The Effect of Inhaled
Insulin on Anatomical Structures
When one takes a breath of insulin powder/liquid via an inhaler
or a spray, only a small part of insulin reaches the depth of the
alveoli, is absorbed by blood in the lungs (pulmonary circulation),
and is distributed throughout the body by the circulating blood.
Before insulin enters the blood, it comes in contact with and gets
deposited in various concentrations on the following:
1. Oral and nasal cavities: many particulates
get attached to the lining of nasal and oral cavity (vestibule
of the mouth).
2. Tongue: villi on the tongue captures insulin as one inhales.
3. Tonsils: particles can enter the crevices and crypts of the
tonsils, which are attached to the lining of the tonsil cells.
4. The epiglottis is constantly exposed to insulin particles during
inhalation and exhalation.
5. Larynx and vocal cords: the space between the vocal cards is
narrow and creates a bottleneck for air passage that all inhaled
and exhaled insulin particles have to pass through. Thus, the
lining of the vocal cords gets the largest deposits of any structure.
6. Pharynx: some insulin particles can stick to pharyngeal wall
as the powder enters the upper airway.
7. Trachea and bronchial air conducting tubes before alveoli:
air passages get most of the inhaled insulin. There is ciliated
epithelium lining the surface of the trachea, bronchus, and bronchiole
air passages. These particles get picked up by the cilia and taken
inside the lining cells -- think sea anemones picking up their
8. Esophagus: some insulin powder is dissolved in the saliva and
mucosa in the mouth and ingested. Some insulin will be deposited
on the esophageal surface as this insulin-containing saliva is
9. Stomach: insulin is dissolved in the secretion of the oral
and nasal cavity. As these secretions are swallowed, the insulin
coats the esophagus inner surface before reaching the stomach
and is inactivated by the acidity of the stomach.
10. As one exhales the air though the nose, insulin-containing
exhaled insulin enters nasal passages, olfactory mucosa, and nasal
air sinuses, all of which pick up insulin particulates.
You can see by this analysis that just
to get enough insulin into blood through the deeper depths (alveoli)
of lungs or mucous membrane of the mouth and nose, these insulin
treatments have to pass through many anatomical and histological
cell structures. In the process, these structures are coated with
large doses of unneeded insulin, which can lead to cell division
and cancers. More or less the same fate also results when the nasal
or oral insulin sprays are used.
Effects of Using Inhalation and Oral And Nasal Spray Insulin Methods
Without going into great detail, let us describe the cells in the
above exposed anatomical structures that are constantly exposed
to the following onslaughts:
1. Infection, including viruses from
air and through personal contact
2. Chronic irritation from working in dirty, dusty, smoky environment
3. Tobacco smoking, snuff use, and tobacco chewing
4. Mechanical and chemical irritation by heat and cold, chemicals,
noxious fumes, etc.
5. Exposure to chemicals, including carcinogenic hydrocarbons
in the workplace, chemicals due to tobacco use, and breathing
dry or humid air daily
6. Trauma to the oral cavity by tooth damage and to the oral cavity
due to passage of hot and cold foods; effects on the esophagus
and stomach of the passage of acidic and alkaline food and drinks
Due to these exposures, the structures
affected by inhaled and nasal and oral sprayed insulin can undergo
changes such as the following:
1. Metaplasia change is a situation
where cells have changed from their original mature differentiated
type into another mature differentiated cell type as an adaptive
2. Dysplasia changes: dysplasia is a combination of two Greek
words: dys-, which means difficult or disordered; and plassein,
to form (from "bad form," in Greek). In other words,
dysplasia is the abnormal or disordered organization of cells
in the tissues. This abnormality in the appearance of cells is
indicative of an early step towards transformation into a tumor
(cancer) development – a precancerous change. More dysplasia
develops in the body with advancing age which can turn to cancer
in above described anatomical sites. Leukoplakia (white patches)
of the mouth (oral cavity) is a good example. All these abnormal
cells have more insulin receptors on their walls to support their
division and rapid growth.
3. Heteroplasia is the abnormal cell growth of cytologic and histologic
elements. Insulin can enhance the growth of normal tissue, ultimately
leading to pathological disease conditions such as thickening
of the blood vessels; and to cardiovascular diseases; the tracheo-bronchial
tree causing obstructive restriction to oxygen flow; and to the
formation of benign and malignant tumors. That is why high levels
of blood insulin in type 2 diabetes contribute to the development
of cardiovascular diseases.
The dysplasic cells are precancerous,
and we should worry when we use inhalation and nasal and oral spray
insulin (as well as oral and rectal insulin delivery systems, which
we will discuss later) for diabetes. Some of these cells already
may be undergoing microscopic cancerous changes, especially in those
who are chronic smokers, nasal snuff users, and tobacco chewers.
The deposition of insulin on these dysplastic abnormal precancerous
and cancerous cells will stimulate multiplication, resulting in
full-blown cancers and their spread.
End Result of Long-Term Use of Inhalation and Nasal and Oral Spray
1. An initial and transient irritation
causing cough, sneezing, shortness of breath, sore throat, and
2. After inhalation and nasal and oral spray insulin use, many
of the insulin particles are deposited on the oral-pharyngeal-laryngeal-tracheo-bronchial
tree, mouth, and nose lining. This high concentration of insulin
is picked up by the insulin receptors acting as tumor promoter.
This will increase the incidence of tumors of the oral cavity,
tongue, larynx, pharynx, trachea, bronchial tree, tonsils, nasal
mucosa, nasal air sinuses, and all the structures where the insulin
particulates are deposited.
3. Increased incidences of lung cancer, oral and tongue cancers,
pharyngeal cancers, nose cancers (especially among those who smoke
and are exposed to irritants, such as miners, granite workers,
workers at petrochemical factories, and other dusty occupations).
Existing cancers of the lungs and mouth and nasal cavities grow
rapidly and spread farther. Inhalation and nasal and oral spray
insulin acts like a "miracle grow plant growth food"
for growing cancer cells, making it more deadly in the nose, mouth,
respiratory tract, and lungs.
4. Increased incidence of cancer at the lower end of the esophagus
due to their exposure to gastroesophageal reflex disorder (GERD)
and Barrette's disease by swallowed insulin dissolved in
5. More nasal polyps and infection of the nasal sinuses and conversion
of polyps to cancers due to stimulation by insulin growth factors
6. In smokers, excess of insulin enters into bloodstream, resulting
in hypoglycemia. Inhalation and nasal and oral spray insulin can
increase the transport of insulin resulting in hypoglycemic effects.16
7. A compromise lung, air passages, oral and nasal cavity functions
is a real possibility.
8. Insulin, a growth promoting protein, can increase the amount
of lung tissue and tracheo bronchial passages, due to the increase
in smooth muscle cells in air passages, increase in number of
fibroblasts, many types of white blood cells in the lungs (including
phagocytes, mast cells becoming larger). Overgrowth of tissues
in the respiratory tracts can narrow these resulting in the following:
1. High resistance to the passage of air in the respiratory tract,
making inhalation insulin unsuitable for patients with obstructive
lung diseases including asthma; 2. Modifications of the lung alveoli
lining (where gas exchange takes place), thus affecting the gas
exchanges (absorption of oxygen and elimination of carbon dioxide)
through alveoli —the primary function of lungs.
9. There are high levels of inhaled insulin inside the peripheral
lungs and oral and nasal mucosa where insulin particles are deposited.
Blood vessels (smooth muscle cells) and other cells (fibroblasts)
come directly in contact with the insulin, similar to insulin
in the blood. It is possible that insulin growth promoting effect
may result in pulmonary (nasal or oral) blood vessel thickening
and other cellular elements surrounding these blood vessels, resulting
in pulmonary hypertension, and ASVD.17
10. Inhalation, nasal and oral spray insulin may have longer-lasting
respiratory, (oral and nasal cavity) changes in people with pre-existing
respiratory diseases.18 Singers may develop more vocal card nodules
and laryngeal tumors.
11. May aggravate asthma, pulmonary fibrosis, sarcoidosis, tuberculosis,
chronic pulmonary afflictions, sinusitis, chronic infection of
oral and nasal cavities, and exacerbation of existing chronic
lung and oral and nasal cavity diseases.
12. Increased incidence of infections where the insulin particles
come in contact with pathological exposed surfaces.
13. Due to rapid absorption of insulin through the lungs and nasal
and oral linings, some patients may develop hypoglycemia when
they can't find help with life-threatening complication.19
14. The next concern we have is the uptake of aerolised insulin
by the olfactory mucosa in the nose. Our studies from Emory University
School of Medicine have shown the pia-arachnoid membranes of the
brain extend all the way to roof of the nose, extending to the
base of the olfactory mucosa in the nose.20 That is
why any inhaled infecting microbes (viruses and bacteria-meningococcus)
from the nasal olfactory mucosa can reach the central nervous
system (CNS)and distributed to cerebrospinal fluid (CSF) with
ease due to the effect of inhaled and oral or nasal spray insulin
on the nasal mucosa. What about the easy and rapid transfer of
infection (meningococcal and viral) from olfactory mucosa to the
brain in tee age school-going children who use inhalation and
nasal and oral spray insulin?20,24
15. Another outcome of inhalation and oral and nasal spray insulin
is increases in the level of insulin antibodies from baseline
levels of 6% to 35%. On the other hand, there is hardly any change
in the patients with subcutaneous insulin therapy.21 The adverse
effects include retarding the action of soluble insulin in the
blood and its removal as immune complex by the immune (reticulo-endothelial)
system, making less insulin available to lower blood sugar at
16. The studies show that the patients with diabetes and asthma
have to inhale more insulin to achieve good metabolic control
of blood sugar.22 This raises the possibility of more insulin
deposits before the insulin reaches the circulatory system, resulting
in more adverse effects with long-term use, such as lung cancers.
These and other unknown adverse effects
of inhalation and oral and nasal insulin spray may not appear for
months. However, continued use will certainly result in the development
of other diseases, since, in these forms, the insulin comes in direct
contact with the above-mentioned structures on its way to deeper
blood vessels and the lungs. We strongly recommend this method not
be used in smokers, in patients with chronic oral-pharyngeal-esophageal-lung-nasal
cavity diseases, or in anyone with a predisposition to dysplasia
or other conditions in which abnormal cells can turn into tumors
(e.g., leukoplakia of oral cavity), both benign and malignant. No
one knows the long-term effects of using inhalation or nasal and
oral insulin spray.
For convenience's sake, patients with type 1 diabetes or insulin-dependent
type 2 diabetes mellitus who have to take insulin shots could benefit
from the occasional use of inhalation and nasal and oral spray insulin
therapy. Unfortunately, these insulin delivery systems are not a
complete replacement for injectable insulin, and I don't believe
they ever will be; they should only be used as a supplement for
mealtime insulin injections. Nighttime injections of insulin are
needed to keep diabetes under control. Fortunately, non-insulin-dependent
diabetics (NIDDM) who can control their blood sugar levels through
weight reduction and oral medications will not need inhalable or
spray insulin or injectable insulin therapy unless the oral anti-diabetic
medications become less effective or altogether ineffective.
Inhalation and nasal and oral spray insulin forms of diabetic therapy
are expensive. So, when their metabolic effect is compared to that
of cheaper methods that offer fewer adverse health ill effects (such
as subcutaneous insulin therapy), why would a health care provider
pay for these forms of insulin therapy? Inhalation and nasal and
oral insulin spray therapies may be suitable in some situations
because they're quick and easy; they may benefit those who
travel frequently, those involved in sports, those who prefer another
method just before meal, and those juvenile diabetics who need help
in taking insulin injections. However, an endless list of drugs
can interact with these insulin forms, and these therapies also
come with many contraindications that a patient would need to consider
before choosing inhalation or spray insulin.
What to Do if a Person Has Diabetes?
Type 1 diabetics: continue subcutaneous insulin injections; control
blood sugar levels by diet and exercise in addition to injections.
Type 2 diabetics: control obesity; restrict excessive caloric intake
and refined carbohydrates such as sugars; exercise to burn fat and
carbohydrates. Do consider taking proven over-the-counter, anti-diabetic,
sugar-reducing supplements, especially the following:
· Cinnamon (acts as an insulin
substitute in type 2 diabetes and triples the insulin efficiency)
· Zinc (enhances insulin production and activity of many
· Vitamin D3 (protects from the immune system attack of
· Alpha lipoic acid (an antioxidant) protects the insulin-producing
· Chromium and vanadium (helps insulin transport sugar
to the cells by binding the insulin to cell membrane)
· Banaba leaf extract (hypoglycemic activity), bilberry,
goat's rue, garlic, mulberry leaves, olive leaves, and ginseng
· Gymnema sylvestre (Indian herb promote insulin secretion
· Momordica also known as bitter gourd (Hypoglycemic compounds
in this vegetable stimulate the glucose receptor protein GLUT-4
to move from the cell interior to the cell surface, thus promoting
more effective glucose absorption and metabolism. Diabetes
Care. 2003; 26: 1277-1294).
· Fenugreek (promotes insulin secretion, lower blood glucose
with reduction of insulin levels, lowers total cholesterol and
triglycerides, and increases HDL– the good cholesterol),
fish oil, CoQ10, Omega 3.
· Consider taking testosterone if blood hormone levels
are low. According to the latest studies, this hormone can lower
the high blood sugar and ameliorate early diabetic condition.23
· Use supplements of vitamin B6 (50 mg a day), biotin,
vitamins B, E, and C, magnesium, potassium, essential fatty acids,
and flaxseed oil; artichokes as part of the diet, a mixture of
Chinese herbs, digestive enzymes to aid digestion, amino acid
to facilitate manufacture of insulin.
· Intravenous chelation therapy using EDTA to clean the
blood is also indicated.
There are other alternative therapies
indicated, such as acupuncture and unproven herbs. If these measures
fail to control blood sugar, resort to physician-prescribed anti-diabetic
oral medications. If all these measures fail to control blood sugar,
add injectable insulin to the regimen.
Future of Antidiabetic
In spite of breakthrough claims in the news media, insulin injection
still is the main therapy for insulin-dependent diabetics. Inhalation
insulin has been withdrawn from the market due to increased incidence
of lung cancer by its use as reported by us and confirmed by Pfizer.17
Nasal and oral insulin sprays have similar effects to inhaled insulin
and should not be FDA-approved. Transdermal patches using absorption
enhancers, ultrasound, iontophoresis, and various transdermal devices
used to deliver insulin are cumbersome, unreliable, and not practical.
Neutralizing the auto antibodies before they attack the insulin
production of beta cells in type 1 diabetes and implantation insulin
production of stem cells are still experimental and do hold promise.
Important advancement can be made if we develop bioactive therapeutic
agents that would stimulate the multiplication and the differentiation
of new insulin-producing islets from preexisting pancreatic progenitor
cells in islets and pancreatic ducts. Development of altered insulin
protein that works even with the insulin resistance needs to be
considered. Attempts are being made to develop long-acting subcutaneous
injections of insulin, and other antidiabetic therapeutics agents
are also on the horizon. Nothing safe yet exists to replace insulin
shots. My advice to type 2 diabetics, "Heed the weight and
cure the disease," still holds good.
At present, we have two patents pending for the painless delivery
of insulin by subcutaneous injections and also a new locally applied
transmucosal insulin delivery system, using existing insulin formulations
that are safe and have been in use for decades. We hope to bring
them to the market so that they will make insulin-dependent diabetics
more compliant in the testing blood sugar and in using insulin –
without the fear of painful shots.
II is also online.
T.R.Shantha, MD, PhD, F.A.C.A
Jessica G. Shantha, Medical Student,
115 Bayberry Hills
McDonough, Georgia 30253
Phone/Fax: 770-507-6564, Cell: 678-640-7705
Dr. Shantha has published more than 125
research papers in distinguished journals such as Nature,
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. Diabetes — Definition: Diabetes
is a life-long disease marked by high levels of sugar in the blood.
Available at: http://www.nlm.nih.gov/medlineplus/ency/article/001214.htm.
Accessed September 26, 2008.
2. Pirisi A. The diabetes epidemic. LE
Magazine. December 2000; MacWilliam L. Diabetes: Understanding
and preventing the next health care epidemic. LE
Magazine. June 2004; Scali B. High blood sugar; Integrative
strategies for supporting healthy metabolism. LE
Magazine. July 2005.
3. Dixon JB, O'Brien PE, Playfair J, et al. Adjustable gastric banding
and conventional therapy for type 2 diabetes: a randomized controlled
trial. JAMA. 2008;299(3):316-323.
McGarry JD. What if Minkowski had been ageusic? An alternative angle
on diabetes. Science. 1992;258(5083):766-770.
4. Unger RH. Minireview: Weapons of lean body mass destruction:
the role of ectopic lipids in the metabolic syndrome. Endocrinology.
Unger RH. Reinventing type 2 diabetes: pathogenesis, treatment,
and prevention. JAMA. 2008;299(10):1185-1187.
5. Lee Y, Hirose H, Ohneda M, Johnson JH, McGarry JD, Unger RH.
Beta-cell lipotoxicity in the pathogenesis of non–insulin-dependent
diabetes mellitus of obese rats: Impairment in adipocyte-beta-cell
relationships. Proc Natl Acad Sci U S A.
6. Navas-Acien A, et al. Exposure and prevalence of type 2 diabetes
in US adults. JAMA. August, 20,
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Company; 1987: 595-604.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. Belfiore A. The role of insulin
receptor isoforms and hybrid insulin/IGF-I receptors in human cancer.
Curr Pharm Des. 2007;13(7):671-86.
14. Heinemann L, Heise T. Current status
of the development of inhaled insulin. Br
J Diabetes Vasc Dis. 2004; 4(5):295-301.
15. 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.
16. Himmelmann A, Jendle J, Mellen A, Petersen AH, Dahl UL, Wollmer
P. The impact of smoking on inhaled insulin. Diabetes
17. 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.
18. Available at: www.Insulin
news.com-Inhalation insulin therapy.
19. 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.
20. Shantha TR, Bourne GH. The "Perineural
Epithelium": A new concept. Its role in the integrity of the
peripheral nervous system. In: GH Bourne, ed. Structure
and Function of Nervous Tissues. Volume I. New York: Academic
Press; 1969: 379-459.
Shantha TR, Nakajima Y. Histological and histochemical studies on
the rhesus monkey (Macaca mulatta) olfactory mucosa. Z.
21. 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.
22. 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;26:764-9.
23. Lichten EM. Testosterone's overlooked role in the treatment
of diabetes in men. Life Extension.
July 2007: 23-29.
24. Shantha. TR. Unknown health risks
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September 2007; 79-82.
Word of Caution to Pharmaceutical
Industry and FDA on the Development and Approval of Nasal and Oral
Insulin Sprays and Oral and Rectal Insulin
Dr. T. R. Shantha has sent detailed letters and published material
to various drug companies involved in developing inhaled insulin
and to FDA about the dangers of inhaled insulin and possible development
of cancers between the years 2005-2007.23 In October
2007, the Pfizer pharmaceutical company withdrew the only FDA-approved
inhaled insulin (Exubera) from the market, taking a 2.5 billion
dollar loss. Some of the other pharmaceutical companies stopped
developing inhaled insulin also. Supporting Dr. T. R. Shantha's
research findings, on April 9, 2008, Pfizer announced findings of
a connection between the development of six lung cancer cases and
the short-term use of inhalation insulin.25
This is great victory for Dr. T. R. Shantha and his research findings
(Shantha TR, Unknown health risks of inhaled insulin, Life
Extension, September 2007:
79-82).23 Can you imagine thousands of diabetics developing
lung, gastrointestinal, oral and nasal cancers from the use of inhaled
insulin? Dr. T. R. Shantha's timely report on the dangers of inhaled
insulin saved thousands of diabetics from developing lung cancer
and billions of dollars in their health care and litigation costs.
We thank him for his research genius and for preventing this evolving
health disaster and saving many hundreds from developing and suffering
from lung, bronchial, oral, laryngeal, pharyngeal, and nasal cancers.
The FDA should consider seriously his warning in this two-part series
on insulin and take all precautions before they approve alternative
methods to replace the subcutaneous insulin delivery system. Dr.
T. R. Shantha firmly believes that nasal- and oral-sprayed insulin,
oral insulin, or rectal insulin suppositories have similar effects
to inhaled insulin. If these products are approved, there will be
meteoric rise in oral, tongue, gum, cheek, tonsilar, pharyngeal,
laryngeal, nasal cavity, gastrointestinal tumors (cancers), and
infections, and countless other health hazards. FDA approval should
be considered only after all the concerns are addressed. These insulin
deliver systems should be approved for use under special circumstances
only; not as replacements for subcutaneous insulin daily injections.