Title: Dietary measures to prevent allergy

Key words: immune, allergen, protein, hapten, Th1, Th2, IgE, IgM, IgG, IgA, infectious theory, interleukin, environment, microbial allergens, food allergy, cow's milk, egg, peanuts, latex, childbirth, gut flora, breast-feeding, formula, omega-3, omega6, palmitic acid, PUFA, selenium, supplementation,

Date: June 2001

Category: Food intolerance/Allergy

Type: Article

Author: Dr M Draper

Dietary measures to prevent allergy

Introduction: Hypotheses of developmental immunology

Allergy can be defined as an inappropriate reaction of the immune system. The allergen is either inhaled, ingested or comes in contact with the skin and is almost invariably a protein or a molecule linked to a protein (hapten), that the immune system recognises as foreign to the body (1). The science of immunology probably started with Jenner's classical study of the role of vaccination in protection against smallpox virus in 1798. Clinical immunology emerged from the 1950's onwards and addressed the nature of the immune response in infective diseases, autoimmunity, organ transplantation, different organs and tissues (2).

In allergic and atopic individuals the body is often responding inappropriately as if the allergen was an invading organism and the IgE response in particular probably evolved to mount an immune response against bowel parasites. The lungs develop embryologically from gut tissue and allergic conditions occur more commonly in the respiratory and digestive tract. In adults 60-70% of immune system activity is centred on the gut. In the foetus the (TH2)(see Appendix Definitions)) IgE antibodies are first to appear at about 3 months (3,4) and at birth are the dominant antibody. (TH1) IgM levels start to rise in pregnancy as do IgG and these rise to adult levels by 1and 6 years old respectively. The low levels in pregnancy of foetal IgM and IgG ensure that no immune response is mounted against the mother. IgA is undetectable in the foetus but rises to adult levels during the first six months presumably in response to the introduction of food, highlighting the importance of IgA in normal gut function. According to the infectious theory, the increased prevalence of allergy (15-30% of population) in Western industralised countries is explained by the lower levels of Interleukin-12 that result in reduced TH1 stimulation. This has caused speculation that the increased prevalence of allergy is due to the failure of the neonate to deviate from its TH2 bias at birth (5). The onset in childhood of allergic symptoms follows an age related pattern (4) of eczema, asthma, food allergy and rhinitis with peaks of incidence at 2, 7 & 12 years respectively. The severity of allergy versus age follows the pattern (4)of eczema, food, asthma and rhinitis at the ages of 15 months, 18 months, 5 years & 12 years.

Genetic Influence in allergy

For allergies the estimated likelihood of a person having allergies, or the potential to develop them, has been estimated to be (6):

# 5-15% if neither parent has allergies.

# 20-40% if one parent has allergies

# 40-60% if both parents have allergies

# 60-80% if both parents have the same allergy

# 25-35% if one sibling has allergies.

The nature of the T cell receptor signalling provided by the allergen-peptide ligand and a disregulation of lL-4 production likely concur to determine the TH2 profile of allergen-specific TH cells, but the genetically determined imbalance in IL-4 production is certainly overwhelming (7). These findings suggest that the upregulation of genes controlling IL-4 expression and/or abnormalities of regulatory mechanisms of the TH2 development and/or function may be responsible for TH2 responses against allergens in atopic people. Il-13 possesses IL-4 like activity and babies at risk of atopic disease in infancy display defective IL-13 production at birth (8). Rational approaches to asthma and allergy (9) involve modulating the genetic and environmental factors as well as interfering with the activated pathways.

Environmental influence in allergy

The rapid rise in allergy over the past 200 years infers that the most important factors are environmental (10). The most potent factor for airway hypersensitivity in children is passive smoking. Evidence that exposure to sulphur dioxide, diesel exhaust (11contests), and ozone is causally linked with the inception of allergic diseases is poor (12). Rather, factors associated with the lifestyle of populations or families, such as socio-economic status, allergen exposure, sibship size, early childhood infections (and, presumably antibiotics), dietary habits, and growing up in anthroposophic families or a farming environment (13,14), may prove to be greater relevance. Possible explanations for lower rates of allergy in children on farms may be the development of immunotolerance or the stimulation of TH1 cells and suppression of TH2 cells by increased exposure to microbial antigens (eg mycobacteria and actinomycetes) in the stable or farmhouse. In Spain a 4 year study (15) of food allergy in children under 2 years old found that 3 items, egg white, cow's milk, and peanuts, represented more than half of the sensitisations.

Infant feeding patterns identify prolonged breast feeding exclusively or combined with infrequent exposure to small amounts of cow's milk during the first 2 months of life induces development of IgE-mediated response to cow's milk (16). A series of papers (17.18,19,20) explore current prevalence and perspectives on food reactions. Recent research has demonstrated the presence of a number of cross- reacting antigens in botanically unrelated, allergenic plant species (21).

Childbirth today, whether by caesarian section or vaginal delivery, involves healthcare workers wearing latex gloves. The newborn infant is therefore exposed immediately via the skin to latex particles which have a cross reaction with a variety of foods including peanuts, treenuts, chestnuts, exotic fruits, celery and tomatoes (1, 3). Prevalence of Type1 Latex allergy in healthcare workers has continually increased and runs at about 10% (22). Scientific experimental and clinical studies have demonstrated that cornstarch on surgical and examination gloves promotes disease by acting as a reactive foreign body in tissue and serving as a vector for latex allergy. A global internet search identified 70 US and 3 European Hospitals using only powder-free gloves (23).

Gut Ecology and Infant feeding: The newborn is inoculated with bacteria from the intestinal and vaginal flora of the mother and these organisms colonise the intestine of the newborn. Under normal conditions , a stable, heterogenous intestinal flora is established within 10 days (24). In breast-fed babies , Bifidobacteria usually become the dominant group, comprising 90-99% of the flora. In contrast formula-fed infants develop a mixed flora with about 68% Bifidobacteria, 17% Enterobacteria, 11% Bacteroides, and 4% Enterococci (25). The predominance of Bifidobacteria in the large intestine may be beneficial through its antibacterial effect in lowering the pH in the colon by stimulating acid secretion; improving host resistance to pathogens by the activation of the immune system; excretion of a metabolic end product that is directly inhibitory to a range of gram-positive and negative pathogenic bacteria (26).

Further evidence (27) shows that Lactobacillus plantarum can preserve key nutrients, vitamins , antioxidants, elimate toxic components from the food, protect food from decay and eradictate pathogens. The initial incidence of breast feeding between 1980 and 1995 for England is 62-65% and falls to 40% at 4 months (end of maternity leave and return to work [28,29]. It is lower in certain regions (eg Scotland and Northern Ireland), increases with maternal age and social class, and is partly determined by the method used to feed the first baby. New infant formulas (eg Omneo Comfort by Cow & Gate (30)) have a relatively high level of palmitic acid in the beta position of the triglyceride which lowers gut pH and encourages the growth of Bifidobacteria. These infant formulas may, therefore, be preferential if the mother is unable or unwilling to breast feed.

 

Nutritional status and allergy

The major changes in nutrition over the period that allergy has been rising include: (A) reduction in the PUFA omega 6 to omega 3 ratio , from 2:1 in 1900 to 6:1 in 1990's (31). It has been shown that atopic individuals have a lower level of arachidonic acid in breast milk compared with non-atopic individuals (32). Diets high in PUFA omega 3 (eg in Inuit eskimos up to 14mls per day) are associated with very low rates of allergy. A theoretical case exists for clean, stable, whole body fish oil supplementation of 5mls per day in normal individuals and higher levels of 10mls per day in atopic mothers. Alternatively flax oil 15-30mls per day has been advocated (33). (B)

Lower micronutrient levels in food (whole food (20-30%ß ) and especially processed (up to 50%ß ) from 1930's onwards (McCance and Widdowson data) and that the ADI (Average Daily Intakes) of young teenage woman was less than the RNI (Reference Nutrient Intakes) for Iron in 89% (LRNI 33%), Zinc in 44%, Folic Acid 51%, and the ADI of Selenium is 29-39 microgms (RNI 60) (34, 35).

Summary of Dietary measures to prevent allergy

Based on the above evidence my advice on a healthy diet for all would-be-mothers is; (a) improve dietary lipids (decrease Omega 6 polyunsaturates (PUFA) and saturates (animal fats), processed PUFA's such as trans-fatty acids in margarines (GR4 p123) and increase Omega 3 PUFA (whole body fish oils and flax seeds or oil) and PUFA Omega 9 (olives & olive oil and sesame seeds and oil). (b) improve micronutrient intake with diet (Five portions of organic vegetables and fruit per day GR3) and increased levels of antioxidants either through bioflavinoids eg citrus flavinoids, liminoids, anthocyanidins, and lycopenes (GR4), and/or appropriate supplementation especially Zinc and Selenium (eg Food State yeast derived minerals). Consider ferritin levels and iron supplementation especially in teenage girls.

(A) during pregnancy continue preconception advice, avoid alcohol, and in atopic mothers reduce exposure to known allergens. Consider probiotics and avoid peanuts from 32 weeks until labour. Aim for a vaginal delivery with low allergen latex gloves.

(B) during lactation eat the healthy diet (with prebiotics from food and functional foods) and add water for extra fluid intake.

(C) during early infant feeding encourage breast feeding for at least 4 months and the slow introduction of small amounts of single foods masticated by the mother. Avoid antibiotics, eggs, cow's milk and peanut butter especially with family history of atopy. Have weekends away on the farm and do not smoke in the house.

Allergy Appendix :*

(A) Allergy Definitions

Adverse Reaction to a food or food additive is synonymous with the term ' food sensitivity '.

Atopy or Allergy refers to an individual who develops a reaction to one or more allergens.

Food allergy means a hypersensitivity reaction of the immune system, and may be a Type l, ll, lll, or lV.

Food Intolerance refers to any non-immune mediated reaction. The term is usually used when the trigger is a man-made chemical, such as a food additive or preservative, or a naturally occurring component of food, which the body is unable to process adequately. The resulting symptoms can be loosely equated with a reaction to a drug.

Food sensitivity refers to an adverse reaction to a food, which encompasses both allergy, immune-mediated, and non-immune mediated responses.

TH1 A subset of Helper T-(Thymus derived)- lymphocytes that interfere with the process of tolerance and cause the TH1 response that involves IgM and IgG antibodies with activation of the complement cascade likely to cause mucosal damage.

TH2 Another subset of Helper T-lymphocytes that leads to a TH2 response mediated by IgE hypersensitivity reaction causing immediate type hypersensitivity or, in severe cases, anaphylaxis.

(B) Types of immune mediated hypersensivity reactions:

Type 1 Hypersensivity reactions involve IgE antibodies (mounted usually on the cell membrane), mast cells (that store histamine and cytokines) and other granulocytes.

The symptoms resulting from this type of reaction are traditionally referred to as atopy, and the allergic individual as atopic eg atopic asthma, eczema, allergic rhinitis etc. For this type of hyper-sensitivity, prior exposure or sensitisation to the allergen must have occurred. The British Thoracic Society has stated an opinion that the presence of a viral infection eg a respiratory tract virus may prime the development of IgE to an inhaled allergen such as the onset of hayfever in child or adulthood.

Type III hypersensitivity involves IgM and IgG antibodies and chemicals involved in the complement cascade. Steps in the reaction are:

# T- cell lymphocytes recognise the antigen as foreign after it is processed by macrophages.

# Igm and later IgG are produced in response to the antigen.

# Antigen-antibody complexes are formed.

# The complement cascade is triggered.

# Anaphylatoxins formed in the complement cascade cause the release of inflammatory mediators.

Type lV Hypersensitivity involves T-cell lymphocytes and cytokines. This reaction is called a contact allergy because the reaction continues as long as the allergen is in contact with body cells.T-cell lympocytes respond to allergenic foods to cause an immediate reaction in the lips, tongue, mouth, and gastrointestinal tract from the release of cytokines.

Allergy as an inflammatory process

All types of hypersensivity reaction cause the release of inflammatory mediators (histamine, prostaglandins, leukotrienes and bradykinin) which together cause swelling, redness and pain. The question is how much can these reactions and substances be modulated by nutritional status.

(C) Symptoms typically occur at the site where the antigen enters the body:

eg asthma (reversible bronchoconstriction) to inhaled allergens or gastrointestinal symptoms (abdominal pain, distension and/or diarrhoea) in response to food.

Respiratory Tract Allergic (eg Hayfever) or perennial rhinitis (nasal congestion)

Rhinorrhea (runny nose)

Allergic conjunctivitis (itchy, watering, reddened eyes)

Serous otitis media (earache with effusion)

Asthma (reversible wheeze)

Laryngeal oedema (tightening of the throat)

Skin Atopic dermatitis (eczema)

Urticaria (hives)- can also be due to salicylate sensitivity in food (see special diets)

Angioedema (swelling of tissues especially the mouth and face)

Pruritis (itching of skin, eyes, ears, and mouth)

Contact dermatitis (eczema due to contact with allergen)

Digestive Tract

Diarrhoea, Constipation, Nausea, Vomiting

Abdominal bloating, distension and /or pain.

Indigestion Belching and flatulence

Nervous system

Migraine Headaches

Spots before the eyes

Lack of concentration

Listlessness

Hyperactivity

Irritability

Tension-fatigue syndrome

Dizziness

Chilliness

Other

Pallor

Dark rings around the eyes

Urinary frequency

Bedwetting

Hoarseness

Low grade fever

Excessive sweating

Muscle aches.

(D) General Therapeutic strategies include:

(1) Avoidance eg filters, masks, dust covers, food exclusions and special diets etc.

(2) pharmaceutical treatments include steroids (inhaled and oral), sodium cromoglycate (inhaled or ingested), and antihistamines.

(3) nutritional advice includes: (a) dietary advice (eg Five portions of vegetables and fruit per day GR3) and modifications based on exclusion diets. (b) altering dietary lipids (decrease Omega 6 polyunsaturates (PUFA) and saturates (animal fats), processed PUFA's such as trans-fatty acids in margarines (GR4 p123) and increase Omega 3 PUFA (whole body fish oils and flax seeds or oil) and PUFA Omega 9 (olives & olive oil and sesame seeds and oil). (c) increasing levels of antioxidants either through bioflavinoids eg citrus flavinoids, liminoids, anthocyanidins, lycopenes and other naturally occuring substances such as pycnogenols (pine bark and grape seed extracts) or supplemention of minerals and vitamins (Selenium (especially in the UK with average adult intakes of 35 microgms per day, range 29-39.), Zinc, Vitamins A (as beta carotene), C and E (as mixed tocopherols).

ALLERGY References:

(1) Joneja, J.V. (1998) 'Dietary Management of Food Allergies and Intolerances'

ISBN 0-9682098-2-3 2nd Edition.

(2) Turk,J.I., (1972) ' Immunology in Clinical Medicine' ISBN 0-433-32851-7

(3) Joneja, J.V. (2001) Module 5 MSc University of Surrey Lecture Notes.

(4) Holgate,S.T. et al. (2001) 'Allergy ' 2nd Edition Mosby, London.

(5) Weiss,S.T. (2000) 'Parasites and asthma/allergy ' J Allergy Clin Immunol 200002,105:2Pt,205-10.

(6) Goldman,A. (1997) Cow milk sensitivity; A review. In 'Food and Immunology'. Symposium of the Swedish Nutrition Foundation X111.Almqvist and Wiksell, Uppsala pp99-104.

(7) Parronchi,P et al. (2001) ' Genetic and environmental factors contributing to the onset of alllergic disorders' Int Arch Allergy Immunol, 200001,121:1,2-9.

(8) Williams,T.J. et al. (2000) ' Fetal and neonatal IL-13 production during pregancy and at birth and subsequent development of atopic symptoms' J Allergy Clin Immunol, 200005,105:5,951-9

(9) Blumenthal,M.N.,(2000) 'Genetics of asthma and allergy' Allergy Asthma Proc, 200000,21:1,55-9.

(10) von Mutius, E.(2000) ' The environmental predictors of allergic disease' J Allergy Clin Immunol, 200001, 105: 1 Pt 1, 9-19.

(11) Takafuji, S. & Nakagawa, T. (2000) ' Air pollution and allergy' J Investig Allergol Clin Immunol, 200000,10: 1,5-10.

(12) Pearce, N. , Douwes, J. & Beaseley, R. (2000) ' Is allergen exposure the major cause of asthma ?' Thorax, 200005, 55: 5,424-31.

(13) Kilpelainen, M et al. (2000) ' Farm environment in childhood protects the development of allergies' Clin Exp Allergy, 200002, 30: 2, 201-8.

(14) Riedler, J et al. (2000) 'Austrian children living on a afarm have less hayfever, asthma, and allergic sensitisation' Clin Exp Allergy, 200002, 30: 2,194-200.

(15) Pascual,C.Y. et al.(2000) ' Food alllergy and intolerance in children and adolescents, an update.' Eur J Clin Nutr, 200003, 54 Suppl 1: S75-8.

(16) Saarinen, K.M., Savilahti, E. (2000) ' Infant feeding patterns affect the subsequent immunological feature in cow's milk allergy ' Clin Exp Allergy, 200003, 30: 3,400-6.

(17) Bender,A.E., Matthews,D.R. ' Adverse reactions to foods' Brit. J Nutri 1981; 46:403-407.

(18) Burr,M.L., 'Food intolerance in a community survey ' .Brit J Nutri 1983;49:217-9.

(19) Anderson, J.A. (1994) 'Milestones marking the knowledge of adverse reactions to food in the decade of the 1980's. Ann Allergy 72:143-154.

(20) Sloan, A.E. , Powers, M.E. (1986) A perspective on popular perceptions of adverse reactions to foods. J Allergy Clin immunol 84:127-133

(21) Vocks,E. et al. (1991) ' Common allergenic structures in hazelnut, rye grain, sesame seeds, kiwi, and poppy seeds ' Allergy 48: 168-172.

(22) Mahler, V et al.(2000) ' Prevention of latex allergy by selection of low-allergen gloves ' Clin Exp allergy, 200004,30: 4,509-20. (23) Jackson, E.M., et al. (2000) ' A global inventory of hospitals using powder-free gloves: a search for principled medical leadership ' J Emerg Med, 200002, 18: 2,241-6.

(24) Gewold, H. et al. (1999) ' Stool microflora in extremely low birth weigt infants 'Arch Dis Child Neonatal Ed 80: F167-173.

(25) Kleessen, B. et al. (1995) 'Influence of two infant formulas and human milk on the development of the faecal flora in newborn infants ' Acta Paediatr 84 : 1347-56.

(26) Gibson, G.R. & Roberffrold, M.B. (1995) ' Dietary modulation of the human colonic microbionta: introducing the concept of probiotics. J Nutr 125: 1401-12.

(27) Bengmark, S. (2000) 'Colonic pre- and probiotics ' Am J |Gastroenterol, 200001, 95: 1 Suppl, S5-7.

(28) Office for National Statistics (1995) Bulletin ' Breast feeding in the United Kingdom in 1995.

(29) Foster, K et al. (1997) ' Infant Feeding ' The Stationary Office, London.

(30) Cow&Gate ' Omneo Comfort ' Technical booklet. Cow & Gate Limited, Trowbridge, Wiltshire BA14 0XQ.

(31) Thijs, C. et al. (2000) Essential fatty acids in breast milk of atopic mothers: comparison with non-atopic mothers, and effect of borage oil supplementation' Eur J Clin Nutri, 20000003, 54: 3,234-8.

(32) Erasmus, V. (1999) 'Fats that heal , Fats that kill ' Alive Books. ISBN 0-920470-38-6.

(33) Winnepeg, M.B. (1995) ' Nutrition Advisory Panel Meeting Executive Summary- Flax Coucil of Canada.

(34) Gregory, J et al. (1990) National Diet and Nutritional Survey of British Adults. HMSO, London.

(35) MAFF (1994) The National and Nutritional Survey of British Adults: Further Analysis. HMSO, London.

General References (GR):

(1) Anthony, H. et al. (1997) ' Environmental Medicine in Clinical Practice ' Chapter 8 ' ' Food Allergy and Intolerance - Investigation and Management' BSNAEM Publications ISBN 0-9523397-2-2.

(2) James, J.M. (1996) Chapter 61 ' Adverse reactions to Foods' in ' Present Knowledge in Nutrition' Edited by Zeigler EE & Filer LJ. ISBN 0-944398-72-3.

(3) National Heart Foundation (1997) ' At Least Five a Day - Strategies to increase vegetables and fruit consumption ' The Stationary Office London ISBN011322002-2.

(4) Clayton, P. (2001) 'Health Defence' ISBN0-905553-63-2.