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1 대한내과학회지 : 제 90 권제 2 호 특집 (Special Review) - 기능성위장관질환에있어서식이및영양요법 기능성위장관질환에있어서식이및영양요법 : 기능성소화불량 서울대학교의과대학분당서울대학교병원내과 신철민 Diet and Nutritional Management in Functional Gastrointestinal Disorder: Functional Dyspepsia Cheol Min Shin Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea Diet play an important role in triggering symptoms in patients with functional dyspepsia. The pathophysiology of functional dyspepsia is characterized by impaired gastric accommodation and visceral hypersensitivity, and patterns of nutrient intake may affect the threshold to dyspeptic symptoms by modulating gastric motor and sensory functions. In addition, cognitive factors are likely to modulate symptom perception in patients with functional dyspepsia. Duodenal hypersensitivity to fat is regarded as an important mechanism of meal-related dyspeptic symptoms, and is associated with increased visceral hypersensitivity and decreased gastric emptying. Among a wide range of foods, fried and fatty foods are most commonly implicated in the induction of dyspeptic symptoms; however, beans, onions, wheat-containing foods, chocolates, coffee, carbonated beverages, and milk and dairy products are also frequently associated with dyspeptic symptoms. In contrast, according to the recent Asian consensus report, rice, tea, and ginger can ameliorate dyspepsia. However, evidence is lacking, as the majority of studies have been retrospective; moreover, the results are inconsistent. Further prospective studies, especially in the Korean population, are necessary to formulate reliable dietary guidelines for patients with dyspepsia. (Korean J Med 2016;90:98-104) Keywords: Functional dyspepsia; Food; Diet, High-fat 서론진료실에서흔히받게되는질문중하나가어떤음식을먹는것이좋고, 어떤음식을피해야하는가이다. 특히소화불량환자들은특정음식에의해증상이악화되거나완화되 는경험을하게되므로이들환자에서식이에대해적절하게조언해주는것이필요하다. 다른기능성위장관질환에서도식이지침에대한근거가불충분하지만, 기능성소화불량의경우아직연구자체가많지않고이론적인근거도부족하다. 본고에서는음식이소화 Correspondence to Cheol Min Shin, M.D., Ph.D. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, 173beon-gil, Bundang-gu, Seongnam 13620, Korea Tel: , Fax: , cmshin@snubh.org Copyright c 2016 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

2 - Cheol Min Shin. Functional dyspepsia and diet - 불량을일으키는근거를간단히정리하고, 현재까지기능성소화불량과관련된식이및영양관련연구들을간략히살펴보며, 기존연구를통해소화불량과연관된것으로알려진음식을알아보고, 여러국내외가이드라인에서제시하고있는식이지침을정리하고, 마지막으로한국인기능성소화불량환자에서바람직한식이에관해제시해보고자한다. 본 Table 1. Possible mechanisms of dyspepsia triggered by food Abnormal gastric motor responses to meal ingestion Hypersensitivity to gastric distension Hypersensitivity to intraluminal nutrients Hypersensitivity to acid Food allergy/intolerance/sensitivity FODMAPs (?) Food chemicals (such as salicylates and amines) Acute ingestion of chili or capsaicin FODMAPs, fermentable oligosaccharides, disaccharides, monosaccharides and polyols. 론 음식이소화불량증상을일으키는근거 이론적근거 로마기준 III에의하면명치작열감 (epigastric burning) 혹은명치통증 (epigastric pain), 식후포만감 (postprandial fullness) 및조기만복감 (early satiation) 이기능성소화불량증상으로분류되며, 주된증상에따라식후불편감증후군 (postprandial distress syndrome) 혹은음식연관기능성소화불량증 (meal-related functional dyspepsia) 과명치통증증후군 (epigastric pain syndrome) 의두아형 (subtype) 으로구분된다 [1]. 음식에의해소화불량증상이발생하는기전으로지금까지제시되고있는것은식후비정상적위운동, 위확장에대한과민반응과십이지장내특정영양성분에대한과민반응등이있다 (Table 1). 기능성소화불량의병태생리는다양하게제시되고있으며, 하나의기전으로설명하기보다는복합적인것으로이해된다. 기능성소화불량환자에서위적응 (gastric accommodation) 이감소되어있고, transient receptor potential cation channel subfamily V member 1 (TRPV1) 과같은통증수용체가과발현되어내장과민성을가지게되며, 위내압력증가에대한역치가정상인에비해감소되어있다 [2,3]. 위내에산을주입하면복부팽만 (bloating, abdominal distension) 이나구역 (nausea), 트림 (belching) 와같은소화불량증상이유발되고일부소화불량증환자에서강력한위산억제제인양성자펌프억제제 (proton pump inhibitor) 의투여로증상이호전됨이보고되어위산도소화불량증상과관련이있는것으로생각된다 [4,5]. 최근십이지장과민성이소화불량증상발생의중요한기전으로정립되고있다 [6]. 십이지장과민성에대한연구는주로산에대한과민성과지방 (fat) 에대한과민성연구가있다. 십이지장의산에대한과민성이소화불량증상과연관되어있는지에대해서는이전연구에서서로일치하지않는결과를보여주었다 [7-10]. 반면, 지방에대한십이지장의과민성은소화불량의중요한기전으로정립되고있다. 정상인은십이지장내에지방혹은포도당을주입하면위내압력증가에따른위역치용적 (gastric threshoud volume) 이증가하는위적응과정이일어나팽만감과불편감이발생하지않는다. 그러나, 기능성소화불량환자는증상을일으키는위역치용적이정상인에비해적고, 지방을주입하는경우는오히려역치가낮아져위용적이조금만증가해도팽만감과불편감을호소하게된다 [11]. 한연구에서는저열량식이 (low calorie diet) 와고열량고탄수화물식이 (high calorie high carbohydrate diet), 고열량고지방식이 (high calorie high fat diet) 를시행하였을때, 기능성소화불량환자는정상인에비해열량혹은영양소구성과관계없이상복부불편감이발현되지만, 구역이나명치통증은고지방식이를하는경우에만발현되어 [12] 음식의열량뿐만아니라지방함량이일부소화불량증상과연관되어있음을보여준다. 현재까지의근거로는기능성소화불량환자에서지방식이는내장과민성을증가시키고, 위운동을저하시켜위배출을감소시키는방향으로작용한다 [13]. 최근 fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) 와과민성장증후군사이의관련성에대한연구가많이진행되고있지만, FODMAP 식이와기능성소화불량에대한연구는부족하다 [14,15]. 소화불량환자에서복부팽만을유발하는식이를시행하는경우복부증상이악화되고, 저 FODMAP 식이를시행하면증상이호전되었다는보고가있다 [16]. 저 FODMAP 식이가소화불량증상을호전시키는것은고 FODMAP 식이로인한장관내가스형성이나복부팽만이감소하고많은환자들이과민성장증후군을함께가지고있기때문일수있다 [17,18]. 음식을어떻게인식하는지가증상발현에중요할수도있다 [14]. 고지방요거트 (yogurt) 와저지방요거트를이용하여요거트의지방함량에대해서정확한정보를알려준군과잘못

3 - 대한내과학회지 : 제 90 권제 2 호통권제 666 호

4 - 신철민. 기능성소화불량과식이 - 된정보를알려준군으로총 4개의군을나누어실험하였을때, 위용적과혈장 cholecystokinin 농도는요거트지방함량에따라예상된결과를보여주는반면, 포만감 (fullness) 이나불편감 (discomfort) 과같은소화불량증상은저지방요거트를섭취하였지만, 고지방요거트로잘못알고있었던환자에서도증가하였다 [19]. 이는기능성소화불량의증상발생기전에정신적인요인이중요함을시사함과동시에소화불량과식이와의연관성연구를어렵게만드는한요인이될수도있다. 요약하면기능성소화불량환자는위운동장애및내장과민성을가지고있는데, 식사량뿐아니라, 위산분비, 영양소중특히지방성분의비율그리고음식에대한인식등이소화불량증상을유발하거나악화시킬것으로생각된다 [20]. 역학적근거기능성소화불량과음식의관련연구는부족하고일치되지않는결과를보이며, 국내연구는드물다. 특히국내연구는드물고각각의연구결과또한일치되지않는부분이있다. 특히음식눈가림 (blind challenging test) 연구들은일관된결과를보여주지못하고있으며, 최근까지의연구결과를정리하면 Table 2와같다 [14]. 기능성소화불량에서식이요인에대한임상연구가어려운이유는대부분의연구가후향적이고, 전향적연구라고하더라도음식섭취와증상발현여부그리고증상의강도를동시에측정한연구가없으며, 음식에대한인지에따라증상에영향을주고환자가음식의성분을어떻게인식하고있는지에따라연구결과가상이할수있어해석이어렵기때문이다. 특정영양소를제한하는식이는불가피하게다른영양소의섭취량에도영양을미칠수있다. 가령지방을제한하는식이는단백질이나총섭취열량에도영향을미치게되는데환자의증상변화가지방때문인지아니면다른요인에의한것인지를구분하는것이쉽지않다. 기능성소화불량의정의와과민성장증후군이나위식도역류질환과같은다른기능성위장관질환과의중복증후군 (overlap syndrome) 등도결과해석을어렵게한다. 흥미로운것은많은기능성소화불량환자들이증상과연관된것으로보고되는대부분의음식을실제정상인과같은정도로섭취하고있다는점이다. 육류 (red meat) 를제외하면증상과연관된것으로생각되는음식섭취가기능성소화불량환자와정상인사이에차이가없었다 [21]. 기능성소화불량환자들이증상과연관된대부분의음식을회피하지않는이유는환자들이증상과음식과의연관성을인지하지못하거나, 혹은연관성을안다고하더라도문화적, 사회환경적인이유로다른음식으로대체하지못하는경우그리고커피등 기호식품의경우증상을유발하더라도일종의습관처럼섭취하게되는것등이제시되고있다. 정상인과기능성소화불량환자사이에총열량및영양소섭취에차이가있는지에관한연구역시일관된결과를보여주지못하고있다 [21-24]. 기능성소화불량환자에서지방이나칼로리를섭취하면포만감이나복부팽만과같은증상이발생하기때문에이를피하기위해지방및칼로리섭취가감소한다고생각하고있지만, 그렇지않다는연구결과도있어결론을내리기는어렵다. 또한식이섬유와기능성소화불량증에관한연구역시일관된결과를보이지않는다 [21,22,25]. 연구가부족하지만불규칙한식사습관, 과식, 빨리먹는습관등이기능성소화불량과관련이있는것으로보고되고있다 [25-28]. 소화불량과연관된음식일반적으로살이붉은고기, 기름에튀긴음식, 케이크등고지방식이는흔하게소화불량증상을일으키며, 특히포만감을유발한다 [24,27,29,30]. 또한콩류, 양파, 양배추, 고추등은포만감, 복부팽만과연관된음식으로보고되고있다 [21,24,27,29,30]. 고 FODMAP 식이가일부소화불량증상과연관되어있을수있으나근거는아직부족하다. 감귤류와같은신과일이나과일주스는주로소화성궤양과유사한소화불량 (ulcer-like dyspepsia) 혹은명치통증이나작열감과연관되며 [21,24,27,29,30], 초콜릿, 커피, 탄산음료등도비교적흔하게소화불량증상과연관된다 [21,24,27,30]. 밀가루음식, 특히파스타, 빵, 케이크등은많은환자에서소화불량증상을유발하는것으로일관되게보고되고있다 [21,24,27,30]. 우유나치즈와같은유제품도흔히소화불량증상과연관되는데, 이는유제품에들어있는지방성분때문일수도있고, 유당 (lactose) 에대한불내성 (intolerance) 도한원인으로생각된다 [21,27,30]. 비교적잘고안된최근의두연구는소화불량의각증상과특정음식사이의연관성을보여주고있다 [21,24]. 주로살이붉은고기, 밀가루음식, 튀긴음식, 콩류, 초콜릿, 당류, 감귤류는식후포만감과연관이있고, 탄산음료, 양파, 콩, 바나나는복부팽만과, 커피, 양파, 후추, 초콜릿등은명치통증과연관되었다. 하지만현재까지한국인을대상으로하는연구는거의없다. 소화불량환자에서추천할만한음식에대한연구는많지않다. 쌀, 차, 생강, 매운음식과관련된연구가있으나상당히제한적이다. 쌀은과민성장증후군에서도권장되는음식

5 - The Korean Journal of Medicine: Vol. 90, No. 2, 이다. 밀가루등다른탄수화물과는달리, 쌀은소장에서완전소화흡수되기때문에가스를적게생성하고음식알레르기를일으키지않아소화불량증환자, 특히식후포만감이나복부팽만이주증상인경우추천할만한음식이다 [31]. 하지만임상적인근거는주로과민성장증후군에서있고기능성소화불량에서쌀음식의유용성에대한연구는부족하다. 쌀섭취가소화불량증을적게일으키기는하지만당뇨환자의혈당조절에는불리한측면이있어각각의환자에따른맞춤설명이필요하겠다. 차는소화불량환자에서유익한음식일수있다 [32]. 이론적근거는부족하지만, 차성분중테오필린 (theophylline) 이명치통증을유발하는아데노신 (adenosine) 수용체에대한길항작용 (antagonistic effect) 을하는것이한기전으로보고되고있다 [33,34]. 하지만임상연구가많지않고, 어떤종류의차를얼마나마시는것이좋은지에대한자료는부족하다 [35]. 2012년기능성소화불량증에대한아시아합의보고 (Asian consensus report on functional dyspepsia) 에서는생강 (ginger) 이소화불량에좋은음식일가능성을제시하였는데, 생강은위전정부의수축및위배출을촉진시켜포만감을감소시킨다 [36]. 하지만최근소화불량증환자를대상으로한전향적연구에서는환자의증상이나소화관호르몬농도에유의한효과가없었다 [37]. 고추나매운음식에많이들어있는캡사이신 (capsaicin) 은 TRPV1 수용체를활성화하여작열감이나통증을유발한다 [38]. 따라서매운음식을먹으면명치통증이나작열감이유발될수있다. 하지만캡사이신을반복적으로투여하면 nociceptive C-fiber 를탈감작화시켜통증자극에대한역치를높일수있다 [39]. 기능성소화불량환자에서캡사이신에대한과민성이유의하게증가되어있지만, 캡사이신을장기간투여하게되면통증에대한역치를증가시켜소화불량증상이유의하게호전되었다는소규모전향적임상연구결과도있다 [40]. 국내외기능성소화불량가이드라인에서의식이지침기능성소화불량환자마다증상을유발시키는음식이제각각이라는점을먼저고려해야한다. 대부분의가이드라인에서제시하는것처럼모든환자에게일관되게적용하기보다는식이일지를쓰는등의방법으로본인에게증상을유발하는음식을찾아피하도록한다. 쌀을주식으로하고섬유소섭취가많고매운음식을많이먹는한국인을대상으로한잘고안된연구는없으므로가이드라인의해석은제한적이다. 2005년미국가이드라인은고지방식이를피하고증상을유발하는특정음식을피하도록권고하고있으며 [41], 기능성소화불량에서음식알레르기는드물다고하였다. 국내소화불량가이드라인에서도증상을유발하는음식을피하고, 커피, 매운음식, 고지방식을피하도록권고하고있다. 2012년에발표된기능성소화불량에대한아시아합의보고는헬리코박터제균치료에도증상호전이없으면식이조절 (dietary modification) 을시행하도록권고하고있다 [35]. 또한특정음식성분이소화불량증상을유발할수있으나, 식이지침으로권고하기에는근거가부족하다고기술되어있다. 기능성소화불량환자에서차섭취는도움이되고, 쌀, 생강등이좋은음식으로제시되고있으며, 지방섭취는증상을악화시킬수있다. 한국인소화불량환자에대한식이권고 ( 안 ) 지금까지정리한음식이소화불량증상을유발하는기전, 임상연구, 가이드라인등을종합하여, 아직부족하지만기능성소화불량증상으로외래를방문하는환자에게무난하게권할수있는식이는다음과같이정리될수있다. 일차적으로본인이섭취하였을때증상을유발하는음식은피한다. 과식이나빨리먹는습관, 불규칙한식사등나쁜식사습관은소화불량증상을악화시킬수있다. 지방이많은음식 ( 기름진음식 ) 을피한다. 콩이나양파등은소화불량증상을악화시킬수도있으며, 탄산음료, 초콜릿등은피하는것이좋다. 유제품 ( 우유, 치즈, 요구르트등 ) 은일부환자에서소화불량증상을악화시킬수있다 밀가루음식보다는쌀로만든음식이증상을덜일으킨다. 커피보다는차를마시는것이좋다. 생강섭취가포만감을감소시키는데도움이될수도있다. 매운음식을평소잘먹지않는다면매운음식을섭취할때속쓰림과소화불량이발생할수있으므로피하는것이좋다. 결론기능성소화불량환자에서위운동기능이상및내장과민성등의병태생리가음식에의해악화될수있으나, 음식과증상과의연관성에대한연구는복잡하고분석이어려우며일관된연구결과를보이지않는다. 그럼에도불구하고많은

6 - Cheol Min Shin. Functional dyspepsia and diet - 연구에서지방섭취가흔히증상과연관되고, 탄산음료나가스를생성할수있는고 FODMAP 식이나밀가루등특정탄수화물, 매운음식등도일부에서증상을유발할수있다. 한국인을대상으로한잘고안된연구가부족하므로향후한국인의식단에맞는소화불량증과연관된음식연구및식이중재 (diet intervention) 역할에대한연구가필요하다. 중심단어 : 기능성소화불량 ; 음식 ; 고지방식이 REFERENCES 1. Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology 2006;130: Miwa H, Watari J, Fukui H, et al. Current understanding of pathogenesis of functional dyspepsia. J Gastroenterol Hepatol 2011;26 Suppl 3: Rhee PL, Kim YH, Son HJ, et al. The etiologic role of gastric hypersensitivity in functional dyspepsia in Korea. J Clin Gastroenterol 1999;29: Miwa H, Nakajima K, Yamaguchi K, et al. Generation of dyspeptic symptoms by direct acid infusion into the stomach of healthy Japanese subjects. Aliment Pharmacol Ther 2007;26: Gwee KA, Hwang JE, Ho KY, Yeoh KG, Lum CF, Ang PK. In-practice predictors of response to proton pump inhibitor therapy in primary care patients with dyspepsia in an Asian population. J Clin Gastroenterol 2008;42: Lee KJ, Tack J. Duodenal implications in the pathophysiology of functional dyspepsia. J Neurogastroenterol Motil 2010; 16: Samsom M, Verhagen MA, vanberge Henegouwen GP, Smout AJ. Abnormal clearance of exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patients. Gastroenterology 1999;116: Lee KJ, Demarchi B, Demedts I, Sifrim D, Raeymaekers P, Tack J. A pilot study on duodenal acid exposure and its relationship to symptoms in functional dyspepsia with prominent nausea. Am J Gastroenterol 2004;99: Bratten J, Jones MP. Prolonged recording of duodenal acid exposure in patients with functional dyspepsia and controls using a radiotelemetry ph monitoring system. J Clin Gastroenterol 2009;43: di Stefano M, Vos R, Vanuytsel T, Janssens J, Tack J. Prolonged duodenal acid perfusion and dyspeptic symptom occurrence in healthy volunteers. Neurogastroenterol Motil 2009;21:712-e Barbera R, Feinle C, Read NW. Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia. Dig Dis Sci 1995;40: Pilichiewicz AN, Feltrin KL, Horowitz M, et al. Functional dyspepsia is associated with a greater symptomatic response to fat but not carbohydrate, increased fasting and postprandial CCK, and diminished PYY. Am J Gastroenterol 2008;103: Feinle-Bisset C, Azpiroz F. Dietary lipids and functional gastrointestinal disorders. Am J Gastroenterol 2013;108: Feinle-Bisset C, Azpiroz F. Dietary and lifestyle factors in functional dyspepsia. Nat Rev Gastroenterol Hepatol 2013; 10: Shepherd SJ, Lomer MC, Gibson PR. Short-chain carbohydrates and functional gastrointestinal disorders. Am J Gastroenterol 2013;108: Manichanh C, Estrella S, Hernandez C, et al. Mo1170 flatulence: is it what it seems? Clinical, physiological and microbiological features. Gastroenterology 2012;142(Suppl 1): S611-S Lee SY, Lee KJ, Kim SJ, Cho SW. Prevalence and risk factors for overlaps between gastroesophageal reflux disease, dyspepsia, and irritable bowel syndrome: a population-based study. Digestion 2009;79: Park JM, Choi MG, Cho YK, et al. Functional gastrointestinal disorders diagnosed by Rome III questionnaire in Korea. J Neurogastroenterol Motil 2011;17: Feinle-Bisset C, Meier B, Fried M, Beglinger C. Role of cognitive factors in symptom induction following high and low fat meals in patients with functional dyspepsia. Gut 2003; 52: Feinle-Bisset C, Horowitz M. Dietary factors in functional dyspepsia. Neurogastroenterol Motil 2006;18: Carvalho RV, Lorena SL, Almeida JR, Mesquita MA. Food intolerance, diet composition, and eating patterns in functional dyspepsia patients. Dig Dis Sci 2010;55: Saito YA, Locke GR 3rd, Weaver AL, Zinsmeister AR, Talley NJ. Diet and functional gastrointestinal disorders: a population-based case-control study. Am J Gastroenterol 2005; 100: Pilichiewicz AN, Horowitz M, Holtmann GJ, Talley NJ, Feinle-Bisset C. Relationship between symptoms and dietary patterns in patients with functional dyspepsia. Clin Gastroenterol Hepatol 2009;7: Filipović BF, Randjelovic T, Kovacevic N, et al. Laboratory parameters and nutritional status in patients with functional dyspepsia. Eur J Intern Med 2011;22: Kearney J, Kennedy NP, Keeling PW, et al. Dietary intakes and adipose tissue levels of linoleic acid in peptic ulcer disease. Br J Nutr 1989;62: Johnsen R, Straume B, Førde OH. Peptic ulcer and non-ulcer

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<B0E6C8F1B4EBB3BBB0FAC0D3BBF3B0ADC1C E687770> 개원의와함께하는임상강좌 2011 역류성식도질환제대로이해하기 Division of Gastroenterology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea Jae-Young Jang, M.D., PhD. 개원의와함께하는임상강좌 2011 109 최신치료