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Garlic & Onions: Insufficient Evidence to Include on the List of Priority Food Allergens in Canada - A Systematic Review

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Table 1: Clinical Studies (Grouped by relevance to garlic, onion and both garlic
and onion & organized chronologically by publication date within groups)
Author, Year, Country	Study Design Details	Subjects	Clinical History	Symptoms & Signs ^{Footnote 1} (before challenge)	Symptoms & Signs ^{Footnote 1} Severity of Rxn ^{Footnote 2} after Challenge	Diagnostic Tests ^{Footnote 3}	Eliciting Dose	Eliciting Allergen	Prevalence	Comments
Garlic
Rancé and Dutau, 1997 France	Open study assessing over 25 allergens including garlic using SPT, prick + prick test IgE LFC and SBPCFC (when LFC negative)	142 SUB (Ch) Age: 7m - 15y Ave - 4.6 y Sex: 95M: 47F	Hx of food allergy	Multiple presenting symptoms in 66% Ch AD 61% Rash 32% AE 25% BA 24% A 4%	Positive Rxn to garlic 1/142 in LFC	SPT, prick + prick test, IgE	1 mg to 5 g for all allergens tested Further details were not provided	Commercial extract and extract from fresh foods	1/142 (1%) positive for garlic allergy LFC	No comments relevant to garlic
Rancé and Dutau, 2002 France	Open allergy study assessing foodstuff including garlic documented by DBPCFC in BA SUB identified by pulmonary function	163 SUB (Ch) Age: 2 - 17 y Ave - 7.2 y Sex: 109M: 54F	Family Hx atopy 91% Hx of ≥ 1 food allergies BA for Ave 5.5y	SK 59% RP 24% GI 12%	Asthma induced by food allergens potentially severe 6% of SUB reported A Rxn	SPT IgE	Details not provided	Various food extracts Further details not provided	Positive allergy to garlic 1% SUB	Prevalence of asthma induced by food allergens: 10%
Onion
Valdivieso et al., 1994 Spain	SPT for onion performed on 106 SUB randomly chosen from allergy clinic, Positive responders participated in one or more of the following: bronchial or nasal provocation, double-blind oral provocation, IgE (RAST)	106 SUB randomly chosen from allergy clinic; 8 SUB positive SPT Rxn (8%) 4/8 SUB has clinical symptoms to onion exposure Age: 31-45 y Sex: 1M: 3F	Hx of food and pollen allergies	Pollen or onion induced: RC (4/4) D (2/4) E (1/4) BA (2/4)	2 SUB had intense RC and 1 SUB had chest tightness, wheezing and D after exposure to smell of onions Oral provocation in 2 SUB did not elicit a Rxn	SPT 106 SUB Bronchial provocation 2 SUB Nasal Provocation 1 SUB Double-blind oral provocation 2 SUB	SPT - 516µg protein/ml Bronchial & Nasal - 1:1 v/v onion extract Oral - 2 g onion powder	Fresh onion, onion powder	8 SUB (8%) positive SPT 3/8 SUB positive IgE onion 4/8 SUB Pollen-specific IgE 2/4 SUB garlic-specific IgE	4 Sub had immediate positive SPT to fresh onion, garlic, fried onion and leek. All showed positive reaction to heated and non-heated onion extract Results suggest respiratory allergy
Garlic and Onion
Boccafogli et al., 1994 Italy	Open study assessing frequency of food-induced symptoms or allergy in SUB monosensitized to grass pollen SPT, MAST-CLA & oral challenge (0.45 mg food administered w/ 10-fold increase in 30 min intervals until cumulative dose of 5 g if no Rxn observed administration up to 50 g in 30 min intervals	169 SUB monosensitize to grass pollen Age: 9 - 54 y Mean 28 y Sex: 84M: 85F Control 50 SUB monosensitize to Derma-tophagoides Age: 10 - 52 y Mean 30.5 y Sex: 25M: 25F	Hx of BA and/or R during grass pollen season or household dust Positive SPT, MAST-CLA and nasal challenge for aero-allergens	Pollen group had increased frequency of adverse food Rxn 81/169 (48%) compared to control 3/50 (6%) Symptoms: U 28/169 (17%) GI 28/169 (17%) Res 13/169 (8%)	Garlic and onion mainly associated w/ U & GI symptoms 19/169 SUB (11%) considered to have food allergies 1/19 garlic 1/19 onion 46/169 SUB (27%) considered to have food intolerance 6/46 garlic 4/46 onion	SPT MAST-CLA Oral challenge	Details not provided	Garlic & Onion No further information provided	19/169 SUB (11%) considered to have food allergies 1/169 garlic (0.5%) 1/169 onion (0.5%) (IgE sensitized, OAS, GI and/or U/AE within 2 hours after ingestion of small quantity)	Number of SUB with food intolerance higher than that of SUB w/ food allergy Cross reactivity between pollen allergens and food allergens may explain food allergy association but not higher incidence of food intolerance, increased intestinal permeability to macro-molecules hypothesised
Romano et al., 1995 & 1998 Italy	Retrospective Food-dependent EIA study in SUB with Hx of EIA within 2 hours after meal 26 food allergens tested by SPT, IgE assay 8/14 SUB participated in food-exercise challenge	14 SUB w/ Hx of food-EIA Age: 16-27 y Mean (20.5±3.6) Sex: 10M: 4F	Family Hx of allergy 50% Hx pollen allergy 29%	Hx of A	14/14 allergic to 2 or more food allergens 10/14 positive for onion and 9/14 positive for garlic by SPT/IgE specific levels 1 SUB participated in food-exercise challenge after consuming garlic - no Rxn observed	SPT RAST (IgE)	Not provided	Onion or garlic no further details provided	10/14 (71%) positive for onion 9/14 (64%) positive for garlic No Rxn observed after garlic-exercise challenge; Onion not tested	Hx data less helpful interpreting positive SPT/RAST for garlic, onion, parsley & basil because patients could not recall if they were part of the EIA - meal
Asero et al., 2007 Italy	Open allergy study assessing vegetable foods including garlic and onions to identify which vegetables are safe for lipid transfer protein-(LTP) allergic SUB to consume	49 SUB (mono-sensitized to LTP) Age: mean 29 y Sex: 21M: 28F Controls: 24 sensitized to birch pollen 18 sensitized to profilin 16 sensitized to LTP & birch pollen	Hx of Rx to vegetables including garlic and onions	Hx of OAS U AE BA A No SUB reported Hx of allergy to garlic 2/49 (4%) reported Hx of allergy to onion	8/36 (22%) SUB positive SPT to garlic 16/41 (39%) SUB positive SPT to onion 4/13 (31%) controls positive SPT to garlic 6/14 (43%) controls positive SPT to onion Results not considered statistically significant	SPT	No provided	Commercial vegetable food extracts No further details provided	8/36 (22%) SUB positive SPT to garlic 16/41 (39%) SUB positive SPT to onion 4/13 (31%) controls positive SPT to garlic 6/14 (43%) controls positive SPT to onion Results not considered statistically significant	Specificity of SPT poor, many patients showed positive SPT to foods that they reported eating without any problems, including garlic and onions

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Table 2: Other Relevant Studies (Grouped by relevance to garlic, onion and both garlic and onion & organized chronologically by publication date within groups)
Author, Year, Country	Study Design Details	Subjects	Clinical History	Symptoms & Signs ^{Footnote 1} (before challenge)	Symptoms & Signs ^{Footnote 1} Severity of Rxn ^{Footnote 2} after Challenge	Diagnostic Tests ^{Footnote 3}	Eliciting Dose	Eliciting Allergen	Prevalence	Comments
Onion
Avila-Castanon et al., 2002 Mexico	Retrospective analysis of 1419 SUB w/ food allergies to determine frequency of hypersensitivity to foods	1419 SUB (Ch) Age: 12m - 18 y Ave - 12.8 y Sex : details not provided	Hx of food allergies	Most allergy affect age groups: 4-7y (49%) 1-3y (24%) 12-17y (14%)	No applicable to study design	SPT	Details not provided	Onion Further details not provided	4% SUB positive SPT to onion	Onion identified in group of foods responsible for 58% of allergic Rxn (fish, milk, seafood, soy, beans, orange, onion, tomato, chicken, nut, lettuce and strawberry)
Garlic and Onion
André et al., 1994 France	Retrospective analysis of 9 y period investigating foodstuff most frequently associated with A Rxn	580 SUB 480 Ad 100 Ch Age: 1-83 y Mean- 30 y Sex: 290M: 290F	Hx of adverse Rxn to food	60/580 (10%) SUB Hx sev Rxn to food A 52/60 (87%) AE 6/60 (10%) Bronchospasm 2/60 (3%)	Not applicable to study design	SPT IgE	Details not provided	Garlic & Onion	Garlic & Onion were not among the top 19 foods most frequently associated with A Rxn (celery 18% to camomile 1%)	Evolution of sensitization over 1984-1992 indicate an overall increasing trend for garlic and onions Increased consumption and more attentive clinical examinations are credited for this evolution
Moneret-Vautrin et al., 2002 Country not cited	Retrospective analysis of a food allergy database (589 SPT) and 1 Case report of onion allergy (case 1) 1 SUB (case 2) DBPCFC for garlic 1 SUB (case 3) SBPCFC for garlic 1 SUB (case 4) LFC for garlic	Food allergy database 589 SUB: 402 Ch Age: < 15 y 187 Ad Age: not reported Sex: not reported	Hx of food allergy	Case 1 w/ systemic mastocytosis & A induced by celery, carrot, onion, hazelnut Case 2 w/ U & AE Case 3 w/ R, BA, & U from fruits and vegetables Case 4 w/ U & A from garlic and onion soup	Case 1: no challenge reported Case 2: U after 45 min SEV: mild Case 3: laryngeal pruitus, rhinorrhea, cough SEV: mild-mod Case 4: positive LFC result	SPT, DBPCFC, SBPCFC, LFC	Case 2: 1000 mg garlic Case 3: 500 mg garlic	No details provided about garlic used in challenge reports	20/265 positive SPT for garlic (8%) 7/263 positive SPT for onion (3%)	In this series, 2 spices responsible for half cases observed: garlic and fennel seed

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Table 3: Case Reports (Grouped by relevance to garlic and onion & organized chronologically by publication date within groups)
Author, Year, Country	Cases	Clinical History	Symptoms & Signs ^{Footnote 1} Severity of Rxn ^{Footnote 2}	Diagnostic Tests ^{Footnote 3}	Eliciting Dose	Eliciting Allergen	Comments
Garlic
Burden et al., 1994 United Kingdom	1 male Age: 58 y	Sev SK Rxn on the hands after taking garlic extract	Double-blind oral provocation w/ garlic tablets once daily for a week result D of the hands; no Rxn to placebo SEV: mild	Oral Challenge	Not provided	Garlic extract & garlic tablet	Lack of systemic Rxn reported when garlic is ingested by SUB w/ contact allergy may either be dose-related or due to the relevant antigens being heat-liable and destroyed by cooking
Asero et al., 1998 Italy	1 female Age: 35 y	Hx of systemic U/AE associated with both raw and cooked garlic No Hx of pollen allergy or to other common food allergens	U/AE but no GI symptoms reported after ingestion of garlic SEV: mild	SPT	Not provided	commercial garlic extract & fresh garlic	In a series conducted by this author w/ over 300 SUB w/ both pollen allergy and OAS no SUB reported garlic intolerance, suggest lability of cross-reactive antigen No GI symptoms of this case suggest garlic allergens destroyed by enzymatic digestion
Perez-Pimiento et al., 1999 Spain	1 female Age : 23 y	Hx of allergy to pollen and dried fruit and food-dependent EIA	An A Rxn after eating young garlic, emergency medical treatment was required SEV: sev	SPT Prick+Prick IgE	Not provided	Young garlic (unripe garlic)	SUB tolerated garlic cloves and other Liliaceae but was sensitized to pollen and foods distantly related to garlic No oral challenge (sev Rxn)
Pries et al., 2002 Portugal	1 male Age: 16 m	Hx of milk and egg white allergy Hx of tolerance of cooked garlic and onion	Oral challenge with raw garlic positive generalized U SEV: mild Oral challenge with cooked garlic negative	SPT Prick+prick	Not reported	commercial garlic extract & fresh garlic	Suggest allergic fraction that this case is sensitized to is denatured by heat
Yin and Li, 2007 China	Case 1: 1 male Age: 42 y Case 2: 1 female Age: 16 y	Both case had Hx of hay fever	Case 1: an A Rxn after eating young garlic (U, AE, throat swelling, D, syncope and hypertension) Case 2: an A Rxn while walking for 10 min after eating young garlic (EIA)	SPT IgE for various foods	No reported	Young garlic	Limited detail provide in the abstract. Challenge study refused by subjects.
Onion
Hicks & Tanner, 1998 USA	1 male Age: 27 y	Hx of food-dependent EIA requiring emergency medical attention	EIA (lightheadedness, generalized pruritus, numbness in jaw, facial swelling) Played basketball after eating SEV: sev	SPT positive for corn, soybeans, peanuts, walnuts, cabbage & onion Self-conducted oral challenge with chicken, peanut, potatoes & onion negative w/out exercise challenge	Not provided	Several foods including onion	Challenge to cooked onion not performed
Arena et al., 2000 Spain	1 female Age: 44 y	No Hx of allergies to areo-allergens or other foods	An A Rxn after eating raw/lightly-cooked onion SEV: sev	Onion-specific IgE Positive for raw onion, negative for cooked onion	Not provided	Raw onion	SUB sensitized to thermolabile antigenic fraction of onion. Cooked onion tolerated
Asero et al., 2001 Spain	1 male Age: 45 y	Hx of OAS and gastric pain after ingesting peaches	Sev systemic U/AE Rxn after eating raw onion SEV: mod Tolerate cooked onion	SPT Onion-specific IgE Total IgE positive	Not provided	Raw onion	No reaction to cooked onion
Perez-Calderon et al., 2002 Portugal	1 female Age: 26 y	Hx of RC & BA due to pollen allergies	Several episodes of A type Rxn after eating onion and exercising (EIA), at least one episode requiring emergency medical treatment SEV: sev	SPT Prick+prick Total IgE positive FC at rest negative FC w/ cooked onion positive after exercise 10 min, 2-hours after eating	30 g cooked onion	Raw & Cooked onion	Observed cross-reactivity w/ other members of the Lilaceae family (garlic, asparagus or leek)
Enrique et al., 2007 Spain	1 female Age: 19 y	Hx of RC and U to mugwart and oral pruritus after eating raw onion and peach	U after eating raw onion SEV: mild	SPT Onion-specific IgE positive	Not provided	Raw onion	Cooked onion extract not tested
Garlic and Onion
Belleau and Blaiss, 2007 USA	1 male Age: 5 y	Hx of perennial allergic R, atopic dermatitis, mild intermittent asthma, egg and peanut allergy	An A Rxn requiring medical intervention after consuming steak seasoned with "Kraft Greek Vinaigrette Dressing"	SPT positive for peanuts, kraft dressing, whole egg, garlic RAST positive for garlic, onion and various foods	Not provided	Garlic and onion in salad dressing	Challenge study considered inappropriate based on severity of Rxn.

Abbreviations: Ad: adult; CH: challenge; Ch: children; DBPCFC: double-blind ,placebo-controlled food challenge; F: female; Hx: history; LFC: labial food challenge; M: male; max: maximum; min: minute; mod: moderate; Mus: mustard; OC: occupational; OFC: oral food challenge; Res: respiratory; Rxn: reaction; Sen: Sensitization; SEV: severity; sev: severe; SBPCFC: single-blind, placebo-controlled food challenge; SUB: subjects; w/: with; (y) years old

Footnotes

Footnote 1

Symptoms and signs: A: anaphylaxis; AD: atopic dermatitis; AE: angioedema; BA: bronchial asthma; C: conjunctivitis; CV: cardiovascular; D: dyspnea; E: eczema; EIA: exercise induced anaphylaxis; GE: generalized eczema; GI: gastrointestinal; OAS: oral allergy syndrome; R: rhinitis; RC: rhinoconjuctivitis; SK: skin; SR: Systemic reaction; U: urticaria (Refer to appendix 2 for a glossary of terms)

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Footnote 2

Severity of reaction: Refer to Methods (Brown, 2004)

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Footnote 3

Diagnostic Tests: ELISA: enzyme-linked immunosorbent assay; IgE: serum immunoglobulin E; RAST: RadioAllergoSorbent Test; SPT: skin prick test

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