Why IgG Testing for Food Intolerance Is Not As Simple As ABC or Doh Ray Mi

What I know about the scientific validity of IgG testing to diagnose food intolerance could be written on a postcard leaving plenty of room for the address and stamp. I'm just mentioning this because it may be time for authors' competing interest declarations to be supplemented with a statement of scope of knowledge/ignorance/belief.

I've been prompted to consider the need for this statement by Patrick Holford's theatrical outrage about BBC Watchdog's Dirty Allergy Trick* (NB, the original article has been removed, I shall do my best to keep up with other links to it). A healthy volunteer participated in three food allergy/intolerance tests – two VEGA tests (conducted at different times and with different operators), a hair test, and two YorkTest IgG Food Intolerance tests (he submitted two blood samples under different names).

The hair and VEGA tests yielded long lists of foodstuffs that should be avoided. The investigative team highlighted the unreliability of the two VEGA tests that yielded different results. The team mentioned that the Yorktest results differed, but far less egregiously than the VEGA tests. According to Holford, this outcome was equivalent to a " [t]humbs up for Yorktest".

The expert they used to pass judgement said that there had been only one study on IgG as a basis for allergy! That is plain deception. If you go into Medline, the on-line database of published research and put in IgG you’ll find 139,473 referenced studies. If you narrow down to IgG + food intolerance it list 85 studies. I referenced 115 studies in my book Hidden Food Allergies (Piatkus). The evidence for IgG antibody reactions as a basis for food intolerances continues to grow, including well designed randomised controlled trials, however, some health professionals just haven’t kept up to date. Perhaps it’s because a ‘home test’ takes the power away from the professional and puts it in your hands.

Should the 'expert' hang his head in shame? Should I break out the sackcloth and ashes for failing to be convinced by both Patrick Holford's erudite assertions and expert support for IgG testing, as listed by YorkTest? Among the experts, Muriel Simmons of Allergy UK is quoted as saying:

The clinically proven YORKTEST Food Intolerance Test and back up support offered to patients provides a wonderful service for food intolerance sufferers worldwide.

To the comparatively uninformed, such as myself, it seems as if Patrick Holford conflates allergy and intolerance, but he endorses the tests enthusiastically:

The vast majority of food allergies happen because individuals produce IgG antibodies to specific foods. If symptoms, pain or energy levels come and go for no obvious reason, then you may have a hidden food allergy or intolerance. A simple YORKTEST Laboratories IgG food allergy home test provides clear, laboratory analysed, scientific results.

I'm going to deal with these endorsements separately. Although it isn't clear from the quotation attributed to her, Muriel Simmons may be relying upon a study into IgG testing and an elimination diet in a group of people with irritable bowel syndrome (IBS). In the abstract for that paper, the authors quite properly restrict the scope of their conclusions:

Food elimination based on IgG antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research. [Emphasis added.]

This is in stark contrast to some of the authorities who lend their YorkTest-styled expertise to endorsing the tests as valid for "food intolerance": a catch-all term that can encompass more than 100 symptoms of varying severity.

Dr. Hunter, who has research interests and publications in IBS, made the following comments about the value of the findings from that study: Food Elimination in IBS: The Case for IgG Testing Remains Doubtful.

The percentage of patients showing substantial benefit from this diet is disappointing. In studies using a well conducted and rigorous elimination diet, the "number needed to treat" is between 1.5 and 2.2 [refs]. The "number needed to treat" in this study was 9. (The value of 2.5, calculated on the basis of those who fully complied with the diet, abrogates the intention to treat principle.)

This seemingly poor response to an IgG based diet confirms the widely held view to date that IgG testing for food intolerance is not of value. [refs] These results suggests that if IgG testing identifies food intolerances at all, it does so fortuituously and with an apparent low degree of accuracy.

Hunter further argues that the study was premature because it is not yet possible to answer the basic research question: "do high levels of IgG against a food predict an adverse reaction to that food?". Three of the four authors of the original paper replied to Hunter and elaborated their view on how their findings should be interpreted (scroll down).

[I]t is entirely possible that IgG antibodies may be important in IBS, where we now know that there is an inflammatory component in some cases, whereas they may not be relevant in food intolerance in general. Furthermore, it is likely that only a subset of patients are likely to have an immuno-inflammatory basis to their condition and these might be the very individuals who respond to dietary exlusion based on IgG antibodies. This would fit with our results where only a proportion of patients responded despite all having antibodies. This, of course, limits the specificity and usefulness of the test unless such subgroups can be indentified beforehand. We should also bear in mind that an immunological reaction in the gut, as opposed to other forms of food intolerance, may make the gut more susceptible to other perturbing stimuli, such as stress, rather than necessarily causing symptoms directly. [Emphases added.]

Unlike YorkTest and some of the experts who endorse the scientific validity of their tests, Prof. Whorwell and his colleagues are punctilious in limiting the scope of their findings to IBS: they acknowledge the relevance of other factors, such as stress, in IBS and are open to the possibility that their findings "may not be relevant in food intolerance in general".

On his own site, Patrick Holford ascribes a far greater diagnostic role for YorkTests and praises their "solid science":

The best tests for food and chemical allergies and intolerances measure the presence of antibodies in the blood called immunoglobulins...
My favourite laboratory is Yorktest Laboratories whose tests are clinically validated...
Yorktest have also carried out a number of ‘double-blind’ trials on their IgG test and have solid science to back up their claims of effectiveness.

Prof. Whorwell and his colleagues made no such claims, so Holford's confident claims presumably arise from that overwhelming number of studies on Medline. And, yes, it is true, if you put IgG into Entrez Pubmed, you will have a huge number of hits returned. I did this, today, and in the 5 weeks since Holford did his search, the number has grown to 140032. Narrowing the search to IgG + food intolerance yielded 86 results: less than 140032 but still a substantial body of research.

Except...not all of those 86 results are relevant. I am both unconvinced of the relevance, and unmoved by the implied plight in Longterm effects in neonatal basal forebrain cholinergic lesions on radial maze learning and impulsivity in rats; I'm similarly stumped by the relevance of Leptin administration prevents spontaneous gestational diabetes in heterozygous Lepr(db/+) mice: effects on placental leptin and fetal growth.

At the risk of appearing specie-ist, I restricted my exploration to those papers that seemed to involve humans or readily generalisable to them. A number of the papers involved variations on the word unproved in their titles; see examples here, here and here. Concentrating on these papers seemed unfair, so I consulted a selection of the others. For reasons of delicacy, I thought that I should likewise ignore papers with, e.g., unreliability in the title.

Working through the studies that remained, most of the authors (like Whorwell and colleagues) were scrupulous in defining the limits of the relevance of their findings to populations with IBS or infants with milk intolerance rather than claiming wider relevance in the field of food intolerance or validation for the IgG tests. Even when authors explored a broader remit, e.g., Alternative Tests in the Diagnosis of Food Allergies, they reported findings that do not support Holford's claims:

We reviewed the scientific evidences of these tests (specificity, sensibility, rationale, reproducibility). According to most studies none of them had to be recommended as useful for the diagnosis of food allergy or intolerance. Physicians should alert patients about the risk of an indiscriminate use of these test in the diagnosis of food allergy. In fact the use of an incorrect diet could be dangerous, particularly in childhood, as recently shown.

Other researchers analysed IgG levels in blood from young, healthy, male volunteers with no previous signs or history of food allergy. Their findings do not support Holford's claims:

Common occurrence of asIgG-4 against food allergens in healthy persons (without any symptoms which could suggest allergy or food intolerance) argues against the possible participation of these antibodies in the pathogenesis of food allergy.

Holford claims that he refers to 115 studies in his book; presumably these are supportive studies. However, it is implausible that many of these studies are drawn from the peer-reviewed studies listed in the Entrez PubMed search. Remember that Holford accused the Watchdog team of a "slight [sic] of hand" yet he has referred to the existence of a vast number of papers as if they are relevant and support his claims.

I would emphasise that I am using the literature search terms that Holford cited to bolster his criticism of the judgment of the Watchdog expert and his attack on the Watchdog team that prompts him to use phrases such as "dirty allergy trick" and "plain deception". Holford has recently compared his own qualifications, knowledge and expertise with that of Dr. Ben Goldacre, believing that it is Goldacre who comes off worse for the comparison. He vaunts his

30 years researching, teaching, writing and practising nutrition.

I admit the limitations of my knowledge of these areas, however, I do not think that even a cursory examination of the research literature supports Holford's claims for the "sound science" of either IgG testing or Yorktests in the diagnosis or validation of food intolerance. Perhaps the matter would be clearer to me if Holford had listed the supportive studies rather than sent me off on a wild-goose chase through the literature.

For a wider discussion of the poverty of evidence behind food intolerance, see Sandy's well-referenced, Fear of foods, contaminants and modern life. She quotes some disturbing findings:

Rona and Chinn found that around one half of parents who thought that their child was food allergic or intolerant altered their child's diet, but only one third sought medical advice, and that some children were 4 cm shorter than controls. Unnecessary environmental and chemical avoidance, creating a perception of organic illness where none exists, or advising physical interventions when psychosocial factors are the source of symptoms, can impact on employment and social functioning.

If the experts who provided testimonials to Yorktest meant to limit the scope of their support to the usefulness of IgG testing in guiding food elimination diets in people with IBS, then they should have stated this clearly. If they believe that research findings can support a more generous interpretation than their own authors would assign to them, then it would be helpful if they stated their reasons for this. If there is "sound science" that confirms the value of IgG testing in diagnosing and confirming food intolerance then it would be a valuable contribution to the public debate if either the experts or the company marketing the test were to provide the references. Holford chooses to deprecate the knowledge of others:

some health professionals just haven’t kept up to date. Perhaps it’s because a ‘home test’ takes the power away from the professional and puts it in your hands.

However, until such time as I see these references, I will reserve my judgment as to which parties are indulging in a "dirty allergy trick" or "plain deception". The parents highlighted in the Rona and Chinn took their power into their own hands because they couldn't obtain formal help for their children's perceived food intolerances; as a consequence, those primary school children are shorter than their non-food-intolerant peers by an average 1.5 cm. Encouraging people to take tests that boost their empowerment and lead to restrictive diets can have consequences: it would be useful if the experts who endorse these tests and diets were explicit on this point.

*Edited 1 March It seems that Holford's article has been removed from the site. I have replaced that link with ones to sites that still have a copy. The original link was BBC Watchdog's Dirty Allergy Trick. At the time of writing, other copies are as follows: BBC Watchdog's Dirty Allergy Trick; Nutritional Therapy: BBC Watchdog's Dirty Allergy Trick; BBC Watchdog's Dirty Allergy Trick. If these links disappear then I shall put up a link to the cached version of the article.