Cacao

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Code: f93
Latin name: Theobroma cacao
Family: Sterculiaceae
Common names: Cacao powder

Food

A food, which may result in allergy symptoms in sensitised individuals. 

Allergen Exposure

Cacao is a seed from the cacao tree, a small (4-8m) evergreen tree in the family Sterculiaceae, native to the tropical region of the Americas. Its seeds are used to make cocoa powder and chocolate. Small, 1-2cm flowers with a pink calyx are produced in clusters directly on the trunk and on older branches. Cacao flowers are pollinated by tiny flies (Forcipomyia midges). The fruit – a cacao pod – is ovoid, 15-30cm long and 8-10cm wide, weighing about 500g, and ripens yellow to orange. Embedded in the white pulp of the pod are around 20 to 60 seeds, usually called ‘beans’. The seeds (from which cacao is produced) are the main ingredient of chocolate. In some countries the pulp is used to prepare a refreshing juice. 

A cacao tree begins to bear when it is four or five years old. A mature tree may produce 6 000 flowers in a year, yet only bear about 20 pods. About 300-600 seeds (10 pods) are required to produce 1kg of cocoa paste. 

All cocoa and chocolate products are made from the seed, which is split open and left to ferment for about a week. This removes the raw taste and develops the oils. The beans are then dried, roasted and ground to make chocolate powder. The cocoa is liquefied (cocoa liquor) and processed in one of three ways: it can be poured into moulds (for baking chocolate); pressed, to separate most of the butter from the cocoa (for cocoa powder); or sweetened and processed into chocolate. 

Cocoa butter is used in manufacturing confections. Cocoa butter substitutes can be produced from soy, maize or corn, palm kernel oil, and cottonseed, and are used in chocolate-flavoured products. 

There are three main cultivar groups of cacao beans used to make cocoa and chocolate. The most prized, rare, and expensive is the Criollo group. Only 10% of chocolate is made from Criollo, which is less bitter and more aromatic than any other bean. The cacao in 80% of chocolate is made using beans of the Forastero group. Forastero trees are significantly hardier than Criollo trees, resulting in cheaper cacao beans. Trinitario, a hybrid of Criollo and Forastero, is used in about 10% of chocolate. (1) 

Chocolate is derived from the roasted seeds of the plant theobroma cacao, and its components are the methylxanthine alkaloids theobromine and caffeine. (2) 

Theobromine (0.7 mol g-1 fresh weight), is a major alkaloid at the young, small fruit stage, followed by caffeine (0.09 mol g-1 fresh weight). At this stage the seed is mainly pericarp. The theobromine content of the pericarp decreases sharply with tissue age, and the caffeine content decreases gradually. A large amount of theobromine (22 mol g (-1) fresh weight) accumulates in seeds (mainly cotyledons) of the large stage of the fruit. Theobromine is also found in the seed coat and placenta. (3) 

Exposure to cacao occurs through chocolate, candies and pastries. All cacao and chocolate products are derived from the seed of the fruit. The powder is used for drinks and confections, and also to make medicines more palatable. Cacao butter is used in making confections. Substitutes for the butter used in chocolate-flavoured products are often derived from palm kernel oil, soy, corn and cotton-seed. 

Cocoa butter is used in chocolate manufacture. If not adequately purified, it may contain cocoa allergens. Chocolate, although containing cacao, may also contain many other ingredients including cocoa butter, sugar, cocoa liquor, milk or milk powder, and flavourants, e.g. vanilla, emulsifiers and butterfat. 

Allergen Description

No allergens have been characterised yet.

A 2S cocoa seed albumin storage protein, a 9 kDa protein, has been isolated. (4, 5, 6) Its allergenic potential was not evaluated; however the protein’s amino acid sequence showed high sequence similarity (>52%) and identity (>38%) to known allergenic plant 2S albumins. (7) 

Potential Cross-Reactivity

Mabinlin, a 2S albumin with similarity to 2S storage albumins of cotton and Brazil nut and sweet protein, was isolated from cocoa bean. Comparison of the translated amino acid sequence shows high sequence similarity (>52%) and identity (>38%) to many plant 2S albumins. The allergenicity of the 2S cocoa albumin protein was not evaluated; therefore it is possible there is a degree of cross-reactivity between cacao and other 2S albumins. (7) 

A minor allergen from walnut belonging to the vicilin family has 90% homology with cocoa vicilin. (8) However, in a study of hazelnut which reported that the allergen Jug r 2 exhibited significant homology with genes encoding the vicilin group of seed proteins, similar to the vicilin-like proteins characterised in cocoa bean and cottonseed (Gossypium hirsutum), a second IgE-binding inhibition experiment showed that there was minimal or no cross-reactivity between Jug r 2 and pea vicilin, peanut proteins, or cacao proteins. (9) The allergenicity of cacao vicilin has not been evaluated to date. 

It has been suggested that when a true chocolate sensitivity exists, cola drinks and karaya gum (often listed as ‘vegetable gum’) should be omitted, since the cacao bean, cola nut and karaya gum all belong to the same botanical family, Sterculiaceae. (10) 

Clinical Experience

IgE-mediated reactions

Anecdotal evidence suggests that cacao may induce symptoms of food allergy in sensitised individuals. However, few studies have been reported to date; it is possible that the allergy occurs more frequently than has been reported. 

Specific IgE antibodies have been found in patients with symptoms such as bronchial asthma and allergic rhinitis after different food intake, of which chocolate was one such food. (11) 

An early study utilising scratch tests with common spices performed in 1 120 atopic and 380 non-atopic patients reported that of 553 atopic patients tested for skin specific IgE to cacao, 12 were positive, versus none of 207 non-atopic patients. (12) 

The main aim of a study conducted at 17 participating clinics in 15 European cities was to describe the differences between some Northern countries regarding what foods (according to the patients) elicit hypersensitivity symptoms. Patients with a history of food hypersensitivity (n = 1139) were asked to fill in a questionnaire in which 86 different foodstuffs were listed. The foods that were reported as eliciting symptoms differed between countries. In Russia, Estonia, and Lithuania, citrus fruits, chocolate, honey, apple, hazelnut, strawberry, fish, tomato, egg, and milk were most often reported as causes of hypersensitivity. In Sweden and Denmark, birch pollen (BP) -related foods such as nuts, apple, pear, kiwi, stone fruits, and carrot were the most common causes. Thirty-two percent of the study group reported symptoms to chocolate and 15% to cocoa. (13) 

A Mexican study examined the epidemiologic features of 60 patients with food allergy attending a clinic in Monterrey. Fifty-one percent of the patients were under 5 years of age. The foods most frequently found to be allergenic were dairy products, egg, fish, shrimp, beans, soy, chili, mango, cacao, and strawberry. Main symptoms were cutaneous in 58% of the patients, followed by gastrointestinal and respiratory. Most common concomitant diseases were urticarial angioedema (38%), allergic rhinitis (20%), atopic dermatitis (15%), and asthma (6.6%). Average time for diagnosis was 1.45 years. (14) 

A cross-sectional study investigating the prevalence and characteristics of IgE-mediated food allergies – in 3 500 randomly-selected 6- to 9-year-old urban schoolchildren in the eastern Black Sea region of Turkey, by way of a self-administered questionnaire completed by the parents and the child – found that 81 (31.6%) reported symptoms to cocoa, of which 13 (14.7%) were skin-prick test-positive and 4 (18.1%) were positive to cocoa in a double-blind placebo-controlled food challenge. (15) 

Another Turkish study (this time conducted in Ankara) – of patients aged 3 months to 16 years with asthma – evaluated 3 025 children (63.3 % boys). The most common allergen was house dust mite, followed by pollen. Allergen sensitivity determined with the skin-prick test found that 30 were sensitised to cacao. (16) A Turkish study (also in Ankara) of food hypersensitivity in patients with seasonal rhinitis resulted in 9 (1.2%) patients reporting adverse reactions to cacao. However, skin-prick tests for cacao were negative. (17) 

An Indian study, of 24 children aged 3 to 15 years with documented deterioration in control of their perennial asthma during the months of August and September, evaluated the effect a specific elimination diet would have on symptoms. Serum-specific IgE was evaluated for a wide range of foods, and 21% (n=5) of patients had raised specific IgE for Cocoa. (18) 

Cocoa has been implicated as a cause of atopic dermatitis in an infant. (19) A study conducted in order to identify the spectrum of specific allergic sensitivities to environmental and food allergens within a series of adult patients with eosinophilic esophagitis found that 19 of 23 (82%) had serum-specific IgE for one or more food-associated allergens (median: 5 foods), with wheat, tomato, carrot, and onion identified most commonly. Three (13%) of the group were sensitised to cocoa. (20) 

Sensitisation to cacao has been reported particularly in occupational settings, and especially in confectionery workers. 

A study assessed immunologic and clinical findings regarding 71 workers in a confectionery plant. The most frequent positive skin reaction occurred with extracts of cacao (31%), followed by reactions to chocolate (9%), cocoa (6%) and hazelnut (6%). Increased serum IgE levels were found in 13%. The prevalence of asthma (26.1%) and dyspnoea (26.1%) was significantly higher in workers with positive skin tests. (21, 22) 

A survey of the respiratory function and immunological status of 40 cocoa- and 53 flour-processing workers employed as packers in a confectionery industry reported a prevalence of positive skin reactions to cocoa (31%). The prevalence of positive skin tests for cocoa in another cohort of 40 cocoa-processing workers was 60.2%. A high prevalence of chronic respiratory symptoms was recorded in exposed workers, varying from 5.0% to 30.0% in cocoa workers and from 5.7% to 28.3% in flour workers. (23) Among these workers, 57.5% had cough as the most acute symptom. Bronchoprovocation testing demonstrated significant decreases in lung function following inhalation of cocoa dust extract and flour dust in workers with respiratory symptoms, and large across-shift reductions in lung function. (23) 

A case study on a confectionery worker complaining of symptoms in the nose and respiratory system reported the presence of specific IgE antibodies to cacao allergens. (24) 

Other reactions

A 7-month-old boy suffering from recalcitrant pompholyx (a skin condition that is characterised by small blisters on the hands or feet) of both soles, in spite of treatment with corticosteroid ointment for three months, was found to be patch-test positive for chromium. His lactating mother had been taking large amounts of chocolate and cocoa every day, both of which contain considerable amounts of chromium. After his mother stopped eating chocolate and cocoa, the pompholyx disappeared within 2 weeks, and recurred within 2 days following oral provocation of chocolate and cocoa to the lactating mother. (25) 

An 8-month history of multiple hospitalisations for recurrent acute severe cutaneous and mucous-membrane vasculitis with large joint involvement was described in a 23-month-old girl. The mother suspected chocolate as a cause. The patient had a slightly elevated total serum IgE level, but negative skin tests to foods, including chocolate. Avoidance of chocolate resulted in remission, except following accidental ingestion of cocoa-containing products. (26) 

Studies have reported that cacao and chocolate, among other foods, may be responsible for migraine headaches in children and young adults. (27) This may be as a result of a number of vasoactive substances present in cacao (including caffeine and tyramine) or others resulting in histamine release without IgE involvement, which may be responsible for other pseudo-allergic reactions. (28) 

Cocoa consumption has been reported to have an aspirin-like effect on primary haemostasis. (29) Whether this may result in abnormal bleeding disorders has not been elucidated. 

Compiled by Dr Harris Steinman.

References

  1. The different varieties of the species Theobroma cacao L. http://www.xocoatl.org/variety.htm. Accessed 1 July 2011.
  2. Patanè S, Marte F, La Rosa FC, La Rocca R. Atrial fibrillation associated with chocolate intake abuse and chronic salbutamol inhalation abuse. Int J Cardiol 2010;145(2):e74-6.
  3. Zheng X-Q, Koyama Y, Nagai C, Ashihara H. Biosynthesis, accumulation and degradation of theobromine in developing Theobroma cacao fruits. J Plant Phys 2004;161(4):363-9(7).
  4. Yavuz MO, Ashton SM, Deakin ED, Spencer ME, Sudbery PE. Expression of the major bean proteins from Theobroma cacao (cocoa) in the yeasts Hansenula polymorpha and Saccharomyces cerevisiae. J Biotechnol 1996;46(1):43-54.
  5. O'Connor J, Revell DF, Masters KE, Connerton IF, Sumner IG. Expression, purification and initial characterization of the recombinant storage protein precursor of Theobroma cacao. Protein Expr Purif 1996;7(4):377-83.
  6. Toros EF, Ejzemberg R, Fuks MA. Immunologic observations on antigens of fermented cacao seeds. [Portuguese] An Microbiol (Rio J) 1980;25:53-60.
  7. Kochhar S, Gartenmann K, Guilloteau M, McCarthy J. Isolation and characterization of 2S cocoa seed albumin storage polypeptide and the corresponding cDNA. J Agric Food Chem 2001;49(9):4470-7.
  8. Pastorello EA, Farioli L, Pravettoni V, Robino AM, Scibilia J, Fortunato D, Conti A, Borgonovo L, Bengtsson A, Ortolani C. Lipid transfer protein and vicilin are important walnut allergens in patients not allergic to pollen. J Allergy Clin Immunol 2004;114(4):908-14.
  9. Teuber SS, Jarvis KC, Dandekar AM, Peterson WR, Ansari AA. Identification and cloning of a complementary DNA encoding a vicilin-like proprotein, jug r 2, from english walnut kernel (Juglans regia), a major food allergen. J Allergy Clin Immunol 1999;104(6):1311-20.
  10. Miller JB. Hidden food ingredients, chemical food additives and incomplete food labels. Ann Allergy 1978;41:93-8.
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  12. Niinimäki A, Hannuksela M. Immediate skin test reactions to spices. Allergy 1981:36:487-93.
  13. Eriksson NE, Moller C, Werner S, Magnusson J, Bengtsson U, Zolubas M. Self-reported food hypersensitivity in Sweden, Denmark, Estonia, Lithuania, and Russia. J Investig Allergol Clin Immunol 2004;14(1):70-9.
  14. Rodríguez-Ortiz PG, Muñoz-Mendoza D, Arias-Cruz A, González-Díaz SN, Herrera-Castro D, Vidaurri-Ojeda AC. Epidemiological characteristics of patients with food allergy assisted at Regional Center of Allergies and Clinical Immunology of Monterrey. [Spanish] Rev Alerg Mex 2009;56(6):185-91.
  15. Orhan F, Karakas T, Cakir M, Aksoy A, Baki A, Gedik Y. Prevalence of immunoglobulin E-mediated food allergy in 6-9-year-old urban schoolchildren in the eastern Black Sea region of Turkey. Clin Exp Allergy 2009;39(7):1027-35.
  16. Dibek Misirlioglu E, Reha Cengizlier M. Skin prick test results of child patients diagnosed with bronchial asthma. Allergol Immunopathol (Madr) 2007;35(1):21-4.
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  19. Høst A, Halken S. A prospective study of cow milk allergy in Danish infants during the first 3 years of life. Clinical course in relation to clinical and immunological type of hypersensitivity reaction. Allergy 1990;45(8):587-96.
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  22. Zuskin E, Kanceljak B, Mustajbegovic J. Epidemiologic study of immunologic status of confectionary workers [Serbo-Croatian]. Lijec Vjesn 1994;116(9-10):240-4.
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  24. Perfetti L, Lehrer SB, McCants M, Malo JL Occupational asthma caused by cacao. Allergy 1997;52(7):778-80.
  25. Adachi A, Horikawa T. Pompholyx of the infant possibly induced by systemic metal allergy to chromium in mother's milk. [Japanese] Arerugi 2007;56(7):703-8.
  26. Businco L, Falconieri P, Bellioni-Businco B, Bahna SL. Severe food-induced vasculitis in two children. Pediatr Allergy Immunol 2002;13(1):68-71.
  27. Guariso G, Bertoli S, Cernetti R, Battistella PA, Setari M, Zacchello F. Migraine and food intolerance: a controlled study in pediatric patients [Italian] Pediatr Med Chir 1993;15(1):57-61.
  28. Moneret-Vautrin DA. Food pseudo-allergy. Pitman Med Publ Co Ltd. London 1979.
  29. Rein D, Paglieroni TG, Wun T, Pearson DA, Schmitz HH, Gosselin R, Keen CL. Cocoa inhibits platelet activation and function. Am J Clin Nutr 2000;72(1):30-5.

 

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.