Enzyme Potentiated Desensitisation (EPD) - how it works

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Enzyme Potentiated Desensitisation (EPD) is a vaccine which can be used to desensitise patients to foods, inhalants and chemicals. It has some bacterial antigens. The vaccine has been developed and refined by Dr Len McEwen over the past thirty years. It is supplied to the doctor who mixes the appropriate dose in a sterile environment, immediately prior to dosing.

Availability of EPD

You can obtain EPD at:

What the vaccine contains:

1-3 diol - a kind of alcohol which activates the enzyme. It is used in a tiny dose.

-glucuronidase - an enzyme. This appears to act as a lymphocyte hormone (lymphokine). It occurs naturally in human blood. The amount present in the vaccine is equivalent to that normally present in 1cc of normal plasma (white cells contain much more). In the vaccine it is thought to be responsible for stimulating the Langerhan cells to migrate to the local lymph glands and "reprogram" a new population of T suppressor lymphocytes. In the presence of antigen in the appropriate concentrations, this will result in a desensitisation. (Conversely in the presence of antigen at a "wrong" concentration you may get a hypersensitisation).

Antigen mixes:

The beauty of EPD is that one injection can be used to desensitise to a great many allergens. There are theoretical and practical reasons for preferring to desensitise with antigen mixes rather than so-called "single allergens". The following mixes are most frequently used:

"X" - mixed foods and additives, mixed moulds, mixed pollens, cat-dog, flock fly mix and bacterial mix.

"I" - inhalants alone. This is used to treat hay fever, cat, dog, horse allergy, pure mould and house dust allergy.

Separate mixes of "odds and ends", laboratory animals and sawdusts are also available.

"Fumes mix" - contains perfume oils, terpenes and other antigens which are not miscible with water unless they are extremely dilute.

Antigen Strengths

EPD works by manipulating the normal immune processes for creating and turning off allergies. Therefore success or failure depends largely on priming the patient in the best possible way. What makes EPD critical "θ" strength, the aim is to have approximately 10,000 molecules of each food antigen for desensitisation present at the injection site. Most patients receive Xθ for food allergy.

  • For inhalant desensitisation of the airways, the best dose (designated "C" strength) is equivalent to that received in a skin prick test. So most patients for seasonal hayfever or asthma would receive IC.
  • Patients with chemical sensitivity receive the fumes mix at θ strength.

Indications For Use

Any condition caused by allergy such as:

  • Asthma, eczema, rhinitis, chronic urticaria, angioneurotic oedema.
  • Hyperkinetic syndrome
  • Migraine and chronic headaches
  • Irritable bowel syndrome
  • Inflammatory bowel disease
  • Food induced psychological states - depression, anxiety.
  • Chronic fatigue syndrome
  • Multiple food allergy
  • In some instances, hyperventilation is caused by food allergy.

I do sometimes use EPD for the worst possible reason, that is I can't think of anything else to do when all else has been tried. However it is surprising how often this works! Hidden allergies to foods, inhalants and chemicals are common causes of recalcitrant symptoms. One of the joys of using EPD is that it desensitises to all allergens across the board, so it is not essential to know all one's allergies for it to work.

Does it work?

A pessimistic estimate would be that EPD will fail in about 20% of suitable patients with known allergies. The rest will experience varying degrees of improvement. Follow up studies after 5 years and double blind trials suggest that EPD has much greater long-term success than any other method of immunotherapy.

How soon will it work?

Because EPD relies on the production of a new generation of cells, the effect of each dose will not be fully developed for at least 3 weeks. Simple allergics, such as hay fever, usually respond to the first dose. But doses of EPD are cumulative and a few of the more complex allergic patients may not start to improve until 8 or more doses have been given. This is the case for many of my CFS patients.

How safe is EPD?

Approximately 350,000 treatments of EPD have been given world wide over the past 30 years. For patients with severe anaphylactic type reactions I first skin test with a tiny dose of antigen. If there is no reaction I then use the "cup" method whereby the epidermis of the skin is scraped off and the vaccine applied in a 1.5 ml hemispherical plastic container. This can be removed and antigen wiped off in the event of any reaction. About 100,000 treatments have been given by the "cup" method. There have been no life threatening reactions with EPD. It must always be remembered that when foreign antigen is injected the usual safety precautions should be taken. I always carry adrenaline, antihistamines, steroids etc but I have never had to use them, or even consider using them in any patient.

EPD by injection

However, nearly all treatments given by me are by injection - the enzyme and antigens are all given in one syringe, total volume of about 0.05ml as an intradermal injection. It feels like a bee sting and brings up a small white "lentil" sized lump on the forearm. After a few minutes this usually disappears, but some patients get slight redness and swelling at the injection site.

Allergen exposure and the time of treatment

Treatment for seasonal allergies should be given at least 4 weeks before the season begins. There is a theoretical risk that one might hypersensitise a patient if he/she is exposed to allergens at treatment time. However, I have now been using EPD for 15 years and have given over 4,000 treatments and have yet to be convinced that this is a real clinical problem. Therefore there are no special environmental precautions to take other than avoid known sensitivities.

Desensitisation for foods works best if the patient sticks to their "safe", ie non-reacting foods for the 24 hours before and 3 days after the EPD injection.

EPD and allergy to gut flora

It is not uncommon to see patients who have become sensitised to their own gut flora. In these cases it is necessary to reduce the antigen load starting 4 days prior to a dose of EPD.

The commonest problem is allergy and gut fermentation and drugs used to pretreat include Sporanox and nystatin powder.

Allergy to gut bacteria requires pretreatment with antibiotics.

For the next thrilling instalment, read...

EPD - the practical details of what to do for each dose

EPD trials

Published double blind trials have shown that EPD is effective in the treatment of seasonal hayfever and asthma (several trials ), ulcerative colitis, childhood migraine and hyperactivity. At the time of writing, EPD has also been successful in further double blind trials studying hay fever (4 trials) and childhood house dust mite asthma. The results of all these trials will be submitted for publication. Uncontrolled trials have also shown benefit in the treatment of eczema, irritable bowel syndrome, urticaria, rhinitis and asthma. Clinical experience from over 100 clinicians working world wide (and growing) is encouraging. More trials are urgently required. The American audit of EPD patients shows results that are so good that I can hardly believe them!

EPD in the USA

From Wikipedia - see WikiDoc - EPD - USA

EPD was available in the United States until 2001, when the Food and Drug Administration revoked approval for an investigative study which it had previously sanctioned which had allowed EPD to be imported into the USA without being licensed. The reason given for revoking approval was that complex mixtures of allergens used in EPD treatments were not allowed under FDA rules. Since then the FDA has banned importation of EPD for the following reasons:-.

*EPD is not licensed
*The labeling of the medicine does not contain adequate directions for use. (EPD is only supplied to doctors who have been through a one-week training course, and instructions supplied with the medicine would not be adequate)

A related treatment, Low Dose Allergens (LDA), has been developed in the US by Dr. Shrader, which, being a compounding rather than a drug, is not regulated by the FDA, and uses a different allergen mix for the US environment.

For more details on LDA please see here - Dr Shrader's website on LDA

Stan Rohrer's excellent EPD FAQ

Please see Stan Rohrer's EPD FAQ for more detail

Facebook Group

There is a small but knowledgeable Facebook Group here - Facebook Group - "EPD (Enzyme Potentiated Desensitization) Help and Support"

Related Articles

External Links


1. McEwen, L.M., Ganderton, M.A., Wilson, C.W.M., Black, J.H.D., Hyaluronidase in the treatment of allergy, Brit. Med. J. (1967) 2: 507-508.

2. McEwen L.M. Effects of sugars and diols on enzyme potentiated hyposensitisation. J. Physiol. 1972. 230: 65-66.

3. McEwen L.M., Starr M.S. Enzyme Potentiated Hyposensitisation I, Int. Arch Allergy. 1972. 42: 152-158. glucuronidase and hyaluronidase was used to potentiate the hyposensitising effect of injected antigen into laboratory animals. Guinea pigs were injected with egg albumin, rats and mice with horse serum and all showed a hyposensitising effect following glucuronidase and hyaluronidase pre-treatment.

4. McEwen L.M. Enzyme Potentiated Hyposensitisation II, Annals of Allergy 1973. 31: 79-83.

In mice sensitised to horse serum, glucuronidase prevents the increased sensitivity which results from a second dose of antigen. glucuronidase loses this activity with age or in the presence of gelatin. In both cases glucose will restore the immunological blocking activity of the enzyme. These results give a reason for the previous variability expressed using different samples of enzyme in earlier experiments. As well as glucose, glucosamine and N-acetyl amino sugars have a similar effect.

5. McEwen L.M., Mary Nicholson, Kitchen I, Sheila White: Enzyme Potentiated Hyposensitisation III: Control by sugars and diols of the immunological effect of glucuronidase in mice and patients with hay fever. Annals of Allergy. 1973. 31: 543-550.

The ability of glucuronidase and a small dose of antigen to modify the anaphylactic reaction of previously sensitised mice has been further investigated. A 1-3 diol structure appears to be most effective in controlling the hyposensitising effect of the enzyme, although some concentrations have the opposite effect of hypersensitisation. The dose response curve is W shaped. A clinical trial on hay fever patients confirms that the results for the diol in mice are clinically relevant.

6. McEwen L.M., Mary Nicholson, Kitchen I., O'Gorman J., Sheila White: Enzyme Potentiated Desensitisation IV. Effects of protamine on the immunological behaviour of glucuronidase in mice and patients with hay fever. Annals of Allergy 1975. 34: 290-295.

Using mice pinnal anaphylaxis, the addition of protamine sulphate to the glucuronidase/diol mixture displaced the dose response curve, with less diol being required to achieve the same immunological effect. Hay fever patients also produced similar results. It is suggested that the protamine helps to stabilise the enzyme mixture, minimising the effect of contaminant proteins.

7. J.W. Hadden, R.G. Coffey, E.M. Hadden, E. Lopez-Corrales and G.H. Sunshine: Effects of Levamisole and Imidazole on Lymphocyte Proliferation and Cyclic Nucleotide Levels

These (above) early reports were published during the development of EPD.

8. McEwen L.M: Enzyme Potentiated Hyposensitisation V: Five case reports of patients with acute food allergy. Annals of Allergy 1975. 35: 98-103. Case reports of five patients successfully hyposensitised to foods including one lady highly sensitive to eggs. Other cases were sensitive to eggs, milk, fruit and nuts.

9. McEwen L.M. Hyposensitisation. In:Brostoff J and Challacombe SJ, Eds Food allergy and intolerance. London; Bailliere Tindall, 1987. 985-994.

10. Fell P., Brostoff J. A single dose desensitisation for summer hayfever. Results of a double- blind study

– 1988. Eur. I. Clin. Pharmacol. (1990) 38; 77-79.

11. Egger J., Stolla A, McEwen L.M. Controlled trial of hyposensitisation in children with food induced hyperkinetic syndrome. Lancet (1992) 339; 1150-1153.

12. Longo G., Poli F. Bertoli G. Efficacia clinica di un nuovo trattamento iposensibilizzante, EPD (Enzyme potentiated desensitisation) nella terapia della pollinosi. Riforma Med. (1992) 107; 171-176.

13. Astarita C., Scala G., Sproviero S., Franzese A. A double blind placebo controlled trial of enzyme potentiated desensitisation in the treatment of pollenosis. J. Invest. Allergol. Clin Immunol., (1996); 6(4):248-255.

14. AngeliniG., Curatoli G., D”Argento V., Vena G.A. Pollinosi: Una nuova metodica di immunoterapia. Medit. J. Surg Med (1993), 253-256. These Italian studies looked at EPD in the treatment of asthma and hay fever.

15. Cantani A., Monteleone M.A., Ragno V., Lucenti P., Buscino L. Enzyme potentiated desensitisation in children with asthma and mite allergy; A double blind study. J. Invest. Allergol. Clin. Immunol., (1996); 6(4); 120, 270-276.

16. Ippoliti F., Ragno V., Del Nero A., McEwen L., McEwen H.C., Businco L. Effect of preseasonal enzyme potentiated desensitisation (EPD) on plasma IL-6 and IL-10 of grass pollen-sensitive asthmatic children. Allergie et Immunologie. (1997); 29(5); 120, 123-125.

17. Egger J., Stolla A., McEwen L.M. Controlled trial of hyposensitisation in children with food-induced migraine. Cephalagia, (1993); 13, (suppl.13); 216.

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