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Relationship Between Symptoms and Dietary Patterns in Patients With Functional Dyspepsia

  • Amelia N. Pilichiewicz
    Affiliations
    University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, Australia

    National Health and Medical Research Council, Centre of Clinical Research Excellence in Nutritional Physiology, Outcomes and Interventions, Adelaide, Australia
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  • Michael Horowitz
    Affiliations
    University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, Australia

    National Health and Medical Research Council, Centre of Clinical Research Excellence in Nutritional Physiology, Outcomes and Interventions, Adelaide, Australia
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  • Gerald J. Holtmann
    Affiliations
    National Health and Medical Research Council, Centre of Clinical Research Excellence in Nutritional Physiology, Outcomes and Interventions, Adelaide, Australia

    Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia
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  • Nicholas J. Talley
    Affiliations
    Mayo Clinic College of Medicine, Jacksonville, Florida

    Department of Medicine, University of Sydney and Nepean Hospital, Sydney, Australia
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  • Christine Feinle–Bisset
    Correspondence
    Reprint requests Address correspondence to: Assistant Professor Christine Feinle-Bisset, PhD, National Health and Medical Research Council of Australia Senior Research Fellow, University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide SA 5000, Australia. fax: (61) 8-8223-3870
    Affiliations
    University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, Australia

    National Health and Medical Research Council, Centre of Clinical Research Excellence in Nutritional Physiology, Outcomes and Interventions, Adelaide, Australia
    Search for articles by this author
Published:September 22, 2008DOI:https://doi.org/10.1016/j.cgh.2008.09.007

      Background & Aims

      Patients with functional dyspepsia (FD) often report that their symptoms are related to food ingestion. However, there is a lack of information about differences in eating patterns and nutrient intake between these patients and healthy individuals or the association with specific symptoms. We performed a prospective trial to evaluate the relationship between FD symptoms and dietary factors.

      Methods

      Twenty patients with FD (17 women) and 21 healthy subjects (18 women) completed detailed diet diaries, recording all foods eaten, drinks consumed, and times of consumption, as well as the occurrence, timing, and severity of dyspeptic symptoms (ie, nausea, discomfort, fullness, bloating, upper-abdominal/epigastric pain) for 7 days. Data from the diet diaries were analyzed for the number of meals, light meals, snacks and drinks, energy intake, and macronutrient distribution.

      Results

      Patients with FD ate fewer meals (P < .01) and consumed less total energy (P = .1) and fat (P = .1) than healthy subjects. Their symptoms were modest in severity (score out of 10; 5 [range, 3–8]) and occurred within 31 minutes (range, 8–64 min) of eating. Fullness was related directly to the amount of fat ingested (z, 1.91; P < .05) and overall energy intake (z, 2.12; P < .05) and related inversely to the amount of carbohydrate ingested (z, −1.9; P = .05). Similarly, bloating was related to the amount of fat ingested (z, 1.68; P = .09). There was no significant relationship between symptom severity and any of the dietary variables measured.

      Conclusions

      Management of patients with FD might be improved by instructing them to consume smaller meals with reduced fat content.

      Abbreviations used in this paper:

      BMI (body mass index), CCK (cholecystokinin), FD (functional dyspepsia), NDI (Nepean Dyspepsia Index)
      The pathophysiology and etiology of functional dyspepsia (FD) remain poorly defined. Many patients report their symptoms are related to the ingestion of food,
      • Kearney J.
      • Kennedy N.P.
      • Keeling P.W.
      • et al.
      Dietary intakes and adipose tissue levels of linoleic acid in peptic ulcer disease.
      • Mullan A.
      • Kavanagh P.
      • O'Mahony P.
      • et al.
      Food and nutrient intakes and eating patterns in functional and organic dyspepsia.
      however, few studies have investigated this putative association. Two studies reported that dyspeptic symptoms were associated with ingestion of onions, peppers, fried and fatty foods, alcohol, citrus fruits, and spicy foods,
      • Kearney J.
      • Kennedy N.P.
      • Keeling P.W.
      • et al.
      Dietary intakes and adipose tissue levels of linoleic acid in peptic ulcer disease.
      • Mullan A.
      • Kavanagh P.
      • O'Mahony P.
      • et al.
      Food and nutrient intakes and eating patterns in functional and organic dyspepsia.
      or rich cakes and carbonated beverages.
      • Mullan A.
      • Kavanagh P.
      • O'Mahony P.
      • et al.
      Food and nutrient intakes and eating patterns in functional and organic dyspepsia.
      Another study, using a questionnaire about 39 different foods, reported that FD patients identified 22 of these as aggravating their symptoms, and, therefore, avoided them.
      • Kaess H.
      • Kellermann M.
      • Castro A.
      Food intolerance in duodenal ulcer patients, non ulcer dyspeptic patients and healthy subjects A prospective study.
      Of these foods, the highest rates of intolerance were for mayonnaise (80%), nuts (70%), fish (66%), and chocolate (62%)—3 out of these 4 foods have a high fat content.
      It is uncertain whether eating patterns and nutrient intake are different in FD. The prevalence of snacking has been reported to be greater (by about 9%), and the number of larger meals to be lower (by about 24%), in FD patients compared with healthy subjects, but these differences were not statistically significant.
      • Mullan A.
      • Kavanagh P.
      • O'Mahony P.
      • et al.
      Food and nutrient intakes and eating patterns in functional and organic dyspepsia.
      Furthermore, in that study only 55% of FD patients consumed 3 meals per day compared with 80% of healthy subjects,
      • Mullan A.
      • Kavanagh P.
      • O'Mahony P.
      • et al.
      Food and nutrient intakes and eating patterns in functional and organic dyspepsia.
      although interpretation of these data is difficult because definitions of “meals” and “snacks” were not provided.
      • Mullan A.
      • Kavanagh P.
      • O'Mahony P.
      • et al.
      Food and nutrient intakes and eating patterns in functional and organic dyspepsia.
      In contrast, a study using food-frequency diaries reported no differences in eating patterns, including the number of regular meals and total number of eating episodes between patients with FD and healthy subjects;
      • Cuperus P.
      • Keeling P.W.
      • Gibney M.J.
      Eating patterns in functional dyspepsia: a case control study.
      however, food intake was evaluated only in food categories. A further study, which used a 7-day diet history to assess nutrient intake, found no significant differences, except that subjects with FD had a significantly lower intake of dietary fiber.
      • Kearney J.
      • Kennedy N.P.
      • Keeling P.W.
      • et al.
      Dietary intakes and adipose tissue levels of linoleic acid in peptic ulcer disease.
      Hence, previous studies have yielded inconsistent observations with regard to eating patterns in FD. Furthermore, none of these studies evaluated the relationship between symptoms with eating patterns concurrently.
      Many FD patients report that they can eat only small meals and do not tolerate fat, consistent with the outcome of laboratory-based studies showing diminished tolerance of volume/pressure, as indicated by increased sensitivity to distension of the proximal
      • Mertz H.
      • Fullerton S.
      • Naliboff B.
      • et al.
      Symptoms and visceral perception in severe functional and organic dyspepsia.
      • Barbera R.
      • Feinle C.
      • Read N.W.
      Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia.
      • Barbera R.
      • Feinle C.
      • Read N.W.
      Abnormal sensitivity to duodenal lipid infusion in patients with functional dyspepsia.
      and distal
      • Caldarella M.P.
      • Azpiroz F.
      • Malagelada J.R.
      Antro-fundic dysfunctions in functional dyspepsia.
      stomach in approximately 35% of patients, reduced ingestion capacity during an oral nutrient drink test in approximately 40% of patients,
      • Tack J.
      • Piessevaux H.
      • Coulie B.
      • et al.
      Role of impaired gastric accommodation to a meal in functional dyspepsia.
      • Tack J.
      • Caenepeel P.
      • Fischler B.
      • et al.
      Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia.
      and increased sensitivity to oral and duodenal fat administration in approximately 60% to 70% of patients;
      • Barbera R.
      • Feinle C.
      • Read N.W.
      Abnormal sensitivity to duodenal lipid infusion in patients with functional dyspepsia.
      • Houghton L.A.
      • Mangnall Y.F.
      • Dwivedi A.
      • et al.
      Sensitivity to nutrients in patients with non ulcer dyspepsia.
      • Feinle C.
      • Meier O.
      • Otto B.
      • et al.
      Role of duodenal lipid and cholecystokinin A receptors in the pathophysiology of functional dyspepsia.
      and our recent study showed that in FD patients, a high-fat test-meal induces more nausea and pain than a high-carbohydrate meal.
      • Pilichiewicz A.
      • Feltrin K.L.
      • Horowitz M.
      • et al.
      Oral carbohydrate and fat differentially modulate symptoms, gut hormones and antral area in functional dyspepsia.
      Patients with FD as a group have more life and psychologic distress, as well as a lower quality of life than healthy individuals.
      • Talley N.J.
      • Phillips S.F.
      • Bruce B.
      • et al.
      Relation among personality and symptoms in nonulcer dyspepsia and the irritable bowel syndrome.
      • Talley N.J.
      • Piper D.W.
      Major life event stress and dyspepsia of unknown cause: a case control study.
      It would not be surprising if eating attitudes in FD were abnormal and impacted on eating behavior and/or symptoms and were related to food intake.
      The aims of this study were to quantify eating habits and dyspeptic symptoms, as well as relationships between them, in FD. We hypothesized the following: (1) that patients with FD would consume smaller meals and experience more meal-associated symptoms, but eat more frequently when compared with healthy subjects, and (2) that symptoms would be related directly to the amount eaten, as well as the amount of fat in the diet.

      Patients and Methods

       Subjects

      Twenty FD patients (17 women, 3 men; age, 45 ± 3 y; range, 23–73 y; body mass index [BMI], 24.0 ± 0.9 kg/m2; range, 19.3–35.7 kg/m2) were recruited through advertisements in a local newspaper (n = 3) and from the endoscopy list and outpatients of the Department of Gastroenterology and Hepatology at the Royal Adelaide Hospital (n = 17). The patients had to have experienced postprandial fullness, bloating, epigastric pain, nausea, or vomiting for more than 3 months of at least a moderate severity, according to the Rome II criteria (Rome III criteria were not available at the time the study was initiated).
      • Talley N.J.
      • Stanghellini V.
      • Heading R.C.
      • et al.
      Functional gastroduodenal disorders.
      Severity was scored on a 0 to 3 scale, with 0 representing symptom not experienced, 1 representing slight symptom, 2 representing moderate symptom, bothering, but not impairing daily activities, and 3 representing severe symptom, impairing daily activities. Subjects were eligible if the total score was 3 or greater, or one symptom scored 2 or greater. Exclusion criteria included any organic cause of dyspepsia, positive ultrasound and upper-gastrointestinal endoscopy performed during the previous 12 months, heartburn or lower-bowel symptoms as predominant symptoms, positive Helicobacter pylori status, and clinically significant positive results on laboratory tests, including biochemistry, hematology, and lactose breath tests.
      Twenty-one healthy subjects (18 women, 3 men; age, 40 ± 4 y; range, 20–74 y; BMI, 22.9 ± 0.5 kg/m2; range, 18.6–26.5 kg/m2) were included as controls. Inclusion criteria were age, sex, and BMI matching those of a patient (FD patients were recruited first), although 6 FD patients, but only 3 healthy subjects, were overweight (BMI > 25), and 1 FD patient was obese (BMI > 30). Exclusion criteria included dyspeptic symptoms or any significant illnesses.
      Patients and healthy subjects also were excluded if they were taking medication known to affect gastrointestinal motility or appetite, smoked, or habitually consumed more than 20 g of alcohol per day. Although 9 of 20 patients reported perceived intolerances of certain foods, including caffeine (n = 2), fatty foods (n = 6), dairy products (n = 3), and others, including citrus fruits, cabbage, and onions, none of the subjects reported any food allergies or gluten intolerance.

       Protocol

      Each patient and healthy subject completed a diet diary, in which they recorded all foods and drinks consumed, and the time of each eating or drinking episode, over an entire 7-day period (ie, 5 weekdays and 2 weekend days),
      • Karvetti R.L.
      • Knuts L.R.
      Validity of the estimated food diary: comparison of 2-day recorded and observed food and nutrient intakes.
      while maintaining their usual eating habits. For this purpose, subjects were asked to weigh as many foods as practical, or, alternatively, to use cup or spoon measures or common serves (eg, slice of bread), and to be as specific as possible (eg, type of bread: white/wholemeal: degree of fat trimming of meat: type of margarine or oil; type of milk; whole-fat or skim); and type of cooking method; fried, boiled, roasted. If a recipe was followed the subject was instructed to record it in the food diary. The diary also evaluated symptoms, where all subjects recorded any symptoms experienced (abdominal pain, cramps, bloating, nausea, uncomfortable fullness after meals), their severity on a scale out of 10 (with 0 representing symptom not present and 10 representing symptom most severe), and the time at which these symptoms occurred.

       Measurements

       Diet diaries

      The total number of consecutive eating/drinking episodes for the week was determined. These episodes were classified into 5 categories: (1) meals, (2) light meals, (3) snacks, (4) caloric drinks, and (5) noncaloric drinks. Breakfast, lunch, and dinner generally were classified as either meals or light meals. Meals were defined as the main eating occasion(s) of the day and comprised foods traditionally eaten as a main meal (eg, continental breakfast, pasta, meat and vegetables, 4 slices of pizza, and so forth). Light meals were defined as episodes in which the amount ingested was less than expected at a main meal (by ∼30%) (eg, cereals, sandwiches, 2 slices of pizza, salads containing meat). Snacks were defined as eating episodes in which consumption was less and which were easier to prepare than meals or light meals, usually consisting of one food item (eg, biscuits, chocolate, crisps, fruit, yogurt, slice of pizza) and consumed at times between meals. A caloric drink was defined as any nutrient-containing beverage (eg, cola, coffee with milk and/or sugar, juice, milkshakes, alcohol). A noncaloric drink was defined as any beverage that contained no calories (eg, water, diet drinks, black coffee/tea).
      Foods consumed within a time interval of less than 15 minutes were considered to be part of one eating episode. Intervals between eating episodes during the day and night also were calculated.

       Symptom diaries

      Symptoms were divided into 3 categories: meal-associated symptoms (bloating, nausea, upper-abdominal pain, belching, epigastric pain, fullness, vomiting, discomfort), which occurred within a 2-hour period after completion of eating;
      • Caldarella M.P.
      • Azpiroz F.
      • Malagelada J.R.
      Antro-fundic dysfunctions in functional dyspepsia.
      other gastrointestinal symptoms, which was any other symptom(s) (heartburn, diarrhea, constipation, lower-abdominal pain) that occurred within a 2-hour period after eating; or meal-unrelated, which was any symptom that occurred more than 2 hours after, or before, an eating episode (eg, when the subject awoke). Symptom severity was classified as follows on a scale of 1 to 10: mild (score, 1–3), not influencing usual activities; modest (score, 4–7), diverting from, but not requiring modification of, daily activities; or strong (score, 8–10), impairing daily activities. The times at which these symptoms occurred were evaluated.

       Behavioral questionnaires

      To obtain behavioral information on each patient and healthy subject, a number of questionnaires were completed. These included the following: (1) Three-Factor Eating questionnaire, which measures 3 dimensions of eating behavior: cognitive restraint, disinhibition of eating, and hunger,
      • Stunkard A.J.
      • Messick S.
      The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger.
      (2) Eating Attitudes Test, which identifies individuals with disordered eating,
      • Garner D.M.
      • Garfinkel P.E.
      The Eating Attitudes Test: an index of the symptoms of anorexia nervosa.
      (3) Northwest Lipid Research Clinical Fat Intake Scale, which estimates fat intake,
      • Retzlaff B.M.
      • Dowdy A.A.
      • Walden C.E.
      • et al.
      The Northwest Lipid Research Clinic Fat Intake Scale: validation and utility.
      (4) Nepean Dyspepsia Index (NDI), which assesses changes in symptoms and quality of life,
      • Talley N.J.
      • Verlinden M.
      • Jones M.
      Validity of a new quality of life scale for functional dyspepsia: a United States multicenter trial of the Nepean Dyspepsia Index.
      (5) Eysenck Personality Questionnaire,
      • Eysenck S.B.
      • Eysenck H.J.
      An improved short questionnaire for the measurement of extraversion and neuroticism.
      and (6) Hospital Anxiety and Depression scale,
      • Zigmond A.S.
      • Snaith R.P.
      The hospital anxiety and depression scale.
      which measures personality and psychologic distress.

       Data and Statistical Analysis

      Questionnaire and eating behavior data were compared between FD patients and healthy subjects using the Mann–Whitney U test. To evaluate relationships between symptoms and variables of food intake, because of repeated measures over time and day, food intake and occurrence/severity were modeled with a generalized estimating question, with multinomial distribution and a cumulative log link. Relationships between NDI subscales, Hospital Anxiety and Depression scores, and eating attitudes with food intake variables were analyzed using the Spearman rho correlations. Statistical significance was accepted at a P value of less than .05, and data are presented as medians (ranges).

      Results

       Eating Behavior

      The number of meals was less in FD patients when compared with healthy subjects (P < .01), and in healthy subjects reflected average Australian eating habits of one main meal per day. There were no other significant differences (Table 1). There was also no difference in the total weight, carbohydrate, protein, or alcohol content of foods consumed, or the percentage of macronutrient distribution, although fat and energy intake tended to be less in the patients (P = .1) (Table 2), the time interval between meals (FD: 162 min; range, 100–320 min; healthy subjects: 172 min; range, 120–347 min), or the duration of the overnight fast (FD: 733 min; range, 450–905 min; healthy subjects: 669 min; range, 527–910 min) between FD patients and healthy subjects.
      Table 1Number of Eating and Drinking Episodes, Meals, Light Meals, Snacks, and Caloric and Noncaloric Drinks During a 7-Day Period in FD Patients and Healthy Subjects
      FD patientsHealthy subjectsP value
      Total number of episodes46 (25–96)44 (21–84).8
      Eating episodes32 (18–40)29 (21–46).9
      Drinking episodes14 (1–57)10 (0–39).6
      Meals5 (1–10)7 (2–16)<.01
      Light meals13 (4–19)10 (4–17).3
      Snacks15 (3–25)11 (0–29).8
      Caloric drinks4 (1–36)3 (0–30).2
      Noncaloric drinks9 (0–21)5 (0–29).7
      % meals12 (2–26)15 (6–52).06
      % light meals28 (6–57)21 (10–57).4
      % snacks30 (8–44)27 (0–54).8
      % caloric drinks10 (2–46)7 (0–46).2
      % noncaloric drinks17 (0–36)10 (0–48).7
      NOTE. Data are shown as median (range) for 20 FD patients and 21 healthy subjects.
      Table 2Energy Intake, Amount Eaten, and Macronutrient Distribution of Fat, Carbohydrate, Protein, and Alcohol During a 7-Day Period in FD Patients and Healthy Subjects
      FD patientsHealthy subjectsP value
      Weight, g16,404 (7827–31,454)18,825 (6683–22,491).6
      Energy, kJ48,131 (17,844–97,548)56,570 (34,780–78,997).1
      Fat, g479 (89–798)564 (301–703).1
      Carbohydrate, g1337 (629–2459)1578 (856–2496).2
      Protein, g511 (237–1051)531 (335–846)1.0
      Alcohol, g14 (0–49)19 (0–28).6
      % fat29.5 (15.3–45.0)28.3 (16.0–38.3).9
      % carbohydrate49.6 (25.8–60.4)51.2 (37.0–62.7).2
      % protein17.8 (10.3–25.1)16.0 (12.5–22.7).2
      % alcohol0.8 (0–2.6)1.3 (0–1.9)1.0
      NOTE. Data are shown as median (range) for 20 FD patients and 21 healthy subjects.

       Symptom Assessment

      No healthy subject experienced any symptoms during the 7-day assessment. FD patients reported a total of 612 symptoms, or 26 (range, 1–92) per patient; 64% (range, 0%–100%) of these were meal-associated with a severity of 5 (range, 3–8) and occurring 31 minutes (range, 8–64 min) after eating, 9% (range, 0%–43%) were other gastrointestinal symptoms with a severity of 5 (range, 3–8) and occurring 25 minutes (range, 5–120 min) after eating, whereas 14% (range, 0%–36%) were meal-unrelated with a severity of 5 (range, 2–7) and occurring 135 minutes (range, −180–0 and 120–200 min) before, or after, eating. Occurrence, severity, and timing of individual meal-associated symptoms are summarized in Table 3.
      Table 3Occurrence and Severity of Individual Meal-Associated Symptoms and the Timing of Their Occurrence After Meals
      Occurrence, %Severity (out of 10)Timing, min
      Bloating28 (7–57)5 (2–9)30 (1–94)
      Nausea11 (4–51)5 (3–8)37 (10–95)
      Upper-abdominal pain11 (2–72)6 (3–8)25 (6–60)
      Belching37 (3–41)4 (3–8)40 (12–59)
      Epigastric pain28 (5–97)4 (3–6)31 (2–105)
      Fullness20 (3–86)6 (2–7)14 (1–68)
      Vomiting3 (3–3)8 (8–8)1 (1–1)
      Discomfort22 (14–50)5 (4–7)45 (16–60)
      NOTE. Data are shown as median (range) for 20 FD patients.

       Eating Attitudes, Gastrointestinal Symptoms, Quality of Life, Personality, and Psychologic Distress

      There was a significant difference in eating attitudes between FD patients and healthy subjects (P < .01). Three of 20 FD patients (15%), but only 1 healthy subject (5%), scored greater than 30 on this scale, indicating disordered eating behavior (Table 4). There were no differences in scores for the Three-Factor Eating questionnaire or the fat intake scale between the 2 groups. Upper-abdominal symptoms, as assessed by the NDI, were greater in FD patients when compared with healthy subjects (P < .0001). There was a significant difference in quality of life between FD patients and healthy subjects. Scores for (1) interference, or difficulty with activities of daily living or work because of dyspepsia, combined with impaired enjoyment of life and emotional well-being (P < .0001), (2) lack of knowledge of, and control over, the illness (P < .0001), (3) disturbances in eating and drinking (P < .0001), and (4) sleep disturbances (P < .001), were greater in FD patients when compared with healthy subjects, indicating poorer quality of life in the patients. There was no difference in personality (ie, neuroticism and extroversion) between the 2 groups. Both FD patients and healthy subjects presented with the same degree of anxiety, however, depression tended to be higher in FD patients (P = .08).
      Table 4Scores for Eating Attitudes, Quality of Life, and Personality/Psychologic Distress in FD Patients and Healthy Subjects
      FD patientsHealthy subjectsP
      Eating attitudes
       Three-Factor eating questionnaire
        (1) Cognitive restraint of eating (cut off, 12; maximum, 21)7 (1–18)6 (1–14).2
        (2) Disinhibition of eating (maximum, 16)4 (0–13)5 (1–10).4
        (3) Hunger (maximum, 14)4 (0–11)4 (1–10).3
       Eating attitudes test (cut off, 30)15 (5–47)9 (1–31)<.01
       Fat intake scale (maximum, 44)26 (15–35)27 (21–40).5
      Upper abdominal symptoms and quality of life (NDI)
       Symptoms (maximum, 195)56 (6–132)4 (0–31)<.0001
       Interference/difficulty with activities (maximum, 65)28 (17–46)13 (13–13)<.0001
       Lack of knowledge or control (maximum, 35)16 (10–28)7 (7–10)<.0001
       Eating/drinking disturbances (maximum, 15)8 (4–14)3 (3–5)<.0001
       Sleep disturbances (maximum, 10)4 (0–10)2 (2–2)<.001
      Personality/psychologic distress
       Eysenck Personality Questionnaire
        Neuroticism (maximum score, 12)4 (0–12)4 (0–9).8
        Extroversion (maximum score, 12)8 (0–11)7 (2–12).9
       Hospital Anxiety and Depression scale
        Anxiety (cut off, 11)14 (7–23)12 (8–17).3
        Depression (cut off, 11)11 (7–20)8 (7–16).08
      NOTE. Data are shown as median (range) for 20 FD patients and 21 healthy subjects.

       Relationships Between Symptoms and Food Intake

      Only relationships between meal-associated symptoms with dietary factors were analyzed because the number of other and meal-unrelated symptoms was low.
      The occurrence of overall meal-associated symptoms was related positively to energy intake (z, 2.02; P < .05), and inversely to carbohydrate ingestion (%: z, −2.08, P < .05). There was no relation between overall symptoms with fat, protein, alcohol (g and %), or weight consumed. For individual symptoms, fullness was related directly to fat (absolute and %: z, 1.91; P < .05), protein (absolute: z, 2.64, P < .001; %: z, 1.82, P = .06) and energy intake (z, 2.12, P < .05), and inversely to carbohydrate consumption (%: z, −1.9; P = .05). Bloating was related to the ingestion of fat (z, 1.68; P = .09). There was no significant relationship between the severity of symptoms and energy intake, or the amount and macronutrient content of foods consumed.

       Relationships Between Quality of Life, Eating Attitudes, Anxiety, and Depression With Food Intake

      There was a direct relationship between fat (r, 0.50; P < .05) and protein (r, 0.4; P = .06), and an inverse relationship between carbohydrate intake (r, −0.60; P < .01), with scores for disturbance in eating and drinking, as measured by the NDI, in FD patients. There were no other significant relationships.

      Discussion

      We formally evaluated eating behavior in FD patients and healthy subjects and the relationships between symptoms with food intake. The major findings in FD patients are as follows: (1) symptoms are related to food intake, specifically, fullness with both fat and energy intake and bloating with fat intake; (2) the number of full meals consumed is less, with no differences in the number of other eating episodes, or the weight or macronutrient content consumed; (3) fat and energy intake tended to be less; (4) symptoms occur within 30 minutes of eating and usually at a modest severity; and (5) fat and protein intake apparently affect quality of life adversely.
      This study established a relationship between symptom occurrence and food intake. Overall symptoms were related directly to energy intake and inversely to the ingestion of carbohydrate, fullness and bloating to the intake of fat, and fullness to energy intake. These observations are consistent with those of a laboratory study in which duodenal infusion of fat, but not glucose, exacerbated symptoms in FD.
      • Barbera R.
      • Feinle C.
      • Read N.W.
      Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia.
      Moreover, in this previous study, duodenal infusion of fat increased the sensitivity to gastric distension in FD patients, in that discomfort was perceived at lower volumes and pressures than during the control infusion, whereas in healthy subjects the lipid infusion reduced the sensitivity to gastric distension. In contrast, glucose infusion reduced gastric sensitivity in both healthy subjects and FD patients, underlining the apparently specific role of lipid in symptom induction.
      The second observation was that although there was no overall difference in the total number of eating episodes, FD patients consumed fewer full meals, although the difference was small and there was considerable overlap with healthy subjects. Taken together, with the outcome of a previous study,
      • Mullan A.
      • Kavanagh P.
      • O'Mahony P.
      • et al.
      Food and nutrient intakes and eating patterns in functional and organic dyspepsia.
      these findings suggest that FD patients may eat smaller meals in an attempt to reduce their symptoms. In the present study there was also a trend for decreased fat and energy intake in FD patients. The absence of significant differences may represent a type 2 error. Given that the occurrence of symptoms was related to fat and energy intake, this may suggest an important first point-of-call for dietary therapy, that is, reducing fat and energy intake (coupled with diminished meal size) may alleviate symptoms, particularly fullness and bloating. It has been reported that there are gender-specific differences in nutrient intakes, that is, energy, carbohydrate, fat, and protein were reported to be less in female FD patients, compared with healthy subjects, with no differences in men.
      • Mullan A.
      • Kavanagh P.
      • O'Mahony P.
      • et al.
      Food and nutrient intakes and eating patterns in functional and organic dyspepsia.
      Because the cohort that comprised the current study only included 3 men, it was not possible to evaluate this.
      All FD patients reported some symptoms throughout the week—this observation is interesting because, despite small differences in fat and energy intake, total energy intake was not different between FD and healthy subjects. The majority of these symptoms, as expected, were meal-associated, reflecting the cohort recruited and rigorous inclusion criteria. These symptoms were perceived approximately 30 minutes after meal ingestion and were of moderate severity. The effect of food intake on these symptoms, within this time frame, may reflect gastrointestinal factors, such as the release of the hormones cholecystokinin (CCK) and peptide YY. Both hormones have been shown to mediate, at least in part, the effect of meals on hunger and fullness.
      • Gutzwiller J.P.
      • Drewe J.
      • Ketterer S.
      • et al.
      Interaction between CCK and a preload on reduction of food intake is mediated by CCK-A receptors in humans.
      • Degen L.
      • Oesch S.
      • Casanova M.
      • et al.
      Effect of peptide YY3-36 on food intake in humans.
      In a recent study
      • Pilichiewicz A.
      • Feltrin K.L.
      • Horowitz M.
      • et al.
      Oral carbohydrate and fat differentially modulate symptoms, gut hormones and antral area in functional dyspepsia.
      we showed that fasting and postprandial CCK concentrations after a high-fat preload are higher in FD patients when compared with healthy subjects. This increase in CCK also was associated with higher scores for nausea and pain.
      A previous study indicated that patients had the capacity to identify foods that exacerbate their symptoms and, therefore, avoided them;
      • Kearney J.
      • Kennedy N.P.
      • Keeling P.W.
      • et al.
      Dietary intakes and adipose tissue levels of linoleic acid in peptic ulcer disease.
      however, this association was anecdotal and was not assessed formally. In the present study, however, there was a significant relationship between fat intake and the subscale of the NDI relating to disturbances in eating or drinking. These items included statements of “the ability to eat/drink is disturbed by stomach problems,” “diet changed due to stomach problems,” and “enjoyment of eating/drinking reduced due to stomach problems.” This observation is consistent with the concept that patients are aware that eating is the cause of their symptoms, as suggested by their responses to the questionnaire at baseline. Although fat intake was less (albeit nonsignificantly) in the FD patients, the differences were small, suggesting that FD patients may not be able to identify foods with a high fat content precisely, which, in turn, may have major implications for dietary counseling. It has been reported that eating attitudes, as assessed by the eating attitudes test, did not differ between patients with IBS and healthy subjects.
      • Sullivan G.
      • Blewett A.E.
      • Jenkins P.L.
      • et al.
      Eating attitudes and the irritable bowel syndrome.
      However, in the current study differences were apparent that were indicative of a higher prevalence of anorectic behaviors in the FD group. Depression scores also were greater in patients than in healthy subjects, consistent with previous observations.
      • Van Oudenhove L.
      • Vandenberghe J.
      • Geeraerts B.
      • et al.
      Relationship between anxiety and gastric sensorimotor function in functional dyspepsia.
      • Soo S.
      • Moayyedi P.
      • Deeks J.
      • et al.
      Psychological interventions for non-ulcer dyspepsia.
      However, there was no association in this cohort between anxiety and depression with food intake, although it is possible that depression, anxiety, and poor quality of life explain a particular dietary behavior or at least the increased aversion to certain foods.
      Our study design warrants some comment. Although our subject numbers were relatively small, the resulting data, particularly those relating symptoms to energy and fat intake, appear clear-cut. Nevertheless, as mentioned, type 2 errors cannot be excluded, and the applicability of our observations to men remains uncertain. Furthermore, we cannot exclude that the dietary intake of FD patients was not influenced by their convictions of associations between food and symptoms, even if they were unaware that the end point was the relationship between symptom occurrence and food intake, or by the fact that some of the patients may have been conscious of their energy intake because they were overweight. Our study focused on the relationship between dietary intake (ie, energy and macronutrients, including total fat intake) and symptoms. It is important to recognize that other nutrient or nonnutrient factors may be important in deteriorating (eg, coffee) or improving (omega-3 fats) symptoms, which deserves evaluation in larger studies, although our data did not indicate differences in intakes of coffee or fish between healthy subjects and FD patients.
      In summary, this study showed the following in a cohort of FD patients: (1) symptoms are related to fat and energy intake; (2) FD patients eat fewer meals than healthy subjects and tend towards lower fat and energy intake; (3) symptoms usually occur within 30 minutes of eating at a moderate severity; and (4) the quality of life was a determinant of fat and protein intake. These observations provide insights into the potential gastrointestinal mechanisms underlying symptom induction; accordingly, the consumption of smaller meals, combined with a reduced fat intake, may prove beneficial in the management of FD.

      Acknowledgements

      The authors thank Ms Nancy Briggs for her assistance with the statistical analysis.

      References

        • Kearney J.
        • Kennedy N.P.
        • Keeling P.W.
        • et al.
        Dietary intakes and adipose tissue levels of linoleic acid in peptic ulcer disease.
        Br J Nutr. 1989; 62: 699-706
        • Mullan A.
        • Kavanagh P.
        • O'Mahony P.
        • et al.
        Food and nutrient intakes and eating patterns in functional and organic dyspepsia.
        Eur J Clin Nutr. 1994; 48: 97-105
        • Kaess H.
        • Kellermann M.
        • Castro A.
        Food intolerance in duodenal ulcer patients, non ulcer dyspeptic patients and healthy subjects.
        Klin Wochenschr. 1988; 66: 208-211
        • Cuperus P.
        • Keeling P.W.
        • Gibney M.J.
        Eating patterns in functional dyspepsia: a case control study.
        Eur J Clin Nutr. 1996; 50: 520-523
        • Mertz H.
        • Fullerton S.
        • Naliboff B.
        • et al.
        Symptoms and visceral perception in severe functional and organic dyspepsia.
        Gut. 1998; 42: 814-822
        • Barbera R.
        • Feinle C.
        • Read N.W.
        Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia.
        Dig Dis Sci. 1995; 40: 1636-1641
        • Barbera R.
        • Feinle C.
        • Read N.W.
        Abnormal sensitivity to duodenal lipid infusion in patients with functional dyspepsia.
        Eur J Gastroenterol Hepatol. 1995; 7: 1051-1057
        • Caldarella M.P.
        • Azpiroz F.
        • Malagelada J.R.
        Antro-fundic dysfunctions in functional dyspepsia.
        Gastroenterology. 2003; 124: 1220-1229
        • Tack J.
        • Piessevaux H.
        • Coulie B.
        • et al.
        Role of impaired gastric accommodation to a meal in functional dyspepsia.
        Gastroenterology. 1998; 115: 1346-1352
        • Tack J.
        • Caenepeel P.
        • Fischler B.
        • et al.
        Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia.
        Gastroenterology. 2001; 121: 526-535
        • Houghton L.A.
        • Mangnall Y.F.
        • Dwivedi A.
        • et al.
        Sensitivity to nutrients in patients with non ulcer dyspepsia.
        Eur J Gastroenterol Hepatol. 1993; 5: 109-113
        • Feinle C.
        • Meier O.
        • Otto B.
        • et al.
        Role of duodenal lipid and cholecystokinin A receptors in the pathophysiology of functional dyspepsia.
        Gut. 2001; 48: 347-355
        • Pilichiewicz A.
        • Feltrin K.L.
        • Horowitz M.
        • et al.
        Oral carbohydrate and fat differentially modulate symptoms, gut hormones and antral area in functional dyspepsia.
        Am J Gastroenterol. 2008; 103: 2613-2623
        • Talley N.J.
        • Phillips S.F.
        • Bruce B.
        • et al.
        Relation among personality and symptoms in nonulcer dyspepsia and the irritable bowel syndrome.
        Gastroenterology. 1990; 99: 327-333
        • Talley N.J.
        • Piper D.W.
        Major life event stress and dyspepsia of unknown cause: a case control study.
        Gut. 1986; 27: 127-134
        • Talley N.J.
        • Stanghellini V.
        • Heading R.C.
        • et al.
        Functional gastroduodenal disorders.
        Gut. 1999; 45: 37-42
        • Karvetti R.L.
        • Knuts L.R.
        Validity of the estimated food diary: comparison of 2-day recorded and observed food and nutrient intakes.
        J Am Diet Assoc. 1992; 92: 580-584
        • Stunkard A.J.
        • Messick S.
        The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger.
        J Psychosom Res. 1985; 29: 71-83
        • Garner D.M.
        • Garfinkel P.E.
        The Eating Attitudes Test: an index of the symptoms of anorexia nervosa.
        Psychol Med. 1979; 9: 273-279
        • Retzlaff B.M.
        • Dowdy A.A.
        • Walden C.E.
        • et al.
        The Northwest Lipid Research Clinic Fat Intake Scale: validation and utility.
        Am J Public Health. 1997; 87: 181-185
        • Talley N.J.
        • Verlinden M.
        • Jones M.
        Validity of a new quality of life scale for functional dyspepsia: a United States multicenter trial of the Nepean Dyspepsia Index.
        Am J Gastroenterol. 1999; 94: 2390-2397
        • Eysenck S.B.
        • Eysenck H.J.
        An improved short questionnaire for the measurement of extraversion and neuroticism.
        Life Sci. 1964; 3: 1103-1109
        • Zigmond A.S.
        • Snaith R.P.
        The hospital anxiety and depression scale.
        Acta Psychiatr Scand. 1983; 67: 361-370
        • Gutzwiller J.P.
        • Drewe J.
        • Ketterer S.
        • et al.
        Interaction between CCK and a preload on reduction of food intake is mediated by CCK-A receptors in humans.
        Am J Physiol. 2000; 279: R189-R195
        • Degen L.
        • Oesch S.
        • Casanova M.
        • et al.
        Effect of peptide YY3-36 on food intake in humans.
        Gastroenterology. 2005; 129: 1430-1436
        • Sullivan G.
        • Blewett A.E.
        • Jenkins P.L.
        • et al.
        Eating attitudes and the irritable bowel syndrome.
        Gen Hosp Psychiatry. 1997; 19: 62-64
        • Van Oudenhove L.
        • Vandenberghe J.
        • Geeraerts B.
        • et al.
        Relationship between anxiety and gastric sensorimotor function in functional dyspepsia.
        Psychosom Med. 2007; 69: 455-463
        • Soo S.
        • Moayyedi P.
        • Deeks J.
        • et al.
        Psychological interventions for non-ulcer dyspepsia.
        Cochrane Database Syst Rev. 2003; 2 (CD002301)