CHARLES DARWIN hated controversy, but from the moment he published The Origin of Species he was probably the most controversial figure in Victorian England. Now, a century after his death, Darwin is again at the centre of a scientific argument. This time, however, the focus of the controversy is not Darwin’s theories but his medical condition.
For nearly 40 years, Darwin was an invalid, almost constantly ill with nausea, vomiting, headaches, fatigue, palpitations and eczema. Theories as to what caused this illness are plentiful, and range from poisoning (he took medicines containing arsenic and mercury), to a viral infection, Chagas’s disease, caught in South America during the voyage of the Beagle. In the end, however, most authorities have settled for a psychosomatic cause for his multiple ailments, especially as the attacks came and went, becoming more severe at times of stress.
A novel explanation for Darwin’s illness has recently revived interest in this long-standing controversy. The new theory attributes his malaise to a much-disputed condition known as food intolerance or ‘masked food allergy’. This is not food allergy of the well-known type in which a person reacts immediately to a food, with severe symptoms ranging from a swollen mouth and face a total collapse that can be fatal (anaphylactic shock). The symptoms of food intolerance, according to those who treat this condition, take far longer to appear, and are much more varied. This delayed reaction, combined with the fact that the offending food is usually a staple, such as wheat or milk in the West, prevents the patient from making the link between the food and the illness.
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Doctors who believe in the reality of food intolerance do not lay claim to any one typical set of symptoms, but all Darwin’s medical problems are among the symptoms that they recognise. Such doctors also report that it is common for symptoms to vary from day to day, and for anxiety to make the patient worse – in the same way that stress can exacerbate asthma, eczema and other classical allergic conditions. Nevertheless, experts such as Ralph Colp, a psychiatrist who has devoted an entire book to Darwin’s illness, remain sceptical. Colp sticks to his original diagnosis of ‘psychic stresses’.
Posthumous diagnosis is a tricky business, and this is an argument that could easily run for another hundred years. But the wrangle over Darwin’s illness is not just a matter of academic or historical interest, because it encapsulates the modern controversy over food intolerance itself . The most spectacular successes of doctors who claim to treat this condition have been with patients suffering from ‘thick-note syndrome’ – those who visit the surgery so regularly, with so many puzzling symptoms, that their notes look like a telephone directory. Invariably, such patients have consulted a long list of specialists, none of whom can find any organic disorder, so their symptoms, like Darwin’s, acquire the label ‘psychosomatic’. Many are now in good health again, following treatment by doctors specialising in food intolerance and the related field of chemical sensitivity. (Such doctors describe themselves as ‘clinical ecologists’ in the US, but most working in Britain prefer not to use this title.)
Despite these apparent successes with often chronically sick patients, and many more with less serious ills, food intolerance remains a dubious diagnosis in the minds of most doctors, who feel that the symptoms are much too close to those of psychosomatic illness for comfort. Doctors who specialise in treating food intolerance turn this argument on its head and suggest that some so-called psychosomatic illness is actually due to food. John Mansfield, a British doctor with more than 10 years’ experience in the field, remarks: ‘Of the patients I see, at least a third have been told by a doctor that their symptoms are psychosomatic. Yet they respond very well to dietary treatment, and they remain well afterwards, which is what matters.’
The medical establishment finds many aspects of food intolerance difficult to swallow, but the main problem is the plethora of symptoms and the variation from one patient to another. Doctors working with food intolerance report more than 40 possible symptoms and conditions, ranging from headaches, depression, asthma, constipation and recurrent mouth ulcers to aching joints, water retention, stomach ulcers and a constant runny nose. Most patients are said to have one, two or more of these symptoms, often acquired gradually over a period of years.
The severity of symptoms also varies. Some patients are said to have nothing more than the occasional migraine or bout of fatigue, while at the other end of the scale the sufferer is unable to work or lead any sort of normal life. In these extreme cases, practitioners in the field usually find that there are multiple sensitivities involving 10 or more different foods, various inhaled antigens, particularly pollens, and chemical factors such as exhaust fumes, chlorine and solvents.
Conventional doctors find food intolerance difficult to accept for another reason too: the causal relationship between the food and the symptoms is rarely obvious. Those doctors who treat food intolerance argue that this is hardly surprising if the response is not immediate and the patient eats the food daily, or several times a day. (Although in the West, this usually means cow’s milk, wheat or maize, a doctor working in Taiwan found that the commonest offender there was rice or soy sauce.) The other confusing and paradoxical factor is that eating the food may make the patient feel better initially, rather than worse, according to doctors who specialise in this field – hence the name ‘masked food allergy’. As a result, many patients apparently crave the particular food (or foods) that causes the problem, and include it, deliberately or unconsciously, in every meal of the day.
When they eliminate this food from their diet, most patients are said to feel a great deal worse initially, often suffering violent attacks of their original symptoms. Eating the offending food, at this stage, can alleviate these symptoms and restore a feeling of well-being. After a few days of abstinence, however, patients report that the ‘withdrawal symptoms’ pass, the original symptoms also disappear, and cravings for the food tend to abate at the same time. In the experience of doctors who use this diet as a method of diagnosis, there follows a period of between two and eight weeks during which the patient will react severely to the offending food. After a couple of months, this peak of sensitivity disappears. Thereafter most patients are said to acquire a certain tolerance of the food – they may never be able to eat it again on a regular basis, but can usually get away with consuming it intermittently. Again, this is in marked contrast to the accepted type of food allergy, which often remains throughout life: eating a minute amount of the same food 20 years later generally produces the same devastating reaction.
Despite many attempts to develop laboratory tests, there are none that can confirm the diagnosis of food intolerance. So the only basis for diagnosis is an ‘elimination diet’, eliminating all or most foods, then testing foods by eating them one-at-a-time. Hundreds of doctors in the US, Britain, Australia and other countries now employ this technique, and the results they describe show an interesting similarity: the sequence of events that occurs when foods are withdrawn from the diet is remarkably consistent, even though the details of the elimination diets vary widely. Some doctors begin with a five-day fast, others with a regime of lamb and pears only, or an artificial ‘elemental diet’, containing free amino acids and the basic nutrients, rather than large molecules such as proteins. Other doctors use a simple ‘low risk’ diet, of between five and 75 foods – the permitted foods are ones that cause reactions relatively rarely, on the basis of past experience.
Whatever the method, the response – if there is one – is surprisingly uniform. Most patients say that they experience withdrawal symptoms in the first four or five days, then a marked return to health. This recovery usually happens six or seven days after the start of the new diet. But in children it happens more rapidly, and in adults with severe symptoms it can take up to 10 days. The consistency of this reaction, and the fact that a variety of symptoms clear simultaneously, has convinced many previously sceptical doctors that there really is such a thing as food intolerance.
The sceptical scientist
Clinical observations of this sort are of interest, but they are not the hard evidence on which medical science is built. In the past seven years, several doctors have carried out controlled trials that attempt a more rigorous analysis of the elimination-diet technique. Gail Darlington, a rheumatologist at Epsom District Hospital, has performed one such trial, in collaboration with John Mansfield. Fifty-three patients with rheumatoid arthritis took part in the trial, half undergoing an elimination diet and the other half (the control group) taking a placebo treatment, an inert compound in capsules. Objective tests of rheumatoid arthritis symptoms showed that the people on the diet improved significantly, much more than those taking the placebo. Three-quarters of the patients who completed the elimination diet felt they had benefited from it, and some showed a dramatic improvement.
In spite of these results, Darlington is in no way a propagandist for the food-intolerance idea: ‘I’m a very routine, orthodox physician and rheumatologist. If I spend the next 10 years of my life helping to prove that the whole thing is a nonsense, or a placebo effect, or a non-specific manipulation of the immune system, I won’t be at all concerned. I simply feel it’s an area that needs to be investigated in just as scientific a way as we look at Drug A versus Drug B. Before 1981, most people in the UK thought that food intolerance was rubbish in a rheumatological context, as indeed I did at that time. But I was impressed by the results I saw in my patients who had gone to other people to have their diets manipulated. After eight years working in this field, I’ve gradually come to believe that it is relevant to some patients. To take one example, I have a patient of 33, who has changed from being a limping acute arthritic, to being a perfectly fit, normal young man – and that is an improvement he has maintained for three-and-a-half years.’
Rheumatologists tend to attribute such results to natural remissions, because rheumatoid arthritis is a disease that comes and goes, and is notoriously susceptible to placebo effect – the enthusiasm of a doctor for a new treatment producing an improvement by psychological means alone. Darlington understands these doubts, but feels they are misplaced: ‘Yes, obviously, it could be purely coincidental, but I do have quite a few patients in this bracket now, and it does seem unlikely that they all just happened to go into natural remission at the moment they began their diet. As for placebo effect, our trial was carefully designed to measure this in the control group. We showed that there was a placebo effect, but that it certainly couldn’t account for all the improvement seen in patients on the diet. What is more, when the control group were later put on elimination diets, they responded just as well as the first group – far better than they had done on the placebo.’
Other trials corroborate Darlington’s results. John Hunter, a gastroenterologist at Addenbrooke’s Hospital in Cambridge, has carried out a controlled trial with Crohn’s disease, a serious bowel disorder in which there is chronic inflammation of the intestine. For this trial, Hunter first put all the patients on an elemental diet or fed them artificially bypassing the digestive tract. Once their symptoms had disappeared, the control group went onto a high-fibre diet, as generally recommended in Crohn’s disease. The others tested individual foods, then avoided those that had made them ill, as in an elimination diet. All those in the control group were ill again within six months, but 70 per cent of the other group remained well. In subsequent trials, with larger groups of patients, Hunter found that 83 per cent responded well to an elimination diet, and only 8 per cent of these relapsed over the next two years.
In similar trials with irritable bowel syndrome – a less severe but very common bowel disease, producing abdominal pain and persistent diarrhoea – the success rate at Addenbrooke’s is 70 per cent. At the conclusion of one such experiment, Hunter retested 11 patients with irritable bowl syndrome by giving them two of their offending foods (those that had produced adverse reactions during the elimination diet). To be valid, such tests must be double-blind: neither the experimenter nor the patient must know the identify of the foods. The design of such a trial poses problems, because the food must somehow avoid, or deceive, the taste buds. Putting the food directly into the stomach via a tube is one solution, although it has practical drawbacks. Using this method, Hunter found that the patients correctly distinguished the offending food from the control (on the basis of which one produced symptoms) in almost 88 per cent of the tests. Another approach is to disguise the taste of the food in a strongly flavoured substrate, lentil puree being the method of choice of Addenbrooke’s. With this technique, the success rate for the tests was 100 per cent, suggesting that absorption through the mouth may contribute to the symptoms.
A third area in which double-blind trials have produced positive results is migraine. Jonathan Brostoff of the Middlesex Hospital and Jean Monro of the Lister Hospital, both in London, have carried out one such trial and found that 70 per cent of their migraine patients responded well to the elimination diet, and reacted consistently to double-blind tests. With children suffering from severe migraine, the response is even better. John Soothill and his colleagues at Great Ormond Street Hospital, London, found that 93 per cent of such children recovered on an elimination diet. In double-blind retesting with one of their incriminated foods, 87.5 per cent of the children reacted to the food but not to the control. An interesting aspect of this trial was that four out of the five researchers began as sceptics. They believed that, if they did observe any effects following dietary manipulation, it would be a placebo response. The results of the double-blind trial completely changed their minds, and they were impressed by the range of other symptoms that cleared up along with the migraine – diarrhoea, hyperactivity, aching limbs and epileptic seizures to name but a few.
The impact of these results on medical opinion has been less than dramatic, mainly because other trials have failed to get the same sort of response. Doctors at Northwick Park Hospital in Middlesex, who carried out an uncontrolled trial of 18 patients suffering from rheumatoid arthritis, found no improvement at all. One reason for this result may be that the diet did not exclude wheat, a very common culprit according to doctors with experience of food intolerance. Potatoes and yeast (in the form of bread) were also part of the diet – again, these foods are said to be frequent offenders. Given the small number of patients involved in the trial, the failure to exclude these foods could easily account for the lack of success.
Another trial produced a relatively poor response to elimination diet in people with irritable bowel syndrome. Half the patients improved on the diet and reacted consistently to food challenges, compared with 70 per cent in Hunter’s trial. But few of these patients responded in the same way when they could not taste the food. Of the 10 patients that did appear to have food intolerance, on the basis of the elimination diet, only three responded correctly to testing under double-blind conditions. David Pearson, a senior lecturer in medicine at Manchester University, carried out this trial, with the help of Stephen Bentley of the University Hospital, and a psychiatrist, Keith Rix.
One of the drawbacks of this trial was that not all the patients embarked on a proper elimination diet: 59 per cent simply cut out ‘all foods considered suspect’, or eliminated foods on a rotation basis, a system that the specialists in this field do not use because they claim it has a low success rate. Michael Radcliffe, a doctor who has 10 years’ experience in the field says: ‘Eliminating foods one at a time isn’t usually very successful. Most patients are sensitive to more than one food – it’s only when all those foods are taken out of the diet at once that you see an improvement.’
Among the foods that Pearson allowed for some of his patients were wheat and oranges, two of the most strongly incriminated foods in other trials. Hunter identified wheat as a cause of irritable bowel syndrome in 60 per cent of his patients, and citrus fruits in 24 per cent, so the lower success rate in this trial is perhaps not surprising. The double-blind retesting of foods by Pearson’s group is also open to criticism because they used a single gelatine capsule, which contains a very small dose of the food: a dozen such capsules give only a tablespoonful. While such a minute dose would produce a response in true food allergy , it does not do so in food intolerance. Not surprisingly perhaps, the three patients in Pearson’s trial who did have reproducible reactions to food in double-blind trials were clearly subjects with classical allergic symptoms, such as asthma, eczema, urticaria or hay-fever. In other words, the Manchester group seem to have designed their trial with IgE-mediated allergy in mind, and so they found only IgE-mediated food allergies.
Misleading trials?
The same group of doctors have carried out another more general trial, involving patients with a variety of symptoms who all believed themselves to be suffering from food intolerance. Of 23 patients, only four reacted to their incriminated foods during a subsequent double-blind trial. As in the irritable bowel syndrome trial, these four showed classical allergic symptoms as well, but again, the double-blind testing relied on a single gelatine capsule.
Rix independently examined these patients for psychiatric disorders, and diagnosed a high level of neurotic depression, other neuroses and personality disorders. He concluded that the patients’ symptoms, such as headaches, bowel disturbances and fatigue, were of psychological origin. Extrapolating from this finding, Pearson believes that ‘a large number of people going to the clinical ecologists and alternative allergists are people with mild psychiatric problems, so it’s not surprising that they can be very easily persuaded that they have food allergy.’ A different view is taken by doctors such as Joseph Miller, a clinical ecologist working in Mobile, Alabama. In his experience: ‘These patients are not basically neurotic, but they are less able to cope with daily problems because their symptoms distract and bewilder them. They shop for relief from physician to physician, their self-esteem diminishes, and their anxieties increase when they are told repeatedly that their symptoms are ‘only due to nerves’. Many become secondarily depressed from the feeling of being hopelessly trapped.’
Naturopaths and holistic nutritional counsellors have rushed in where rheumatologists and gastroenterologists fear to tread. They have brought with them a host of diagnostic techniques that aim to bypass the laborious process of the elimination diet. These include the cytotoxicity test, in which blood cells are mixed with different food extracts: the offending foods are said to cause visible damage to the cells. Trials show the method to be highly inaccurate unless carried out under the most stringent conditions, but it is still on offer as a form of postal diagnosis. Others diagnose food intolerance by holding a tubeful of food extract close to the patient, by dowsing rods, or by swinging a pendulum over a sample of hair – or even over a list of foods. Other fringe practitioners do not attempt individual diagnoses at all, but simply put every patient on the same rigorous diet. If, after several months of near-starvation, patients complain of feeling unwell, the practitioner generally tells them that they are undergoing a ‘healing crisis’ and urges them to persevere.
Many doctors, particularly paediatricians, are now seeing cases of severe malnutrition in patients following strict diets for supposed food intolerance. In a few cases, fringe practitioners have mistaken serious illnesses, such as gall-stones or stomach cancer, for food intolerance. It is cases like these that have appalled doctors such as Pearson, and fuelled their vociferous criticism of the whole field: ‘I have seen patients who are on diets that are incompatible with life. I think that’s a totally disgusting situation.’
While the concern of doctors such as Pearson is understandable, their energetic attempts to discredit the whole idea of food intolerance may, in the end, be helping to create the very situation that they deplore. Most doctors have shunned the idea of food intolerance and derided attempts by open-minded colleagues to investigate it scientifically. In the absence of orthodox treatment, many patients who suspect that food is their problem turn to fringe practitioners, so perpetuating the situation.
Yet medical opinion is now slowly changing. Most conventional allergists concede that foods can cause far more symptoms than was originally thought, and several are using elimination diets to diagnose their own patients. But this change is of little benefit to those who might be sufering from food intolerance – most will never get to see an allergist, because they do not display symptoms such as hay fever.
A few GPs have begun to take the idea of food intolerance seriously. One such doctor is Ronald Williams, a GP working in central London: ‘I have seen this type of treatment completely transform people’s lives. These are often the polysymptomatic patients who’ve tried everything else – everyone’s thrown the book at them. Then you put them on an elimination diet and the effect is absolutely amazing.’ Williams is convinced that this form of treatment is better for the patient. ‘Why use drugs to damp down a reaction such as migraine or rheumatoid arthritis, when you might be able to prevent it, if you find out what’s causing it?’
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Defining allergy – linguistic confusion amid scientific controversy
THE controversy over reactions to food is inextricably caught up in a dispute about terminology, particularly over the meaing of ‘allergy’. For a word that is little more than 80 years old, it has had a chequered career. A Viennese paedia-trician, Baron Clemens von Pirquet, first used it in 1906 to mean ‘altered reactivity’ – any idiosyncratic response to the environment. But in 1925, as knowledge about allergies increased, most of those working in the field decided to limit the definition. Only altered reactions in which the immune system was demonstrably involved would henceforth qualify as allergies. So conditions such as asthma, eczema, hay fever, non-seasonal rhinitis (running nose) and urticaria (nettle-rash) became the only legitimate subjects for study. In these illnesses, now known as ‘classical allergic disorders’, skin-prick tests demonstrate an immunological reaction to the offending substance (the antigen).
By the 1920s, several doctors in the US were already studying ‘delayed’ or ‘masked’ food allergies, and while they protested at this redefinition, they lost out to the newly arisen orthodoxy. Pressure from the medical establishment (and, in some cases, from large food manufacturers who were funding research) forced such unconventional allergists out of the medical mainstream and into private practice, where they continued to use ‘allergy’ according to von Pirquet’s original broad definition. The tradition has continued in the US, and many modern clinical ecologists still use allergy in this way. Other doctors (especially in Britain) prefer the less controversial terms ‘food intolerance’ or ‘food sensitivity’, which make no assumptions about mechanism.
A major advance in classical allergy – and one that helped to widen the rift with the unorthodox food allergists – was the discovery of immunoglobulin E in the 1960s. This type of immunoglobulin, or antibody, is the main villain in the classical allergic conditions. It can bind to the surface of cells known as mast cells, that occur in tissues throughout the body. The immunoglobulin E (IgE) molecules bind to the mast cell, leaving the other end of the molecule (which binds the antigen) free. If the IgE molecules on the surface of a mast cell then become crosslinked, by binding to their antigen, they stimulate the mast cell to release several chemical mediators. These include histamine, serotonin and prostaglandins, and they cause a variety fo reactions, including contraction of smooth muscle, capillary dilation and an increase in the permeability of the blood vessels. It is these mediators that produce the symptoms of allergy: inflammation of the nasal membranes causes hay fever, for example; contraction of smooth muscle in the bronchi (the tubes leading to the lungs) causes an asthma attack. A sudden increase in the permeability of blood vessels causes the massive drop in blood pressure that characterises anaphylactic shock.
The discovery of IgE was a breakthrough for classical allergists. Laboratory tests showed raised levels of total IgE in most atopic patients (those displaying classical allergic symptoms). Where the patient knew what antigen caused their symptoms, a test that could measure IgE for specific antigens, known as RAST (radio-allergosorbent test), usually confirmed that the IgE level to the incriminated antigen was high. In a very short space of time, IgE became the touchstone of respectability for classical allergists. Some even changed the definition of allergy, yet again, to mean reactions involving only IgE.
When immunologists tried RASTs on patients diagnosed as food-allergic, they found a basic division. Those with immediate, violent reactions, even to a very small amount of the offending food, gave a positive RAST for that food, confirming the status of such reactions as classical allergies. Those with delayed or ‘masked’ reactions to foods – the clinical ecologists’ patients – rarely produced positive RAST tests for their culprit foods. More recently, some studies have shown that there may be a small IgE component in food intolerance, probably involving mast cells in the lining of the gut. But IgE is certainly not the major factor in most food intolerance.
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The piglet and the soya bean – a cautionary tale
FOOD intolerance is not unique to humans, or so it would appear from studies by the immunology group of the Department of Veterinary Medicine at the University of Bristol. They have spent several years investigating post-weaning diarrhoea in piglets, a problem in modern intensive pig farming where the farmer takes the piglets from the sow at about three weeks old, to induce the sow to breed again. If left to themselves, piglets continue to suckle for several months, and the researchers wondered whether early weaning might cause diarrhoea by exposing them to new food antigens (usually soya bean protein) before they were ready.
They were able to show that their idea was correct: the problem was that piglets were getting too many novel antigens too soon. Normally there would be a gradual transition to solid food which would allow a piglet’s immune system to learn to tolerate the new foods. The researchers found an immune reaction in the piglets’ intestines, and visible damage to the villi – the projections that increase the absorptive surface of the small intestine. The villi secreted more fluids, lost some of their capacity to absorb substances, and were less efficient at producing enzymes to break down sugars. This in turn led to overgrowth of certain bacteria and further damage.
These discoveries about pigs reveal many interesting parallels with the phenomenon of food sensitivity in humans. Studies of children with sensitivity to cow’s milk show that this problem is far more likely to develop in bottle-fed babies. Early weaning, before the age of about three months, also seems to predispose children to food intolerance and food allergy.
Linda Gamlin is a freelance science writer and the author, with Jonathan Brostoff, of The Complete Guide to Food Allergy and Intolerance (Bloomsbury, Pounds sterling 9.95). Next week, she looks at the physiological mechanisms of food intolerance.
