Commentary
FOOD ADDITIVES IN CLINICAL MEDICINE BEN F. FEINGOLD, M.D.
Chief Emeritus, Department of Allergy, KaiserRermanente Medical Center San Francisco, California
Each individual has a unique biological profile which determines his pharmacologic reactions.^ The pharmacologic response of any compound is governed by proteins wbich have a high degree of specificity. Cenetic variations can influence the quantity and quality of these proteins and are reflected in the behavior of the chemicals as indicated by their metabolism, transport and reactions with receptors. In other words, both wanted and unwanted responses to any compound in great measure depend upon the genetic pattern of the individual. This concept generally is recognized as it applies to chemicals used as drugs but frequently is not realized in the evaluation of food chemicals. Except for terminology, food additives and drugs are identical. Both are low molecular weight compounds with a potential for adverse responses governed by the genetic profile of the individual. The list of 13 categories in Table 1 was compiled from data gathered in 1965 by the Food Protection Committee of the National Research Council and National Science Foundation.2 All the additives in use are not contained in this list; there are many more, but the pre cise number is not known. Fragmentation of licensing and supervision among 9 governmental agencies defies any attempt at exact compilation.
Most of the clinical problems produced by additives are attributed to synthetic colors and flavors, which together number 2,000 chemicals and account for approximately 80% of all additives. This does not imply that tbe remaining categories do not cause adverse reactions. As stated, any chemical may induce a reaction; however, experience to date would indicate that the incidence of involvement by chemicals other than the synthetic colors and flavvors is considerably lower. Since the adverse reactions induced by the synthetic colors and flavors can involve any body system (Table 2),-^ it is important for physicians of every discipline to be alerted to the problem. For the dermatologist, in particular, such awareness can frequently resolve the etiology of a case of baffling and puzzling pruritus, acute and chronic urticaria, angioedema, buccal chancres, and even localized skin pathology which may even be labeled neurodermatitis, nummular eczema, and dermatitis herpetiformis. Although the clinical patterns induced by synthetic colors and flavors are suggestive of an immunological or allergic response, the evidence favors a nonimmunologic reaction. The nature of the mechanism is not known. Despite the fact that many of the chemicals involved have no similarity in structure, they can induce identical clinical patterns. This, too, contributes to the complexities encountered in determining the nature of the pharmacologic response.
112
Table 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
113
FOOD ADDITIVES • Feingold
No. 2 Classifications
of
Additives*
33 Preservatives 28 Antioxidants Sequestrants 111 Surface active agents 39 Stabilizers, thickeners 24 Bleaching and maturing agents 60 Buffers, acids, alkalies 34 Food colors Nonnutritive and special dietary sweeteners 117 Nutritive supplement 1,610 Flavorings—Synthetic 502 Flavorings—Natural Miscellaneous: yeast foods, texturizers, firming agents, binders, anticaking 157 agents, enzymes 2,764 TOTAL
* 2,764 additives classified.
The inhibition of the synthesis of prostaglandins (PGEo), as reported by Vane and Ferreira"* for aspirin and indomethacin, was postulated as a mechanism; however, studies by Ferreira' with tartrazine (FD&C yellow #5) could not confirm such a relationship. Observations by Freese'' on cultures of human cells using tartrazine (FD&C yellow #5) also were not helpful; nevertheless, Freese proposes a reasonable hypothesis to explain this ability of dissimilar compounds to produce identical clinical patterns, based on the presence on the cell wall of receptor sites specific for each compound. In the absence of a known mechanism, identifying tests are not available. Diagnosis depends upon a high degree of suspicion, in addition to a careful bistory. Other possible factors such as allergy, infection and specific drug involvement should be excluded.'' Since individuals sensitive to aspirin frequently react to other unrelated chemicals, e.g., tartrazine (FD&C yellow #5), a history of aspirin intolerance can serve
Table 2.
Adverse Reactions Induced by Flavors and Colors
Respiratory Rhinitis Nasal polyps Cough Laryngeal edema Hoarseness (laryngeal nodes) Asthma Skin Pruritus Dermatographia Localized skin lesions Urticaria Angio-edema Gastrointestinal Macroglossia Flatulence and pyrosis Constipation Buccal chancres Neurological Symptoms Headaches Behavioral disturbances Skeletal System Arthralgia with edema
as a guideline for both diagnosis and management. The reaction to aspirin need not be grossly manifest as in urticaria, angioedema or asthma. Frequently, the intolerance occurs as an unobtrusive comTable 3.
Foods Containing
Natural Salicylates
Almonds Apples (cider & cider vinegars) Apricots Blackberries Cherries Cloves . Cucumbers and pickles Currants Gooseberries Grapes or raisins (wine & wine vinegars) Mint flavors Nectarines Oranges Peaches ' Plums or prunes . . Raspberries ,. . Strawberries All tea Tomatoes Oil of wintergreen
^
114
INTERNATIONAL JOURNAL OF DERMATOLOGY
plaint such as gastric distress (pyrosis). The patient frequently fails to make the correlation. With such a history, dietary management which excludes all foods with natural salicylates (Table 3) as well as all foods with synthetic colors and flavors, can be very effective. The necessity for absolute compliance with the elimination diet is recognized with the realization that a single bite of a restricted food, a single swallow of a prohibited drink or a single dose of a medication with artificial colors and flavors can often induce a complete recurrence of the clinical pattern within hours. The diet is liberal and nutritious. Except for the fruits and vegetables (Table 3) that contain natural salicylates, any food or beverage free of artificial colors and flavors is permissible. The absolute dietary control necessitated by this program demands careful shopping which involves checking of all labels for ingredients. The lack of legibility of the labels and incomplete disclosure of the chemical content frequently makes absolute compliance difficult for the patient. To expedite shopping, a symbol has been designed to appear on all packages of foods and beverages to indicate the complete absence of artificial colors and
March 1975
Vol. 14
flavors. This policy places no restrictions or prohibitions upon the manufacturer or processor regarding the use of any authorized color or flavor. A recent interpretation of the FD&C Act by the legal department of the FDA indicates that the use of such a label is permissible. Following general adoption of tbe symbol and through public education, the consumer will learn that absence of a symbol on the package means the presence of artificial colors and flavors which could be injurious to his health. References 1. LaDu, B. N., Pharmacogenetics: Defective enzymes in relation to reaction to drugs. Ann. Rev. Med. 23:453, 1972. 2. Chemicals Used in Food Processing. Washington, D. C , Food Protection'Committee, National Academy of Sciences-National Research Council Publications 1274, 1965. 3. Feingold, B. F., Introduction to Clinical Allergy, Springfield, Charles C Thomas, 1973. 4. Ferreira, M. S., Vane, J. R., Indomethacin and aspirin abolish prostaglandin release frrom spleen. Nature New Biology, 231:237 1971. 5. Ferreira, M. S., Personal communication. 6. Freese, E., Personal communication. 7. Feingold, B. F., Why Your Child Is Hyperactive, New York, Random House, 1975.
Notes from Crocker. Acne Vulgaris: In cases with large acne papules and pustules about the best thing that can be done is to open the pustules and disinfect them thoroughly . . . Alopecia (sic) (injections of Pilocarpine for): In boy 18 years old in which there is complete alopecia of all the hairy areas Crocker is injecting Pilocarpine, with thus far no indications of improvement.—Recorded by William Allen Pusey in his notebook from London, 1892 and deposited in the American Academy of Dermatology Collection at the Library of the College of Physicians of Philadelphia.
FOOD ADDITIVES IN CLINICAL MEDICINE BEN F. FEINGOLD, M.D.
Chief Emeritus, Department of Allergy, KaiserRermanente Medical Center San Francisco, California
Each individual has a unique biological profile which determines his pharmacologic reactions.^ The pharmacologic response of any compound is governed by proteins wbich have a high degree of specificity. Cenetic variations can influence the quantity and quality of these proteins and are reflected in the behavior of the chemicals as indicated by their metabolism, transport and reactions with receptors. In other words, both wanted and unwanted responses to any compound in great measure depend upon the genetic pattern of the individual. This concept generally is recognized as it applies to chemicals used as drugs but frequently is not realized in the evaluation of food chemicals. Except for terminology, food additives and drugs are identical. Both are low molecular weight compounds with a potential for adverse responses governed by the genetic profile of the individual. The list of 13 categories in Table 1 was compiled from data gathered in 1965 by the Food Protection Committee of the National Research Council and National Science Foundation.2 All the additives in use are not contained in this list; there are many more, but the pre cise number is not known. Fragmentation of licensing and supervision among 9 governmental agencies defies any attempt at exact compilation.
Most of the clinical problems produced by additives are attributed to synthetic colors and flavors, which together number 2,000 chemicals and account for approximately 80% of all additives. This does not imply that tbe remaining categories do not cause adverse reactions. As stated, any chemical may induce a reaction; however, experience to date would indicate that the incidence of involvement by chemicals other than the synthetic colors and flavvors is considerably lower. Since the adverse reactions induced by the synthetic colors and flavors can involve any body system (Table 2),-^ it is important for physicians of every discipline to be alerted to the problem. For the dermatologist, in particular, such awareness can frequently resolve the etiology of a case of baffling and puzzling pruritus, acute and chronic urticaria, angioedema, buccal chancres, and even localized skin pathology which may even be labeled neurodermatitis, nummular eczema, and dermatitis herpetiformis. Although the clinical patterns induced by synthetic colors and flavors are suggestive of an immunological or allergic response, the evidence favors a nonimmunologic reaction. The nature of the mechanism is not known. Despite the fact that many of the chemicals involved have no similarity in structure, they can induce identical clinical patterns. This, too, contributes to the complexities encountered in determining the nature of the pharmacologic response.
112
Table 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
113
FOOD ADDITIVES • Feingold
No. 2 Classifications
of
Additives*
33 Preservatives 28 Antioxidants Sequestrants 111 Surface active agents 39 Stabilizers, thickeners 24 Bleaching and maturing agents 60 Buffers, acids, alkalies 34 Food colors Nonnutritive and special dietary sweeteners 117 Nutritive supplement 1,610 Flavorings—Synthetic 502 Flavorings—Natural Miscellaneous: yeast foods, texturizers, firming agents, binders, anticaking 157 agents, enzymes 2,764 TOTAL
* 2,764 additives classified.
The inhibition of the synthesis of prostaglandins (PGEo), as reported by Vane and Ferreira"* for aspirin and indomethacin, was postulated as a mechanism; however, studies by Ferreira' with tartrazine (FD&C yellow #5) could not confirm such a relationship. Observations by Freese'' on cultures of human cells using tartrazine (FD&C yellow #5) also were not helpful; nevertheless, Freese proposes a reasonable hypothesis to explain this ability of dissimilar compounds to produce identical clinical patterns, based on the presence on the cell wall of receptor sites specific for each compound. In the absence of a known mechanism, identifying tests are not available. Diagnosis depends upon a high degree of suspicion, in addition to a careful bistory. Other possible factors such as allergy, infection and specific drug involvement should be excluded.'' Since individuals sensitive to aspirin frequently react to other unrelated chemicals, e.g., tartrazine (FD&C yellow #5), a history of aspirin intolerance can serve
Table 2.
Adverse Reactions Induced by Flavors and Colors
Respiratory Rhinitis Nasal polyps Cough Laryngeal edema Hoarseness (laryngeal nodes) Asthma Skin Pruritus Dermatographia Localized skin lesions Urticaria Angio-edema Gastrointestinal Macroglossia Flatulence and pyrosis Constipation Buccal chancres Neurological Symptoms Headaches Behavioral disturbances Skeletal System Arthralgia with edema
as a guideline for both diagnosis and management. The reaction to aspirin need not be grossly manifest as in urticaria, angioedema or asthma. Frequently, the intolerance occurs as an unobtrusive comTable 3.
Foods Containing
Natural Salicylates
Almonds Apples (cider & cider vinegars) Apricots Blackberries Cherries Cloves . Cucumbers and pickles Currants Gooseberries Grapes or raisins (wine & wine vinegars) Mint flavors Nectarines Oranges Peaches ' Plums or prunes . . Raspberries ,. . Strawberries All tea Tomatoes Oil of wintergreen
^
114
INTERNATIONAL JOURNAL OF DERMATOLOGY
plaint such as gastric distress (pyrosis). The patient frequently fails to make the correlation. With such a history, dietary management which excludes all foods with natural salicylates (Table 3) as well as all foods with synthetic colors and flavors, can be very effective. The necessity for absolute compliance with the elimination diet is recognized with the realization that a single bite of a restricted food, a single swallow of a prohibited drink or a single dose of a medication with artificial colors and flavors can often induce a complete recurrence of the clinical pattern within hours. The diet is liberal and nutritious. Except for the fruits and vegetables (Table 3) that contain natural salicylates, any food or beverage free of artificial colors and flavors is permissible. The absolute dietary control necessitated by this program demands careful shopping which involves checking of all labels for ingredients. The lack of legibility of the labels and incomplete disclosure of the chemical content frequently makes absolute compliance difficult for the patient. To expedite shopping, a symbol has been designed to appear on all packages of foods and beverages to indicate the complete absence of artificial colors and
March 1975
Vol. 14
flavors. This policy places no restrictions or prohibitions upon the manufacturer or processor regarding the use of any authorized color or flavor. A recent interpretation of the FD&C Act by the legal department of the FDA indicates that the use of such a label is permissible. Following general adoption of tbe symbol and through public education, the consumer will learn that absence of a symbol on the package means the presence of artificial colors and flavors which could be injurious to his health. References 1. LaDu, B. N., Pharmacogenetics: Defective enzymes in relation to reaction to drugs. Ann. Rev. Med. 23:453, 1972. 2. Chemicals Used in Food Processing. Washington, D. C , Food Protection'Committee, National Academy of Sciences-National Research Council Publications 1274, 1965. 3. Feingold, B. F., Introduction to Clinical Allergy, Springfield, Charles C Thomas, 1973. 4. Ferreira, M. S., Vane, J. R., Indomethacin and aspirin abolish prostaglandin release frrom spleen. Nature New Biology, 231:237 1971. 5. Ferreira, M. S., Personal communication. 6. Freese, E., Personal communication. 7. Feingold, B. F., Why Your Child Is Hyperactive, New York, Random House, 1975.
Notes from Crocker. Acne Vulgaris: In cases with large acne papules and pustules about the best thing that can be done is to open the pustules and disinfect them thoroughly . . . Alopecia (sic) (injections of Pilocarpine for): In boy 18 years old in which there is complete alopecia of all the hairy areas Crocker is injecting Pilocarpine, with thus far no indications of improvement.—Recorded by William Allen Pusey in his notebook from London, 1892 and deposited in the American Academy of Dermatology Collection at the Library of the College of Physicians of Philadelphia.
