Oral immunotherapy: switching off food allergies using food

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(By Dr Sarah Myhill and Craig Robinson)

The theory

Oral immunotherapy (OIT) was first proposed as a method of treatment for allergic disease in the early 1900s. In the 1980s, properly designed clinical trials first demonstrated a dose-dependent therapeutic response with specific and well-characterised aeroallergens. In 2006, the World Health Organization recognised the cumulative evidence that OIT represented a viable alternative to subcutaneous immunotherapy (SCIT) and encouraged continued clinical investigation to characterise optimal techniques. (Reference to WHO recognition - Bousquet J., Sublingual Immunotherapy: Validated! Allergy 2006; 61 (supplement 81):5-6.)

We now have several studies that demonstrate how allergy can be switched off by using tiny doses of the offending allergen given by mouth. For example, studies have shown efficacy in switching off allergies to peanuts, birch pollen and grass pollen using OIT as follows:

  1. Anagnostou, K. et al. Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial. The Lancet 2014 (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)62301-6/abstract ). The interpretation of the abstract from this paper reads thus – ‘OIT successfully induced desensitisation in most children within the study population with peanut allergy of any severity, with a clinically meaningful increase in peanut threshold. Quality of life improved after intervention and there was a good safety profile. Immunological changes corresponded with clinical desensitisation.’ Mild allergic reactions did occur but only one of the 76 participants required adrenalin by injection. Over 80% of the children desensitized successfully over the six months of increasing dose of peanut.
  2. Kopac, P. et al. Continuous apple consumption induces oral tolerance in birch-pollen-associated apple allergy. Allergy 2012 Feb;67(2):280-5 (http://www.ncbi.nlm.nih.gov/pubmed/22070352). The conclusion to this paper reads thus – ‘In patients with OAS (Oral Allergy Syndrome) to apple, tolerance can be safely induced with slowly, gradually increasing consumption of apple.’
  3. Multiple studies assessing the efficacy of treating grass pollen allergy via the use of grass pollen sublingual tablets - please see Sublingual and oral immunotherapy for allergic rhinitis - http://www.uptodate.com/contents/sublingual-immunotherapy-for-allergic-rhinoconjunctivitis-and-asthma. For example, one study (Dahl, R. et al. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis.J Allergy Clin Immunol. 2006;118(2):434-40 - see http://www.ncbi.nlm.nih.gov/pubmed/16890769) concluded that ‘Mean rhinoconjunctivitis symptom scores and medication scores (30 and 38 percent, respectively) improved significantly compared with placebo. Additionally, there were significant increases in the number of well days (53 versus 44 percent) and improvements in quality of life in the treatment group.’
  4. Tang M L K et al. Administration of a probiotic with peanut oral immunotherapy: A randomized trial. This is a very recent trial, published January 2015, in The Journal of Allergy and Clinical Immunology (http://www.jacionline.org/article/S0091-6749%2814%2901737-0/fulltext). This trial involved the use of a probiotic, Lactobacillus rhamnosus, alongside standard peanut oral immunotherapy. The inclusion of the probiotic seemed to make the therapy more effective. As a result, I am currently investigating the use of this probiotic alongside my oral immunotherapy. It is easily grown at home - even I can do it! See Probiotics-we should all be taking these all the time and double the dose following antibiotics and gastroenteritis which gives details as to how it can be grown. I suggest using 2 cups daily - I suspect lactobacilli are the microbes in the gut which induce immune tolerance to gut contents - foods and microbes.

The idea of oral immunotherapy is to start with tiny doses, build these doses up slowly, and as a result, over time, the immune system will develop tolerance to that particular substance.  This technique was used in the NHS during the 1970s to treat pollen allergies. At that time, it was given by injection, starting off with tiny doses, and then the dose would be increased every week until after about ten weeks tolerance to grass pollen was achieved in the majority of patients.  Unfortunately, this type of low dose immunotherapy was banned because some authorities started to use multiple allergens. This use of multiple allergens meant that, in order to prevent immediate reactions, the allergen mixes were put in an oil soluble medium so that the antigens would be released slowly.  The effect of this change in administration technique was that, if a patient was going to suffer a serious reaction, then this serious reaction invariably happened at home because of the delayed release effect. This in turn meant that patients were suffering serious reactions where basic resuscitation assistance was not available – i.e. at home.  As a result some patients died, leading to a ban of this kind of low dose immunotherapy. The baby was thrown out with the bath water!

Recently, a new study, (study number 1 above), has been published demonstrating how anaphylactic reaction to peanut can be ‘’switched’’ off by administering tiny doses of peanut given by mouth and then by gradually increasing the dose of peanut slowly over time.

What were the basic results? Ninety-nine children took part in the trial (five of the original 104 did not react during their first peanut "challenge").

The researchers found that:

  • 62% of children in the OIT group had become desensitised to peanuts at six months, compared with none in the control group.
  • 84% (95% confidence interval [CI] 70-93) of the OIT group tolerated daily consumption of 800mg protein (equivalent to roughly five peanuts).
  • average increase in the maximum amount of daily peanut tolerated after OIT was 1,345mg, an increase of more than 25 times the original amount they could tolerate.
  • After the second phase in which the control group were offered OIT, 54% tolerated a 1,400mg peanut "challenge" (equivalent to roughly 10 peanuts) and 91% tolerated a daily ingestion of 800mg protein.
  • The children reported a better quality of life after OIT.
  • Side effects after OIT were mostly mild. Gastrointestinal symptoms were the most common (31 participants with nausea, 31 with vomiting, and one with diarrhoea), followed by oral itching (affecting 76 children after 6.3% of doses) and wheeze (affecting 21 children after 0.41% of doses).
  • One child needed an adrenaline injection on two occasions.

Turning this to practical use

I do not see why this idea could not be extended to all foods and with this in mind I am preparing some food mixes.  The idea here would be to have different mixes for different food groups say, meats, vegetables, salads, nuts, fruits or whatever so that people could choose the group of food that they wish to try.  One would then start off with a very low dose, say 1-2 mg a day (i.e. the same dose as the peanut anaphylactic study).  If this was not tolerated, then one would reduce the dose.  If it was tolerated, then one would gradually increase the dose. 

I think one reason why low dose immunotherapy is so successful has to do with the mechanism by which the immune system identifies good and bad, or, to put it another way, right from wrong.  It is a very difficult job for the immune system to recognise a piece of DNA from something safe, such as cabbage, as opposed to a piece of DNA from something potentially unsafe such as a virus.  The way it achieves this is by constantly looking at what is normally present in the background environment and, largely speaking, this means the gut. This is because 90% of the immune system is gut associated.  When the immune system identifies something that is new and novel, this will flag up a concern which may or may not result in an immune system reaction such as inflammation. The reason for the immune system reacting in this way is because inflammation, of course, is very good at killing viruses.   The problem with modern Western lifestyles is that we are constantly exposed to new immunological challenges.  This may arise as a result of a number of factors:

  • We can now eat a wider variety of foods than ever before
  • International travel, which means that we are now exposed to more viruses than ever before,
  • Exposure to substances such as antibiotics which change the normal gut flora
  • Exposure to adjuvants such as vaccinations and toxic metals which fire up the immune system.

Of course, what should happen in Nature is that we should all be born and bred in one place, live our lives in that place, only eat locally grown foods and perhaps meet the occasional traveller once a year. (Although even this lifestyle can result in disaster! Think of poor Tess of the d’Ubervilles and her chance meeting with the traveller Angel Clare! However, here, love was the killer not exposure to a new antigen……)

A baby is born with the ‘’hardware’’ of an immune system. This hardware then needs programming with the ‘’software’’. So, how is the software downloaded onto the hardware? Primarily it is by exposure. This early programming of the software is vital to the immune system. This is because it is at this stage that the immune system learns what is normal background ‘’stuff’’ which can be safely ignored.  It is when the immune system experiences a new substance later on in life that there is a potential for it [the immune system] to be switched on to this new substance.  A good example of how this "plays out in real life" can be demonstrated by looking at peanut allergy again. In Israel allergic reaction to peanut is extremely rare.  One possible explanation for this is that a commonly used baby rusk contains peanut i.e. those Israeli babies are routinely exposed to peanut early in life and so the "software" that "says" peanuts are "normal" is downloaded very early in these children’s lives. So, the immune system of these children learns to accept peanut as normal. 

So the idea of low dose food desensitisation is gradually to "introduce" the immune system to tiny and then increasing doses of foods in order to induce immune tolerance.  This means these antigens become normal "background noise". Indeed this may be part of the mechanism by which other recognised forms of desensitisation such as enzyme potentiated desensitisation [EPD] work.  In EPD, treatment is given intra-dermally with an immune stimulant, namely, the enzyme beta-glucuronidase.  This helps to induce immune tolerance with a once every two to three months injection.  In EPD, all the common foods are present. 

It is also important that the food is prepared using normal kitchen methods. The reasoning for this is as follows. All foods are contaminated by the gut flora of the cook. At miniscule doses this causes no problems – indeed it generates oral tolerance to normal gut flora and is thus a good thing. We now recognise that many diseases are driven by allergy to gut flora and so developing tolerance to normal gut flora is very helpful to good health in general. Indeed the hygiene hypothesis shows us that those children exposed to normal amounts of "dirt" are less likely to be allergic. The mechanism of this is likely to be oral tolerance.

NB: The Hygiene Hypothesis states that a lack of early childhood exposure to infectious agents, symbiotic microorganisms (e.g., gut flora or probiotics), and parasites increases susceptibility to allergic diseases by suppressing the natural development of the immune system. In particular, the lack of exposure is thought to lead to defects in the establishment of immune tolerance.

Practical details

Food mixes can be supplied and each mix will contain ten foods of a particular type. It does not matter that not all foods are represented. This is because similar foods have shared antigens. We know this from practical experience using enzyme potentiated desensitisation (EPD). Not every possible food is present in EPD. So, for example, simply the presence of orange’s antigen in EPD will switch off allergy to all the citrus group foods. Here is a list of mixes that will be available:

  • Meats – beef, pork, lamb, chicken, duck, goose, venison (red deer, fallow), pheasant, rabbit, egg.
  • Vegetables – potato, sweet potato,  swede, parsnip, carrot, beetroot, cabbage, onions, leek, mushroom,
  • Salad – lettuce, tomato, cucumber, pepper, radish, celery, avocado, watercress, chicory, cress
  • Nuts – peanut, cashew, hazel, walnut, brazil, pecan, macadamia, almond, coconut, pistachio
  • Berries – apple, pear, strawberry, blackcurrant, gooseberry, raspberry, blueberry, grape (white and red), blackberry,
  • Fruits – melon, pineapple, banana, orange, lemon, grapefruit, rhubarb, papya, mango, lychee
  • Fish – cod, haddock, trout, tuna, herring, sardine, salmon, crab, prawn, mussel,  
  • Pulses and beans – soya, peas, chick peas, beans (various), lentils, chocolate, coffee,
  • Cereals – wheat, corn,  sweetcorn, rye, oats, barley, rice, quinoa, buckwheat
  • Dairy – cow’s milk, goat milk, sheep milk, cheddar cheese, stilton, yoghurt, cream, butter,
  • Universal mix – all of the above

The three weakest mixes will all be universal mix. They will be in bottles with GREEN, AMBER and RED labels to denote the strength of the mix. Above the RED bottle strength the mix will be food group and so the relevant food group(s) must be chosen.

Here is the food content of the various mix strengths:

  • Green bottle - 1 mg of total food per ml
  • Amber bottle - 10 mg of total food per ml
  • Red bottle - 100 mg of total food per ml
  • White bottle 1000 mg (1 g) of total food per ml

The above mixtures will use vitamin C as a preservative and be made up with spring water.  There will be no other additives. The vitamin C will be sourced from sago as sodium ascorbate - it is very unusual to be allergic to sago. 

The idea is to choose which food group or combination of food groups you wish to desensitise to and to start off with one drop from the green bottle with every meal. If tolerated, then the dose can be increased until you get to 10 drops from the green bottle with every meal, at which point you can move up to the amber bottle – the medium strength.  10 drops from the weak green bottle is equivalent to one drop of the amber bottle.

If you tolerate 1 drop from the amber bottle, again build up slowly until you get to 10 drops per meal from the amber bottle and then move up to the red bottle.  And again, one drop from the red bottle is worth 10 drops from the amber bottle.

Once you get up to 10 drops three times daily from the red bottle, that will be equivalent to a daily dose of 100 mg of each food. At this point move to the WHITE bottle of your selected food group.

The peanut trial spent six months getting up to high doses of peanut. I would think that at least three months is required. This squares with how long it takes for the bone marrow to generate a new population of white cells, and how long a dose of EPD lasts.

1 ml of mixture fluid is 30 drops.

If there is history of anaphylactic reactions

Any patient who has ever had an anaphylactic reaction from a food should not include that food in their desensitisation unless they are being overseen by a hospital with full resuscitation equipment.  The potential for harm using the above system of Green, Amber, Red and White bottles is miniscule, but one should always err on the side of ultra-caution when dealing with desensitisation. 

The future

I see no reason why oral immunotherapy should not be effective for inhalant sensitivities and chemical sensitivities. Watch this space!!!

How can I try oral immunotherapy?

For my existing patients, for whom I hold their medical history, it is a matter of ordering the required bottles from my office. For anyone with food allergies who is not my patient but would like to use the food drops as a therapy to turn off their food allergies, you will need to complete and let me have your medical questionnaire (accessible from the page Ordering Tests). I will review the questionnaire and write to your GP with my opinion and advising him/her that you will be starting oral immunotherapy as set out in this page. The cost of my review and letter is currently £110. Please, note that the food drops are posted to UK addresses only.

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References



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