Table 7.11.1 Vitamins and the immune system Vitamin Importance for the immune system Effect of deficiency on immune system Possible effects of supplementation Retinol carotenoids Differentiation of epithelial cells Development of lymphocytes ↑ Specific lymphocyte subgroups Enhances activity of NK cells Stimulates production of cytokines Activates phagocytic cells May be beneficial for individuals with compromised immune systems Does not stimulate immune responses of healthy adults with adequate intakes In elderly, enhances NK cell activity, but no effect on T-cell mediated immunity Conclusion: little value in well nourished populations Vitamin D Immune system regulator (Lips, 2006) Stimulates production of antimicrobial peptides (including those in epithelial cells of the respiratory tract) Role in production of TNF Powerful antioxidant ? Reduces prostaglandin synthesis ? Prevents oxidation of PUFA in cell membranes Effects on cytokine production ↓ Physical barriers and impairs mucosal immunity ↓ Total number of lymphocytes ↓ Lymphocyte function Altered cytokine networks Altered antibody responses to antigens Impaired antibody production ↓ Phagocytic activity of neutrophils No alteration of neutrophil numbers (in absence of infection) ↓ Number and activity of NK cells Impaired growth, activation and function of B lymphocytes ? ↑ Immune response to flu virus ? Predisposes children to respiratory infections ↑ Susceptibility to infections due to impaired localised innate immunity and defects in cellular immune response Impairs B and T cell immunity (Pekmezci, 2011) ↓ Lymphocyte proliferation responses ↑ Serum IgM concentrations, but impaired antibody production Impaired function of phagocytes Vitamin E Vitamin C Vitamin B6 Folate Vitamin B12 Stimulant of leucocyte functions, especially neutrophil and monocyte movement (important in phagocytosis and lymphocyte functions) Antioxidant protection at inflammatory sites, preventing oxidant mediated tissue dammage ? Regulation of inflammatory response Required for synthesis and metabolism of amino acids, and so for the formation of many immune cells and substances ↑ Production of interleukins Important in protein synthesis Impaired lymphocyte proliferation of T cells Impaired inflammatory response Impaired function of phagocytes Interactions with folate mechanism Regulatory agent for cellular immunity Alterations in immunoglobulin secretion and antibody response ↓ Number of lymphocytes Suppresses NK cell activity Modifies and impairs antibody production Modifies T cell activity Lymphocyte growth and maturation altered Affects cell mediated immunity by reducing proportion of circulating T lymphocytes, leading to ↓ resistance to infections NK, natural killer; TNF, tumour necrosis factor; PUFA, polyunsaturated fatty acid. Manual of Dietetic Practice, Fifth Edition. Edited by Joan Gandy. © 2014 The British Dietetic Association. Published 2014 by John Wiley & Sons, Ltd. Companion Website: www.manualofdieteticpractice.com ↑ Subgroups of T cells in women at low doses ? ↓ Incidence of viral respiratory infections (Cannell et al., 2006) Conclusion: none confirmed ? Enhances immune functions (at doses higher than recommended levels) in elderly people (↑ antibody production; ↓ incidence of infections) ? Reduces exercise induced muscle damage and that associated with antiretroviral drugs Conclusion: may improve immune status, particularly in elderly, but conflicting results on decreased respiratory tract infections Enhances neutrophil chemotaxis In reponse to infection, enhances T lymphocyte proliferation (↑ cytokine production, ↑ synthesis of immunoglobulins) Conclusion: no consistent effect on incidence of colds, but possible modest effect in decreasing duration and severity Correction of deficiency rectifies effects on the immune status Conclusion: no additional benefit to healthy adults ? In elderly, improves immune function by altering age related ↓ in NK cell activity Conclusion: possible protection against infections in elderly, but conflicting results with suggested mechanisms Reverses deficiency effects Conclusion: no additional benefit to healthy adults Table 7.11.2 Minerals, trace elements and the immune system Mineral/trace element Importance for the immune system Effect of deficiency on immune system Possible effects of supplementation Iron (Munoz et al., 2007) Proliferation of lymphocytes Part of iron metalloenzymes involved in oxidative processes May favour infectious pathogens by providing them with a supply of iron for growth and replication (SACN, 2010) ? Effect on morbidity and mortality from infections is uncertain Conclusion: no evidence to suggest that in the UK this has adverse effects on infectious disease incidence or morbidity. Possibly adverse effects on individuals with HIV and children at risk of diarrhoea Zinc (Prasad, 2008; Prasad et al., 2007; Ibs & Rink, 2004) Cofactor for substances that modulate cytokine release and thus essential for highly proliferating cells Helps to maintain skin and mucosal membrane integrity Antiviral effect Regulates activation of acute phase response Selenium (Beckett et al., 2004) Component of selenoproteins with some enzymes that exert antioxidant activity (involved in the removal of excess potentially damaging radicals) Essential for both cellmediated and humoral immunity Stimulates lymphocytes and NK cells Interactions with vitamin E Cofactor in copper dependent enzymes that are important in antioxidant defence (diminishes damage to lipids, proteins and DNA) Intracellular killing of pathogens impaired Slight ↓ in macrophage cytotoxicity ↓ T lymphocyte count Absence of normal immune response to a particular antigen or allergen ↓ T cell function ↓ Innate immune response Altered balance between pro- and anti-inflammatory cytokines ↓ B and T lymphocyte proliferation and imbalance in T cell subpopulations Defects in cell mediated immunity demonstrated by a depression in delayed hypersensitivity responses ↑ Susceptibility to infections ↓ Number of mature T cells and ↑ in immature T cells Damages protective barrier of the skin, respiratory and gut linings and impaired wound healing Impairs innate immunity (impaired chemotaxis by neutrophils and macrophages, ↓ NK cell activity) Compromises neutrophil chemotaxis and macrophage function and subsequent killing of phagocytosed bacteria ↑ Oxidative damage in immune cell membranes ↓ Resistance to viruses Impaired antibody production ? ↑ Risk of developing some cancers ↓ Number of circulating neutrophils Affects synthesis and secretion of cytokines In animals, impairments in immune function (↓ thymus weight, ↓ production of antibodies, ↓ activity of NK cells, ↓ antimicrobial activity of phagocytes) ↑ Thymus cell proliferation ↑ Levels of interleukins and TNF ↓ Levels acute phase proteins and complement Influences cytotoxicity of T cells and functioning of adhesion molecules ↓ Lymphocyte antioxidant enzyme activity In animals, ↓antibody synthesis and secretion ? Correction of deficiency rectifies effects on the immune status (phagocytic index returns to normal values) ? Immunosuppressive at high levels Conclusion: further clinical trials needed. Copper Magnesium Component of enzymes and needed for normal functioning Manganese Component of enzymes and needed for normal functioning Antioxidant activity NK, natural killer; TNF, tumour necrosis factor. ↑ Cellular components of innate immunity, antibody responses and number of cytotoxic cells ↓ Induced apoptosis of macrophages and T cells Reversal of T cell reduced responses when deficiency corrected High levels cause impairment in immunity (in phagocytic cell and lymphocyte function) Conclusion: zinc has a major role in the immune system at all levels and deficiency manifests with increased susceptibility to infectious agents. Zinc supplementation may help reduce the incidence of infections, especially in the elderly ↑ Cytotoxic action against virus infected cells Eradication of Keshan disease Improved immune system function Conclusion: correction of deficiency rectifies effects on the immune status. Possible role in cancer prevention and therapeutic effect on some inflammatory diseases Conflicting results on improvement of asthma symptoms Conclusion: additional studies warranted ?Antibody production improved, but only to certain level (in large amounts inhibition of production occurs) Can cause secondary iron deficiency leading to iron deficiency induced immune system abnormalities Conclusion: none confirmed Table 7.11.3 Summary of nutrient requirements for the functioning of the immune system (Maggini et al., 2007) Body’s defence system Nutrients required Skin barrier function Vitamins A, C and E Zinc Vitamins A, B6, B12, C, D and E Folic acid Iron Zinc Copper Selenium Manganese Magnesium PUFA Methionine Cysteine Synergistic working to support protective activities in immune cells (cellular immunity) Antibody production B cell proliferation Promotion of humoral immunity Indirect action on protein synthesis and/or cell growth PUFA, polyunsaturated fatty acid. Vitamin B6 Selenium Copper Zinc Glutamine Vitamins A, D and E Arginine Vitamin B12 Folic acid Magnesium Manganese Table 7.11.4 Symptoms hypersensitivity experienced with food Target organ Symptoms Skin Pallor Erythema Pruritus Urticaria Angio-oedema Eczema Dermatitis herpetiformis Oral allergy syndrome Food protein enteropathy syndrome Gastro-oesophageal reflux Allergic eosinophilic gastroenteritis/ oesophagitis Oral itch, throat itch, lip swelling Diarrhoea, nausea, vomiting Abdominal pain Enteropathy Proctocolitis Enterocolitis Coeliac disease Constipation Heiner’s syndrome Rhinorrhoea Asthma Hypotension Anaphylaxis Exercised induced anaphylaxis Otitis media Hyperactivity Migraine/abdominal migraine Enuresis Irritability Listless with other symptoms Gastrointestinal tract Respiratory tract Multisystem Controversial symptoms Other Table 7.11.5 Allergy prevention advice Who is at risk? Breastfeeding recommendations Alternatives if breastfeeding not possible or insufficient AAP position statement ESPACI/ESPGHAN (1999) EAACI (2008) If both parents or parent and sibling have documented allergic disease Exclusive breastfeeding up to 6 months Use an eHF, but a pHF could be considered If have one affected parent or one affected sibling If have one first degree relative with documented allergic disease Exclusive breastfeeding 4–6 months Use formula with proven reduced allergenicity Exclusive breastfeeding, preferably for 6 months but for at least 4 months Use an eHF until 4 months of age. A pHF may have an effect, although it seems to be less effective than eHF AAP, American Academy of Pediatrics; ESPACI, European Society of Pediatric Allergology and Clinical Immunology; ESPGHAN, European Society for Pediatric Gastroenterology, Hepatology and Nutrition; EAACI, European Academy of Allergology and Clinical Immunology; eHF, extensively hydrolysed formula; pHF, partially hydrolysed formula. Table 7.11.6 Less restrictive few foods diet (Vikerstaff Joneja, 1998) Meat and alternatives Acceptable grains and flours Lamb Turkey Chicken Potato flour, rice flour, cornflour, arrowroot, sago, tapioca, millet, buckwheat Starchy foods Rice (white), pudding rice, rice noodles, rice cakes – plain, Rice Krispies Cornflour, corn flakes, maize flour, polenta – (not sweetcorn) Potatoes (no skin) – cooked in any way as long as permitted margarines or oils are used in their preparation ‘Kettles’ potato chips, only lightly salted flavour Oven chips or micro chips with no preservatives added Baking aids Cream of tartar, sodium bicarbonate, pectin Fruit Pears Nectarines Peaches Mango Fruit should be washed thoroughly and peeled before it is eaten Tinned fruit in syrup or fruit sorbet made from the allowed fruit is acceptable, but make sure that no preservatives or colourings have been added Adding extra calories to food Sugar, golden syrup Vegetables Carrots Parsnip Greens – only broccoli, marrows and courgettes Swede French beans Squash Sweet potatoes No other foods are allowed at all This includes sweets, chewing gum, popcorn or corn snacks, fizzy drinks or squashes (and alcoholic drinks) This also means no milk or any dairy products. No vinegar or bottled sauces are allowed Milk substitutes Suitable gluten and wheat free products that may be purchased from your pharmacy Ener-G Rice loaf Ener-G Rice pasta Glutano Gluten free pasta Glutano Crispbread Trufree Cake mix Trufree Pastry mix Dr. Schar Mix A – Cake mix Dr. Schar Mix C – Flour mix for cooking Rice milk with added calcium Fats and oils Margarine made from vegetable oil, e.g. Pure, Granose vegetable margarine, Vitaquelle or Vitaseig Supermarket’s own brand of milk free/soya free margarines. Soya margarines are not allowed Any oil, e.g. sunflower, olive, rape seed, vegetable, will be suitable. Flavourings Sea salt and pepper in moderation Herbs – mint, parsley, sage, thyme, basil, oregano, rosemary We do not recommend using a lot of herbs, just a little bit of your favourites Drinks 7-Up (non diet) limit to 1–2 cans/day Water (filtered if possible) Juices from allowed fruit but make sure that they do not contain any colourings or preservatives * Basic instructions • You will have started by following the observation phase for 7 days, recording foods and drinks normally taken and symptoms experienced on your normal diet. • During the observation phase you will have time to plan and shop ahead. It will be necessary to have plenty of appropriate foods to hand. • The menu is simple – without spices, butter or condiments. • Do not start at Christmas or around birthdays. • Use as many fresh food sources as possible. • Frozen food is the next best alternative. • You may initially feel worse, but your symptoms should improve within 3–4 days. This diet should always be followed under the supervision of your dietitian Foods will be reintroduced one at a time after a * day period Please do not hesitate to contact the dietitian on: * Number of days and contact details to be supplied by local practitioners. Table 7.11.7 Subjective and objective symptoms during food challenge (Niggemann, 2010) Possible problems with interpretation Subjective symptoms Nausea Stinging/burning of tongue or mouth Itching Heart palpitations Sleeplessness Irritability Excitement General change of behaviour/sense of impending doom Diarrhoea Abdominal pain and cramps Objective symptoms Flushing Urticaria Slight worsening of eczema Vomiting Cardiovascular symptoms – especially a drop in blood pressure Respiratory symptoms Dyspnoea/difficulty breathing All difficult to interpret due to the subjective nature of the symptoms Highly predictive of a positive challenge Could be caused by stress Could be caused by stress, but also a sign of impending anaphylaxis Difficult to interpret if subsides very quickly Could be contact urticaria if only around the mouth Generalised urticaria (in the absence of chronic urticaria) is almost always a sign of a positive challenge Difficult to interpret/could be contact related However, scored index increase of >15 points is very indicative of positive reactions – may need to wait 48 hours for assessment Could be caused by food aversion – may need to ensure that vomiting occurs more than once and is severe in nature for a positive result Almost always a sign of a positive challenge Could be aero allergen related/generally uncontrolled symptoms However, stridor, wheeze, watery rhinitis, redness of eyes and nose, and tears are almost always signs of a positive reaction Could be aero allergen related but is often a sign of a positive challenge Table 7.11.8 Criteria for major and minor criteria for outcome of challenge Major criteria Minor criteria ≥3 hives ≥1 site of angio-oedema Wheezing Dyspnoea Stridor Dysphonia Aphonia Severe persistent abdominal symptoms for ≥30 minutes, e.g. abdominal pain/stillness, vomiting, nausea or diarrhoea Hypotension for age Eczematous pruritic rash (worsening to ≥10 SCORAD points)* 1–2 hives ≥1 of sneezing, congestion or rhinorrhoea Conjunctivitis ≥1 of nausea, vomiting or diarrhoea for <20 minutes A change in behaviour, e.g. irritability, drowsiness, decreased activity, anxiety, distress • Positive food challenge: presence of ≥1 major criteria or ≥2 minor criteria. • Negative food challenge: absence of a major or minor criteria. *Worsening of eczema alone is not a stopping criterion during the challenge. However, if a worsening of eczema to >10 SCORAD points is observed at the end of the active arm of the double blind placebo controlled food challenges (DBPCFC) with no worsening of eczema with the placebo challenge, the diagnosis of cow’s milk allergy will be given. Table 7.11.9 Nutritionally complete milk substitutes for use in cow’s milk hypersensitivity Type of milk hypersensitivity Product type* Product name (manufacturer) Used for IgE and non-IgE mediated cow’s milk allergy Soya based** Do not use before 6 months unless no other choice, e.g. vegan or refusal of all other suitable formula Casein based hydrolysed cow’s milk Infasoy (Cow & Gate) Wysoy (SMA) Lactose intolerance only Nutramigen Lipil 1 and 2 (MJN) Pregestimil (with MCT oils) (MJN) Whey based hydrolysed cow’s milk Pepti Junior (Cow & Gate) Pepti 1 and 2 (Aptamil) Amino acid Neocate LCP (SHS) Neocate Advance and Neocate Active if over 12 months (SHS) Nutramigen AA (MJN) NB: Some of the above products may also be suitable for lactose intolerance; check prescribing indications Usually contain whole cow’s milk Enfamil Lactofree (MJN) protein SMA LF (SMA) *The choice of product depends on the age of the child, the level of sensitivity to milk and the presence of coexisting allergies. Check compositional details and prescribing indications for suitability. Choice may also be dictated by the infant’s palate. **Infants under the age of 6 months should not use a soya formula as the first choice due to their phyto-oestrogen content and the risk of becoming sensitised to soya. It can be used if other formulae are either not suitable, not acceptable or not tolerated by the infant, or if the mother is vegan. See www.bda.uk.com for the BDA Paediatric Group Position Statement on the use of soya protein for Infants. Further details of products currently available and their prescribing indications can be found in the British National Formulary (BNF) or the Monthly Index of Medical Specialities (MIMS) or obtained directly from the manufacturers. Further information is also available to dietitians in the Special Foods for Children booklet compiled by the Dietetic Department, Children’s Hospital, Birmingham. MCT, medium chain triglyceride. Table 7.11.10 General guidance for milk exclusion Exclude Examples of foods to exclude Notes Cow’s milk Liquid whole, semi skimmed or skimmed milk Evaporated or condensed milk Dried full fat or skimmed milk powder Fresh and UHT Dairy products Butter Margarine or fat spreads containing milk derivatives Cheese and cheese spreads Yogurt Fromage frais Creme fraiche Cream Ice cream May be described on ingredients lists as: milk, milk solids, non-fat milk solids, milk protein; skimmed milk, skimmed milk powder Casein or caseinates Whey; whey solids; buttermilk *Lactose, milk sugar, whey sugar, whey syrup sweetener. Within the European Union the presence of milk must be clearly labelled Goat’s, sheep’s and other mammalian milk should not be used as an alternative to cow’s milk. They are also unsuitable for people requiring total exclusion of lactose or galactose Butter and some hard cheeses may be tolerated by people with mild lactose intolerance Milk or milk derivatives in manufactured foods Lactose in flavourings and medications may be a problem in some severely allergic patients *It may not be necessary to exclude lactose and other milk sugars in all cases of cow’s milk allergy but, for practical purposes, their presence is usually taken as indicative of the presence of milk, and foods containing them are excluded. Table 7.11.11 Types of manufactured foods that may contain milk or milk derivatives Food type Foods to check Cereals Bread and rolls Breakfast cereals Cakes Biscuits and crackers Pizza Pasta (both fresh and tinned) Vegetables canned in sauce Instant potato Baked beans Battered or breadcrumbed vegetables and potato products Meat and fish products, e.g. beef burgers, fish fingers, sausages, ready meals Canned and packet soups Instant gravies Sauces/ketchups Crisps and savoury snack foods Instant desserts Dairy desserts Ice cream Custards Chocolate Toffee Fudge Caramel Margarines and fat spreads Instant drinking chocolate Malted milk drinks Coffee whiteners Pineapple and coconut juice drink Fruit and vegetables Meat, fish and alternatives Other savoury items Desserts Confectionery Fats and spreads Beverages NB: This list is far from exhaustive and all food labels must be checked carefully and checked every time as ingredients do change. Most of these products can also be milk free if you shop around or use ‘free from lists’ to locate them. Table 7.11.12 Guidance for peanut and tree nut avoidance Exclude Examples Notes Peanuts and tree nuts Peanut Brazil Walnut Hazelnut Almond Cashew Pistachio Pecans Macadamia Peanut butter and other nut spreads Praline Noisette Marzipan Frangipan Amaretto products Macaroons Bakewell tarts Almond essence Marron, e.g. marron glacé Some of these may be described as: Mixed nuts Ground nuts Monkey nuts Earth nuts Goober nuts Nutmeg, coconut, pine nut and palm nut are not classified as nuts Worcester sauce Satay sauce Korma sauce Pesto sauce Hydrolysed vegetable protein Contains walnuts Contains peanuts Contains almonds and sometimes peanut paste Made from pine nuts, but could contain other nuts Usually from soya or wheat but can be derived from peanut, but this should be labelled clearly on prepacked manufactured foods in the European Union Nut cheeses sold on deli counters can contaminate other products Refined oils present in manufactured foods or sold as cooking oils are free from nut protein but still have to be declared on food labels Spreads Sweets Desserts and dessert topping Sweet paste or ice cream Sauces Hydrolysed vegetable protein Cheese Oils Manufactured foods containing traces of peanuts or nuts Nut containing or nut coated cheeses Cold pressed gourmet oils, also called unrefined oils Peanut oil Arachis oil Groundnut oil Walnut oil Almond oil Hazelnut oil This can include almost any food but particularly: Cakes, biscuits and pastries Ice cream, desserts and dessert toppings Chocolate bars Cereal bars and confectionery Savoury snack foods Breakfast cereals, especially muesli or nut mixtures Products containing hydrolysed vegetable protein Oriental/Asian food Sauces and salad dressings Mixed salads Wild rice Almond paste used in curries often contains peanuts Usually made from hazelnuts but mixed nuts can be used Contain almonds but cheaper brands may contain peanut flour as an extender Made from chestnuts but other nuts may be included All manufactured foods should be considered a source of peanuts/nuts until it is known that this is not the case Table 7.11.13 Soya containing foods (L’Hocine & Boye, 2007) Whole bean products Hull products Protein products Oil products Emerging products Soya sprouts, edamame, soya milk, tofu, miso, natto, yuba, tempeh, soya sauce, soya nuts, soyanut butter, soya cereals, soya cheese, soya milk, soya ice cream/ yoghurt/desserts Bread, bakery products, snack bars Soya flour, protein concentrate, protein isolate, textured soya Baby foods, infant formulae, bread, biscuits, pancakes, pastry, crackers, snack foods, noodles, pizza, breakfast cereals, soya milk, ice cream, soya yoghurt and cheese, sausages, tinned meat and fish, soups and gravy, beef burgers, salad dressing, stock cubes, sauces Refined oil, lecithin Cooking oil, salad oil, margarine, salad dressing, mayonnaise, coffee whiteners, chocolate, sweets, pastry filling, cheese dips, emulsifying agents, dietary supplements and body building agents Isoflavones, functional foods, medications Table 7.11.14 Sesame products Alternative names Foods containing sesame Ajonjoli Benne/benne seed Gomasio Gingelly Sesamum indicum Sim sim Oleum Teel Till Falafel Burger buns Bread sticks Pastries Pretzels Bagels Biscuits Rice cakes Crackers Sandwiches Halva Hummus Tahini Salad dressing Soups Sauces Noodles Samosa Dips Aqua Libra Table 7.11.15 Classification of egg containing foods Well cooked egg Lightly cooked egg Raw egg Cakes Biscuits Dried egg pasta Pancakes and Yorkshire pudding Egg in sausages, both vegetarian and meat varieties, and also in other processed meats such as burgers Prepared meat dishes Well cooked fresh egg pasta Quorn Sponges and sponge fingers Chocolate bars that contain nougat or dried egg, e.g. Milky Way, Mars bar or Creme egg Some soft centred chocolates Soft fruit chews Egg in some gravy granules Dried egg noodles Waffles Commercial marzipan Scrambled egg Boiled egg Fried egg Omelette Egg fried rice Meringues Some marshmallows Lemon curd Quiche Poached egg Pancakes Egg in batter Egg in breadcrumbs, e.g. on fish fingers and chicken nuggets Hollandaise sauce Quiche and flans (fruity and savoury) Egg custard and egg custard tarts Crème caramel Crème brulée Real (egg) custard Tempura batter Yorkshire pudding – some patients who can eat well cooked egg can tolerate this, but it depends on how well cooked they are and if they contain any uncooked batter inside Fresh mayonnaise Fresh mousse and shop bought mousse that contains egg Fresh ice cream Sorbet Royal icing (both fresh and powdered icing sugar) Home made marzipan Raw egg in cake mix and other dishes awaiting cooking (children of all ages love to taste or lick the spoon!) Egg glaze on pastry Horseradish sauce Tartar sauce Cheese containing egg white in the form of lysozyme Mayonnaise Salad cream Table 7.11.16 Cross reacting plant food allergens Birch pollen Birch/mugwort Grass Ragweed Plane tree Latex Apple, pear, cherry, peach, nectarine, apricot, plum, kiwi, hazelnut, other nuts, almond, celery, carrot, potato Celery, carrot, spices, sunflower seed, honey Melon, watermelon, orange, tomato, potato, peanut, Swiss chard Watermelon and other melons, banana, courgette, cucumber Hazelnut, peach, apple, melon, kiwi, peanuts, maize, chickpea, lettuce, green beans Avocado pear, chestnut, banana, passion fruit, kiwi fruit, papaya, mango, tomato, pepper, potato, celery Table 7.11.17 Dietary guidance for wheat exclusion Cereal foods that must be excluded Other foods that may need to be excluded Cereal foods that can be included All types of bread, including rolls, malt bread, chapatti, pitta, naan, paratha, croissants, soda bread and fancy breads Some gluten free breads Breakfast cereals unless derived solely from oat, rice and/or maize (corn) Cakes, biscuits and crackers Flour and all foods containing wheat, e.g. pastry, pies, batters, pancakes, sauces Bran Pasta Semolina, couscous Pizza Proprietary gluten free foods containing wheat starch Whole wheat or wheat grains Wheat flour Wheat starch (or modified starch) Wheat bran Wheat germ Wheat binder Wheat gluten Wheat thickener Cereal filler Rusk Breadcrumbs or bread Manufactured foods containing any of the following ingredients: Modified starch (mostly from maize derived) Wheat germ oil Wheat thickener Raising agent containing wheat starch Hydrolysed wheat protein Spelt Oats* Rye* Barley* Triticale* Rice and rice flour Corn (maize) and cornflour (polenta) Millet Arrowroot Buckwheat Sago and sago flour Tapioca Quinoa Proprietary gluten free, wheat free foods (NB: only prescribable for coeliac disease, not wheat intolerance per se) *Some patients may have a cross sensitisation with these grains. Table 7.11.18 Ethnicity of HIV infected individuals seen for care in the UK Ethnicity 2000 2009 White Black Caribbean Black African Asian/Oriental Other/mixed 66.5% 2.5% 23.3% 2.4% 6.4% 52.0% 3.0% 36.2% 3.0% 5.9% Table 7.11.19 CDC classification system for HIV infected adults and adolescents CD4 cell category ≥500 cells/μL 200–499 cells/μL <200 cells/μL Clinical category A Asymptomatic, acute HIV or PGL B* Symptomatic conditions, not A or C C# AIDS indicator conditions A1 B1 C1 A2 B2 C2 A3 B3 C3 Patients in shadedd categories are considered to have AIDS. PGL persistent generalised lymphadenopathy; CDC, USA Centers for Disease Control. Table 7.11.20 Recommendations for when to initiate therapy Presentation When to treat Primary HIV infection Treatment in clinical trial Or when there is neurological involvement Or when CD4 <200 cells/mL for >3 months Or AIDS defining illness Established HIV infection CD4 <200 cells/mL CD4 201–350 cells/mL CD4 351–500 cells/mL CD4 >500 cells/mL AIDS diagnosis Treat Treat as soon as possible when patient ready Treat in specific situations with higher risk of clinical events – see text Consider enrolment into ‘when to start’ trial Treat (except for tuberculosis when CD4 >350 cells/mL) Table 7.11.21 Anthropometric and related assessments of individuals with HIV infection Measurements Anthropometric Weight Body mass index Waist circumference Mid upper arm circumference Triceps skinfold Mid arm muscle circumference Hip circumference Waist to hip ratio Other skinfold measurements Other measurements Bioelectrical impedance analysis Handgrip strength Indication of Overall nutritional status; however, must be interpreted in individuals with caution and with a view to evaluating other aspects of body composition Good marker of nutritional status in populations; can determine if overweight, obese or underweight; interpret with caution in individuals A good correlate of visceral fat and an indicator of metabolic syndrome Reflection of muscle and subcutaneous fat stores; can compare with reference values and evaluate changes over time Subcutaneous fat stores; can compare against reference values and serial changes in an individual A good marker of lean body mass; useful in assessing changes in individuals On its own can reflect buttock muscle and fat stores and can be monitored serially in individuals Use with reference values, but interpret in light of potential fat loss from lipoatrophy Can be used to assess overall subcutaneous fat and estimate total body fat percentage Low phase angles have been shown to be of prognostic relevance in HIV infected patients (Kyle et al., 2004); however, are not sensitive to detect changes in body shape, nor should be used to evaluate fat atrophy (Schwenk et al., 2001). Can measure body cell mass, which is a component of some definitions of HIV related wasting (see Table 7.11.23) A measure of muscle strength; correlates well with nutritional status; however interpret with caution as limited reference values, and consider factors such as mood, mobility and peripheral neuropathy Table 7.11.22 Laboratory markers used in patients with hiv infection Use to assess Plasma markers Urea Creatinine Potassium Phosphate Liver function tests (LFTs) CD4 T cell count Viral load Albumin Vitamin B12, folate Ferritin transferrin saturation, total iron binding capacity, etc. Zinc, selenium Calcium Vitamin D, parathyroid hormone (PTH) Other fat soluble vitamins Hormones: testosterone, oestradiol, thyroid Fasting lipids (total cholesterol, HDL, LDL, triglycerides) Fasting glucose Urine markers Protein : creatinine Fractional excretion of phosphate (FePi) Faecal markers 1-alpha antitrypsin Pancreatic elastase Hydration status, renal function (usually measured in an inpatient setting) Renal function (also useful to calculate estimated glomerular filtration rate) (Labarga et al., 2010)) Can be low in poor nutritional states and high in chronic renal disease Measure of phosphate intake; however, hypophosphataemia is very common in people with HIV infection (Assadi, 2010) and needs to be interpreted in view of dietary intake, malabsorption, vitamin D deficiency and, importantly, tubular renal losses most commonly due to antiretroviral therapy and hyperparathyroidism. A fractional excretion of phosphate will help to determine the cause of hypophosphataemia Increased LFTs can be an indicator of liver function, especially considering the high prevalence of coinfection with hepatitis B and C; however, if only alkaline phosphatase is raised, it may be due to increased bone turnover and/or vitamin D deficiency See text See text Indicator of visceral protein status and related to inflammatory states, e.g. difficult to assess in cases of liver disease and acute infection. It is also an indicator of disease state and mortality. Can be low in malabsorption and states of protein loss Low in macrocytic anaemia, can be related to low dietary intakes or other causes Low in microcytic anaemic, can be related to low dietary intakes or other causes Need to be interpreted with caution in inflammatory states (see Micronutrients section) Plasma levels are bound to plasma proteins (such as albumin) and are tightly regulated, so are not a good reflector of dietary calcium intake Vitamin D deficiency is common in HIV as it is in many other individuals. Vitamin D deficiency or dietary calcium deficiency can result in secondary hyperparathyroidism Can be useful to measure in patients with fat malabsorption Measured to rule out secondary causes of wasting and low bone mineral density Use local reference values and national guidelines for target levels Increased fasting or random glucose should warrant an oral glucose tolerance test to rule out diabetes, impaired glucose tolerance or impaired fasting glucose. It has been suggested that fasting insulin and glucose should be routinely measured, and HOMA-IR calculated, particularly in those at highest risk, such as those with metabolic syndrome, obesity, lipodystrophy or a longer exposure to antiretrovirals (Gianotti et al., 2011). Reflects renal protein loss and is more sensitive than a dipstick test. Should be measured annually in all patients on ART FePi = (urine phosphate × serum creatinine × 100)/(serum phosphate × urine creatinine). This should be done fasting and can be used to determine whether hypophosphataemia is a result of renal losses or inadequate dietary intake/reduced gastrointestinal absorption A protein synthesised in the liver that is neither actively secreted nor absorbed. Use with serum levels to determine clearance in order to help diagnose protein losing enteropathy if indicated (Umar & DiBaise, 2010) Used to determine exocrine pancreatic function that may result in fat malabsorption and diarrhoea Table 7.11.23 Dietetic interventions and outcomes for treating nutritional problems in patients with HIV infection Patients requiring a dietetic referral Dietetic interventions and outcomes of referral All patients with HIV Healthy eating principles that ensure adequate nutrition and promote a healthy immune system to reduce infections and prevent development of metabolic comorbidities Food and water safety counselling to reduce the risk of developing food and water borne illnesses Antenatal and postnatal nutrition and breastfeeding education (see Chapter 3.8.2) Improving micronutrient deficiency (including iron) and constipation Nutrition strategies for symptom management, e.g. anorexia, early satiety, swallowing problems, thrush, nausea and vomiting, diarrhoea, food intolerances Outcomes may be improved diarrhoea and improved dietary intake ensuring adequacy of macro- and micro-nutrients (prevention of weight loss and loss of lean body mass, which is known to increase mortality) Identifying food–medication interactions and strategies to ensure optimal medication efficacy and provide adherence support Immunocompromised (e.g. CD4+ cell count <200 cells/mL) Pregnant women Poor dietary intake due to disease or side effects of treatment Patients taking antiretrovirals or other medications relating to opportunistic infections or comorbidities Loss of >5% of usual weight Dyslipidaemia and/or lipodystrophy and/or obesity and/or diabetes and/or insulin resistance Bone disease (osteoporosis, osteopaenia, osteomalacia) Allergies/intolerances or patients following special diets/taking excess supplementation Patients requiring weight loss or gain of lean body tissue Alteration in bowel habit Alternative feeding methods, e.g. oral supplementation, tube feeding and parenteral nutrition Outcomes may be reduced risk of infections, mortality, hospital admissions (if an outpatient) and length of stay (if inpatient), and improve patient experience (quality of life and energy levels) Strategies for treatment of body fat changes and altered metabolism (in collaboration with the clinician) include exercise, lipidlowering medications, dietary modifications, glycaemic control, hormonal normalisation and anabolic medications Outcomes may be prevention of cardiovascular disease events, reduced hospital admissions and improved quality of life (obesity related) Assessment of dietary and lifestyle factors influencing bone mineral density (dietary protein, calcium, phosphorus and vitamin D; exercise, risk of falls, smoking, alcohol) and advice on altering these as needed Advising on vitamin D ± calcium supplementation Outcomes may include prevention of falls, fractures and hospital admissions Evaluation of nutrition information, special diets, vitamin or mineral or other dietary supplementation, and other nutrition practices Prevention of toxic effects of hypervitaminosis, improved patient experience/wellbeing; ensuring nutritional adequacy, prevention of interactions with ART or other medications Additional activities and therapies that support good nutrition, e.g. physical exercise, medications for symptom management, chronic disease management, etc., including referral to appropriate exercise facilities See outcomes for dyslipidaemia Assessment of impact on quality of life and diet, dietary advice to improve symptoms (constipation/diarrhoea), discussion with patient about lifestyle factors;.liaising with specialist gastroenterology team/dietitian, communication with GP if supplements or medicines are required Outcomes may be improved quality of life, prevention of nutritional deficiencies and enhanced medication absorption ART, antiretroviral therapy. Table 7.11.24 Definitions of HIV related wasting CDC (Centers for Disease Control, 1987) Consensus panel (Wanke et al., 2004) NFHL (Wanke et al., 2000) Involuntary weight loss of >10% of baseline body weight + either chronic diarrhoea or chronic weakness and documented fever in the absence of concurrent illness or condition 10% unintentional weight loss over 12 months Or 7.5% unintentional weight loss over 6 months Or 5% unintentional weight loss over 3 months Or in men: BCM <35% of total BW with BMI <27 kg/m2 Or in women: BCM <23% of total BW with BMI <27 kg/m2 In either men or women, regardless of BCM: BMI <20 kg/m2 Unintentional loss of >10% of body weight Or BMI <20 kg/m2 Or Unintentional loss of >5% of body weight in 6 months and persisting for at least 1 year BW, body weight; BMI, body mass index; BCM, body cell mass. Table 7.11.25 Observational studies of micronutrient deficiencies in relation to HIV disease Micronutrient Observational findings in HIV Vitamin A Low vitamin A levels have been associated with quicker progression of HIV disease and mortality in adults (Semba et al., 1995, Tang et al., 1993) Low vitamin D has been associated with HIV disease progression (Viard et al., 2011; Mehta et al., 2010). In the general population, vitamin D deficiency has been associated with cardiovascular disease, diabetes, immune functioning and mortality (Melamed et al., 2008) Serum zinc levels have been linked to HIV disease progression, decreased CD4+ cell counts, and increased mortality (Baum et al., 1997; 2003). An association was seen between people who took over the counter zinc supplements and a more rapid progression to AIDS and mortality (Tang et al., 1993; 1996). This may be because adults with more advanced or symptomatic HIV disease are more likely to take more supplements (Bormann et al., 2009) Low levels have been linked with progression of HIV disease (Baum et al., 1997) Several studies have found that a high percentage of HIV infected individuals have inadequate dietary calcium intake (Arpadi et al., 2009; Bonjoch et al., 2010; Jacobson et al., 2008). An increased dietary calcium intake has been associated with greater bone mineral density in HIV (McComsey et al., 2007) Iron deficiency is common, especially in women and in developing countries, and dietary iron appears to be a contributing factor (Castro & Goldani, 2009; Shet et al., 2012) Hypophosphataemia is commonly seen in patients with HIV regardless of ART use (Day et al., 2005). It is thought that use of tenofovir contributes to renal tubular losses of phosphate; however, vitamin D deficiency, malabsorption and use of antacids can also be contributing factors (Assadi, 2010). Vitamin D Zinc Selenium Calcium Iron Phosphate ART, antiretroviral therapy. Table 7.11.26 Interventional studies of micronutrients in people living with HIV/AIDS Micronutrient Findings from randomised controlled trials (RCTs) Vitamin A No trials reviewed (Irlam et al., 2010) showed a reduction in disease progression in adults with vitamin A supplementation. In children, vitamin A supplementation showed a reduction in mortality and moderate evidence for morbidity and growth benefits Limited RCTs have been done in adults or children. The doses used in trials thus far have been inadequate to achieve optimal repletion of vitamin D stores. One trial found that vitamin D3 supplementation decreased the risk of developing diabetes (Guaraldi et al., 2011). No risks have been seen to date (Wejse et al., 2009, Arpadi et al., 2009) No benefit of zinc supplements have been seen in pregnant women, furthermore, zinc inhibits iron absorption so mitigates increases in haemoglobin levels, which are often low in pregnancy. In drug users in Florida, those who took the dietary reference intake (DRI) of zinc as a supplement, had a decrease in immunological failure (defined as CD4+ <200 cells/mm3) and less diarrhoea, compared to those taking placebo (Baum et al., 2010). In children, supplementation reduced risk and progression of diarrhoea in several studies (in Africa), but not prophylactically (Irlam et al., 2010) Reduced diarrhoeal morbidity in pregnant women in Tanzania, and reduced viral load in two separate small trials in American adults (with high drop out rates) (Irlam et al., 2010) Calcium with vitamin D supplements have been given in the control arm of several trials investigating the role of bisphosphonates in treating osteoporosis. These studies found that there was a trend for bone mineral density increases, albeit non-significantly, in those receiving calcium supplements only; however, this was significantly less than in those on bisphosphonates (Mondy et al., 2005, McComsey et al., 2007) To date, no RCTs have evaluated the influence of diet on iron or phosphate stores in patients with HIV infection. Iron supplements have been given in conjunction with multivitamins to women with hepatitis C (Semba et al., 2007) and improved iron stores and anaemia. The results from this trial cannot be generalised to the HIV infected population as a whole due to the narrow inclusion criteria and short duration Multi micronutrient formulations have shown a reduction in mortality in patients with a CD4 of <100 cells/mm3 in Thailand (Jiamton et al., 2003), an increase in CD4 in the US (Kaiser et al., 2006) and an improvement in benefits to mothers and offspring in Tanzania (Fawzi et al., 2004) Vitamin D Zinc Selenium Calcium Iron and phosphate Other
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