Editing Food intolerance

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'''Food intolerance''' is a detrimental reaction, often delayed, to a food, beverage, [[food additive]], or compound found in foods that produces symptoms in one or more body organs and systems, but generally refers to reactions other than [[food allergy]]. Food hypersensitivity is used to refer broadly to both food intolerances and food allergies.<ref name=":0">{{Cite journal|last=Lomer|first=M. C. E.|date=2015-02-01|title=Review article: the aetiology, diagnosis, mechanisms and clinical evidence for food intolerance|journal=Alimentary Pharmacology & Therapeutics|language=en|volume=41|issue=3|pages=262–275|doi=10.1111/apt.13041|pmid=25471897|s2cid=8243181 |issn=1365-2036}}</ref>

Food allergies are immune reactions, typically an [[Immunoglobulin E|IgE]] reaction caused by the release of [[histamine]] but also encompassing non-IgE immune responses.<ref name=":0" /> This mechanism causes allergies to typically give immediate reaction (a few minutes to a few hours) to foods.

Food intolerances can be classified according to their mechanism. Intolerance can result from the absence of specific [[chemical]]s or [[enzyme]]s needed to [[digestion|digest]] a food substance, as in [[hereditary fructose intolerance]]. It may be a result of an abnormality in the body's ability to absorb nutrients, as occurs in [[fructose malabsorption]]. Food intolerance reactions can occur to naturally occurring chemicals in foods, as in [[salicylate sensitivity]]. Drugs sourced from plants, such as aspirin, can also cause these kinds of reactions.

== Definitions ==
Food hypersensitivity is used to refer broadly to both food intolerances and food allergies.<ref name=":0" /> There are a variety of earlier terms which are no longer in use such as "pseudo-allergy".<ref>{{cite journal|date=August 2003|title=[Revised terminology for allergies and related conditions]|journal=Ned Tijdschr Tandheelkd|language=nl|volume=110|issue=8|pages=328–31|pmid=12953386|vauthors=Gerth van Wijk R, van Cauwenberge PB, Johansson SG}}</ref>

Food intolerance reactions can include [[pharmacologic]], metabolic, and gastro-intestinal responses to foods or food compounds. Food intolerance does not include either psychological responses<ref name="pmid11551246">{{cite journal|last4=Bruijnzeel-Koomen|first4=C.|last5=Dreborg|first5=S.|last6=Haahtela|first6=T.|last7=Kowalski|first7=M. L.|last8=Mygind|first8=N.|last9=Ring|first9=J.|date=September 2001|title=A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force|url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0105-4538&date=2001&volume=56&issue=9&spage=813|archive-url=https://archive.today/20130105093126/http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0105-4538&date=2001&volume=56&issue=9&spage=813|url-status=dead|archive-date=2013-01-05|journal=Allergy|volume=56|issue=9|pages=813–24|doi=10.1034/j.1398-9995.2001.t01-1-00001.x|pmid=11551246|author=Johansson SG|name-list-style=vanc|author2=Hourihane JO|author3=Bousquet J|display-authors=3|url-access=subscription}}</ref> or [[foodborne illness]].

A non-allergic food hypersensitivity is an abnormal physiological response. It can be difficult to determine the poorly tolerated substance as reactions can be delayed, dose-dependent, and a particular reaction-causing compound may be found in many foods.<ref name="vic">{{cite web|url=http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Food_allergy_and_intolerance|title=Food allergy and intolerance &#124; Better Health Channel|publisher=betterhealth.vic.gov.au|access-date=27 June 2014|archive-date=12 October 2015|archive-url=https://web.archive.org/web/20151012213917/http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Food_allergy_and_intolerance|url-status=dead}}</ref>

*Metabolic food reactions are due to [[inborn error of metabolism|inborn]] or acquired errors of metabolism of nutrients, such as in [[lactase deficiency]], [[phenylketonuria]] and [[favism]].
*Pharmacological reactions are generally due to low-molecular-weight chemicals which occur either as natural compounds, such as [[salicylate sensitivity|salicylates]], [[amine]]s and [[Monosodium glutamate|glutamates]] or to [[food additive]]s, such as preservatives, colouring, emulsifiers and flavour enhancers. These chemicals are capable of causing drug-like (biochemical) side effects in susceptible individuals.<ref name = "Clarke" />
*Gastro-intestinal (GI) reactions can be due to [[malabsorption]] or other GI tract abnormalities.
*Immunological responses are mediated by non-IgE immunoglobulins, where the immune system recognises a particular food as a foreign body.
*Toxins may either be present naturally in food, be released by bacteria, or be due to contamination of food products.<ref name = "Clarke" /> Toxic food reactions are caused by the direct action of a food or substance without immune involvement.<ref name = "Clarke" />
*Psychological reactions involve manifestation of clinical symptoms caused not by food but by [[emotions]] associated with food. These symptoms do not occur when the food is given in an unrecognisable form.<ref name = "Clarke" />

[[Elimination diet]]s are useful to assist in the diagnosis of food intolerance. There are specific diagnostic tests for certain food intolerances.<ref name = "Clarke" /><ref name="pmid16782524" /><ref name="pmid16687980" />

==Signs and symptoms==

Food intolerance is more chronic, less acute, less obvious in its presentation, and often more difficult to diagnose than a food allergy.<ref name="pmid10565387">
{{cite journal |author=Vanderhoof JA |title=Food hypersensitivity in children |journal=Current Opinion in Clinical Nutrition and Metabolic Care |volume=1 |issue=5 |pages=419–22 |year=1998 |issn=1363-1950 |pmid=10565387 |doi=10.1097/00075197-199809000-00009}}</ref> Symptoms of food intolerance vary greatly, and can be mistaken for the symptoms of a [[food allergy]]. While true allergies are associated with fast-acting [[immunoglobulin]] IgE responses, it can be difficult to determine the offending food causing a food intolerance because the response generally takes place over a prolonged period of time. Thus, the causative agent and the response are separated in time, and may not be obviously related. Food intolerance symptoms usually begin about half an hour after eating or drinking the food in question, but sometimes symptoms may be delayed by up to 48 hours.<ref name="pmid18594978" />

Food intolerance can present with symptoms affecting the skin, [[respiratory tract]], [[gastrointestinal tract]] (GIT) either individually or in combination. On the skin may include [[skin rashes]], [[urticaria]] (hives),<ref name="pmid12590308">{{cite journal |vauthors=Maurer M, Hanau A, Metz M, Magerl M, Staubach P |title=[Relevance of food allergies and intolerance reactions as causes of urticaria] |language=de |journal=Hautarzt |volume=54 |issue=2 |pages=138–43 |date=February 2003 |pmid=12590308 |doi=10.1007/s00105-002-0481-2 |s2cid=24220704 }}</ref> [[angioedema]],<ref name="pmid12843808">{{cite journal |author=Moneret-Vautrin DA |title=[Allergic and pseudo-allergic reactions to foods in chronic urticaria] |language=fr |journal=Ann Dermatol Venereol |volume=130 Spec No 1 |pages=1S35–42 |date=May 2003 |pmid=12843808 |url=http://www.masson.fr/masson/MDOI-AD-05-2003-130-HS1-0151-9638-101019-ART7}}</ref> dermatitis,<ref name="pmid11298023">{{cite journal |vauthors=Novembre E, Vierucci A |title=Milk allergy/intolerance and atopic dermatitis in infancy and childhood |journal=Allergy |volume=56 |pages=105–8 |year=2001 |issue=Suppl 67 |pmid=11298023 |doi= 10.1111/j.1398-9995.2001.00931.x|s2cid=46144087 }}{{dead link|date=February 2019|bot=medic}}{{cbignore|bot=medic}}</ref> and [[eczema]].<ref name="pmid18971901">{{cite journal |author=Cardinale F |title=[Intolerance to food additives: an update] |language=it |journal=Minerva Pediatr. |volume=60 |issue=6 |pages=1401–9 |date=December 2008 |pmid=18971901 |name-list-style=vanc|author2=Mangini F |author3=Berardi M |display-authors=3 |last4=Sterpeta Loffredo |first4=M |last5=Chinellato |first5=I |last6=Dellino |first6=A |last7=Cristofori |first7=F |last8=Di Domenico |first8=F |last9=Mastrototaro |first9=MF}}</ref> Respiratory tract symptoms can include [[nasal congestion]], [[sinusitis]], [[Human pharynx|pharyngeal]] irritations, [[asthma]] and an unproductive [[cough]]. GIT symptoms include [[mouth ulcer]]s, abdominal cramp, [[nausea]], [[flatulence|gas]], intermittent [[diarrhea]], [[constipation]], [[irritable bowel syndrome]] (IBS),<ref name="pmid16782524">
{{cite journal |vauthors=Ortolani C, Pastorello EA |title=Food allergies and food intolerances |journal=Best Pract Res Clin Gastroenterol |volume=20 |issue=3 |pages=467–83 |year=2006 |pmid=16782524 |doi=10.1016/j.bpg.2005.11.010}}</ref><ref name="pmid16687980">
{{cite journal |vauthors=Pastar Z, Lipozencić J |title=Adverse reactions to food and clinical expressions of food allergy |journal=Skinmed |volume=5 |issue=3 |pages=119–25; quiz 126–7 |year=2006 |pmid=16687980 |doi=10.1111/j.1540-9740.2006.04913.x}}</ref><ref name="pmid18594978">
{{cite journal |vauthors=Ozdemir O, Mete E, Catal F, Ozol D |title=Food intolerances and eosinophilic esophagitis in childhood |journal=Dig Dis Sci |volume=54 |issue=1 |pages=8–14 |date=January 2009 |pmid=18594978 |doi=10.1007/s10620-008-0331-x|s2cid=3076884 }}</ref> and may include [[anaphylaxis]].<ref name="pmid18971901"/>

Food intolerance has been found associated with irritable bowel syndrome and [[inflammatory bowel disease]],<ref name="pmid17206644">
{{cite journal |author=MacDermott RP |s2cid=24307163 |title=Treatment of irritable bowel syndrome in outpatients with inflammatory bowel disease using a food and beverage intolerance, food and beverage avoidance diet |journal=Inflamm Bowel Dis |volume=13 |issue=1 |pages=91–6 |year=2007 |pmid=17206644 |doi=10.1002/ibd.20048|doi-access=free }}</ref> chronic constipation,<ref name="pmid16635922">
{{cite journal |author=Carroccio A |title=Multiple food hypersensitivity as a cause of refractory chronic constipation in adults |journal=Scand J Gastroenterol |volume=41 |issue=4 |pages=498–504 |year=2006 |pmid=16635922 |doi=10.1080/00365520500367400 |name-list-style=vanc|author2=Di Prima L |author3=Iacono G |display-authors=3 |last4=Florena |first4=Ada M. |last5=d'Arpa |first5=Francesco |last6=Sciumè |first6=Carmelo |last7=Cefalù |first7=Angelo B. |last8=Noto |first8=Davide |last9=Averna |first9=Maurizio R.|hdl=10447/10104 |s2cid=24551094 |url=https://iris.unipa.it/bitstream/10447/10104/2/Scand%20J%20Gastroenterol%202006%2041%20498-504.pdf |hdl-access=free }}</ref> chronic hepatitis C infection,<ref name="pmid16632081">
{{cite journal |author=Lang CA |title=Symptom prevalence and clustering of symptoms in people living with chronic hepatitis C infection |journal=J Pain Symptom Manage |volume=31 |issue=4 |pages=335–44 |date=April 2006 |pmid=16632081 |doi=10.1016/j.jpainsymman.2005.08.016 |name-list-style=vanc|author2=Conrad S |author3=Garrett L |display-authors=3 |last4=Battistutta |first4=D |last5=Cooksley |first5=W |last6=Dunne |first6=M |last7=MacDonald |first7=G|doi-access=free }}
</ref> eczema,<ref name="pmid16675339">
{{cite journal |vauthors=Maintz L, Benfadal S, Allam JP, Hagemann T, Fimmers R, Novak N |title=Evidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema |journal=The Journal of Allergy and Clinical Immunology |volume=117 |issue=5 |pages=1106–12 |date=May 2006 |pmid=16675339 |doi=10.1016/j.jaci.2005.11.041 |doi-access=free }}
</ref> NSAID intolerance,<ref name="pmid16247191">
{{cite journal |author=Raithel M |title=Significance of salicylate intolerance in diseases of the lower gastrointestinal tract |journal=J. Physiol. Pharmacol. |volume=56 |pages=89–102 |date=September 2005 |pmid=16247191 |url=http://www.jpp.krakow.pl/journal/archive/0905_s5/pdf/89_0905_s5_article.pdf |name-list-style=vanc |author2=Baenkler HW |author3=Naegel A |display-authors=3 |last4=Buchwald |first4=F |last5=Schultis |first5=HW |last6=Backhaus |first6=B |last7=Kimpel |first7=S |last8=Koch |first8=H |last9=Mach |first9=K |issue=Suppl 5 |access-date=14 April 2009 |archive-url=https://web.archive.org/web/20090326175200/http://www.jpp.krakow.pl/journal/archive/0905_s5/pdf/89_0905_s5_article.pdf |archive-date=26 March 2009 |url-status=dead}}
</ref> respiratory complaints,<ref name="pmid9543285">
{{cite journal |vauthors=Woods RK, Abramson M, Raven JM, Bailey M, Weiner JM, Walters EH |title=Reported food intolerance and respiratory symptoms in young adults |journal=Eur. Respir. J. |volume=11 |issue=1 |pages=151–5 |date=January 1998 |pmid=9543285 |doi= 10.1183/09031936.98.11010151|doi-access=free }}
</ref> including asthma,<ref name="pmid17490952">
{{cite journal |vauthors=Maintz L, Novak N |title=Histamine and histamine intolerance |journal=Am J Clin Nutr |volume=85 |issue=5 |pages=1185–96 |year=2007 |pmid=17490952 |doi=10.1093/ajcn/85.5.1185|doi-access=free }}</ref> [[rhinitis]] and headache,<ref name="pmid18649066">
{{cite journal |vauthors=Böttcher I, Klimek L |title=[Histamine intolerance syndrome. Its significance for ENT medicine] |language=de |journal=HNO |volume=56 |issue=8 |pages=776–83 |date=August 2008 |pmid=18649066 |doi=10.1007/s00106-008-1793-z |s2cid=39347593 }}
</ref><ref name="pmid9012205">
{{cite journal |author=Götz M |title=[Pseudo-allergies are due to histamine intolerance] |language=de |journal=Wien Med Wochenschr |volume=146 |issue=15 |pages=426–30 |year=1996 |pmid=9012205 }}
</ref> [[functional dyspepsia]],<ref name="pmid16918725">
{{cite journal |vauthors=Feinle-Bisset C, Horowitz M |title=Dietary factors in functional dyspepsia |journal=Neurogastroenterol. Motil. |volume=18 |issue=8 |pages=608–18 |date=August 2006 |pmid=16918725 |doi=10.1111/j.1365-2982.2006.00790.x |s2cid=22115920 }}
</ref> [[eosinophilic esophagitis]]<ref name="pmid18594978"/> and ear, nose and throat (ENT) illnesses.<ref name="pmid18649066"/><ref name="pmid14743781">
{{cite journal |author=Gordon BR |title=Approaches to testing for food and chemical sensitivities |journal=Otolaryngol. Clin. North Am. |volume=36 |issue=5 |pages=917–40 |date=October 2003 |pmid=14743781 |doi= 10.1016/S0030-6665(03)00059-8}}
</ref>

==Causes==

Reactions to chemical components of the diet may be more common than true food allergies,{{Citation needed|date=April 2009}} although there is no evidence to support this. They are caused by various organic chemicals occurring naturally in a wide variety of foods, animal and vegetable, more often than to food additives, preservatives, colourings and flavourings, such as [[Sulfite food and beverage additives|sulfite]]s or dyes.<ref name="pmid18971901"/> Both natural and artificial ingredients may cause adverse reactions in sensitive people if consumed in sufficient amounts, the degree of sensitivity varying between individuals.

Pharmacological responses to naturally occurring compounds in food, or chemical intolerance, can occur in individuals from both allergic and non-allergic family backgrounds. Symptoms may begin at any age, and may develop quickly or slowly. Triggers may range from a viral infection or illness to environmental chemical exposure. Chemical intolerance occurs more commonly in women, which may be because of hormone differences, as many food chemicals mimic hormones.{{Citation needed|date=May 2014}}

A deficiency in digestive enzymes can also cause some types of food intolerances. [[Lactose intolerance]] is a result of the body not producing sufficient [[lactase]] to digest the lactose in milk;<ref name="pmid16951027">{{cite journal |author=Heyman MB |title=Lactose intolerance in infants, children, and adolescents |journal=Pediatrics |volume=118 |issue=3 |pages=1279–86 |date=September 2006 |pmid=16951027 |doi=10.1542/peds.2006-1721 |last2=Committee On |first2=Nutrition|s2cid=2996092 |doi-access= }}</ref><ref name="pmid9742907">{{cite journal |vauthors=Srinivasan R, Minocha A |title=When to suspect lactose intolerance. Symptomatic, ethnic, and laboratory clues |journal=Postgrad Med |volume=104 |issue=3 |pages=109–11, 115–6, 122–3 |date=September 1998 |pmid=9742907 |doi=10.3810/pgm.1998.09.577 |url=http://www.postgradmed.com/index.php?art=pgm_09_1998%3Farticle%3D577 |access-date=16 April 2009 |archive-date=19 February 2021 |archive-url=https://web.archive.org/web/20210219135026/https://www.tandfonline.com/toc/ipgm20/current |url-status=dead |url-access=subscription }}</ref> dairy foods which are lower in lactose, such as cheese, are less likely to trigger a reaction in this case. Another carbohydrate intolerance caused by enzyme deficiency is [[hereditary fructose intolerance]].

[[Celiac disease]], an autoimmune disorder caused by an immune response to the protein gluten, results in gluten intolerance and can lead to temporary lactose intolerance.<ref name="pmid16313685">{{cite journal |vauthors=McGough N, Cummings JH |title=Coeliac disease: a diverse clinical syndrome caused by intolerance of wheat, barley and rye |journal=Proc Nutr Soc |volume=64 |issue=4 |pages=434–50 |date=November 2005 |pmid=16313685 |doi= 10.1079/PNS2005461|doi-access=free }}</ref><ref name="pmid15137480">{{cite journal |author=Rousset H |title=[A great imitator for the allergologist: intolerance to gluten] |language=fr |journal=Eur Ann Allergy Clin Immunol |volume=36 |issue=3 |pages=96–100 |date=March 2004 |pmid=15137480 }}</ref>

The most widely distributed naturally occurring food chemical capable of provoking reactions is [[salicylate]],<ref name="pmid16247191"/> although [[tartrazine]] and [[benzoic acid]] are well recognised in susceptible individuals.<ref name="pmid17218045">{{cite journal |author=Elhkim MO |title=New considerations regarding the risk assessment on Tartrazine An update toxicological assessment, intolerance reactions and maximum theoretical daily intake in France |journal=Regul. Toxicol. Pharmacol. |volume=47 |issue=3 |pages=308–16 |date=April 2007 |pmid=17218045 |doi=10.1016/j.yrtph.2006.11.004 |name-list-style=vanc|author2=Héraud F |author3=Bemrah N |display-authors=3 |last4=Gauchard |first4=Françoise |last5=Lorino |first5=Tristan |last6=Lambré |first6=Claude |last7=Frémy |first7=Jean Marc |last8=Poul |first8=Jean-Michel}}</ref><ref name="pmid15491435">{{cite journal |vauthors=Nettis E, Colanardi MC, Ferrannini A, Tursi A |title=Sodium benzoate-induced repeated episodes of acute urticaria/angio-oedema: randomized controlled trial |journal=Br. J. Dermatol. |volume=151 |issue=4 |pages=898–902 |date=October 2004 |pmid=15491435 |doi=10.1111/j.1365-2133.2004.06095.x |s2cid=22547849 }}</ref><ref name="pmid11251628">{{cite journal |vauthors=Worm M, Vieth W, Ehlers I, Sterry W, Zuberbier T |title=Increased leukotriene production by food additives in patients with atopic dermatitis and proven food intolerance |journal=Clin. Exp. Allergy |volume=31 |issue=2 |pages=265–73 |date=February 2001 |pmid=11251628 |doi= 10.1046/j.1365-2222.2001.00979.x|s2cid=33634326 }}</ref> Benzoates and salicylates occur naturally in many foods, including fruits, juices, vegetables, spices, herbs, nuts, tea, wines, and coffee. [[Salicylate sensitivity]] causes reactions to aspirin and other NSAIDs, and also in foods which naturally contain salicylates, such as cherries.

Other natural chemicals which commonly cause reactions and cross reactivity include [[amines]], [[nitrates]], [[sulphites]] and some antioxidants. Chemicals involved in aroma and flavour are often suspect.<ref name="pmid17490952"/><ref name="pmid10413828">{{cite journal |vauthors=Schnyder B, Pichler WJ |title=[Food intolerance and food allergy] |language=de |journal=Schweiz Med Wochenschr |volume=129 |issue=24 |pages=928–33 |date=June 1999 |pmid=10413828 }}</ref><ref name="pmid12657413">{{cite journal |vauthors=Millichap JG, Yee MM |title=The diet factor in pediatric and adolescent migraine |journal=Pediatr. Neurol. |volume=28 |issue=1 |pages=9–15 |date=January 2003 |pmid=12657413 |doi= 10.1016/S0887-8994(02)00466-6}}</ref><ref name="pmid8795668">{{cite journal |vauthors=Hodge L, Yan KY, Loblay RL |title=Assessment of food chemical intolerance in adult asthmatic subjects |journal=Thorax |volume=51 |issue=8 |pages=805–9 |date=August 1996 |pmid=8795668 |pmc=472547 |doi= 10.1136/thx.51.8.805}}</ref>

The classification or avoidance of foods based on botanical families bears no relationship to their chemical content and is not relevant in the management of food intolerance.{{Citation needed|date=May 2014}}

Salicylate-containing foods include apples, citrus fruits, strawberries, tomatoes, and wine, while reactions to chocolate, cheese, bananas, avocado, tomato or wine point to amines as the likely food chemical. Thus, exclusion of single foods does not necessarily identify the chemical responsible as several chemicals can be present in a food, the patient may be sensitive to multiple food chemicals and reaction more likely to occur when foods containing the triggering substance are eaten in a combined quantity that exceeds the patient's sensitivity thresholds. People with food sensitivities have different sensitivity thresholds, and so more sensitive people will react to much smaller amounts of the substance.<ref name = "Clarke">
{{cite journal |author=Clarke L |year=1996 |title=The dietary management of food allergy and food intolerance in children and adults |journal=Aust J Nutr Diet |volume=53 |issue=3 |pages=89–98 |issn=1032-1322 |name-list-style=vanc|author2=McQueen J |display-authors=2 |author3=<Please add first missing authors to populate metadata.>}}</ref><ref name="pmid18594978" /><ref name="pmid17490952" /><ref name="pmid12657413" /><ref name="pmid8795668"/><ref name="pmid17361633">
{{cite journal |vauthors=Layer P, Keller J |title=[Therapy of functional bowel disorders] |language=de |journal=Praxis |volume=96 |issue=9 |pages=323–6 |year=2007 |pmid=17361633 |doi=10.1024/1661-8157.96.9.323}}
</ref><ref name="pmid11982551">
{{cite journal |vauthors=Parker G, Watkins T |title=Treatment-resistant depression: when antidepressant drug intolerance may indicate food intolerance |journal=The Australian and New Zealand Journal of Psychiatry |volume=36 |issue=2 |pages=263–5 |year=2002 |pmid=11982551 |doi=10.1046/j.1440-1614.2002.00978.x|s2cid=46611658 }}
</ref><ref name="pmid16394795">
{{cite journal |author=Iacono G |title=Food intolerance and chronic constipation: manometry and histology study |journal=European Journal of Gastroenterology & Hepatology |volume=18 |issue=2 |pages=143–50 |year=2006 |pmid=16394795 |doi=10.1097/00042737-200602000-00006 |name-list-style=vanc|author2=Bonventre S |author3=Scalici C |display-authors=3 |last4=Maresi |first4=Emiliano |last5=Prima |first5=Lidia Di |last6=Soresi |first6=Maurizio |last7=Ges?? |first7=Giuseppe Di |last8=Noto |first8=Davide |last9=Carroccio |first9=Antonio|s2cid=20007207 |hdl=10447/4967 |hdl-access=free }}
</ref><ref name="pmid15090915">
{{cite journal |author=Asero R |title=Food additives intolerance: does it present as perennial rhinitis? |journal=Current Opinion in Allergy and Clinical Immunology |volume=4 |issue=1 |pages=25–9 |year=2004 |pmid=15090915 |doi=10.1097/00130832-200402000-00006|s2cid=21383210 }}
</ref><ref name="pmid17357334">
{{cite journal |vauthors=Semeniuk J, Kaczmarski M |title=Gastroesophageal reflux (GER) in children and adolescents with regard to food intolerance |journal=Adv Med Sci |volume=51 |pages=321–6 |year=2006 |pmid=17357334 }}</ref>

==Pathogenesis==
{{Expand section|date=January 2009}}
Food intolerance are all other adverse reactions to food. Subgroups include enzymatic (e.g. lactose intolerance due to lactase deficiency), pharmacological (e.g. reactions against biogenic amines, [[histamine intolerance]]), and undefined food intolerance (e.g. against some food additives).<ref name="pmid19340768">{{cite journal |author=Wüthrich B |title=[Food allergy, food intolerance or functional disorder?] |language=de |journal=Praxis |volume=98 |issue=7 |pages=375–87 |date=April 2009 |pmid=19340768 |doi=10.1024/1661-8157.98.7.375 }}</ref>

Food intolerances can be caused by enzymatic defects in the digestive system, can also result from pharmacological effects of vasoactive amines present in foods (e.g. histamine),<ref name="pmid16782524" /> among other metabolic, pharmacological and digestive abnormalities.

Allergies and intolerances to a food group may coexist with separate pathologies; for example, cow's [[milk allergy]] (CMA) and lactose intolerance are two distinct pathologies.

==Diagnosis==
Diagnosis of food intolerance can include [[hydrogen breath test]]ing for lactose intolerance and [[fructose malabsorption]], professionally supervised [[elimination diet]]s, and [[ELISA]] testing for IgG-mediated immune responses to specific foods. It is important to be able to distinguish between food allergy, food intolerance, and autoimmune disease in the management of these disorders.<ref name="pmid9196849">
{{cite journal |author=Kitts D |title=Adverse reactions to food constituents: allergy, intolerance, and autoimmunity |journal=[[Can J Physiol Pharmacol]] |volume=75 |issue=4 |pages=241–54 |year=1997 |pmid=9196849 |doi=10.1139/cjpp-75-4-241 |name-list-style=vanc|author2=Yuan Y |author3=Joneja J |display-authors=3 |last4=Scott |first4=F. |last5=Szilagyi |first5=A. |last6=Amiot |first6=J. |last7=Zarkadas |first7=M.}}</ref> Non-IgE-mediated intolerance is more chronic, less acute, less obvious in its clinical presentation, and often more difficult to diagnose than allergy, as skin tests and standard immunological studies are not helpful.<ref name="pmid10565387" /> Elimination diets must remove all poorly tolerated foods, or all foods containing offending compounds. Clinical investigation is generally undertaken only for more serious cases, as for minor complaints which do not significantly limit the person's lifestyle the cure may be more inconvenient than the problem.<ref name = "Clarke" />

Immunoglobulin (IgG) tests measure the types of food-specific antibodies present. There are four types of IgG, IgG1 makes up 60-70% of the total IgG, followed by IgG2 (20-30%), IgG3 (5-8%), and IgG4 (1-4%). Most commercially available tests only test for IgG4 antibodies, however some companies such as YorkTest Laboratories test for all four types.<ref>{{Cite web|title=What is the difference between IgG food intolerance tests?|url=https://www.yorktest.com/what-is-igg/|access-date=2020-07-09|website=YorkTest|language=en-GB}}</ref>

IgG4 only tests are debatably invalid; IgG4 presence indicates that the person has been repeatedly exposed to food proteins recognized as foreign by the immune system which is a normal physiological response of the immune system after exposure to food components.<ref name="pmid18489614">
{{cite journal |author=Stapel SO |title=Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report |journal=Allergy |volume=63 |issue=7 |pages=793–6 |date=July 2008 |pmid=18489614 |doi=10.1111/j.1398-9995.2008.01705.x |url=http://www.zora.uzh.ch/id/eprint/14049/1/IgG4.pdf |name-list-style=vanc|author2=Asero R |author3=Ballmer-Weber BK |display-authors=3 |last4=Knol |first4=E. F. |last5=Strobel |first5=S. |last6=Vieths |first6=S. |last7=Kleine-Tebbe |first7=J. |last8=Eaaci Task |first8=Force|s2cid=14061223 }}</ref><ref name=":0" /> Although elimination of foods based on IgG-4 testing in [[Irritable bowel syndrome|IBS]] patients resulted in an improvement in symptoms,<ref>{{cite journal|pmid=15361495|year=2004|last1=Atkinson|first1=W|last2=Sheldon|first2=TA|last3=Shaath|first3=N|last4=Whorwell|first4=PJ|title=Food elimination based on IgG antibodies in irritable bowel syndrome: A randomised controlled trial|volume=53|issue=10|pages=1459–64|doi=10.1136/gut.2003.037697|pmc=1774223|journal=Gut}}</ref> the positive effects of food elimination were more likely due to wheat and milk elimination than IgG-4 test-determined factors.<ref>{{cite journal|pmid=    16009694|year=2005|last1=Hunter|first1=JO|title=Food elimination in IBS: the case for IgG testing remains doubtful|volume=54|issue=8|pages=1203|pmc=1774875|journal=Gut}}</ref> The IgG-4 test specificity is questionable as healthy individuals with no symptoms of food intolerance also test positive for IgG-4 to several foods.<ref>{{cite journal|pmid=7487363|year=1994|last1=Kruszewski|first1=J|title=High serum levels of allergen specific IgG-4 (asIgG-4) for common food allergens in healthy blood donors.|volume=42|issue=4|pages=259–61|journal=Arch Immunol Ther Exp (Warsz)}}</ref>

Diagnosis is made using medical history and cutaneous and serological tests to exclude other causes, but to obtain final confirmation a double blind controlled food challenge must be performed.<ref name="pmid16782524" /> Treatment can involve long-term avoidance,<ref>{{cite web |url= http://www.healthyfutures.com/allergiesandsymptoms/allergy-sensitivity-intolerance |title= What's the difference between an allergy, an intolerance and a sensitivity? |author= Editorial Staff |publisher= Healthy Futures |access-date= 24 August 2010 |archive-url= https://web.archive.org/web/20101116171457/http://www.healthyfutures.com/allergiesandsymptoms/allergy-sensitivity-intolerance |archive-date= 16 November 2010 |url-status= dead}}</ref> or if possible re-establishing a level of tolerance.

The [[antigen leukocyte cellular antibody test]] (ALCAT) has been commercially promoted as an alternative, but has not been reliably shown to be of clinical value.<ref name="pmid16047707">{{cite journal |author=Wüthrich B |title=Unproven techniques in allergy diagnosis |journal=J Investig Allergol Clin Immunol |volume=15 |issue=2 |pages=86–90 |year=2005 |pmid=16047707 |url=http://www.jiaci.org/issues/vol15issue02/1.pdf }}</ref><ref name="pmid20200768">{{cite journal |journal=Singapore Med J  |date=January 2010 |volume=51 |issue=1 |pages=4–9 |title=Diagnostic tests for food allergy |vauthors=Gerez IF, Shek LP, Chng HH, Lee BW |pmid=20200768 }}</ref><ref name="pmid16097911">
{{cite journal |journal=Med J Aust |year=2005 |volume=183 |issue=4 |pages=173–4 |author1=Mullins Raymond J |author2=Heddle Robert J |author3=Smith Pete |title=Non-conventional approaches to allergy testing: reconciling patient autonomy with medical practitioners' concerns |url=http://www.mja.com.au/public/issues/183_04_150805/mul10358_fm.html|pmid=16097911|doi=10.5694/j.1326-5377.2005.tb06986.x |s2cid=30242205 |url-access=subscription }}</ref>

==Prevention==
There is emerging evidence from studies of cord blood that both sensitization and the acquisition of tolerance can begin in pregnancy, however, the window of main danger for sensitization to foods extends prenatally, remaining most critical during early infancy when the immune system and intestinal tract are still maturing.{{Citation needed|date=May 2014}} There is no conclusive evidence to support the restriction of dairy intake in the maternal diet during pregnancy, and this is generally not recommended since the drawbacks in terms of loss of nutrition can out-weigh the benefits. However, further randomised, controlled trials are required to examine if dietary exclusion by lactating mothers can truly minimize risk to a significant degree and if any reduction in risk is out-weighed by deleterious impacts on maternal nutrition.<ref name="pmid16373958">
{{cite journal |vauthors=Crittenden RG, Bennett LE |s2cid=1325287 |title=Cow's milk allergy: a complex disorder |journal=J Am Coll Nutr |volume=24 |issue=6 Suppl |pages=582S–91S |date=December 2005 |pmid=16373958 |doi=10.1080/07315724.2005.10719507}}</ref>

A Cochrane review has concluded feeding with a soy formula cannot be recommended for prevention of allergy or food intolerance in infants. Further research may be warranted to determine the role of soy formulas for prevention of allergy or food intolerance in infants unable to be breast fed with a strong family history of allergy or cow's milk protein intolerance.<ref name="pmid17054183">
{{cite journal |vauthors=Osborn DA, Sinn J|editor1-last=Sinn |editor1-first=John KH |title=Soy formula for prevention of allergy and food intolerance in infants |journal=Cochrane Database Syst Rev |issue=4 |pages=CD003741 |year=2006 |volume=2010 |pmid=17054183 |doi=10.1002/14651858.CD003741.pub4 |pmc=6885056 }}</ref> In the case of allergy and celiac disease others recommend a dietary regimen that is effective in the prevention of allergic diseases in high-risk infants, particularly in early infancy. The most effective dietary regimen is exclusive breastfeeding for at least 4–6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cow's milk for the first 4 months.<ref name="pmid18199086">
{{cite journal |author=Høst A |title=Dietary prevention of allergic diseases in infants and small children |journal=Pediatr Allergy Immunol |volume=19 |issue=1 |pages=1–4 |date=February 2008 |pmid=18199086 |doi=10.1111/j.1399-3038.2007.00680.x |name-list-style=vanc|author2=Halken S |author3=Muraro A |display-authors=3 |last4=Dreborg |first4=Sten |last5=Niggemann |first5=Bodo |last6=Aalberse |first6=Rob |last7=Arshad |first7=Syed H. |last8=Von Berg |first8=Andrea |last9=Carlsen |first9=Kai-Håkon|s2cid=8831420 }}</ref><ref name="pmid17308459">
{{cite journal |author=Chertok IR |s2cid=25021206 |title=The importance of exclusive breastfeeding in infants at risk for celiac disease |journal=MCN Am J Matern Child Nurs |volume=32 |issue=1 |pages=50–4; quiz 55–6 |year=2007 |pmid=17308459 |doi= 10.1097/00005721-200701000-00011}}</ref>

==Management==
Individuals can try minor changes of diet to exclude foods causing obvious reactions, and for many this may be adequate without the need for professional assistance. For reasons mentioned above foods causing problems may not be so obvious since food sensitivities may not be noticed for hours or even days after one has digested food. Persons unable to isolate foods and those more sensitive or with disabling symptoms should seek expert medical and dietitian help. The dietetic department of a [[teaching hospital]] is a good start.

Guidance can also be given to your general practitioner to assist in diagnosis and management. Food [[elimination diet]]s have been designed to exclude food compounds likely to cause reactions and foods commonly causing true allergies and those foods where [[enzyme deficiency]] cause symptoms. These [[elimination diet]]s are not everyday diets but intended to isolate problem foods and chemicals.

It takes around five days of total abstinence to unmask a food or chemical, during the first week on an [[elimination diet]] withdrawal symptoms can occur but it takes at least two weeks to remove residual traces. If symptoms have not subsided after six weeks, food intolerance is unlikely to be involved and a normal diet should be restarted. Withdrawals are often associated with a lowering of the threshold for sensitivity which assists in challenge testing, but in this period individuals can be ultra-sensitive even to food smells so care must be taken to avoid all exposures.{{Citation needed|date=May 2014}}

After two or more weeks if the symptoms have reduced considerably or gone for at least five days then challenge testing can begin. This can be carried out with selected foods containing only one food chemical, to isolate it if reactions occur. In Australia, purified food chemicals in capsule form are available to doctors for patient testing. These are often combined with [[placebo]] capsules for control purposes.{{Citation needed|date=May 2014}} This type of challenge is more definitive. New challenges should only be given after 48 hours if no reactions occur or after five days of no symptoms if reactions occur.

Once all food chemical sensitivities are identified a [[dietitian]] can prescribe an appropriate diet for the individual to avoid foods with those chemicals. Lists of suitable foods are available from various hospitals and patient support groups can give local food brand advice. A dietitian will ensure adequate nutrition is achieved with safe foods and supplements if need be.

Over a period of time it is possible for individuals avoiding food chemicals to build up a level of resistance by regular exposure to small amounts in a controlled way, but care must be taken, the aim being to build up a varied diet with adequate composition.<ref name = "Clarke" /><ref name="pmid17206644" /><ref name="pmid16635922" /><ref name="pmid9196849"/><ref name="pmid10972377">
{{cite journal |author=Jacobsen MB |title=Relation between food provocation and systemic immune activation in patients with food intolerance |journal=Lancet |volume=356 |issue=9227 |pages=400–1 |year=2000 |pmid=10972377 |doi=10.1016/S0140-6736(00)02536-8 |name-list-style=vanc|author2=Aukrust P |author3=Kittang E |display-authors=3 |last4=Müller |first4=F |last5=Ueland |first5=T |last6=Bratlie |first6=J |last7=Bjerkeli |first7=V |last8=Vatn |first8=MH|s2cid=24311710 }}</ref><ref name="pmid9577245">
{{cite journal |author=Gaby AR |title=The role of hidden food allergy/intolerance in chronic disease |journal=Alternative Medicine Review |volume=3 |issue=2 |pages=90–100 |year=1998 |pmid=9577245 }}</ref><ref name="pmid17229899">
{{cite journal |vauthors=Drisko J, Bischoff B, Hall M, McCallum R |title=Treating irritable bowel syndrome with a food elimination diet followed by food challenge and probiotics |journal=J Am Coll Nutr |volume=25 |issue=6 |pages=514–22 |year=2006 |pmid=17229899 |doi=10.1080/07315724.2006.10719567|s2cid=9314332 }}</ref>

==Prognosis==
The prognosis of children diagnosed with intolerance to milk is good: patients respond to diet which excludes cow's milk protein and the majority of patients succeed in forming tolerance.<ref name="pmid19007035">
{{cite journal |vauthors=Casado Dones MJ, Cruz Martín RM, Moreno González C, Oya Luis I, Martin Rodríguez M |title=[Children who are allergic to cow's milk. Nutritional treatment] |language=es|journal=Rev Enferm |volume=31 |issue=9 |pages=51–8 |date=September 2008 |pmid=19007035 |issn=0210-5020 }}</ref> Children with non-IgE-mediated cows milk intolerance have a good prognosis, whereas children with IgE-mediated cows milk allergy in early childhood have a significantly increased risk for persistent allergy, development of other food allergies, asthma and rhinoconjunctivitis.<ref>
{{cite journal |vauthors=Høst A, Halken S, Jacobsen HP, Christensen AE, Herskind AM, Plesner K |title=Clinical course of cow's milk protein allergy/intolerance and atopic diseases in childhood |journal=Pediatr Allergy Immunol |volume=13 |issue=Suppl 15 |pages=23–8 |year=2002 |doi=10.1034/j.1399-3038.13.s.15.7.x |pmid=12688620 |s2cid=536883 }}{{dead link|date=February 2019|bot=medic}}{{cbignore|bot=medic}}</ref>

A study has demonstrated that identifying and appropriately addressing food sensitivity in IBS patients not previously responding to standard therapy results in a sustained clinical improvement and increased overall well-being and quality of life.<ref name="pmid17229899" />

==Epidemiology==
Estimates of the prevalence of food intolerance vary widely from 2% to over 20% of the population.<ref name="pmid18584930">
{{cite journal |vauthors=Nelson M, Ogden J |title=An exploration of food intolerance in the primary care setting: the general practitioner's experience |journal=Soc Sci Med |volume=67 |issue=6 |pages=1038–45 |date=September 2008 |pmid=18584930 |doi=10.1016/j.socscimed.2008.05.025 |url=http://epubs.surrey.ac.uk/732548/1/Ogden%202008%20An%20exploration%20of%20food%20intolerance%20%20miaGP.pdf}}</ref> So far only three prevalence studies in Dutch and English adults have been based on double-blind, placebo-controlled food challenges. The reported prevalences of food allergy/intolerance (by questionnaires) were 12% to 19%, whereas the confirmed prevalences varied from 0.8% to 2.4%. For intolerance to food additives the prevalence varied between 0.01 and 0.23%.<ref name="pmid8693302">
{{cite journal |author=Wüthrich B |title=[Food allergy: definition, diagnosis, epidemiology, clinical aspects] |language=de |journal=Schweiz Med Wochenschr |volume=126 |issue=18 |pages=770–6 |date=May 1996 |pmid=8693302 }}</ref>

Food intolerance rates were found to be similar in the population in Norway. Out of 4,622 subjects with adequately filled-in questionnaires, 84 were included in the study (1.8%) Perceived food intolerance is a common problem with significant nutritional consequences in a population with IBS. Of these 59 (70%) had symptoms related to intake of food, 62% limited or excluded food items from the diet.
Tests were performed for food allergy and malabsorption, but not for intolerance. There were no associations between the tests for food allergy and malabsorption and perceived food intolerance, among those with IBS. Perceived food intolerance was unrelated to musculoskeletal pain and mood disorders.<ref name="pmid16391571">
{{cite journal |vauthors=Monsbakken KW, Vandvik PO, Farup PG |title=Perceived food intolerance in subjects with irritable bowel syndrome-- etiology, prevalence and consequences |journal=Eur J Clin Nutr |volume=60 |issue=5 |pages=667–72 |date=May 2006 |pmid=16391571 |doi=10.1038/sj.ejcn.1602367 |s2cid=6382678 |doi-access= }}</ref>

According to the RACP working group, "Though not considered a "cause" of CFS, some patients with chronic fatigue report food intolerances that can exacerbate symptoms."<ref name="pmid12056987">{{cite journal |title=Chronic fatigue syndrome. Clinical practice guidelines&mdash;2002 |journal=Med. J. Aust. |volume=176 Suppl |issue= S9|pages=S23–56 |date=May 2002 |pmid=12056987 |author1= Working Group of the Royal Australasian College of Physicians}}</ref>

==History==
In 1978 Australian researchers published details of an 'exclusion diet' to exclude specific food chemicals from the diet of patients. This provided a basis for challenge with these additives and natural chemicals. Using this approach the role played by dietary chemical factors in the pathogenesis of [[chronic idiopathic urticaria]] (CIU) was first established and set the stage for future DBPCT trials of such substances in food intolerance studies.<ref name="pmid661687">
{{cite journal |vauthors=Gibson AR, Clancy RL |s2cid=8897411 |title=An Australian exclusion diet |journal=Med J Aust |volume=1 |issue=5 |pages=290–2 |date=March 1978 |pmid=661687 |doi= 10.5694/j.1326-5377.1978.tb112553.x}}</ref><ref name="pmid7460264">
{{cite journal |vauthors=Gibson A, Clancy R |s2cid=12346266 |title=Management of chronic idiopathic urticaria by the identification and exclusion of dietary factors |journal=Clinical & Experimental Allergy |volume=10 |issue=6 |pages=699–704 |date=November 1980 |pmid=7460264 |doi=10.1111/j.1365-2222.1980.tb02154.x }}</ref>

In 1995 the European Academy of Allergology and Clinical Immunology suggested a classification on the basis of the responsible pathogenetic mechanism; according to this classification, non-toxic reactions can be divided into 'food allergies' when they recognize immunological mechanisms, and 'food intolerances' when there are no immunological implications. Reactions secondary to food ingestion are defined generally as 'adverse reactions to food'.<ref name="pmid18431058">
{{cite journal |author=Montalto M |title=Adverse reactions to food: allergies and intolerances |journal=Dig Dis |volume=26 |issue=2 |pages=96–103 |year=2008 |pmid=18431058 |doi=10.1159/000116766 |name-list-style=vanc|author2=Santoro L |author3=D'Onofrio F |display-authors=3 |last4=Curigliano |first4=Valentina |last5=Gallo |first5=Antonella |last6=Visca |first6=Dina |last7=Cammarota |first7=Giovanni |last8=Gasbarrini |first8=Antonio |last9=Gasbarrini |first9=Giovanni|hdl=11383/2076128 |s2cid=10055914 |hdl-access=free }}</ref>

In 2003 the Nomenclature Review Committee of the World Allergy Organization issued a report of revised nomenclature for global use on food allergy and food intolerance, that has had general acceptance. Food intolerance is described as a 'non-allergic hypersensitivity' to food.<ref>
{{cite journal |author=Johansson SG |title=Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003 |journal=The Journal of Allergy and Clinical Immunology |volume=113 |issue=5 |pages=832–6 |date=May 2004 |pmid=15131563 |doi=10.1016/j.jaci.2003.12.591 |name-list-style=vanc|author2=Bieber T |author3=Dahl R |display-authors=3 |last4=Friedmann |first4=Peter S |last5=Lanier |first5=Bobby Q |last6=Lockey |first6=Richard F |last7=Motala |first7=Cassim |last8=Ortega Martell |first8=Jose A |last9=Platts-Mills |first9=Thomas A.E|doi-access=free }}</ref>

==Society and culture==
In the UK, scepticism about food intolerance as a specific condition influenced doctors' perceptions of patients and of the patients' underlying problems. However, rather than risk damaging the [[doctor-patient relationship]], general practitioners (GPs) chose - despite their scepticism and guided by an element of awareness of the limitations of modern medicine - to negotiate mutually acceptable ground with patients and with patients' beliefs. As a result, whether due to a placebo effect, a secondary benefit, or a biophysical result of excluding a food from the diet, the GPs acknowledge both personal and therapeutic benefits.<ref name="pmid18584930" />

In the Netherlands, patients and their doctors (GPs) have different perceptions of the efficacy of diagnostic and dietary interventions in IBS. Patients consider food intolerance and GPs regard lack of fibre as the main etiologic dietary factor. It has been suggested that Dutch GPs explore the patients' expectations and potentially incorporate these in their approach to IBS patients.<ref name="pmid12813601">
{{cite journal |vauthors=Bijkerk CJ, de Wit NJ, Stalman WA, Knottnerus JA, Hoes AW, Muris JW |title=Irritable bowel syndrome in primary care: the patients' and doctors' views on symptoms, etiology and management |journal=Can J Gastroenterol |volume=17 |issue=6 |pages=363–8; quiz 405–6 |date=June 2003 |pmid=12813601 |doi= 10.1155/2003/532138|doi-access=free }}</ref>

New food labeling regulations were introduced into the US and Europe in 2006,<ref name="pmid16670512">
{{cite journal |vauthors=Taylor SL, Hefle SL |title=Food allergen labeling in the USA and Europe |journal=Current Opinion in Allergy and Clinical Immunology |volume=6 |issue=3 |pages=186–90 |date=June 2006 |pmid=16670512 |doi=10.1097/01.all.0000225158.75521.ad |s2cid=25204657 }}</ref> which are said to benefit people with intolerances.<ref name="pmid16881903">
{{cite journal |author=MacDonald A |title=Better European food labelling laws to help people with food intolerances |journal=Matern Child Nutr |volume=1 |issue=3 |pages=223–4 |date=July 2005 |pmid=16881903 |doi=10.1111/j.1740-8709.2005.00038.x |pmc=6860939 }}</ref> In general, food-allergic consumers were not satisfied with the current labelling practices.<ref name="pmid17584733">
{{cite journal |vauthors=Cornelisse-Vermaat JR, Voordouw J, Yiakoumaki V, Theodoridis G, Frewer LJ |title=Food-allergic consumers' labelling preferences: a cross-cultural comparison |journal=Eur J Public Health |volume=18 |issue=2 |pages=115–20 |date=April 2008 |pmid=17584733 |doi=10.1093/eurpub/ckm032 |doi-access=free }}</ref>
In the USA food companies propose distinguishing between food allergy and food intolerance and use a mechanism-based (i.e., immunoglobulin-E-mediated), acute life-threatening anaphylaxis that is standardized and measurable and reflects the severity of health risk, as the principal inclusion criterion for food allergen labeling.<ref name="pmid10914674">
{{cite journal |vauthors=Yeung JM, Applebaum RS, Hildwine R |title=Criteria to determine food allergen priority |journal=J Food Prot |volume=63 |issue=7 |pages=982–6 |date=July 2000 |pmid=10914674 |doi= 10.4315/0362-028X-63.7.982|doi-access=free }}</ref> Symptoms due to, or exacerbated by, food additives usually involve non-IgE-mediated mechanisms (food intolerance) and are usually less severe than those induced by food allergy, but can include anaphylaxis.<ref name="pmid18971901" />

==Research directions==
{{more medical citations needed|section|date=October 2023}}
[[FODMAP]]s are fermentable [[oligosaccharide|oligo-]], [[disaccharide|di-]], [[monosaccharides]] and [[polyol]]s, which are poorly absorbed in the small intestine and subsequently fermented by the bacteria in the distal [[small intestine|small]] and proximal [[large intestine]]. This is a normal phenomenon, common to everyone. The resultant production of gas potentially results in bloating and [[flatulence]].<ref name="Gibson2010">{{cite journal|author=Peter R Gibson|author2=Susan J Shepherd|s2cid=20666740|name-list-style=amp|title=Evidence-based dietary management of functional gastrointestinal symptoms: The FODMAP approach|journal=Journal of Gastroenterology and Hepatology|year=2010|volume=25|pages=252–258|doi=10.1111/j.1440-1746.2009.06149.x|pmid=20136989|issue=2|doi-access=free}}</ref> Although FODMAPs can produce certain digestive discomfort in some people, not only do they not cause intestinal inflammation, but they avoid it, because they produce beneficial alterations in the intestinal flora that contribute to maintain the good health of the colon.<ref name="MakhariaCatassi2015">{{cite journal| vauthors=Makharia A, Catassi C, Makharia GK| title=The Overlap between Irritable Bowel Syndrome and Non-Celiac Gluten Sensitivity: A Clinical Dilemma. | journal=Nutrients | year= 2015 | volume= 7 | issue= 12 | pages= 10417–26 | pmid=26690475 | doi=10.3390/nu7125541 | pmc=4690093 | type=Review | doi-access=free }}</ref><ref name="GreerOKeefe2015">{{cite journal| vauthors=Greer JB, O'Keefe SJ| title=Microbial induction of immunity, inflammation, and cancer. | journal=Front Physiol | year= 2011 | volume= 1 | pages= 168 | pmid=21423403 | doi=10.3389/fphys.2010.00168 | pmc=3059938 | type=Review | doi-access=free }}</ref><ref name="AndohTsujikawa2003">{{cite journal|vauthors=Andoh A, Tsujikawa T, Fujiyama Y| title=Role of dietary fiber and short-chain fatty acids in the colon. | journal=Curr Pharm Des | year= 2003 | volume= 9 | issue= 4 | pages= 347–58 | pmid=12570825 | type=Review | doi=10.2174/1381612033391973 }}</ref> FODMAPs are not the cause of irritable bowel syndrome nor other [[functional gastrointestinal disorder]]s, but rather a person develops symptoms when the underlying bowel response is exaggerated or abnormal.<ref name="Gibson2010" /> A [[low-FODMAP diet]] might help to improve short-term digestive symptoms in adults with irritable bowel syndrome,<ref name="TurcoSalvatore2018">{{cite journal| vauthors=Turco R, Salvatore S, Miele E, Romano C, Marseglia GL, Staiano A| title=Does a low-FODMAPs diet reduce symptoms of functional abdominal pain disorders? A systematic review in adult and paediatric population, on behalf of Italian Society of Pediatrics. | journal=Ital J Pediatr | year= 2018 | volume= 44 | issue= 1 | pages= 53 | pmid=29764491 | doi=10.1186/s13052-018-0495-8 | pmc=5952847 | type=Systematic Review | doi-access=free }}</ref><ref name=Staudacher>{{cite journal |vauthors=Staudacher HM, Irving PM, Lomer MC, Whelan K |title=Mechanisms and efficacy of dietary FODMAP restriction in IBS |journal=Nat Rev Gastroenterol Hepatol |volume=11 |issue=4 |pages=256–66 | date=April 2014 |pmid=24445613 |doi=10.1038/nrgastro.2013.259 |s2cid=23001679 |type=Review |quote=An emerging body of research now demonstrates the efficacy of fermentable carbohydrate restriction in IBS.&nbsp;[...]&nbsp;However, further work is urgently needed both to confirm clinical efficacy of fermentable carbohydrate restriction in a variety of clinical subgroups and to fully characterize the effect on the gut microbiota and the colonic environ¬ment. Whether the effect on luminal bifidobacteria is clinically relevant, preventable, or long lasting, needs to be investigated. The influence on nutrient intake, dietary diversity, which might also affect the gut microbiota,137 and quality of life also requires further exploration as does the possible economic effects due to reduced physician contact and need for medication. Although further work is required to confirm its place in IBS and functional bowel disorder clinical pathways, fermentable carbohydrate restriction is an important consideration for future national and international IBS guidelines. }}</ref><ref name="MarshEslick2015">{{cite journal |vauthors=Marsh A, Eslick EM, Eslick GD |title=Does a diet low in FODMAPs reduce symptoms associated with functional gastrointestinal disorders? A comprehensive systematic review and meta-analysis |journal=Eur J Nutr |volume= 55|issue= 3|pages= 897–906|year=2015 |pmid=25982757 |doi=10.1007/s00394-015-0922-1 |s2cid=206969839 }}</ref><ref name=Rao2015>{{cite journal |vauthors=Rao SS, Yu S, Fedewa A |title=Systematic review: dietary fibre and FODMAP-restricted diet in the management of constipation and irritable bowel syndrome |journal=Aliment. Pharmacol. Ther. |volume=41 |issue=12 |pages=1256–70 |year=2015 |pmid=25903636 |doi=10.1111/apt.13167|s2cid=27558785 |doi-access=free }}</ref> but its long-term follow-up can have negative effects because it causes a detrimental impact on the [[gut microbiota]] and [[metabolome]].<ref name="TuckMuir2014">{{cite journal|last1=Tuck|first1=CJ|last2=Muir|first2=JG|last3=Barrett|first3=JS|last4=Gibson|first4=PR|title=Fermentable oligosaccharides, disaccharides, monosaccharides and polyols: role in irritable bowel syndrome|journal=Expert Rev Gastroenterol Hepatol|date=2014|volume=8|issue=7|pages=819–834|doi=10.1586/17474124.2014.917956|pmid=24830318|s2cid=28811344 }}</ref><ref name=Staudacher /><ref name=Rao2015/><ref name="HeimanGreenway2016">{{cite journal| vauthors=Heiman ML, Greenway FL| title=A healthy gastrointestinal microbiome is dependent on dietary diversity. | journal=Mol Metab | year= 2016 | volume= 5 | issue= 5 | pages= 317–320 | pmid=27110483 | doi=10.1016/j.molmet.2016.02.005 | pmc=4837298 | type=Review }}</ref> It should only be used for short periods of time and under the advice of a specialist.<ref name="StaudacherWhelan2017">{{cite journal| vauthors=Staudacher HM, Whelan K| title=The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in IBS. | journal=Gut | year= 2017 | volume= 66 | issue= 8 | pages= 1517–1527 | pmid=28592442 | doi=10.1136/gutjnl-2017-313750 | s2cid=3492917 | type=Review | url=https://kclpure.kcl.ac.uk/portal/en/publications/the-low-fodmap-diet(c7f6c885-e206-4fa4-8206-576e70bd3d59).html }}</ref> More studies are needed to assess the true impact of this diet on health.<ref name=Staudacher /><ref name=Rao2015/>

Also, when a low FODMAP diet is used without a previous complete medical evaluation can cause serious health risks. It can ameliorate and mask the digestive symptoms of serious diseases, such as [[celiac disease]], [[inflammatory bowel disease]] and [[colon cancer]], avoiding their correct diagnosis and therapy.<ref name=WGO2016>{{cite web|url=http://www.worldgastroenterology.org/guidelines/global-guidelines/celiac-disease/celiac-disease-english|title=Celiac disease|date=July 2016|publisher=[[World Gastroenterology Organisation]] Global Guidelines|access-date=4 June 2018|url-status=live|archive-url=https://web.archive.org/web/20170317123604/http://www.worldgastroenterology.org/guidelines/global-guidelines/celiac-disease/celiac-disease-english|archive-date=17 March 2017| quote= Celiac disease (CD) is a chronic, multiple-organ autoimmune disease that affects the small intestine&nbsp;[...]&nbsp;Patients with (long-term untreated) celiac disease have an elevated risk for benign and malignant complications, and mortality. * Cancer – highest risk in the initial years after diagnosis, decreases to (near) normal risk by the fifth year [96], overall risk increment 1.35. * Malignant lymphomas * Small-bowel adenocarcinoma * Oropharyngeal tumors * Unexplained infertility (12%) * Impaired bone health and growth (osteoporosis 30–40%) * Bone fractures – increased risk 35% for classically symptomatic celiac disease patients [97,98] * The mortality risk is elevated in adult celiac patients, due to an increased risk for fatal malignancy (hazard ratio, 1.31; 95% confidence intervals, 1.13 to 1.51 in one study) [64] * Adverse pregnancy outcome [99]&nbsp;[...]&nbsp;Diagnostic tests&nbsp;[...]&nbsp;Biopsies must be taken when patients are on a gluten-containing diet.}}</ref>
<ref name="Barrett2017">{{cite journal| author=Barrett JS| title=How to institute the low-FODMAP diet. | journal=J Gastroenterol Hepatol | year= 2017 | volume= 32 | issue=Suppl 1 | pages= 8–10 | pmid=28244669 | doi=10.1111/jgh.13686 |type=Review | quote= Common symptoms of IBS are bloating, abdominal pain, excessive flatus, constipation, diarrhea, or alternating bowel habit. These symptoms, however, are also common in the presentation of coeliac disease, inflammatory bowel disease, defecatory disorders, and colon cancer. Confirming the diagnosis is crucial so that appropriate therapy can be undertaken. Unfortunately, even in these alternate diagnoses, a change in diet restricting FODMAPs may improve symptoms and mask the fact that the correct diagnosis has not been made. This is the case with coeliac disease where a low-FODMAP diet can concurrently reduce dietary gluten, improving symptoms, and also affecting coeliac diagnostic indices.3,4 Misdiagnosis of intestinal diseases can lead to secondary problems such as nutritional deficiencies, cancer risk, or even mortality in the case of colon cancer.| doi-access=free }}</ref> This is especially relevant in the case of celiac disease. Since the consumption of [[gluten]] is suppressed or reduced with a low-FODMAP diet, the improvement of the digestive symptoms with this diet may not be related to the withdrawal of the FODMAPs, but of gluten, indicating the presence of an unrecognized celiac disease, avoiding its diagnosis and correct treatment, with the consequent risk of several serious health complications, including various types of cancer.<ref name="Barrett2017" />

A three-month randomized, blinded, controlled trial on people with irritable bowel syndrome found that those who withdrew from the diet the foods to which they had shown an increased IgG antibody response experienced an improvement in their symptoms.<ref name="IkechiFischer2017">{{cite journal|vauthors=Ikechi R, Fischer BD, DeSipio J, Phadtare S| title=Irritable Bowel Syndrome: Clinical Manifestations, Dietary Influences, and Management. | journal= Healthcare| year= 2017 | volume= 5 | issue= 2 | pages=  21| pmid=28445436 | doi=10.3390/healthcare5020021 | pmc=5492024 | doi-access=free }}</ref>  In individuals with Crohn's disease and ulcerative colitis food-specific-IgG-based elimination diets have been shown to be effective at reducing symptoms.<ref>{{Cite journal |last1=Bentz |first1=S. |last2=Hausmann |first2=M. |last3=Piberger |first3=H. |last4=Kellermeier |first4=S. |last5=Paul |first5=S. |last6=Held |first6=L. |last7=Falk |first7=W. |last8=Obermeier |first8=F. |last9=Fried |first9=M. |last10=Schölmerich |first10=J. |last11=Rogler |first11=G. |date=2010 |title=Clinical relevance of IgG antibodies against food antigens in Crohn's disease: a double-blind cross-over diet intervention study |url=https://pubmed.ncbi.nlm.nih.gov/20130407 |journal=Digestion |volume=81 |issue=4 |pages=252–264 |doi=10.1159/000264649 |issn=1421-9867 |pmid=20130407|s2cid=9556315 }}</ref><ref>{{Cite journal |last1=Jian |first1=Liu |last2=Anqi |first2=He |last3=Gang |first3=Liu |last4=Litian |first4=Wang |last5=Yanyan |first5=Xu |last6=Mengdi |first6=Wang |last7=Tong |first7=Liu |date=2018-08-16 |title=Food Exclusion Based on IgG Antibodies Alleviates Symptoms in Ulcerative Colitis: A Prospective Study |url=https://pubmed.ncbi.nlm.nih.gov/29788288 |journal=Inflammatory Bowel Diseases |volume=24 |issue=9 |pages=1918–1925 |doi=10.1093/ibd/izy110 |issn=1536-4844 |pmid=29788288}}</ref><ref>{{Cite journal |last1=Jones |first1=V. A. |last2=Dickinson |first2=R. J. |last3=Workman |first3=E. |last4=Wilson |first4=A. J. |last5=Freeman |first5=A. H. |last6=Hunter |first6=J. O. |date=1985-07-27 |title=Crohn's disease: maintenance of remission by diet |url=https://pubmed.ncbi.nlm.nih.gov/2862371 |journal=Lancet |volume=2 |issue=8448 |pages=177–180 |doi=10.1016/s0140-6736(85)91497-7 |issn=0140-6736 |pmid=2862371|s2cid=21174037 }}</ref>

[[Intestinal permeability#Clinical significance|Increased intestinal permeability]], so called [[Intestinal permeability|leaky gut]], has been linked to food allergies<ref name="pmid16292078">{{cite journal |author=Heyman M |title=Gut barrier dysfunction in food allergy |journal=Eur J Gastroenterol Hepatol |volume=17 |issue=12 |pages=1279–85 |date=December 2005 |pmid=16292078 |doi= 10.1097/00042737-200512000-00003|s2cid=21021624 }}</ref> and some food intolerances.<ref name="pmid12394645">{{cite journal |vauthors=Baumgart DC, Dignass AU |title=Intestinal barrier function |journal=Current Opinion in Clinical Nutrition and Metabolic Care |volume=5 |issue=6 |pages=685–94 |date=November 2002 |pmid=12394645 |doi=10.1097/00075197-200211000-00012|s2cid=2326543 }}</ref><ref name="pmid19148789">{{cite journal |vauthors=Bjarnason I, Takeuchi K |title=Intestinal permeability in the pathogenesis of NSAID-induced enteropathy |journal=J. Gastroenterol. |volume=44 |pages=23–9 |year=2009 |issue=Suppl 19 |pmid=19148789 |doi=10.1007/s00535-008-2266-6 |s2cid=24383744 }}</ref> Research is currently focussing on specific conditions<ref name="pmid18806699">{{cite journal |author=Fedorak RN |title=Understanding why probiotic therapies can be effective in treating IBD |journal=J. Clin. Gastroenterol. |volume=42 Suppl 3 Pt 1 |pages=S111–5 |date=September 2008 |pmid=18806699 |doi=10.1097/MCG.0b013e31816d922c |s2cid=6855166 }}</ref><ref name="pmid18621505">{{cite journal |vauthors=Salvatore S, Hauser B, Devreker T, Arrigo S, Vandenplas Y |title=Chronic enteropathy and feeding in children: an update |journal=Nutrition |volume=24 |issue=11–12 |pages=1205–16 |year=2008 |pmid=18621505 |doi=10.1016/j.nut.2008.04.011 }}</ref><ref name="pmid17245093">{{cite book |vauthors=Gibbons T, Fuchs GJ |chapter=Chronic Enteropathy: Clinical Aspects |title=Nutrition Support for Infants and Children at Risk |s2cid=32663610 |volume=59 |pages=89–101; discussion 102–4 |year=2007 |pmid=17245093 |doi=10.1159/000098529 |series=Series Set, 2007 |isbn=978-3-8055-8194-3}}</ref> and effects of certain food constituents.<ref name="pmid17973645">{{cite journal |vauthors=Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ |title=Review article: the role of butyrate on colonic function |journal=Aliment. Pharmacol. Ther. |volume=27 |issue=2 |pages=104–19 |date=January 2008 |pmid=17973645 |doi=10.1111/j.1365-2036.2007.03562.x |s2cid=22698080 |doi-access= }}</ref><ref name="pmid17951508">{{cite journal |author=Veereman G |title=Pediatric applications of inulin and oligofructose |journal=J. Nutr. |volume=137 |issue=11 Suppl |pages=2585S–2589S |date=November 2007 |pmid=17951508 |doi= 10.1093/jn/137.11.2585S|doi-access=free }}</ref><ref name="pmid18931598">{{cite journal |author=Vanderhoof JA |title=Probiotics in allergy management |journal=J. Pediatr. Gastroenterol. Nutr. |volume=47 |pages=S38–40 |date=November 2008 |issue=Suppl 2 |pmid=18931598 |doi=10.1097/01.mpg.0000338810.74933.c1 |s2cid=9220248 |doi-access=free }}</ref> At present there are a number of ways to limit the increased permeability, but additional studies are required to assess if this approach reduces the prevalence and severity of specific conditions.<ref name="pmid19148789"/><ref name="pmid17973645"/>

==See also==
{{div col|colwidth=20em}}
* [[Drug intolerance]]
* [[Egg allergy#Non-allergic intolerance|Egg intolerance]]
* [[Elimination diet]]
* [[Favism]]
* [[Fructose malabsorption]]
* [[Gluten sensitivity]]
** [[Gluten-sensitive enteropathy]]
* [[Hereditary fructose intolerance|Fructose intolerance]]
* [[Histamine intolerance]], also related to [[biogenic amine intolerance]] (BAI)
* [[Lactose intolerance]]
* [[Orthorexia nervosa|Orthorexia]]
* [[Salicylate sensitivity]]
* [[Sodium phosphates]]
* [[Sucrose intolerance]]
{{div col end}}

== References ==
{{Reflist}}

== External links ==
* [https://web.archive.org/web/20120305155416/http://www.foodintoleranceawareness.org/default.htm Food Intolerance Awareness] from British Allergy Foundation
{{Medical resources
|  DiseasesDB     = 
|  ICD10          = {{ICD10|K|90|4|k|90}}-{{ICD10|Z|71|3|z|71}} 
|  ICD9           = {{ICD9|V69.1}} 
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|  MedlinePlus    = 
|  eMedicineSubj  = 
|  eMedicineTopic = 
|  MeshID         =
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{{Authority control}}

{{DEFAULTSORT:Food Intolerance}}
[[Category:Sensitivities]]
[[Category:Food sensitivity|Intolerance]]