Seasonal allergies

The Case for Neutralizing (Optimal Dose) Immunotherapy

by Joseph B. Miller, M.D.

("The Environmental Physician", Fall 1991)

The neutralizing (optimal dose) method of intradermal skin testing and subcutaneous immunotherapy represents a major technological advance. It constitutes the safest, most effective, and most rapidly beneficial method of allergy skin testing and immunotherapy available today.

Each subcutaneous immunotherapeutic injection usually provides rapid relief of allergy symptoms, often in 30 minutes. The unusual rapidity, effectiveness, and safety of this response is based on the fact that the absolute precise best dose of each individual allergen is included in the treatment solution.

The Rapid-Relief Response

Bookman(1) has described what experienced allergists have always known. He reported that an occasional patient on build-up inhalant injection therapy would note marked improvement within 30 minutes to two hours after an injection of a given submaximal dose of an inhalant allergy extract. Usually the relief would continue for nearly a week. This near-universal clinical observation has been recently confirmed by a carefully controlled study at Johns Hopkins which reported favorable response to ragweed extract long before the maximum tolerated dose was reached.(2)

Allergists have long been puzzled by this rapid-relief phenomenon. Relief was not supposed to occur after any one injection.

Until recently, we had no technique for deliberately reproducing this rapid-relief effect. Now, by optimal-dose testing and treatment, we can reproduce this rapid-relief effect for all of the allergens in the treatment solution with a high degree of reliability.

How is the Rapid-Relief Response Achieved?

Optimal-dose testing involves administering intradermal test injections, one at a time, of 0.01 ml of consecutively stronger or weaker concentrations of an allergy extract in a 1:5 dilution series every 7-10 minutes. The first goal of testing is to determine the strongest concentration which produces a negative wheel. The second goal is to determine the strongest negative-wheal concentration that relieves any symptoms induced by preceding test doses. The two concentrations are usually the same, i.e. the strongest negative wheal concentration is almost always the concentration that relieves test-symptoms, if such symptoms occur.

The optimal dose (treatment dose) is 0.05 ml of this concentration. This has provided protection and relief in 99.7% of tests in my patients. My books and other publications detail the technique and many of its applications.(3-24)

The Maximum Tolerated Intradermal Concentration is the Optimal or Rapid-Relief Concentration and is Both Effective and Safe

The optimal intradermal test dose produces a negative wheal (no local reaction) and relieves (not causes) any symptoms that may have been induced by preceding test doses (no systemic reactions). Therefore, it is properly termed the "maximum tolerated intradermal concentration". This terminology is to distinguish it from the conventionally employed maximum tolerated subcutaneously administered dose, which can cause both local and systemic reactions.

The maximum tolerated intradermal concentration is truly the maximum tolerated. The next stronger concentration would invariably produce a positive wheal (local reaction) or symptoms (systemic reaction), or both. The absence of both local and systemic reactions, and the marked effectiveness in protecting from and relieving symptoms induced by subsequent natural exposure to the antigen, make this a uniquely safe and effective procedure.

This safety allows the patient to self-administer his injections for protection on a regular schedule. He can also self-administer additional ("booster") injections for quick relief whenever he encounters a sufficient natural exposure to an allergen to breach the protection of his regularly scheduled injections. Furthermore, the same system of testing and treatment are equally applicable to foods as well as inhalants, and also to many other substances (hormones, viruses, contactants, chemicals, etc.).

The Imprecision of Orthodox Allergy Procedures

Orthodox allergy skin testing provides no information concerning the precise dosage needed for each individual allergen. Therefore, orthodox allergy treatment solutions usually contain equal amounts of all allergens, regardless of the fact that the patient may be much more sensitive to some allergens than to others.

Subcutaneous injections of this solution in increasing dosage usually are administered until a large local or significant systemic reaction occurs. This is usually followed by a reduction in dosage.

This reduction is usually temporary in order to keep the dosage maximally strong, and yet (hopefully) not cause major local or systemic side effects. In practice, however, major local and/or systemic side effects do occur at times, sometimes including urticaria, laryngeal edema, acute severe asthma attacks, or anaphylaxis.

These reactions to orthodox build-up therapy occur chiefly because patients are not usually equally allergic to all their allergens. Their adverse reaction is to the one or more allergens in the solution to which they are most sensitive.

Subcutaneous optimal-dose treatment injections simply do not cause these severe reactions because they contain the "just right" dose of each individual allergen. With optimal-dose immunotherapy, each allergen dose is analogous to Goldilocks' bowl of porridge. It is not too strong and not too weak, but "just right". Therefore, no build-up of dosage is required. The first dose is the maintenance dose.

The Rapidity of the Optimal-Dose Response

Some patients report relief while still undergoing testing. Thirty percent of patients report relief after the first post-testing treatment injection. Ninety-five percent have reported marked relief by the tenth injection (3 or 4 weeks). If "rush" immunotherapy is desired for rapid relief, several injections can be administered safely each day without the dangers of the urticaria, laryngeal edema, acute asthma, or anaphylaxis often encountered in orthodox rush immunotherapy.(25,26)

After this initial relief has been established, each optimal-dose injection will usually provide relief of symptoms induced by natural exposure to any or all of these allergens. This relief usually occurs within 30 minutes to two hours. Furthermore, in contrast to orthodox build-up injections, optimal-dose injections provide protection from and relief o the patient's actual symptoms, not a hoped for but seldom achieved beneficial change in igG and igE levels which may have no relationship to patient benefit.

The Objectivity of the Optimal-Dose Test

Each relief dose is precisely determined by objective parameters, namely measurement to determine if the wheal has grown 2mm or more in 10 minutes, plusinspection and palpation of the wheal to determine the presence or absence of blanched, hard, raised, and discoid characteristics. (A discoid wheal is "ballooned up" and has a sharply demarcated border like a disc, rather than being frayed out around the edges, "deflated", and absorbing into the surrounding skin.)

A positive wheal typically grows at least 2mm in 10 minutes and is blanched, hard, raised, and discoid. If test doses induce no symptoms, the optimal dose is 0.05 ml of the strongest concentration which does not produce a positive wheal. If test symptoms occur, the optimal dose is 0.05 ml of the strongest concentration which does not produce a positive wheal and which also relieves the induced symptoms.

In a recent study of 24,556 consecutive intradermal optimal-dose tests for inhalants and foods performed over a period of two years in my office, the first (strongest) negative wheal concentration was the treatment concentration in 99.7% of tests. In 0.27%, the second negative wheal concentration was the treatment concentration, and in 0.02%, the third. No tests in this series required any weaker concentrations than this.

The Dangers of Orthodox Immunotherapy

Optimal-dose immunotherapy conveys none of the three main dangers involved in conventional immunotherapy. These consist of starting injection therapy with a too-strong starting dose of one or more antigens in the treatment solution; building immunotherapy dosage to a gross overdose and causing a reaction along the way; or maintaining very strong doses in a brittle or asthmatic patient whose health and strength are not necessarily at the same level with every injection and who may suffer a severe reaction to a dosage which has been tolerated in the past.

The Slow Response to Orthodox Immunotherapy

Textbooks of orthodox immunotherapy suggest that the allergist warn the patient in advance that he may not notice improvement for a year or two. Furthermore, if he has not noted slight improvement after two or three years, a discussion of whether or not to continue therapy may be considered.

This contrasts with the marked and almost invariable improvement that occurs within one to three weeks with optimal-dose immunotherapy. Furthermore, this same testing technology and the same safety and benefits of treatment occur with foods and many other antigens as well as inhalants, thus greatly increasing the number of patients that can be helped by clinical allergy procedures.

Both Orthodox and Optimal-Dose Procedures
are Based on Clinical Experience

It is paradoxical that orthodox allergists attack optimal-dose procedures because they were derived from clinical experience rather than research. The fact is that orthodox procedures are also based on opinions derived from clinical experience, not research. Here are three quotations from the "bible" of conventional methodology.(27) The underlined and parenthetical material is mine.

  1. "...the scientific data now available simply do not provide information sufficient for physicians to make totally objective decisions. There are answers based on the approaches that have evolved through long and extensive clinical experience. In spite of the lack of directed clinical research, this experience provides background for decisions about many details. These questions and answers present one viewpoint, with the full recognition that these opinions are not derived from research in many cases but rather from experience."
  2. Physicians "customarily include equal concentrations of each antigen (in the treatment solution) once a decision has been made to include that particular antigen in the treatment schedule."
  3. "If immunotherapy that is being given (in addition to environmental control and medication compliance) does not seem to be effective after a period of two to three years, then serious consideration should be given to its continuation."

The Body Requires a Specific Optimal Treatment Dose for Each Individual

Antigen, and Changes its Needs from Time to Time

The fact is that one allergen may require a relatively strong dose, another a relatively weak dose. Other allergens may require doses of various intermediate strengths.

The body's dosage needs for individual allergens may vary over time. Whenever the body's dosage needs change, the new dosage needs can be determined quickly and precisely by retesting. Retesting restores optimal response immediately.

Thus, each optimal-dose injection contains the just-right dose for each allergen in each patient's treatment solution for the state of his immune mechanism at a given time. In summary, the optimal-dose system provides a safe, effective, rapidly beneficial, precise, objectively-determined, patient-specific, allergen-specific and time-specific treatment.

Optimal-Dose Immunotherapy Saves Time and Money

An additional benefit of optimal-dose immunotherapy is the tremendous saving of time and money. Each orthodox build-up injection requires a visit to a physician's office for safety. It is recommended that these injections be given only in office with resuscitative equipment.

Furthermore, in Britain, the post-injection waiting period in the office has recently been required by decree of the Committee on Safety in Medicine (equivalent to our FDA) to be increased from the old standard of twenty minutes to a new standard of two hours. This has virtually eliminated the use of orthodoximmunotherapy in Britain.

However, the use of optimal-dose immunotherapy has not been affected by this ruling, as the injections are eminently safe and can be self-administered by the patient in his own home. This is much more practical and economical, since it does not require the time loss and inconvenience of having to go to an appropriate physician's office or hospital for each injection.

In addition many patients are seeing one or more other specialists (e.g. neurologists for migraine, gastroenterologists for diarrhea, etc.), taking multiple medications, and undergoing repeated diagnostic workups or hospitalizations. These can be very expensive, and can usually be markedly decreased or eliminated by optimal-dose therapy.

Optimal-Dose Immunotherapy is the True Gold Standard

The gold standard of orthodox allergists for food testing is the prick test followed by double-blind placebo-controlled challenges with opaque capsules containing powdered food antigens. Actually, prick tests for foods are very unreliable, and an opaque capsule challenge usually provides too small a dose to be an adequate stimulus to evoke an allergic response. Furthermore, capsules cannot be swallowed by small children.

Symptom induction by oral challenge usually requires four days of avoidance followed by at least two or more large closely-spaced feedings. Sometimes several feedings each day for several days or even for 1-2 weeks are required to induce symptoms. But even if orthodox procedures were reliable for diagnosis, they would still offer no information as to the precise treatment dose for each antigen, as does optimal-dose testing.

A New Approach is Required

Continued re-examination of limited old concepts, such as prick tests, opaque capsule challenges and orthodox rush procedures is analogous to earlier attempts to breed stronger horses and build better buggies. Applying the principles of the internal combustion engine to transportation was not initiated by horse-breeders or buggy-builders. It took a different mindset, beginning with a determination to find a better solution to the problem, even if novel, rather than an attempt to improve a technology which is well-established but limited. Hopefully, we can all open our minds to new approaches and move into the 21st century a stronger and more effective medical specialty.

Why is Change so Urgently Needed?

The 40 million patients with inhalant sensitivities can be provided far greater, safer, and quicker relief by optimal-dose immunotherapy rather than by orthodox immunotherapy. In addition, optimal-dose immunotherapy for foods can provide relief for most of the 24 million patients with migraine, the 18 million patients with gastrointestinal allergies (abdominal pain, diarrhea, "irritable bowel syndrome", chronic ulcerative colitis, and Crohn's disease), the 15 million children (and uncounted adults) with attention deficit hyperactivity and hypoactivity disorder, the 15 million patients with atopic dermatitis, and the 15 million people with chronic urticaria (total: 127 million).

Also, optimal-dose immunotherapy with influenza virus vaccine can provide the same 30-minute relief response for untold millions of patients with acute influenza. It is highly effective for the millions of patients with infections caused by members of the herpes virus family (herpes simplex I and II, herpes zoster, infectious mononucleosis, varicella).

Optimal-dose treatment with progesterone for premenstrual syndrome, dysmenorrhea, and hyperemesis gravidarum can provide the same rapid relief response in the many millions of women with these conditions.

Optimal-dose immunotherapy with oak/ivy extract can provide the same rapid relief response for millions of people suffering from oak/ivy dermatitis. Optimal-dose immunotherapy with extracts of Candida albicans can provide much relief to the millions of women with resistant vaginal candidiasis.

Additional uses of this exciting procedure are being studied. Investigation into the applicability of other extracts, vaccines, hormones, contactants, etc. is sorely needed. This is an expanding field with many additional potential applications. Decades may pass before sufficient i's are dotted and t's are crossed to satisfy all the no-sayers.

As physicians, we cannot in good conscience continue to withhold this valuable treatment. Patients with known responsive syndromes should not be made to suffer needlessly on when relief is safe, effective, quick, and available.

This is Only the Beginning

The discovery and development of the optimal-dose system seems to me to be in the same echelon of importance as the discovery of anesthetic agents, antibiotics, corticosteroids, and ground-breaking surgical procedures such as open-heart, endoscopic, and laser surgery. It is not just a superb method of treating food allergy (which it is), but a comprehensive system for re-balancing faulty, ongoing imbalanced immunologic mechanisms for a great many specific allergens and other incitants.

This does not make it a panacea any more than did the landmark discovery of the agents and procedures just listed. Each of these discoveries has started simple, just as did food neutralization. Each then developed into a major system of managing many medical problems. An example is the growth of the antibiotic concept from the first antibiotic to the many now available. The same is true of anesthetic agents, uses of steroid hormones, expanding surgical procedures, etc.

Furthermore, optimal-dose therapy is specific to the incitant being treated, which is the opposite of a panacea. The great breadth of applications is based only on the great breadth of ills caused by specific immunologic dysfunctions.

For the first time, we have a system for safely controlling immune dysfunction. We have barely begun. It will be fascinating to see the many new applications not yet dreamed of that the future will bring. It would be a shame if this great potential were to be suppressed by individuals and agencies who simply are not knowledgeable about its usage and its vast implications for the relief of the human condition.


  1. Bookman R: Observations and reflections of a practicing allergist. Annals of Allergy 45:4, pp 264-266, 1980.
  2. Hedlin G, Silber G, Naclerio R, Proud D, Eggleston P, Adkinson NF Jr: Attenuation of allergen sensitivity early in the course of ragweed immunotherapy. J Allergy Clin Immunol, September 1989, pp 390-399.
  3. Miller JB: Intradermal provocative-neutralizing food testing and subcutaneous food extract injection therapy, in Food Allergy and Intolerance, Brostoff J and Challacombe SJ (Ed.). London: Bailliere Tindall, 1987, pp 932-946.
  4. Miller JB: Food Allergy: Provocative Testing and Injection Therapy, Charles C Thomas, 1972.
  5. Miller JB: Relief at Last! Neutralization for Food Allergy and Other Illnesses, Charles C Thomas, 1987.
  6. Miller JB, Lee C, Binkley EL, and Hardt SH: Relief of influenza symptoms by the provocative-neutralizing method--A preliminary report, Journal of the Medical Association of the State of Alabama, Vol. 41, No. 7, January, 1972, pp 493-502.
  7. Miller JB: Relief of premenstrual symptoms, dysmenorrhea, and contraceptive tablet intolerance, The Journal of the Medical Association of the State of Alabama, Vol. 44, No. 2, August, 1974, pp 57-60.
  8. Miller JB: Influenza: Rapid relief without drugs, Clinical Medicine, Vol. 81, No. 9, September, 1974, pp 16-19.
  9. Miller JB: Influenza neutralization, Transactions of the American Society of Ophthalmologic and Otolaryngologic Allergy, Vol. 14, No. 1, October, 1974, pp 159-168.
  10. Miller JB: Management of migraine headaches, in Current Therapy of Allergy, Frazier CA (Ed.) New York: Medical Examination Publishing Company, Inc., 1974, pp 224-225.
  11. Miller JB: Food allergy: Technique of intradermal testing and subcutaneous injection therapy, Transactions of the American Society of Ophthalmologic and Otolaryngologic Allergy, Vol. 16, No. 1, October, 1976, pp 154-168.
  12. Miller JB: Virus and hormone neutralization, in Clinical Ecology, Dickey LD, (Ed.), Springfield: Charles C Thomas, Publisher, 1976, pp 597-605.
  13. Miller JB: A double-blind study of food extract injection therapy: A preliminary report, Annals of Allergy, Vol. 38 No. 3, March, 1977, pp 185-191.
  14. Miller JB: Management of migraine headaches, in Current Therapy of Allergy, Frazier CA (Ed.), New York: Medical Examination Publishing Company, Inc., 1978, pp 307-320.
  15. Miller JB: Optimal dose method of food allergy management, The Journal of Continuing Education in O.R.L. and Allergy, Vol. 40, No. 5, May 1978, pp 37-50.
  16. Miller JB: Hidden food ingredients, chemical food additives, and incomplete food labels, Annals of Allergy, Vol. 41, No. 2, August, 1978, pp 93-98.
  17. Miller JB: Immunotherapy of virus infections, Transactions of the American Society of Ophthalmologic and Otolaryngologic Allergy, Vol. 18, N. 1, September, 1978, pp 144-148.
  18. Miller JB: Treatment of active herpes virus infections with influenza virus vaccine, Annals of Allergy, Vol. 42, No. 5, May, 1979, pp 295-305.
  19. Miller JB: Management of food allergy, in Food Allergy: New Perspectives, Gerrard JW (Ed.), Charles C Thomas, Inc., September, 1980.
  20. Miller JB: The optimal-dose method of food allergy management, in Otolaryngologic Allergy, King HC (Ed.), Symposia Specialists, Inc., 1981, pp 253-283.
  21. Miller JB: Rapid relief of varicella and infectious mononucleosis through immunotherapy, Annals of Allergy, Vol. 47, No. 5, 1981, pp 135-136.
  22. Miller JB: Neutralization therapy update, in Allergy--Immunologic and Management Considerations, Spencer JT (Ed.), MEDED Publishers, Inc., 1982.
  23. Miller JB: Herpes: Rapid relief with influenza virus vaccine, The Journal of the Alabama Dental Association, Vol. 68, No. 3, Summer, 1984.
  24. Miller JB: Mini-dose therapy may relieve progesterone intolerance, Clinical Ecology, Vol. 2, No. 4, Fall, 1984, pp 224-226.
  25. Armentia-Medina A, Blanco-Quiros A, Martin-Santos JM, Alvarex-cuesta E, Moneo-Goiri I, Carreira P, Losada-Cosmes E: Rush immunotherapy with a standardized Bermuda grass pollen extract. Annals of Allergy, Volume 63: August 1989, pp 127-135.
  26. Horst M, Hejjaoui A, Horst V, Michel FB, Bousquet J: Double-blind, placebo-controlled rush immunotherapy with a standardized Alternaria extract. J Allergy Clin Immunol, February 1990, pp 460-472.
  27. Patterson R, Lieberman P, Irons JS, Pruzansky JJ, Metzger WJ, Zeiss CF: Immunotherapy, Allergy Principles and Practice, Middleton E Jr, Reed CE, Ellis EF, Second Edition, CV Mosby Co., 1983, p. 1131.

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