Caballero B. (ed.) Encyclopaedia of Food Science, Food Technology and Nutrition. Ten-Volume Set

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product stability, absorption, and lower cost, and

development efforts need to continue.

Regulations, Guidelines, and Standards for

Fortification

0036 The objective of the regulations and guidelines should

be (1) to protect the population who buy and con-

sume the product and (2) establish standards and

guidelines to which all producers of the fortified

products should conform.

0037 The regulation and guidelines should include the

following:

0038 A rationale for fortification The decision to fortify a

product with particular nutrient has to be based on

scientific data obtained through dietary surveys and

biochemical and/or clinical studies.

0039 Recommended minimum and maximum level(s) of

nutrient added per serving The level of the fortifi-

cant added should not be too low to have little or no

impact on the nutrition status of the population. At

the same time, the level added should not be in excess

to cause toxicity.

0040 Establishing RDA This is essential as a reference for

fortification and in communicating the amount of the

nutrients per serving to the population that consume

the fortified product.

0041 Establishing labeling standards The goal is to detail

only relevant information.

0042 Establishing guidelines for making nutritional and

health claims Claims made on the nutritional and

health benefits of the product should be supported

by scientific data.

0043 Establishing a monitoring and surveillance

system For the regulations and guidelines to be

effective, there should be a monitoring and surveil-

lance system established.

Quality Assurance

0044 The success of producing and distributing a micronu-

trient-fortified product is dependent on the placement

of a quality assurance program that includes the

following:

0045 Finished product specification and description In

order to build quality into the fortified product, the

specification and description of the finished product

must be established prior to its manufacture. The

manufacturing process should be detailed in written

operating procedures. Based on the claim to be made,

the type and dosage of the micronutrients and the

form and source of fortificants are specified.

0046Raw materials The quality of the raw materials for

both the product and packaging play an important

role in the quality of the final micronutrient fortified

product. The micronutrient fortificants should meet

established specifications. In addition, premix pur-

chases are made from approved suppliers that follow

good manufacturing practices (GMP). Once received,

the fortificants are recorded and stored as specified in

an appropriate condition.

0047Production and Packaging A quality product is en-

sured by following GMP. The micronutrient sources

are added into the product formulation by using

already-specified procedure and equipment. The

amount of each fortificant added is recorded. Finally,

the amount in the finished product is verified by using

a validated analytical method.

0048Release of finished product The product released

for distribution should meet all final product specifi-

cations. This includes the safety of the product and

the level of the micronutrients claimed. There should

be a system for (1) monitoring and correcting devi-

ations from specification and (2) identifying the prod-

uct in case there is a complaint from the consumer.

0049Documentation Accurate recording is essential for

(1) identifying and correcting deviations, (2) recalling

a product with serious problems, and (3) making an

improvement on the quality of the product.

0050Training All personnel involved in the development,

manufacturing, packing, and storage of the fortified

product should be trained in quality assurance.

Advocacy and Social Communications

0051An effective communications campaign supported by

the government should necessarily accompany any

major fortification effort in order to gain the under-

standing and support of key sectors from policy-

makers and legislators to medical professionals,

health workers and consumer groups.

Monitoring and Evaluation

0052As micronutrient fortification programs expand in

countries around the world, the need to monitor the

quality of the fortified food (in terms of its micro-

nutrient content) and evaluate its contribution to the

alleviation of micronutrient deficiencies will increase.

Monitoring activities should ensure that a fortified

product contains a sufficient amount of the micronu-

trient and that it reaches the target population. The

2618 FOOD FORTIFICATION

indicators used to monitor fortification efforts reflect

the need to determine the quality and safety of the

products and their availability to the populations at

greatest risk. Monitoring is carried out at various

levels – production or importation, wholesale and

retail and household. The production and import-

ation levels are the most important point for monitor-

ing the fortification activity.

0053 Monitoring is vitally important to the success of a

fortification program for the following reasons:

0054 To improve program effectiveness A fortification

program can be effective only if a high-quality forti-

fied is produced, delivered, accepted, and consumed

by the target population on a continuous and self-

sustaining basis.

0055 To ensure compliance with government

standards Monitoring systems will provide infor-

mation on the extent to which the product conforms

to national standards at points of production and

consumption. This information is needed to enforce

compliance through regulation and encourage volun-

tary corrective action by the producer.

0056 To identify problem points in the fortification

process As food moves from the factory to the

household, it generally goes first to distributors,

then to retail outlets. In some cases, foods are fortified

outside the country and imported for eventual con-

sumption. Monitoring must occur at various critical

points starting at the production level and ending at

the household level, where the fortified food is stored,

prepared, and consumed.

0057 To ensure safety Effective monitoring will ensure

that the micronutrient content of the fortified food

is within the desired range.

0058 As a final indication of effectiveness, an impact

evaluation conducted after 2 or 3 years will determine

whether the micronutrients are absorbed well and are

preventing recurrences of micronutrient deficiencies

in the population.

Progress in Food Fortification

0059 Key global developments to address specific micronu-

trient deficiencies through food fortification are sum-

marized below.

0060 Iodine Over the past 60 years, a variety of vehicles

including bread, flour, sugar, and salt have been

proposed as carriers for iodine. Among these, salt

iodization has witnessed a remarkable growth in ap-

plication globally over the past decade. A significant

proportion of the populations in over 110 countries

have access to iodized salt. Once established in a

country, salt iodization is a permanent and long-

term solution to the problem of iodine deficiency.

Depending upon per-capita salt consumption and an-

ticipated iodine losses between production and con-

sumption, iodine dosage ranges from 20 to 100 mg

per kilogram of salt. These losses are dependent upon

the quality of salt and packaging. Toxicity issues are

negligible, and cost considerations fairly small. Al-

though there is considerable progress in streamlining

control programs through salt iodization in several

countries, producer compliance, quality assurance,

logistic problems, and bottlenecks do remain. The

challenge is to systematically identify and tackle

these constraints through effective advocacy, social

communications, monitoring of salt iodine levels,

regulation, and enforcement. In many developing

countries, salt iodization is the first large-scale experi-

ence in national fortification of a commodity. It has

provided valuable lessons in collaboration between

government, industry, nongovernmental organiza-

tions, the media, and other sectors. It has also given

insights into building and sustaining an intervention

politically, technically, financially, and culturally.

0061Iron Although iron has potential for use in more

food vehicles than iodine or Vitamin A, fortification

with iron is technically more difficult than with other

nutrients, since iron reacts with several food ingredi-

ents. There are a number of iron compounds that are

approved for food fortification. The greatest chal-

lenge with iron is to identify a form that is adequately

absorbed and yet does not alter the appearance or

taste of the food vehicle. The buff-colored, insoluble

iron phosphate compounds are stable under a variety

of storage conditions but are poorly absorbed. The

soluble iron salts like ferrous sulfate are well

absorbed but easily discolor by reacting with food

ingredients. In addition to the general fortification

criteria, iron fortification needs to take into account

certain specific considerations:

0062The vehicle should be a component of all meals,

because absorption varies inversely with the iron

content of the meal.

0063It should not require prolonged storage particu-

larly under hot and humid climatic conditions,

since this could cause organoleptic problems.

0064Vehicles that are dark in color or have a strong

taste or odor permit the use of more reactive iron

compounds.

0065Segregation of iron should not occur during

mixing or storage.

Reducing the global prevalence of iron deficiency

anemia will require the use of several alternative

FOOD FORTIFICATION 2619

fortification compounds and food vehicles,

depending upon the local dietary patterns. Some

promising possibilities are:

0066 Wheat/corn flour and bakery products In developed

countries like the USA, Sweden, and Canada, these

foods have had significant success as vehicles for iron.

Flour fortification ensures an even meal distribution

of the added iron and provides a reasonably constant

iron supply to each individual. More recently, all corn

and wheat flour in Venezuela was fortified with

iron (mixture of ferrous fumarate and reduced iron),

vitamin A, and B vitamins.

0067 Condiments In Thailand, fish sauce, which is con-

sumed in many parts of the country, has been tested as

a vehicle for iron [in the form of sodium iron ethyl-

enediaminetetraacetic acid (EDTA) ] and has shown a

good hemoglobin response. Fish sauce and fish pastes

have also been tried as vehicles in the Philippines

and Vietnam. Curry powder used by an Indian popu-

lation in South Africa has been fortified with sodium

iron EDTA with successful results. In China, the feasi-

bility of using soy sauce as a carrier for iron is being

examined.

0068 Processed foods There is a growing trend in several

developing countries increasingly to use processed

foods such as noodles, cereals, and soup cubes.

Weaning foods for children are also becoming popu-

lar. Elemental iron of small particle size is being used

for the fortification of processed cereals in several

developed countries. In Mexico, a chocolate milk

powder is fortified with iron. In Tanzania, a fortified

orange beverage drink has proved effective in improv-

ing the iron and vitamin A status among school

children and pregnant mothers.

0069 Salt Recent work has focused on developing a for-

mulation that would permit the addition of both

iodine and iron. (The acidic medium in which the

iron compound is stable causes the rapid oxidation

of iodide/iodate to free iodine, which vaporizes

and is lost). A promising approach uses dextrin-

encapsulated potassium iodide/iodate mixed with

encapsulated ferrous fumarate to provide a barrier

between the iron and iodine and improving stability.

The successful testing and large-scale application of

available technology for the double fortification of

salt could represent a major breakthrough for com-

bined iron and iodine delivery.

0070 Zinc Several zinc compounds are available for food

fortification ranging in solubility from very soluble

(sulfate and chloride), freely soluble (acetate), to

almost insoluble (carbonate and oxide). The soluble

compounds, especially sulfate and chloride, are most

preferred as fortificants. Unlike iron, zinc does not

undergo oxidation–reduction. As a result, it does

not cause the development of undesirable color and/

or flavor when added to foods and beverages. How-

ever, like iron, it does cause metallic aftertaste and

astringency. Currently, only infant formulas, cereal

products (especially infant cereals), and dietetic prod-

ucts (e.g., products used for enteral feeding) are forti-

fied with zinc.

0071Calcium Foods normally fortified with calcium in-

clude cereals and beverages, foods sold as a replace-

ment to milk/yogurt, e.g., soy milk/yogurt, infant

formula, weaning foods, enteral foods, slimming

foods, and meal replacements. Flour is one of the

best examples of fortification of cereal products. A

range of breakfast cereals, rice, and corn products are

also fortified with calcium in a few countries. More

recently, orange juice and concentrates have been

fortified with calcium. The compounds commonly

used for fortification include carbonate, phosphate/

lactate, citrate malate, or gluconate.

0072Vitamins A and D Vitamin A has been successfully

added to foods such as milk (various forms of liquid

and dry milk), butter, cheese, flour, bread and cereal

product, snacks, and beverages. The most widespread

application is in oils or fats that are dietary ingredi-

ents of most populations. It is essential that foods

fortified with vitamin A are sealed in opaque or

dark-colored glass containers with closures to elimin-

ate the effect of light, a stimulant to oxidative pro-

cesses. Edible antioxidants may also be added to

protect both the oil and the added vitamin A from

oxidation. Fortification of margarine is widely prac-

ticed (at levels of 20 000–50 000 IU kg

1

) to equal or

exceed the average levels of this nutrient in butter.

Often, vitamins D and E are also added. If synthetic

b-carotene is also to be used, both color and vitamin

A can be added simultaneously. When fat is removed

from whole fluid milk, all fat-soluble vitamins, in-

cluding vitamin A, are removed. All skim milk or

low-fat liquid or dry milk products should have vita-

min A added and, if given to infants, should probably

have vitamins D, E, and possibly C as well. Sugar is

another vehicle for vitamin A in Central American

countries like Costa Rica, Guatemala, Panama, and

Honduras.

0073B vitamins and folate Thiamine, riboflavin and

niacin have been traditionally added to wheat flour

in many countries for several decades. As a result,

several vitamin B deficiency conditions like beriberi

2620 FOOD FORTIFICATION

and pellagra have been eliminated. Most recently, the

addition of folate to grain products was made man-

datory to reduce the prevalence of neural-tube defects

and other congenital abnormalities in children caused

by folate deficiency in the mothers during pregnancy.

See also: Calcium: Properties and Determination;

Carotenoids: Occurrence, Properties, and

Determination; Cholecalciferol: Properties and

Determination; Iodine: Properties and Determination;

Iodine-deficiency Disorders; Niacin: Properties and

Determination; Quality Assurance and Quality Control;

Riboflavin: Properties and Determination; Thiamin:

Properties and Determination; Vitamins: Overview; Zinc:

Properties and Determination

Further Reading

Bauernfeind JC and Lachance PA (eds) (1991) Nutrition

Addition to Foods; Nutritional, Technological and Regu-

latory Aspects. Trumbull, CT: Food and Nutrition Press.

Clydesdale FM and Wiemer KL (eds) (1985) Iron Fortifica-

tion of Foods. London: Academic Press.

Codex Alimentarius Commission (1994) Codex Alimen-

tarius. General Principles for the Addition of Essential

Nutrients to Foods, vol. 4. CAC/GL 09-1987. Rome:

Food and Agriculture Organization.

Food Fortification to End Micronutrient Malnutrition.

State of the Art (1998) Proceedings of the Satellite Con-

ference of the XVI International Congress of Nutrition.

Ottawa: The Micronutrient Initiative.

Hurrell RH (ed.) (1999) The Mineral Fortification of

Foods. Leatherhead, UK: Leatherhead International Ltd.

Lotfi ML, Venkatesh Mannar MG, Merx RH and Naber

van den Heuvel P (1996) Micronutrient Fortification of

Foods. Current Practices, Research and Opportunities.

Ottawa: The Micronutrient Initiative, Ottawa &

Wageningen: International Agricultural Centre.

Micronutrient Fortification of Foods. Current Practices, Re-

search and Opportunities. Ottawa: The Micronutrient

Initiative: Ottawa, Canada & Wageningen, The Nether-

lands: International Agricultural Centre.

Mason JB, Lotfi M, Dalmiya N, Sethuraman K and Deitch-

ler M (2001) The Micronutrient Report. The Micro-

nutrient Initiative.

Nestel P (1993) Food in Fortification Developing Coun-

tries. Washington, DC: USAID/Vital.

Richardson DP (1997) The addition of nutrients to foods.

Proceedings of the Nutrition Society 56: 807–825.

Food Intake See Dietary Surveys: Measurement of Food Intake; Surveys of National Food Intake; Surveys

of Food Intakes in Groups and Individuals

FOOD INTOLERANCE

Contents

Types

Food Allergies

Milk Allergy

Lactose Intolerance

Elimination Diets

Types

J Gray, Guildford, Surrey, UK

W Chan, London, UK

Introduction

0001 The umbrella term ‘adverse reactions to food’ has

been adopted to describe a range of different types

of responses to food, in particular food intolerance,

food aversion, and food poisoning (Table 1). One

way of distinguishing food intolerance and food

poisoning is to consider the former as a defect in the

individual and the latter as that of the food. The

mechanisms underlying food intolerance are numer-

ous, complex, and incompletely understood. It is cer-

tain that far fewer reactions are due to true allergy

(involving the immune system) than is commonly

believed. This article discusses the definitions and

FOOD INTOLERANCE/Types 2621

mechanisms of the various types of food intolerance,

as well as the clinical symptoms, diagnosis, treatment,

and prevalence of food intolerances and their predis-

posing factors.

0002 Much of the confusion surrounding this topic has

arisen from the lack of universal agreement about

definitions of the terms used to describe food intoler-

ance. There is also a difference in terminology used in

the UK and in the USA. For the purposes of this

review, the definitions based on those developed by

the British Nutrition Foundation Task Force (2001)

will be used (Table 1).

Food Intolerance

0003 Food intolerance is the term used to describe a range

of responses to food, including allergic reactions, ad-

verse reactions resulting from enzyme deficiencies,

pharmacological reactions, and responses to toxic or

irritant components of food (Table 1). All the adverse

reactions categorized under this heading share one

specific characteristic: they are reproducible adverse

reactions to specific foods or food ingredients.

Allergic Reactions

0004 These are abnormal reactions of a person’s immune

system to foreign but normally harmless substances,

such as pollen grains or food constituents. These

reactions may often be mediated by immunoglobulin

E (IgE), but there are some reactions which are

delayed and which do not involve IgE.

IgE-mediated reactions

0005 Allergic reactions with IgE involvement are immedi-

ate, can be severe, and are mediated by IgE antibodies

which trigger mast cells (andother cells). The mast cells

are present below the surface of the skin and in the

membranes lining the nose, respiratory tract, eyes,

intestine, and other mucosal sites. During an IgE-me-

diated reaction, histamine and other proinflammatory

substances which are present in these cells are released,

causing symptoms such as rhinitis, asthma, dilation of

blood vessels and flushing, swelling (e.g., of the lips),

and difficulty in breathing. These allergic reactions are

usually localized to one or two organs of the body.

0006Genetic factors are considered to be of particular

importance in the development of IgE-mediated reac-

tions. Atopy is the term used to describe a situation

where there is a predisposition to the production of

IgE antibodies and development of allergic disease.

0007Children with IgE-mediated reactions often react

to more than one food and high levels of IgE anti-

bodies to common food proteins, such as those pre-

sent in eggs and cows’ milk, are often predictive of

later allergy to inhalants such as house dust and

pollen. Food allergy does not commonly develop for

the first time in adults. However, oral allergy syn-

drome is sometimes seen in adults who have previ-

ously suffered hayfever. Oral allergy syndrome is an

IgE-mediated reaction, characterized by an initial ir-

ritation to the lips, oral mucosa and palate, followed

by edema within minutes of ingestion of the trigger

food, which is frequently a raw fruit or vegetable,

although the syndrome is also associated with the

consumption of tree nuts, peanuts, egg, fish, or milk.

0008Allergic reactions to food vary considerably in their

severity and the discomfort they cause, but the major-

ity are not life-threatening. However, anaphylactic

reactions can be very severe and even fatal. The

term anaphylaxis is now mainly applied to severe

reactions of rapid onset, often accompanied by a fall

in blood pressure and severe shock. Peanuts are well

known for causing this type of extreme reaction.

Other foods that are known occasionally to cause a

severe (IgE-mediated) reaction are tree nuts, seeds,

eggs, milk, and shellfish. Although most children

with sensitization to eggs or milk usually spontan-

eously recover in 12–24 months, sensitization to

peanut protein typically is more persistent.

Non-IgE-mediated reactions

0009These reactions are delayed and complex. Celiac dis-

ease is the best-defined example of this form of re-

sponse. It is a disease that involves a sensitivity to

gluten and appears to be mediated by the cells of

the immune system. Most experts agree that celiac

disease is a non-IgE-mediated reaction occurring in

genetically susceptible individuals and triggered by

exposure to the gluten fraction of wheat and other

related cereal grains, such as rye and barley.

0010Delayed reactions to food may take several hours

or days to develop. Reactions to cows’ milk are often

delayed and the majority are not accompanied by

detectable IgE antibodies.

Enzyme Deficiencies

0011The most common intolerance linked to an insuffi-

ciency of an enzyme is lactose intolerance (also

known as lactose maldigestion). Before it can be

tbl0001 Table 1 Adverse reactions to food

Foodaversion Foodintolerance Foodpoisoning

Food avoidance Allergic reactions Bacteria and

virusesPsychological

intolerance

Enzyme deficiencies

MoldsPharmacological reactions

ChemicalsToxic and irritant effects

Toxins

2622 FOOD INTOLERANCE/Types

absorbed and utilized by the body as fuel, lactose (the

sugar in milk) has to be broken down to its two

component sugars, glucose and galactose. This re-

quires the enzyme lactase. If lactase is produced in

insufficient quantities, some of the lactose can pass

undigested into the large intestine, causing symptoms

such as diarrhea and flatulence. The symptoms result

from bacterial fermentation of lactose in the colon

and the associated osmotic effects.

0012 In most populations, especially where the consump-

tion of milk beyond infancy is culturally uncommon,

lactase levels decline in childhood. The deficiency is

present in about 70% of the world population, par-

ticularly among those of African, Asian, and Jewish

descent. In South-east Asia, India, the Middle East and

parts of Africa, maldigestion of lactose in adults may

affect about one-third of the population. However, in

the UK, only 1–2% of adults are affected.

0013 On occasions other enzyme deficiencies can result

in an inability to handle specific dietary carbohydrates

such as galactose and sucrose. These conditions

are very rare. (See Inborn Errors of Metabolism:

Overview.)

Pharmacological Reactions

0014 There are many food components that can produce a

pharmacological effect. These effects are usually in-

significant in clinical terms, unless the substance is

consumed in very large quantities, e.g., the methyl

xanthine caffeine. (See Caffeine.)

0015 Also sometimes responsible for this type of reaction

is the group of substances known as vasoactive

amines, including histamine and tyramine (Table 2).

These are normal constituents of a variety of foods

such as cheese, pickled fish, yeast extract, chocolate,

bananas, avocados, citrus fruits, and wine. It is often

stated that some foods have a histamine-releasing

action, e.g., egg whites, shellfish, strawberries, toma-

toes, and chocolate.

0016 Histamine may also accumulate in several foods as

a result of microbial action during spoilage. During

this process, histidine in the food is converted to

histamine and it is believed that bacterial decarboxy-

lase enzymes are responsible. (See Histamine.)

0017High levels of histamine are responsible for scom-

brotoxin illness which can occur following the inges-

tion of scombroid fish, such as mackerel, which has

been stored inappropriately and has undergone spoil-

age. This type of problem can be prevented by insur-

ing that fish are properly refrigerated throughout the

processing and distribution chain. (See Fish: Spoilage

of Seafood.)

0018Histamine-induced symptoms are similar to those

found with IgE-mediated food allergy, which also

involves the release of histamine and other chemical

mediators from mast cells. The two conditions can be

distinguished by the relatively large amount of the

substance needed to trigger histamine-induced symp-

toms, in contrast to the minute quantity needed to

trigger an allergic reaction.

0019There is some evidence that reactions to certain

food additives, including some coloring agents, such

as tartrazine, and some preservatives, such as the

benzoates and sulfites, are also pharmacological in

origin, and may result from the release of histamine

or other chemical mediators. Although these reactions

may emulate allergic reactions, convincing evidence

to support an immunological basis for them is lacking.

Nevertheless, the expression of such reactions is so

variable that the possibility of an interaction between

biochemically and immunologically mediated mech-

anisms cannot be excluded until further research is

carried out. (See Food Additives: Safety.)

Toxic and Irritant Effects

0020Some foods contain natural toxins or substances that

can irritate the lining of the intestine. Examples of

natural toxins include protease inhibitors in legumes,

cyclopeptides, and muscarine in mushrooms, and ox-

alates in spinach and rhubarb. Spices and chilli may

irritate the gut mucosa and cause rapid intestinal

transit times. This may be confused with other types

of food intolerance. Some people are more susceptible

to these effects than others and irritation is more

likely if the mucosa is diseased.

Food Aversion

0021Food aversion is the alteration of eating behavior

for psychological reasons. It may manifest as

tbl0002 Table 2 Examples of vasoactive amines in foods

Vasoactive amine Food

Tyramine Cheese

Pickled fish

Phenylethylamine Chocolate

Serotonin Bananas

Octopamine Citrus fruit

Histamine Fermented foods, e.g., blue cheeses,

pickled fish

H C CCH

CH(NH

)COOH HC CCH

+ CO

Histidine Histamine

Decarboxylase

FOOD INTOLERANCE/Types 2623

psychological food intolerance, where there is an ad-

verse physical reaction associated with the ingestion

of a particular food, or food avoidance.

Psychological Food Intolerance

0022 This response may be associated with symptoms that

may be similar to those associated with true food

intolerance. Such reactions are psychosomatic and

do not occur when the food or food ingredient is

administered in disguised form. Anecdotally, in

some cases the bodily reaction can even be repro-

duced by the mere suggestion that a particular food

may have been consumed. Development of an aver-

sion to specific foods is recognized to occur occasion-

ally following vomiting associated with medical

treatments, where the food has been eaten at about

the same time.

0023 In some individuals food aversion can manifest

itself as hyperventilation syndrome in response to

food. In such cases, when faced with the food, indi-

viduals may hyperventilate to the extent that they

suffer severe symptoms and may even lose conscious-

ness. A variant of this form of aversion has been

dubbed ‘food intolerance by proxy.’ This has become

increasingly recognized in children. It occurs when an

individual’s family is unable to accept the symptoms

and behavior of the person, except in terms of a

physical illness. The belief that the problem is due to

an ‘allergy’ is continuously reinforced within the

family, but there is no evidence of a physical intoler-

ance on double-blind challenge.

Food Avoidance

0024 Food avoidance is quite common in the population

as a whole, especially in preschool children and

adolescents. It may manifest as the avoidance of all

food, or of particular foods or food types. It is most

prevalent in teenage girls who are frequently ob-

sessed with losing weight and maintaining a particu-

lar body image. The extremes of this type of behavior

manifest as the eating disorders anorexia nervosa and

bulimia nervosa. (See Anorexia Nervosa; Bulimia

Nervosa.)

Clinical Manifestations

0025 The symptoms which can occur as a result of reac-

tions to food fall into three main groups: immediate

(within 1 h of ingestion); delayed or late (more than

1 h after ingestion); and remote.

0026 Examples of these symptoms are as follows:

0027 immediate gastrointestinal symptoms, e.g., lip and

tongue swelling, mouth tingling, vomiting, ab-

dominal pain

0028late gastrointestinal symptoms, e.g., diarrhea,

bloating, constipation

0029remote symptoms, e.g., anaphylaxis, angiedema,

rhinitis, urticaria, eczema, asthma, joint pains,

headaches, depression, irritability

Diagnosis

0030The diagnosis of food intolerance and specifically of

food allergy is not straightforward in most cases be-

cause of the nonspecific nature of many of the symp-

toms. The first stage is to take a careful medical and

family history. A positive family history of atopy

increases the likelihood of the diagnosis of allergy in

an individual.

0031The timing of development of reactions to foods is

also an important part of the diagnosis. The time

course of some common symptoms of food intoler-

ance is shown in Figure 1.

0032A reaction that may involve swelling of the lips and

tongue, vomiting, rhinorrhea, urticaria, and asthma

within minutes of ingesting a food is evidence of an

immunological mechanism. When the symptoms

occur more than an hour after the food is consumed,

or only after repeated exposure to the food, an

immune basis for the reaction is less frequently found.

0033Laboratory investigations may be used to confirm

the diagnosis, especially when food allergy is sus-

pected. The immediate type of allergic response is

frequently associated with increased blood levels of

IgE and the presence of IgE antibodies to food pro-

teins. Skin prick tests and the radioallergosorbent test

(RAST) are used to identify the presence of IgE. The

procedure for RAST is as follows: a sample of blood is

placed on paper impregnated with purified antigen;

the amount of antibody that interacts is estimated by

Lip swelling

Vomiting

Rhinorrhea

Urticaria

Diarrhea

Asthma

Eczema

Headache, irritability, malaise

12472

Time (h)

fig0001Figure 1 Symptoms and time course of food intolerance. From

Lessof MH (1983) Reactions to food in adults. In: Lessof MH (ed.)

Clinical Reactions to Food, p 112. Chichester: John Wiley.

2624 FOOD INTOLERANCE/Types

the use of radioactive markers. These tests are widely

used in the diagnosis of allergic disease which is not

related to food. The results are likely to be positive in

cases of immediate reactions to food, but general use

of these tests in the diagnosis of food allergy is con-

troversial because of difficulties in obtaining pure

food proteins for testing and frequent false-positive

responses.

0034 The measurement of blood levels of histamine, of

histamine release, and of other mediators from white

blood cells has been investigated as another diag-

nostic technique. As yet, the results have been too

variable for these tests to become part of routine

diagnoses.

0035 The only sure diagnostic approach in food intoler-

ance is the use of some form of elimination diet. The

nature of the diet will depend on the clinical symp-

toms and provisional diagnosis. This may simply in-

volve the elimination of individual suspect foods, or

the exclusion of all foods commonly associated with

adverse reactions. These include milk products, eggs,

wheat products, fish, nuts, pork, chocolate, coffee,

tea, citrus fruits, and foods containing preservatives

and coloring agents. In some cases an extremely

restricted or ‘oligoantigenic’ (few foods) diet of

lamb, rice, and pears is used.

0036 If the symptoms disappear over the course of the

diet, the patient is ‘challenged’ with the suspect food

or ingredient. If there are many foods involved, these

must be reintroduced slowly, one at a time and over a

period of weeks or months, to see if the symptoms

recur. In some cases it is necessary to confirm the

diagnosis by a double-blind challenge, in which the

suspect food is given in disguised form so that both

the patient and doctor or dietitian are unaware of

what has been ingested.

0037 There are also numerous unorthodox diagnostic

tests for which extravagant claims are made. In gen-

eral these have been shown to be of little value in

diagnosis and in some cases to be misleading and

potentially dangerous because the false diagnoses

resulting from their use can lead to inappropriate

treatments. These include the pulse test, the sublin-

gual test, the interdermal skin test, cytotoxic tests,

and hair sample tests.

Treatment

0038 Once the food or range of foods or ingredients has

been identified as the cause of intolerance, a diet

which avoids these foods must be followed. If this

only involves the removal of a few foods which are

‘nonessential’, e.g., strawberries or shellfish, then this

is straightforward. Where important groups of foods

must be excluded, such as cereals or milk products,

the advice of an experienced dietitian is essential and

supplements may be necessary to insure nutritional

adequacy of the diet, particularly in children.

0039Various drug treatments such as antihistamines and

antiinflammatory drugs may be used as an adjunct to

the diet, depending on the severity of the condition.

Predisposing Factors to Food Intolerance

0040There is still much to be learnt about the predisposing

factors to food intolerance. It is established that

enzyme defects are inherited and that the predispos-

ition to the true food allergy is also inherited. Food

allergies are certainly more common in the offspring

of atopic parents. In some individuals, more than one

type of intolerance may coexist. For example, a

person might display an allergic (IgE-mediated) reac-

tion to certain foods and a pharmacological sensitiv-

ity to other foods. Much more research is needed to

explain the causes of food intolerance and to establish

what factors, both genetic and environmental, deter-

mine an individual’s susceptibility.

Prevalence

0041Assessment of the prevalence of food intolerance is

also difficult, and wide ranges of incidence have been

reported in the scientific literature. This is not surpris-

ing as many of the estimates are based on selected

populations and the diagnostic criteria and testing

procedures used in different studies vary consider-

ably.

0042When adverse reactions to food occur, intolerance

rather than true allergy is usually the problem. With

the exception of the very rare inborn errors of metab-

olism, which are usually diagnosed in the neonatal

period, there are few reliable estimates of the preva-

lence of nonallergic reactions.

0043Food additive intolerance has been studied more

carefully and it is estimated that between 0.01% and

0.23% of the general population in the UK may have

adverse reactions to some food additives. The inci-

dence of such reactions rises dramatically in sensitive

populations, such as those suffering from chronic

urticaria. Reports in the scientific literature suggest

that as many as 30–50% of such populations may

display sensitivity to certain additives.

0044Estimates of the prevalence of food intolerance in

the general population are no more than 5–6% and

an estimated 2% of the population may have IgE-

mediated food allergies, whereas as many as 20–

30% of the UK population perceive themselves to be

food-intolerant, or in common parlance, ‘allergic’ to

food. However, as yet there are no systematic data

which enable the accurate calculation of the incidence

FOOD INTOLERANCE/Types 2625

and prevalence of adverse reactions to food, either in

the UK or elsewhere.

0045 Adverse reactions to food are more frequently

reported in infants and young children, with varying

prevalence estimates from 0.3% to 20% of children.

However, the majority of such reactions resolve them-

selves in childhood and certainly by adolescence. The

prevalence of IgE-mediated reactions is higher in

young children than adults, with an estimate of

about 5%.

0046 It has been suggested that inhalant and possibly

food allergies have increased in prevalence, but the

swiftness with which apparent change has come

about precludes a change in the gene pool being re-

sponsible. There has been an increase in the numbers

of people suffering from food-induced anaphylaxis;

the reason for this is uncertain.

See also: Anorexia Nervosa; Bulimia Nervosa; Caffeine;

Fish: Spoilage of Seafood; Food Additives: Safety;

Histamine; Inborn Errors of Metabolism: Overview