Randomised, double blind, crossover challenge study of allergenicity of peanut oils in subjects allergic to peanuts

Subject selection

From a group of 215 adult subjects who participated in a questionnaire study of peanut allergy conducted by the University of Southampton,12 69 subjects volunteered to participate in this study. All were skin prick tested with peanut (1:10 wt/vol peanut mix, (Runner, Virginia, Spanish) Miles, Indiana) and with each peanut oil. The result was considered positive if the test elicited a weal equal to or greater than the response to 1% histamine (positive control) in the absence of any reaction to saline (negative control). Subjects who had a negative skin prick test result with peanut were offered an open peanut challenge to prove or disprove peanut allergy.13 Subjects who had positive skin prick results with peanut undertook the oil challenges on the same day in a clinical investigation unit equipped for resuscitation.14

Historical reactions and reactions observed during the challenges were defined as mild, moderate, or severe. Mild reactions were pruritus, rhinoconjunctivitis, local urticaria, swollen lips swelling, and erythema. Moderate reactions were facial swelling and pharyngolaryngeal oedema. Reactions that were characterised by dyspnoea, wheeze, cyanosis, or hypotension were considered severe.

All subjects gave personal and informed written consent. This study was approved by the local hospital ethics subcommittee.

Double blind challenge protocol

The oils (crude or refined) were tested in random order determined by a member of staff not involved in the evaluation of the subjects. Forty subjects (63%) received the refined oil first. Each oil was administered in increasing doses of 1, 5, and 10 ml disguised with 0.1% peppermint oil or 1% cocoa malt flavouring. Six subjects were offered the oil with bread and one with soya milk. The remaining subjects were given the oil mixed with rice pudding. An interval of 10 to 15 minutes between the doses was allowed for observation of the onset of any symptoms. If a reaction occurred to the first oil at least an hour was allowed to elapse before the second oil was administered.

Peanut challenge

Protein comprises 24.3% of the average weight of a peanut kernel.15 We found that 100 peanut kernels (roasted and salted, KP Foods, Leicester, bought in the hospital newsagent's shop) weighed 66.35 g. The average protein content of one peanut kernel was therefore 0.6635 gx24.3%=161 mg; 32 peanuts contain 5.16 g of protein.

If the subject reacted to neither oil up to the maximum dose of 10 ml (total dose 16 ml of each oil) a controlled open challenge with peanuts was undertaken. The peanut challenge was performed with increasing doses starting with peanut rubbed on the lip (labial challenge). The dose was increased in steps until a reaction was observed or until the subject had eaten up to an arbitrary total of 32 peanuts without reaction. Subjects were observed for one hour after the completion of the challenge or until one hour after any symptoms had subsided.

Skin prick tests

Seven subjects (10%) had negative results on skin prick tests with peanut, of whom six also had negative responses to challenge with peanuts. The remaining subject developed symptoms four days after exposure to peanuts and was therefore considered unsuitable for this study (table 1). The 62 remaining subjects (90%) underwent oil challenges.

Challenges

Oil challenges–No subject reacted to refined peanut oil. Six subjects (10%) reacted to crude oil (table 2).

Peanut challenge–Fifty eight peanut challenges were undertaken by subjects who had positive results on skin prick testing with peanut. Four subjects who reacted positively to skin prick testing with peanut did not have peanut challenges because they reacted to challenge with crude oil. Two subjects who had positive results on skin prick testing with peanut had negative results on peanut challenges. Both ate a cumulative dose of 32 peanuts without any reaction (table 1). Fifty six patients with positive results on peanut skin prick test had positive results on challenges to peanut. If we included the four subjects who reacted to crude oil but were not challenged with peanut a positive response to peanut was seen in 60 of 62 subjects positive for skin prick tests (96%) (table 3 and table 4). Twenty nine (48%) had reacted to peanut in the preceding year; only six (10%) had avoided peanuts successfully for more than five years.1 Table 5) summarises other atopic disorders reported by the subjects with proved peanut allergy.

Importance of study's findings

Peanut allergy is the commonest cause of fatal and near fatal allergic reactions to foods in the United States.3 It is being recognised increasingly in the United Kingdom12 16 and may affect as many as 1-2% of 4 year old children.17 The increasing incidence probably reflects increasing consumption of peanuts in a wide range of food products. Heightened public awareness has driven increased medical involvement in the care of affected people who previously have had little access to scientific and medical information. Affected people have rarely had adequate provision and training in the use of rescue treatments such as adrenaline inhalers and injections.

In addition to reporting that they felt ill equipped to treat reactions to peanut themselves, many allergic people have commented that they have greater fear of exposure to the more widespread peanut oil than to peanut itself. Peanut oil is often implicated by those allergic to peanut as a cause of an allergic reaction, particularly in restaurant meals. The absence of antigenic protein in refined peanut oil5 6 and its presence in such oil after cooking peanuts in the oil6 suggest that oils may become adulterated with allergenic peanut proteins rather than being intrinsically allergenic themselves.

We believe our results confirm that refined peanut oil is safe for most people who are allergic to peanuts. This finding supports those of previous small studies1 9 and provides statistically sound data on which to base more confident recommendations to patients, regulatory authorities, and the food and catering industries.

Reactions to crude peanut oil

Six subjects (10%) reacted to crude peanut oil. All these patients had had moderate or severe reactions previously, but only one suffered a comparable reaction to the crude oil. Four of these six had subjective reactions to the crude oil–there were no visible or measurable signs of reaction. These reactions may have been psychologically mediated and the real rate of measurable reaction to crude oil may be 3.3% (2/60) rather than 10% (6/60) of those with peanut allergy. The double blind nature of the challenge minimises the role of psychological reactions, and we have therefore considered the subjective, mild reactions to be real.

The low rate of reaction to crude peanut oil and the generally mild nature of the observed reactions to crude oil provide reassurance to sufferers that the reactions to crude oil are generally considerably less severe than reactions to peanut itself, even in those who normally have severe reactions. This may be a dose effect. Sufferers must continue to avoid the so called “gourmet oils” that are deliberately blended with crude peanut oil to give them a characteristic peanut flavour. Different crude peanut oils may contain different concentrations of peanut protein,5 so the relative risk of other crude oils may differ from that of the oil we tested in this study.

Peanut challenges

There was a striking disparity between the severity of previous reactions and reactions observed during supervised peanut challenge. This is probably due to a combination of two factors. Firstly, the subjects were evaluated when they were otherwise well and were being supervised in a calm, clinical setting with all appropriate precautions taken. Clearly, anxiety that is generated by reactions away from medical help may exacerbate reactions. Also, the controlled dose of peanut that elicited reactions in the challenges was probably much lower than the dose to which subjects are exposed in meals and prepared foods that caused reactions in the community.

Use of refined peanut oil

Our results do not suggest that it is completely safe for all people with peanut allergy to eat in restaurants where refined oils are used. Such oils may come into contact with peanuts and thereby become contaminated.6 This risk, of course, applies to any oil used in cooking,2 not just to peanut oil. To minimise the risk to people allergic to peanuts and other foods, it is vital to increase awareness of food allergy among catering and restaurant staff. They must be aware of the risk to people with life threatening reactions to foods of reuse of oils, especially after cooking foods that are known to be allergenic, such as peanuts, tree nuts, fish,2 and shellfish.

Labelling

Discontinuation of the use of the term groundnut and clear labelling distinctions between refined and crude oils would simplify many of these issues. Such steps are now justified as a consequence of this study. Refined peanut oil does not seem to pose a risk to most people with peanut allergy.