ARCHIVED - Garlic and Onions: Insufficient Evidence to Include on the List of Priority Food Allergens in Canada: A Systematic Review [Health Canada, 2009?]

Executive Summary:

Health Canada scientists have conducted a systematic literature review of the available information on the allergenicity of garlic and onions in order to determine whether there is sufficient scientific evidence to justify including garlic and/or onion on the list of defined priority food allergens in Canada. Information that was considered relevant to the evaluation was assessed using Canadian criteria established to amend the list of priority allergenic foods in Canada.

A total of 36 publications from the scientific literature were considered relevant to the assessment of garlic and/or onion as food allergens. However, the assessment of the current database does not provide sufficient evidence to fulfill the Canadian criteria for addition of a new food to the list of priority allergens. Although there is scientific evidence that suggests that some individuals experience severe reactions to the consumption of garlic and/or onion, the prevalence of food allergies to garlic and/or onion in children and adults remains unknown and there are insufficient clinical data to establish a credible cause-effect relationship for the oral allergenicity of garlic and/or onion. Furthermore, based on information within the current database, the potential for severe allergic reactions as a result of hidden sources of garlic and/or onion in pre-packaged foods is considered minimal.

Therefore, at this time, it is recommended that garlic and onions not be included on the Canadian list of priority food allergens and that the proposed amendments to the Food and Drug Regulations (1220 - Enhanced labelling for Food Allergen and Gluten Sources and Added Sulphites) would not be applicable to the use of garlic and/or onion in foodstuff.

Issue:

On July 26, 2008, Health Canada published its proposed amendments to the Food and Drug Regulations (1220 - Enhanced Labelling for Food Allergens and Gluten Sources and Added Sulphites) in Canada Gazette, Part I (CGI). Just over 140 comments were received from the general public, patient groups, health professionals, a consumer organization, and governmental agencies during the public consultation regarding the proposed amendments.

Of the responses, 10% requested that garlic and/or onion be added to the list of priority allergens in the regulatory amendments based on observations or personal experiences of adverse reactions associated with the consumption of garlic and/or onion.

In response to the feedback received during the public consultation, Health Canada initiated a systematic review of the available literature in order to determine the scientific validity of the inclusion of garlic and/or onion on the list of priority food allergens in Canada. Foods that are listed in the definition of a "food allergen" as proposed in the amendments to the Food and Drug Regulations would require that the source of the food allergen be declared on the label of pre-packaged food products.

Objective:

In order to determine the scientific validity of including garlic and/or onion on the Canadian list of food allergens, the information obtained from a systematic review of available literature regarding the potential allergenicity of garlic and/or onion must fulfill the Canadian criteria for amending the list of priority allergenic foods.

Methods:

Methods for the management and evaluation of available scientific information have been previously outlined in order to ensure a consistent and transparent approach for the assessment of the potential allergenicity of a food or food ingredient. The Canadian Criteria For The Establishment of New Priority Food Allergens

Systematic Data Collection

An electronic database search of publications in English, French or Spanish was conducted utilizing the following databases: Ovid Medline (R) In-Process & Other Non-Indexed Citations and Ovid Medline (R) 1950 to Present; Ovid Medline (R) In-Process & Other Non-Indexed Citations, November 18, 2008; Ovid Embase, 1980 to 2008 Week 45; FSTA Direct, last updated 10 Nov 2008. Details of the search terms used are provided in Appendix 1.

Organization and Tabulation of Data

Studies fulfilling the selection criteria (see methods) were reviewed and assessed based on the strength of evidence. Publications which could not be categorized by these criteria were referenced in the results under the heading (A) Characterization of Garlic and Onion. Evidence from publications that fulfilled the strength-of-evidence parameters were tabulated under the following categories:

(B) Clinical Studies (Table 1) - evidence from quasi-experimental studies

(C) Other Relevant Studies (Table 2) - evidence from non-experimental descriptive studies (comparative/correlation)

(D) Case reports (Table 3) - evidence from non-experimental descriptive studies

Results:

A total of 411 publications were identified through the database search using the terms denoted in Appendix 1. However, based on the inclusion and exclusion criteria, only 65 publications were selected and considered relevant to the objectives of this review. Of these 65 publications, 20 were grouped by the strength-of-evidence to support regulatory recommendations in Tables 1 to 3. The remaining 45 publications were not included in the risk analysis; however, 16 publications that provided information with regard to the characterization of garlic and onion were considered relevant to the evaluation. A total of 36 publications from the scientific literature were considered relevant to the assessment of garlic and/or onion as food allergens.

A. Characterization of Garlic and Onion

Garlic and onion are herbaceous perennial flowering plants belonging to the family Alliaceae (formerly classified under the lily family (Liliaceae)). Within the Alliaceae family the genus Allium includes vegetables with bulbs or corms (Fay and Chase, 1996). A bulb is an underground bud with thick, fleshy scales and a corm is a short, solid, vertical underground stem with papery thin leaves (McGovern and LaWarre, 2001). Garlic (Allium sativum L.), onions (Allium cepa), shallots (Allium oschaninii), leeks (Allium porrum) and chives (Allium schoenoprasum) are classified under this genus (Fay and Chase, 1996).

Both garlic and onions have been used as food or medicine for thousands of years (Zohary and Hopf, 2000). They are rich in volatile sulphur-containing compounds that are responsible for their pungent flavour and odour as well as for many of their health-promoting effects. Due to the pungent flavour of these vegetables they are typically used as a seasoning or condiment in food preparations. In addition to the use of fresh garlic and onion in cooking, many commercial preparations are available for both garlic and onion, including but not limited to: pickled, dehydrated, powdered, oil or oil macerates.

Garlic is one of the most investigated medicinal plants. During 1960 to 2007, more than three thousand research papers were published on the chemistry and biological effects of garlic and garlic preparations. These studies mainly focus on the cardiovascular, anti-microbial and anti-cancer effects of garlic (Signh and Signh, 2008). Similar health claims have been made for onions; however, there is less detailed biochemical information available in the literature.

The amount of chemical constituents in garlic varies substantially based on where and how it is grown, as well as how the end product is prepared and stored (Morbidoni et al., 2001). Intact garlic cloves contain only a few active compounds, the main chemical constituent being the amino acid alliin, an alkyl derivative of cysteine alkyl sulphoxide. The content of alliin may vary from 0.2 to 2% fresh weight of garlic. Crushing, chewing or cutting (or exposing dehydrated, pulverized garlic to water) of garlic cloves release the enzyme allinase that rapidly lyses the cytosolic cysteine sulphoxide to form sulphenic acid which immediately condenses to form diallylthiosulfinate (allicin). The formation of allicin occurs within 0.2 to 0.5 minutes at room temperature. Allicin represents 70-80% of the total thiosulphinates and is the least stable of the thiosulphinates formed. The thiosulphinates released from crushed garlic are reactive molecules and undergo a number of transformations, depending on the temperature, pH and solvent conditions. The principal transformation products after incubation of thiosulphinates in water are diallyl trisulphide, diallyl disulphide and allyl methyl trisulphide (Singh and Singh, 2008).

Similar to garlic, the enzyme allinase is released when the cells in onion are broken through crushing, chewing or cutting. The enzyme rapidly breaks down amino acid sulphoxides and generates sulphenic acids and subsequently allicin. As described for garlic, allicin can generate numerous transformation products depending on the environmental conditions to which it is exposed and the unstable sulphenic acids can further spontaneously rearrange into a volatile gas called syn-propanethial-S-oxide, which is an eye irritant (Thomas, 1999).

The majority of available research has focused on characterizing the irritant and contact sensitization properties rather than the systemic allergenicity of garlic and onion. Low molecular weight proteins which are usually responsible for allergic contact dermatitis reactions have been detected in garlic extracts via patch tests and dermal sensitization experiments in guinea-pigs and identified as: diallyl disulphide, allylpropyl disulfide and allicin (Bleumink et al., 1972; Papageorgiou et al., 1983). However, an irritant type of reaction could not be excluded for allicin in these studies. Eliciting agents of systemic allergic reactions are typically proteins of a higher molecular weight (Bleumink et al., 1972). Most known food allergens have a molecular weight between 10 kDa and 70 kDa (Taylor and Lehrer, 1996).

Immunoblotting analyses conducted with serum from individuals in case reports have identified IgE-binding proteinic bands with molecular masses of approximately 12 kDa and 40-50 kDa in both garlic and onion. Using the serum of a woman who experienced exercise-induced anaphylaxis (EIA) after the consumption of young unripe garlic, a 12 kDa band was identified on an IgE immunoblot for extracts of young garlic, garlic, onion, leek, hazelnut and mugwort pollen (Perez-Pimiento et al., 1999). Enrique et al., (2007) also reported a single 12 kDa band using onion extract and the serum of a woman who developed urticaria after consuming raw onion. Asero et al., (1998) found bands with molecular masses of 10, 20 and 40 kDa using garlic extract and the serum of a woman who had urticaria after the ingestion and contact with raw and cooked garlic and also reported that the serum of a man who experienced urticaria/angioedema after consuming raw onion had IgE reactivity to 15 kDa and 43 kDa bands in an onion extract (Asero et al., 2001). Further characterization of these proteins has not been described in the literature (Borrelli et al., 2007; McGovern and LaWarre, 2001).

In contrast, Kao et al., (2004) studied the antigenicity, allergenicity and IgE-binding cross-reactivity of a 56 kDa protein purified from the sera of 15 subjects with reported garlic allergies. The isolated protein was identified as alliin lyase. Skin tests confirmed that alliin layse elicited IgE-mediated hypersensitive responses in subjects with garlic allergies. IgE cross-reactivity and IgE-inhibition analyses demonstrated that garlic alliin lyase showed high cross-reactivity with alliin lyase from other Allium species such as, leek, shallot and onion. Furthermore, carbohydrate epitopes were found to contribute to the binding of IgG and IgE to alliin lyase (Kao et al., 2004). The analysis of the homology between the alliin lyase of garlic and onion by Nock and Mazelis (1989) indicated that the enzymes have very little homology in structure; similar sized subunits and the carbohydrate moieties are quite different in each case. These results may explain why reports of cross-reactivity among different Alliaceae vegetables vary greatly within the literature. It is also suggested in the literature that the varying reports of cross-reactivity may be due to the level of cross-reactivity varying among individuals (Sanchez-Hernandez et al., 2000; Pries et al., 2002). However, the effect of the carbohydrate moieties in garlic and onion on allergenicity and cross-reactivity requires further investigation because carbohydrate epitopes can bind human IgE from allergic subjects and have a role in cross-reactivity between allergens from unrelated sources (Hiemori et al., 2000; Iacouacci et al., 2001).

None of the studies that identified IgE reactive proteins in garlic and/or onion conducted enzymatic or heat stability tests on the proteins. However, available evidence from case studies indicates that the allergenic proteins are susceptible to digestive enzymes and heat. Two subjects who had positive skin prick test (SPT) and serum IgE results for onion did not experience allergic reactions after consuming onion powder (Valdivieso et al., 1994) and several cases reported a history of allergic reactions after consuming raw garlic and onion but a tolerance to cooked garlic and onion.

B. Clinical Studies (Table 1)

Pivotal clinical studies that include evidence from meta-analysis of randomized controlled trials, individual randomized controlled trials or non-randomized controlled trials were not available for the allergenicity assessment of either garlic or onion. However, 6 studies were identified in the literature that were conducted using an open allergenicity assessment that included garlic (2 studies), onion (1 study) or both garlic and onion (3 studies) as part of the foodstuffs tested. These assessments utilized labial (LFC) or oral food challenges (OFC) and/or a combination of skin prick test (SPT), RadioAllergoSorbent Test (RAST) and determinations of serum immunoglobulin E (IgE) specific to garlic and/or onion, in order to verify an allergic response and quantify the prevalence of reactions to certain foodstuff. These studies are tabulated in Table 1.

Rance and Datau (1997) examined over 25 food allergens among 142 children with a history of food allergies. Subjects submitted to LFC for various foodstuffs and when the results of the LFC were negative, SBPCFC were conducted. One subject (1%) had a positive LFC response to garlic. Egg (75%), peanut (60%) and mustard (16%) were the most common food allergens in this study. In 2002 Rance and Dutau also reported a garlic allergy prevalence of 1% among 163 children previously identified as having bronchial asthma by pulmonary function (Rance and Dutau, 2002).

Valdivieso et al., (1994) performed SPT for onion allergies among 106 subjects randomly selected from an allergy clinic. Of the 106 subjects, 8 (8%) had positive SPT results for onion and 4 of those 8 subjects experienced clinical symptoms such as, rhinoconjuctivitis, dyspnea, eczema and bronchial asthma. These 4 subjects participated in bronchial, nasal and/or oral provocation tests. All subjects showed positive reactions to heated and non-heated onion extracts. Two subjects experienced intense rhinoconjuctivitis and 1 subject had chest tightness and wheezing and dyspnea after exposure to the smell of onions. Only 2 subjects participated in the double-blind oral provocation with 2 g of onion powder, however, neither experienced allergic responses. In the author's opinion these results suggest that onion is a respiratory allergen.

An open study examining the frequency of reported food-induced symptoms, food allergy or food intolerance in 169 subjects mono-sensitized to grass pollen, reported that the number of subjects with food intolerances were higher than that of subjects with food allergies (Boccafogli et al., 1994). A positive food allergy was defined by evidence of IgE sensitization to food and the demonstration of oral allergy syndrome, gastrointestinal symptoms and urticaria-angioedema within two hours of the ingestion of small quantities of food. Out of the 169 subjects, 19 (11%) were considered to have food allergies and 46 (27%) were considered to have food intolerances. Positive serum specific IgE results for garlic and onion were reported in 58% (7/12) and 33% (3/9) of subjects tested, respectively. Oral challenge confirmed that 1 subject had a garlic allergy and 1 subject had an onion allergy (1/169; 0.6%). A garlic-intolerance was exhibited in 6 subjects (4%) and an onion-intolerance in 4 subjects (2%). Subjects who were challenged with garlic and/or onion mainly experienced urticaria and gastrointestinal symptoms. No respiratory symptoms were observed among the subjects (Boccafogli et al., 1994). These reactions are considered mild to moderate in severity (Brown, 2004).

A retrospective study was conducted using 26 food allergens and 14 subjects who had a history of food-dependent-exercise-induced-anaphylaxis (EIA) (Romano et al., 1995 & 1998). Of the 14 subjects, 10 (71%) were positive for onion and 9 (64%) for garlic via SPT and/or RAST IgE. One subject participated in a food-exercise challenge after consuming garlic. However, no reaction was observed. Onion was not tested in a food-exercise challenge. Authors noted the clinical history data for the subjects was not as helpful in the interpretation of positive SPT/RAST results for garlic, onion, parsley and basil because subjects generally did not recall if these ingredients were part of the meal that caused EIA.

Asero et al., (2007) conducted an open allergy study assessing vegetables including garlic and onion in order to identify which vegetables are safe for consumption by individuals with a lipid transfer protein (LTP) allergy. LTP is the main food-related allergen identified in Southern Europe (Enrique et al., 2007). Forty-nine subjects were selected who were monosensitized to LTP and control groups of subjects sensitized to pollen (24 subjects), profilin (18 subjects) and LTP and pollen (16 subjects) were also selected. A history of reactions after consuming garlic or onion was reported in 0 and 2 subjects, respectively. The positive SPT results for garlic and onion were not statistically significant between the monosensitized LTP subjects and the controls. Out of 36 LTP subjects, 22% (8/36) and 31% (4/13) of controls had a positive SPT to garlic and 39% (16/41) LTP subjects and 43% (6/14) of controls had a positive SPT to onion. The specificity of the SPT was considered poor by the authors who report that many subjects showed positive SPT results to foods that they reported eating without any problems, including garlic and onions.

C. Other Relevant Studies (Table 2)

Three non-experimental, descriptive studies were identified in the literature search as being relevant to the assessment of the allergenicity of onion (1 study) and both garlic and onion (2 studies). These studies are tabulated in Table 2.

Avila-Castanon et al., (2002) conducted a retrospective analysis of 1419 subjects with food allergies in order to determine the frequency of hypersensitivity to specific foods. Positive SPT results for onion occurred among 4% (56 subjects) of the study group. Garlic was not tested in this study.

A retrospective analysis conducted by Andre et al. (1994) examined which foods were most frequently associated with an anaphylactic reaction over a 9-year period in France. Neither garlic nor onions were among the 19 foods most frequently associated with anaphylactic reactions in 580 subjects. The authors noted an increasing trend in the frequency of sensitization to garlic and onions over time; however, increased consumption and more attentive clinical examinations were credited for this evolution.

Moneret-Vautrin et al., (2002) conducted a retrospective analysis of a food allergy database which contained the SPT results of 589 subjects and 4 case reports which were relevant to garlic or onion. The SPT results showed positive responses for garlic in 20 (10 adult & 10 children) (8%) subjects out of 265 tests and 7 (5 adult & 2 children) (3%) subjects out of 263 tests for onion. The case reports involved 3 garlic and 1 onion allergy. The garlic cases were challenged either by a double or single blind, placebo controlled food challenge or a LFC. All 3 garlic cases were positive. In one case, after the ingestion of 1000 mg of garlic, urticaria was observed. This reaction is considered to be mild in severity (Brown, 2004). In another case the ingestion of 500 mg of garlic lead to laryngeal pruritus, rhinorrhea and coughing. This reaction was considered moderate in severity (Brown, 2004). The last case reported positive LFC results but no further information was provided. The case of the onion allergy was not challenged because the subject had a history of systemic mastocytosis and anaphylaxis after the consumption of celery, carrot, hazelnut and onion.

D. Case reports (Table 3)

A total of 12 case reports of allergic responses to garlic (6 cases), onions (5 cases) or both garlic and onion (1 case) were identified in the literature. These case reports are tabulated chronologically by publication date in Table 3 and provide descriptions of the severity of reactions to garlic or onion as well as identifying the sources of garlic or onion exposure.

For most cases, the information provided was limited as only 3 of the case reports included oral challenges and only one reported the eliciting dose. However, the case reports provided valuable information regarding the severity of reactions and conditions under which the reaction was elicited. Reactions ranged from acute anaphylaxis to generalized skin manifestation. Of the 12 case reports, 7 (3 garlic, 3 onion, 1 both) individuals reported anaphylactic-type reactions and 4 (1 garlic, 2 onion, 1 both) required emergency medical interventions. The case reports provided evidence that the allergenic proteins in garlic and onions are susceptible to enzymatic digestion and/or heat. Several cases reported a history of allergic reactions after consuming raw garlic and onion but a tolerance to cooked garlic and onion. An oral challenge with cooked garlic provided negative results (Pries et al., 2002). Four of the 5 cases reported allergies to raw onion; however, an EIA food challenge had positive results after consuming cooked onion and exercising but negative results without exercise. This reaction to cooked onion was elicited after the consumption of 30 g of onion and running for 10 minutes (Perez-Calderon et al., 2002).

Discussion:

An overall assessment of the available literature suggests that a limited scientifically based database exists to assess the potential food allergenicity of garlic and/or onion. The following limitations of the systematic literature review were taken into consideration when determining the scientific validity of including garlic and/or onion on the Canadian list of priority food allergens.

A large number of publications identified in the initial database search were screened out of our assessment because the studies were only relevant to either skin, respiratory and/or occupational exposures. These data were not considered to be pertinent to the issue of food allergenicity; however, it is recognised that this information is important for those in the clinical field in assessing the possibility of occupational or environmental disorders, particularly in areas where garlic and/or onion is processed.

Data relevant to the assessment of the allergenicity of garlic or onion were often contained within publications in which the main objective of the study did not include reporting specifically on the allergenicity of garlic and/or onion. This fact made the identification of relevant information more challenging and may have led to the exclusion of available information on garlic and/or onion.

There were no DBPCFC studies designed specifically to assess the allergenicity of garlic and/or onion identified in the literature. The studies available were not designed specifically to assess the allergenicity of garlic and/or onion and consequently qualitative and quantitative details about the garlic or onion preparations were not provided. Furthermore, study designs assessing numerous foodstuffs did not report whether appropriate controls were employed in order to differentiate between allergic responses and the irritant effects associated with the sulphur-containing compounds within garlic and onions.

Based on the identified limitations of the systematic literature review, the strength-of-evidence is considered insufficient to fulfill the Canadian criteria for the introduction of food to the priority list of food allergens.

The first criterion of the Canadian adopted Joint Expert Committee on Food Additives (JECFA) recommendations stipulates the existence of a credible cause-effect relationship, based upon positive DBPCFC studies or unequivocal reports of reactions with typical features of severe allergenic or intolerance reactions. In the absence of DBPCFC studies, supporting studies were evaluated as per the strength of evidence provided by the study designs (ACAAI, 2006) (Tables 1-3).

The available evidence is not sufficient to support the determination of a credible cause-effect relationship for the allergenicity of garlic and/or onion. The positive results obtained from diagnostic tests (SPT/IgE), which were utilized in the majority of the supportive studies, were not considered sufficient to substantiate a cause-effect relationship because evidence within the database suggests that SPT and IgE diagnostic tests may not provide an accurate reflection of the potential for allergic reactions after the consumption of garlic and/or onion.

Valdivieso et al., (1994) reported a prevalence (8%) of onion allergies among 106 adults randomly selected for SPTs from a food allergy clinic. However, only 4 of these 8 subjects experienced clinical symptoms associated with onion exposure and only 3 of these 8 subjects had positive onion-specific IgE results. Furthermore, an oral provocation with onion was conducted with 2 of these subjects and both had negative results (Valdivieso et al., 1994). The standard diagnostic tests utilized in this study (SPT & IgE) did not provide an accurate indication of allergic reactions to the consumption of onion. The Broccafogli et al., (1994) study further showed inconsistent results between positive IgE and oral challenge results. In this study, 58% (7/12 cases) and 33% (3/9 cases) had positive serum specific IgE for garlic and onion, respectively, but only 1 case in each of the groups had a confirmed allergy after an oral challenge. Asero et al., (2007) also reported that the results of SPT were not reliable for garlic and onion as many of the positive SPT subjects in their study consumed garlic and onion without experiencing any symptoms. Furthermore, studies that only reported the prevalence of positive SPT responses to garlic and/or onion among study populations did not consider the irritant properties of the sulphur-containing compounds within garlic and onions. Without further confirmation of a food allergy these irritant effects cannot be discounted when interpreting the results. Without evidence from a DBPCFC study, the small number of positive oral challenges reported in the supportive studies and the uncertainty in the results due to the inconsistencies observed between the reported positive diagnostic results and the few reports of allergenic or intolerance reactions after oral challenges, the strength-of-evidence in the current database is not considered sufficient to establish a credible cause-effect relationship for the oral allergenicity of garlic and/or onion.

The second criterion of the Canadian adopted JECFA recommendations calls for reports of severe systemic reactions following the exposure to foodstuff. Anaphylactic reactions associated with the consumption of garlic and/or onions have been reported in specific cases, although the prevalence of severe anaphylaxis-type reactions reported to be associated with the ingestion of garlic and/or onion is considered low. A retrospective analysis reported the incidence frequency of the top 19 foodstuffs involved in anaphylactic reactions over a 9-year period in France (1984-1992) (Andre et al., 1994). Garlic and/or onion were not among the top 19 foods associated with anaphylaxis. The foods associated with anaphylactic reactions ranged from 1 to 18% incidence frequency in sensitive individuals. Of the 12 specific cases reported, 7 (3 garlic, 3 onion, 1 both) individuals reported anaphylactic-type reactions and 4 (1 garlic, 2 onion, 1 both) required emergency medical interventions. In some cases, subjects who experienced anaphylactic reactions to a particular form of garlic and/or onion on the other hand exhibited tolerance to garlic and/or onion in a different form. The case that reported an anaphylactic reaction after the consumption of young unripe garlic also reported that the subject had a tolerance to the consumption of garlic cloves and onion (Perez-Pimiento et al., 1999). Two cases that reported EIA associated with the consumption of onion reported that no allergic reaction was observed after consuming onion and refraining from exercise (Hicks and Tanner, 1998; Perez-Calderon et al., 2002) and the other case reported reactions only associated with consumption of raw onion and a tolerance for cooked onion (Arena et al., 2000). The tolerance for cooked garlic and/or onion was also reported in several other cases that exhibited less severe reactions to raw preparations of these vegetables. It is suggested that the lability of the antigens in garlic and onions to heat and digestive enzymes are the reasons for these observed tolerances and may explain the previously noted low prevalence of anaphylactic reactions associated with the ingestion of garlic and/or onion. In an open study examining the frequency of food-induced symptoms among 169 subjects mono-sensitized to grass pollen, the consumption of garlic or onion was mainly associated with urticaria and gastrointestinal symptoms (Boccafogli et al., 1994). These symptoms are considered mild to moderate reactions (Brown, 2004).

The third, and last, criterion of the Canadian adopted JECFA recommendations requires the assessment of all available Canadian prevalence data in children and adults, supported by appropriate clinical studies or alternatively available data from other countries supported as per the first criterion. Currently, prevalence data are not available for Canada or other regions of the world.

Although some scientific evidence indicates that some individuals experience a severe reaction to the consumption of garlic and/or onion, the prevalence of food allergies to garlic and/or onion in children and adults remain unknown and there is insufficient clinical data to establish a credible cause-effect relationship for the oral allergenicity of garlic and/or onion. Therefore, the overall strength-of-evidence to fulfill the Canadian criteria required to add new allergens to the list of priority allergens is considered inadequate at this time.

Despite the limitations of the current database, in accordance with the proposed amendments to the Food and Drug Regulations (1220 - Enhanced labelling for Food Allergen and Gluten Sources and Added Sulphite), this review gave consideration to the likelihood of allergic reactions occurring as a result of non-declared sources of garlic and/or onion in pre-packaged foods. Based on available evidence, the potential for severe allergic reactions after the consumption of hidden sources of garlic and/or onion within pre-packaged products is considered unlikely. The prevalence of severe allergic reactions after the ingestion of garlic and/or onion are considered low compared to other food allergens based on the results of a retrospective study conducted over a 9 year period. Furthermore, the majority of reported allergic reactions occur after the consumption of raw garlic and/or onion. Although the allergenic proteins in garlic and onion that elicit systemic allergic reactions have yet to be fully identified and characterized, reports of tolerances to cooked garlic and/or onion indicate that the antigens are labile to heat and/or digestive processes. Based on this evidence, the likelihood of consuming raw garlic and/or onion present in pre-packaged foods is considered minimal, as it can reasonably be assumed that the vast majority of pre-packaged foods undergo heating either as part of the manufacturing process or during the preparation of the foodstuff for consumption. Also of note, there were no reports of exposure to garlic and/or onion through hidden sources or cross-contamination of foodstuff. There is insufficient information in the database to estimate a dose-threshold for garlic or onion, as only 3 case reports provided the eliciting amount garlic or onion ingested before an allergic reaction was observed. However, the lowest eliciting dose in the database was reported in a case who experienced laryngeal pruritus, rhinorrhea and coughing after ingesting 0.5g of garlic (30 mg protein 1) (Moneret-Vautrin et al., 2002). The current limited data indicates that moderate amounts 2 of garlic and/or onion may be required to elicit allergic reactions in sensitized individuals; therefore, the potential risk of allergic reactions being elicited after the consumption of garlic and/or onion used as an undeclared spice or seasoning is considered minimal.

Conclusions:

An assessment of the current allergenicity database for garlic and/or onion does not provide sufficient evidence to fulfill the Canadian criteria required to add new allergens to the list of priority allergens. Although there is scientific evidence that suggests that some individuals experience severe reactions to the consumption of garlic and/or onion, the prevalence of food allergies to garlic and/or onion in children and adults remain unknown and there is insufficient clinical data to establish a credible cause-effect relationship for the oral allergenicity of garlic and/or onion. Furthermore, based on information within the current database, the potential for severe allergic reactions as a result of hidden sources of garlic and/or onion in pre-packaged foods is considered minimal.

In conclusion, at this time the overall strength-of-evidence is considered inadequate to support the declaration of garlic and/or onion as priority food allergens, and therefore the Food and Drug Regulations (1220 - Enhanced labelling for Food Allergen and Gluten Sources and Added Sulphite) is not applicable to the use of garlic and/or onion in foodstuff.

Recommendations:

Based on the conclusions of this report, it is recommended at this time that garlic and/or onions not be included on the Canadian list of priority food allergens.

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1 Assuming the case consumed raw garlic, nutrition data indicates that 136 g of raw garlic contains 9 g protein ( Nutrition Data http://www.nutritiondata.com)

2 Published LOAELs for Food Allergens: egg (0.13 to 1.0 mg protein (P)), peanut (0.25 to 10 mg P), milk (0.36 to 3.6 mg P), tree nuts (0.02 to 7.5 mg P), soy (88 to 522 mg P) and fish (1 to 100 mg P)

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