004;27:162-7.
19. Mordes JP, Schirf B, Roipko D, Greiner DL, Weiner H, Nelson P, Rossini AA. Oral insulin does not prevent insulin-dependent diabetes mellitus in BB rats.
Ann N Y Acad Sci. 1996;778:418-421; Bellmann K, KoIb H, Rastegar S, Jee P, Scott FW. Potential risk of oral insulin with adjuvant for the prevention of type I diabetes: A protocol effective in NOD mice may exacerbate disease in BB rats. Diabetologia. 1998;41:844-847.
20. Hartwich A, Konturek SJ, Pierzchalski P. Zuchowicz M, Labza H, Konturek PC, Karczewska B, Bielanski W, Marlica K, Starzynska T, Lawniczak M, Hahn EG. Helicobacter pylori infection, gastrin, cyclooxygenase-2, and apoptosis in colorectal cancer.
lnt I Colorectal Dis. 200i;16:202-210; Copps J, Ahmed S, Murphy RF, Lovas S. Gastrin 1-6 promotes growth of colon cancer cells through non-CCK receptors. Peptides. 2007 Mar;28(3):632-5. Epub 2006 Nov 28.
21. Renga M, Brandi G, Paganelli C, Calabrese C, PapaS, I'osti A, Tomassetti P, Miglioli M, Biasco C. Rectal cell proliferation and colon risk in patients with hypergastrineinia.
Gut. 19974;1:330-332. Lipkin M, Blattner W, Fraumeni JJ, Lynch H, Deschner E, Winawer R. Tritiated thymidine labeling (phi p. phi h) distribution as a marker for hereditary predisposition to colon cancer. Cancer Res. 1983;43:1899-1904.
22. Clarke PA, Dickson IH, Harris JC, Grahowska A, Watson SA. Gastrin enhances the angingenic potential of endothelial cells via modulation of heparin-binding epidermallike growth factor.
Cancer Res. 2006;66:3504-3512; Beales IL, Ogunwobi O. Glycine-extended gastrin inhibits apoptosis in colon cancer cells via separate activation of Akt and INK pathways. Mol Cell Endocrinol. 2006;247:140-149; Ogunwobi 0, Beales II,: Glycine-extended gastrin stimulates proliferation and inhibits apoptosis in colon cancer cells via cyclo-oxygenase-independent pathways. Regul Pept. 2006;134:l-8.
23. Smith AM, Watson SA. Review article: Gastrin and colorectal cancer.
Aliment Pharmacol Ther. 2000;14:1231-1247.
24. Miyazaki Y, Shinomura Y, Tsutsui S, Zushi S, Higashimoto Y, Kanayama S, Higashiyama S, Taniguchi N, Matsuzawa Y. Gastrin induces heparin-binding epidermal growth factor-like growth factor in rat gastric epithelial cells transfected with gastrin receptor.
Gastroenterology. 1999 Jan; 116(1):78-89.
25. Laheij RJF, Sturkenboom MCJM, Hassing R-J, Dieleman J, Stricker BHC, Jansen JBMJ. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs.
JAMA. 2004;292(16):1955-60.
26. Branswell H. McGill researchers say re-analysis confirms antacids raise risk of C. difficile. CBC News. September 25, 2006. Available at: Accessed January 15, 2007.
27. Yang, YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture.
JAMA. 2006;296(24): 2947–53.
28. Seppa N. Bad to the bone: Acid stoppers appear to have a downside.
Science News. 2007;171(1):3.




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