Ideas presented here are an example of history repeating itself. The non-diabetic use of insulin was popular a few decades ago (around 400 articles published before 1938) and now its popularity is rising again. My experiences and observations are laid forth here to stimulate those who are research oriented and to offer an additional approach to some of the problems that face the health professional daily.

    Forty years ago a study club of 62 physicians and two dentists found a myriad of uses for small doses of insulin totally unrelated to diabetes. Many of these uses are potential aids for helping our patients today. Dosages far below the average diabetic need produced rapid healing in a number of diseased tissues. In fact, when slightly larger doses are administered, the reactions described here will not be seen. At low levels, insulin seems to stimulate activity in certain tissues, thus improving their efficiency, while it has little or no effect on other tissues.

Background

    It is worthwhile to describe the historic progress which culminated in the non-diabetic uses for insulin. D. C. Jarvis, an M.D. living in Vermont, was the mentor of a "postal" study club. Although there were men who were members for over 30 years, many knew each other only by correspondence; for there were no formal meetings as far as my records show, and I draw my information from over 20,000 pages of their correspondence furnished to me by Dr. M.E. Page, one-time secretary of the organization.

    As members would find a promising remedy for a specific condition they would write their findings to Dr. Jarvis, who in turn would filter, observe and mimeograph the information. As information was spread, each member was encouraged to use the remedy and write in his own observations. By taking isolated events in their chronological order, I will endeavor to reconstruct what may have been the logic that molded Jarvis’ thinking toward the discovery of the non-diabetic uses for insulin.

    One member, Dr. Beales from the east coast, reported having used 3 units of insulin two or three times a week on cancer patients after surgery or radiation therapy. He noted that tumors secondary to radiation therapy responded and resolved when 3 units of insulin were used. It was stated in Jarvis’ report that possibly insulin was doing something similar to what radiation was doing to the tumors. Another man reported success in tumor reduction, but reported that there was simultaneous improvement in the patient’s "swimming ear." Another doctor said he had used insulin for the ear problem on a young boy and noted a simultaneous improvement in his acne. Yet another man used insulin for acne and saw a vast improvement in the patient’s inflamed gums. Still another, using insulin for a periodontal case, found simultaneous improvement in the patient’s long standing double vision.

    Observer and organizer that he was, Jarvis sat down with this information and sought a common denominator. His background in developmental anatomy or embryology, was what pulled this information together for him. All tissues that responded were of ectodermal origin. In a lengthy letter he reported his ideas, pointing out what tissues were of ectodermal origin. He encouraged the membership to try small doses of insulin when problems arose in ectodermal areas.

    Briefly, the following summarizes what Jarvis communicated to his members:

1. Ectoderm covers the entire body and serves as a protective shield against bacterial invasion into the body.

2. Ectoderm gives rise to the nervous system and sense organs through which sensations are received from the outer world.

3. The mouth is a combination of ectoderm and endoderm, but generally the vestibule and much of the palate and lateral walls are ectoderm.

4. A portion of the tongue epithelium and the lining of the nose and soft palate are ectoderm.

5. Salivary glands are ectodermal.

6. Nails and hair are modifications of ectoderm which correspond to claws and hoofs of lower mammals.

7. Sebaceous glands, sweat glands and mammary glands — whether associated with hair or not — are ectodermal.

8. The suprarenal gland has a double origin and in reality is two distinct glands secondarily combined as one within a common capsule. The cortex of the suprarenal gland is derived from ectodermal tissue. This being true then small doses of plain insulin should have a favorable nutritional influence on the medulla portion of this gland.

9. The taste buds are ectodermal in origin and are supplied by nerve fibers of the seventh, ninth and tenth cranial nerves.

10. In communication with the nasal cavity are several irregular chambers known collectively as the paranasal sinuses. All are first indicated at about the fourth month. Destruction of neighboring bone is followed at equal pace by an evagination of the nasal epithelium which serves thereafter as a lining to the sinuses.

11. The eye derives its origin from all three sources. (1) The optic nerve and retina are derivatives of the forebrain which is ectodermal; (2) the lens arises from the ectoderm of the head; (3) the accessory tunics and mechanism of accommodation differentiate from adjacent mesoderm.

12. The internal ear. The epithelium of the internal ear is derived from the ectoderm.
The middle ear. The tympanic cavity and eustachian tube are derived from the endoderm.

    At first thought it is difficult to reconcile such a long list of clinical conditions helped by insulin, but if one uses the embryological approach then the results obtained are more readily understood for they are as a rule clinical results obtained when the clinical condition is one affecting ectodermal tissue.

    Why the effect, where, and when to use insulin are the immediate questions that arise, as well as how much, how often, and the side effects of its use. Insulin is quite safe to use when used as described here. Some have used the philosophy of, "If a little is good and have caused themselves problems. All these areas will be covered in the following order: (1) exactly what are we using, (2) what is the effect, (3) why the effect, (4) when and where can it be used. And (5) untoward reactions and contraindications. 

A Dental Practitioner’s Experience

    There are many types and concentrations of insulin. Probably any of them would produce similar effects used in the same manner, but one has two features that make it particularly suited for our use. Time release and dilution.

    Protamine Zinc Insulin (PZI) is presently the insulin of choice. It is available in 40 unit per cubic centimeter concentration which makes it ideal for calibrating the dosage most frequently used —3 units. Its release is over a 28 to 36-hour period, rendering it quite safe where having a drop in blood sugar might be undesirable. It is best administered in a 40-unit insulin syringe. Caution: the tuberculin syringe looks similar, but the calibrations are different. Do not substitute. A 100-unit insulin syringe is similar also, but do not substitute, because it is calibrated for the 100 unit per cc solution.

 What is the Effect of Protamine Zinc Insulin?

    Increased cellular efficiency is the best overall description of the action of PZI. Clinical improvements can be expected in healing, toxic reactions, increased circulation, blood pressure, migraine headaches, periodontal disease, endodontics, infection and pain control.

    Clinical observations show greatly accelerated healing with a noticeable reduction in pain. Advantages are less "down time" for the patient, less discomfort and less drug administration. We are constantly bombarded with new deficiencies and/or side effects from drugs — pain medication and antibiotics included — so must count less medication as a strong plus. (Antibiotic properties of PZI are covered later.)

Why the Effect?

The known properties of insulin that best answer the question, "What is the biochemistry that explains the observation," are: (1) insulin increases the vascularization of areas adjacent to the injection; (2) zinc itself has the property of reducing pain messages from cut or injured nerve endings; (3) insulin at any physiological dosage improves glucose tolerance, and (4) both insulin and zinc increase cellular permeability. Two properties, increased vascularization and increased cellular permeability, work together to permit faster exchange of toxins, nutrients and metabolic waste products. Zinc has been noted by Pones and Strain to go to the site of injury but requires three weeks to mobilize.

When and Where can PZI be Used?

    The most dramatic and the most beneficial use of small doses of insulin is to accentuate healing. In dentistry I have noted post surgical healing occurring in about one-third the time usually required, and this finding has been confirmed by my colleagues who utilize insulin in their practices and by colleagues visiting in my office.

    "Dry sockets" are observed to heal better if PZI is used as therapy, but many can probably be prevented if PZI is used immediately after surgery. If there is a history of dry socket or visually the tissues look sick (inflamed, superlative, swollen) PZI is indicated. Three units of PZI is administered with the 40-u insulin syringe 5 to 10 minutes after surgery is finished. This allows time for the initial clot formation, and decreases the possibility of loss of the insulin through post operative or surgical bleeding. Injection is made near the surgical area. Most often I give it in the same area that was used for the anesthetic for maxillary surgery, and in the buccal or labial fold for mandibular surgery. Injection is subcutaneous; that is, penetrating only 2 to 4 mm.

    If four wisdom teeth were removed, or 32 teeth for that matter 3 units could be given twice. Three units can be given in the left tuberosity area, and 3 units in the right tuberosity area (where the anesthetic was given). Three units is the most effective dose for a focal area, but if 8 units or more are given, either the opposite effect or no effect will be noted. For this reason 3 units are used at one or two sites, but 6 units total is the maximum dosage to consider.

     In the medical profession when surgery has been performed an a wrist, ankle, arm, leg, or elsewhere than the mouth, subcutaneous injections are preferred, Timing is usually post surgical, although some physicians have used it presurgically with good results. The needle is inserted subcutaneously just 2 to 4 mm with the syringe parallel to the tissue being injected. Aspiration is always advised, but when injections are given an the lateral aspects of limbs, there is less chance of entering a vessel. Generally in surgical cases one injection is all that is necessary. Occasionally, a second one is used one to two days later. Not only will healing proceed faster, but also swelling and discoloration will be less. In trauma cases where there is existing swelling and discoloration, they can resolve — sometimes within a few hours. In trauma cases injection is recommended near the site of injury, but not necessarily within the injured tissue. Some physicians have told me that due to lymphatic drainage they expected to see a difference in action depending upon whether injection was made proximal or distal to the injury. Clinical experience did not bear this out. Just get close.

    Other forms of trauma include breaks and sprains. Three units of insulin used three times a week has been shown to initiate healing of fractures that have experienced non-union for many months. When used two to three times a week immediately after a fracture there is a good chance of reduced cast time. Let X rays and clinical judgment be the guide as always. Sprains — even bad ones of the ankle — have been reported to heal within one to three days when 3 units were administered. This means that the patient should be able to walk cautiously without pain and without the need for crutches. This one must see to believe.

    PZI has been used topically for improvements in burn or open ulcer cases. Here 4 to 6 units can be squirted onto cotton, then dabbed onto the affected area. Burns require a multiple approach, but increased healing can be expected when PZI is used both topically and by injection. Injection should be near, but not in the burned area. Some success has been reported using PZI topically on poison ivy.  I have no personal experience here but certainly think it is worth reporting.

    When localized areas require increased vascularization, think of PZI. Cases of gangrene and frostbite have been reported to respond well when PZI was used close to the area. Strangely, only one to three injections is all that is required for treatment of these problems.

    Dramatic results have been noted in people with certain eye problems. Retrobulbar neuritis has responded back to normal with three injections over a period of two weeks. "Leaky" retinas have stopped leaking after two to three injections, but treatment is usually continued for three weeks. Injections for eye problems (ectodermally related) are given where a dentist gives an anesthetic for an upper first or second bicuspid. Injection is shallow.

    Henry Schroeder (1973) stated that cadmium contamination is the major cause of high blood pressure in America today. Since zinc is an antagonist to cadmium, PZI should have an effect on reducing the body stores of cadmium. Physicians have reported a rapid effect on reducing blood pressure (especially the diastolic) and it is hard to differentiate whether its effect is directed toward the autonomic nervous system or cadmium contamination. Either way, the end result is desirable. Jarvis pointed out that high blood pressure was found in the sympathetic dominant person more often than in the parasympathetic dominant. Three units of insulin does appear to have the ability to either stimulate the parasympathetic nervous system or calm the sympathetic nervous system. At any rate, better balance is achieved, and perhaps some cadmium is eliminated from the system. Treatment consists of using 3 units of PZI Monday, Wednesday and Friday for two weeks, then only once every month or two as indicated by the blood pressure. This treatment will have little or no effect on tumor induced high blood pressure or damaged kidney vessels. It will not "cure" every case of high blood pressure, but it happens frequently enough to merit consideration in light of drug side effects. Test the blood pressure one hour after the initial injection. In all ten hypertensive doctors given PZI at a study club meeting, the diastolic pressure dropped from 10 to 30 mm Hg within one hour.

Insulin in Fatigue

    From checking the symptoms listed under patient information, I have found "chronic fatigue" to be the number one problem of patients whose chemistries are sent through our laboratory. Fatigue can be related to many chemical tests including hemoglobin, hematocrit, B-l2, folic acid, glucose, copper, iron, manganese, T_3, T₄, as a minimum. The Jarvis group placed emphasis on diet — In particular, foods affecting cellular oxidation. They recognized the need for copper, iron, manganese, iodine, thyroid function, and even arsenic for proper cellular oxidation. They also recognized that if any of these minerals were in excess, the system wouldn’t work effectively. They watched for foods that caused a block in cellular oxidation and attempted to eliminate those from the fatigued patient’s diet. Foods most apt to cause the block were reported to be wheat, sugar and citrus fruits. Cellular oxidation is important in the context of this article, because this block primarily affects tissues of ectodermal origin. Substitution was suggested first, with rye, corn meal and oatmeal flour replacing wheat; honey replacing sugar; and apples and grape juice replacing oranges, grapefruit, lemon, pineapple and their juices. Then 3 units of insulin were administered two to three times a week for several weeks (variation depending upon changes in physical signs). Insulin is used here as an oxidizing catalyst.

Insulin in Infections

    Awareness is beginning to focus on side effects, synergistic reactions, and tissue pathology induced by the increased use of drugs in medicine. These findings alone suggest that perhaps we should be looking for a more physiological approach to treating disease when it is possible. Many references in the past have indicated the potential in insulin for control of infections (Moen & Reimann; Harrower, 1913, 1935; King, et al., 1928; Williams & Dick, 1932; Benn, et al., 1932).

    Pollack (1933) called attention to the fact that there is lowered carbohydrate tolerance in the presence of infection. As far back as 1913, Harrower mentioned pancreatic activity associated with the control of infection. Moen and Reimann observed the limitation of antigen formation during infection, and that this could be increased by the use of insulin.

    William and Dick (1932) found reduced carbohydrate tolerance in scarlet fever, typhoid fever, measles, tonsillitis, pneumonia, periodontal disease and influenza. Thirty-eight of 40 cases studied responded when 3 units of insulin were used. Influenza created the greatest carbohydrate intolerance. The conclusion here was that either toxins produced by the infections interfered with the action of insulin, or with the production of insulin. Because of the carbohydrate intolerance, the same treatment was recommended for infections and slow healing that was previously described for insulin in fatigue.

    A similar biochemical pattern was noted in cases of slow healing after traumatic injury. Non-union of fractures, burns and crushing injuries were frequently associated with glucose levels between 130 mg% and 260 mg%. Although these levels are almost diabetic levels of glucose, healing progressed and the glucose came down with small doses of insulin and dietary correction.

Summary

    Evidence from the past and present confirmation indicates that there is a great potential value for the non-diabetic use of insulin. Tissues that respond are those of ectodermal origin and the mode of action seems to be through increasing cellular permeability. Pain control and increased healing potential have made renewed interest in the non-diabetic use of insulin of value to clinical health professionals as well as a stimulant to the research oriented doctor.

References

Benn, E.C., Hughes, E.W. and Alstead, S., Toxic diphtheria-combined antitoxin and dextrose-insulin therapy, The Lancet, 1:281, 1932.

Harrower, H.R., The relation of the adrenal system to infections and infectious diseases, Clin. Med. and Surg., 42:176 (April), 1935; and Practitioner, 91:289, 1913.

King, L., Kennerway, E.L. and Piney, A., A note on the action of insulin in normal persons, J. Physiol., 66:400, 1928.

Moen and Reimann, Referred to by Pollack.

Pollack, H., Conditions associated with unusual requirements for insulin, Proc. Staff Meet., Mayo Clinic, 8:453, July 26, 1933.

Schroeder, H.A., The Trace Elements and Man, Devin-Adair Company, 97-114, 1973.

Williams, J.L. and Dick, G.F., Decreased dextrose tolerance in acute infectious diseases, Arch. Int. Med., 50:801, 1932.