Journal of the Formosan Medical Association (2018) 117, 973e978

Available online at www.sciencedirect.com

ScienceDirect

journal homepage: www.jfma-online.com

Original Article

The effect of dietary carbohydrate on

gastroesophageal reflux disease
Keng-Liang Wu a,b,c, Chung-Mou Kuo a,b, Chih-Chien Yao a,
Wei-Chen Tai a,b, Seng-Kee Chuah a,b, Chee-Sang Lim d,
Yi-Chun Chiu a,b,*

a
Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung
Memorial Hospital, Taiwan
b
Chang Gung University College of Medicine, Kaohsiung, Taiwan
c
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital,
Kaohsiung, Taiwan
d
Department of Hepatology, Hospital Selayang, Lebuh Raya Selayang-kepong, 68100 Batu Caves,
Selangor, Malaysia

Received 12 August 2017; received in revised form 10 October 2017; accepted 2 November 2017

KEYWORDS Abstract Background: Acid changes in gastroesophageal reflux with vary component in the
Gastroesophgeal food have less been studied, especially carbohydrate. We plan to clarify the effect of different
reflux disease; carbohydrate density on low esophageal acid and reflux symptoms of patients with gastroe-
Diet; sophgeal reflux disease.
Esophagitis; Methods: Twelve patients (52
12 years old; five female) with gastroesophageal reflux disease
Ambulatory were recruited for the prospective crossover study. Each patient was invited for panendoscope,
esophageal pH manometry and 24 h pH monitor. The two formulated liquid meal, test meal A: 500 ml liquid
monitoring; meal (containing 84.8 g carbohydrate) and B: same volume liquid meal (but 178.8 g carbohy-
Carbohydrate drate) were randomized supplied as lunch or dinner. Reflux symptoms were recorded.
Results: There are significant statistic differences in more Johnson-DeMeester score
(p Z 0.019), total reflux time (%) (p Z 0.028), number of reflux periods (p Z 0.026) and longest
reflux (p Z 0.015) after high carbohydrate diet than low carbohydrate. Total reflux time and
number of long reflux periods more than 5 min are significant more after high carbohydrate diet.
Conclusion: More acid reflux symptoms are found after high carbohydrate diet. High carbohy-
drate diet could induce more acid reflux in low esophagus and more reflux symptoms in patients
with gastroesophageal reflux disease.
Copyright ª 2018, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/
by-nc-nd/4.0/).

* Corresponding author. Diversion of Hepatogastroenterology, Department of internal medicine, Kaohsiung Chang Gung Memorial Hospital
123, Ta-Pei Road, Niao Sung District, Kaohsiung City 83301, Taiwan. Fax: þ886 7 7322402.
E-mail address: chiuku@ms14.hinet.net (Y.-C. Chiu).

https://doi.org/10.1016/j.jfma.2017.11.001
0929-6646/Copyright ª 2018, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
974
Introduction
Gastroesophageal reflux disease (GERD) is a disease due to
abnormal reflux of the gastric contents into the esophagus,
causing reflux symptoms, such as heartburn, acid regurgi-
tation or esophageal mucosal damage which may also lead
to long-term complications, such as Barrett’s esophagus or
stricture.1,2 It is a common disease in the western countries
and affects about 10%e30% of the population. The preva-
lence of GERD was increasing in trend, based on the current
reports, the prevalence in certain parts of China and
Taiwan varies from 2.5% to 15.7%.3e6 Various studies had
reported that gastroesophageal reflux increased after
meals compare to fasting.7,8 It is postulated that gastric
distension may be a contributing factor.9 Emerging evi-
dence had shown that patients with heartburn were asso-
ciated with large meals and fat ingestion.10
Patients presented with heartburn and acid regurgitation
were often told to avoid large meals as numerous reports had
shown that patients will have worsening of reflux symptoms
after ingesting large meals. This advice was based on epide-
miological surveys that report a link between high volume
intake with the symptoms of GERD.11,12 At present, there are
only a few studies comparing symptoms of GERD with
selected diet, especially with carbohydrate.14,15 In order to
evaluate the effect of carbohydrate density in large volume
liquid diet16,17 in relation with the symptoms of GERD,13 a
study was conducted to assess liquid meal with different type
of dietary carbohydrate density in influencing the esophageal
pH and reflux symptoms in patients with GERD.
Material and methods
Subject selection criteria
Twelve patients (52
12 years old; five female) with
gastroesophageal reflux disease were recruited in this
prospective crossover study (Table 1). Exclusion criteria
were 1.age less than 20 years, 2.present or previous angina
pectoris, 3.history of upper gastrointestinal surgery,
4.ingestion of medication that affects either gastrointes-
tinal function (acid suppression such as PPI or H2 receptor
blocker etc which was stopped 7 days before the study),
5.pregnancy, 6.consumption of PPI&1 month before the
study, 7.esophageal stricture, ulcer, Barrett’s esophagus
and 8.gastroduodenal ulceration, 9.abdominal malignant
Table 1 Characteristic of patients with gastroesophageal
reflux disease (No:12).
Female/Male 5/7
Age 52
12 years old
BMI 24.3
3.8 Kg/m2
Abdominal circumflex 82.7
6.9 cm
Buttock circumflex 93.1
4.5 cm
Smoking 0
Alcohol 0
NERD/GERD GrA/GrB 5/3/4
GERD Q 17
9
BMI: body mass index; NERD: non-erosive reflux disease; GERD:
gastroesohageal reflux disease; Gr: grade.
K.-L. Wu et al.
tumor, diabetes mellitus, scleroderma and 10. other
gastrointestinal motility disease. This study was conducted
at the Kaohsiung Chang Gung Memorial Hospital between
Sep, 2012, and July, 2013, and all the participants had given
their written consent to participate in this study. The study
protocol was reviewed and approved by the Institutional
Review Board of Kaohsiung Chang Gung Memorial Hospital.
In this study, heartburn was defined as a burning
sensation arising from the stomach or lower chest and was
aggravated after the patient bend forward or after pressure
was placed on the abdomen. Patients who were presented
with a history of heartburn at least twice in a week over the
previous month were enrolled in this study. Esophagitis was
graded by panendoscope using the Los Angeles classifica-
tion.18 Non-erosive reflux disease (NERD) was defined as a
subcategory of GERD characterized by troublesome reflux-
related symptoms in the absence of esophageal mucosal
erosions or breaks at conventional endoscopy and without
recent acid suppressive therapy.19
An endoscopy examination and a 24 h pH monitoring test
were performed in the study. During 24-h esophageal pH
monitoring test, patients were provided with two different
liquid meal tests, 500 mls each for lunch and dinner. Reflux
symptoms, such as acid regurgitation, heartburn, others
abdomen discomfort, as well as the duration of lying down
and sleeping were also recorded. Patients were forbidden
to lie down or sleep for 2 h after taking the Test Meals. The
study protocol was shown in Fig. 1.
Questionnaire GERDQ
The modified Chinese GERDQ questionnaire includes questions
about the severity and frequency of the symptoms of regur-
gitation and heartburn, and the answers were graded based on
a three-point Likert scale as follows: mild Z presence of
symptoms, but the symptom can be easily ignored,
moderate Z presence of symptoms but the symptom can be
easily tolerated, and advanced severity Z symptoms that
interfered with normal daily activities. The symptoms of GERD
that occur at least once per month, at least once a week, and
at least once a day were classified as low, middle and high
frequency symptoms, respectively.20
Test meals
The test meals were prepared in-house by nutrition
research scientists.21 The two formulated liquid meals, test
meal A: 500 ml liquid meal (containing 474.4 kcal (10.4 g
protein, 10.4 g fat, 84.8 g carbohydrate) and test meal B:
500 ml liquid meal (containing 850.4 kcal (the same protein
and fat, but 178.8 g carbohydrate). The liquid meal was
boiled and subsequently cooled to 37  C. The test meals
were provided in a randomized order. Subjects consumed
each meal within 20 min. Water, food, acid-suppressant
medications and other medication that may influence
GERD were prohibited during the study.
Endoscopy
Endoscopy was performed 3 days before the 24 h pH
monitoring test using a high-resolution magnifying
Carbohydrate on reflux disease
Figure 1 Flow chart of the study procedure.
endoscopy (Olympus GIF 240Z, 115X, Olympus Medical
Systems Corp, Tokyo, Japan) and the lower esophagus was
closely examined after it was rinsed with water and classify
in accordance with the stage of esophagitis based on LA
classification.
Ambulatory esophageal pH monitoring
An esophageal manometry study was performed for the
patient who had fasted overnight to determine the location
of the lower esophageal sphincter (LES). Subsequently a
commercially available pH probe (MMS Orion II, Medical
measurement system Corp, Netherlands) that contained
two pH sensors (located every 5 cm, with the distal sensor
at the tip of the catheter) was inserted intranasal into the
esophagus. The tip of the probe was placed 5 cm above the
LES determined by manometry. The pH probe was then
connected to a portable digital recording device22 and a
portable data logger (Ohmega, MMS, Enschede, The
Netherlands). The recording began and pH signals were
relayed and stored in a digital system using a sample fre-
quency of 2 Hz. All the participants were instructed to
change position from time to time and to report symptoms
during the recording. The electrode was calibrated in a
buffer system of pH 4 and 7 respectively pre and post-
measurement. An electrode drift of less than 0.2 pH units
was acceptable in this test. The results of the tests will be
evaluated and analyzed according to Johnson-DeMeester
score.
GERD was determined by the validated Johnson-
DeMeester score. This scoring method takes into the ac-
count of six parameters which include: total percentage of
time pH below 4, percentage of time pH below 4 in the
upright position, percentage of time pH below 4 in the su-
pine position, the total number of reflux episodes, the
number of reflux episodes longer than 5 min and the longest
975
reflux episodes in minutes. A composite score was then
calculated and a score of greater than 14.7 was indicative
of GERD.
Statistical analysis
This crossover clinical experiment was a repeated measure
design in each patient in this trial was assigned to 2
formulated liquid meals with carbohydrate in two different
density (high density vs low density). This crossover design
had “balance” which means that all patients will receive
the same volume of liquid meal and participate for the
same duration during the study. Demographic data were
presented as mean
SD. Statically analysis with paired t-
tests were used to analyze all the primary outcomes of
interest, which included changes in the Johnson -
DeMeester score, percentage total time with pH < 4.0 in
the distal esophagus, duration, number of reflux and reflux
symptoms. The data were then analyzed using a standard
statistical package (SPSS, 10.0). After this assessment,
parametric data, such as esophageal acid exposure, were
summarized as mean
SD or standard error of the mean. A
p value of less than 0.05 was considered significant.
Results
In this study, comparison between study group of high
carbohydrate diet and low carbohydrate diet had shown
that the Johnson - DeMeester score were higher
(39.7
11.0; 14.3
5.3, p Z 0.019) (Fig. 2A), the total
reflux time were longer (21.8
5.7; 8.8
3.8%, p Z 0.028)
(Fig. 2B). and more numbers of reflux periods were noted
(12.7
2.1; 7.1
2.3, p Z 0.026) (Fig. 2D) in patients who
took high carbohydrate diet. In addition, more numbers of
reflux periods longer than 5 min (1.3
0.5; 0.3
0.3,
976 K.-L. Wu et al.

Figure 2 The esophageal pH monitor between high carbohydrate and low carbohydrate diet. More Johnson-DeMeester score
(39.7
11.0; 14.3
5.3, p Z 0.019) (Fig.2A), total reflux time (%) (21.8
5.7; 8.8
3.8, p Z 0.028) (Fig. 2B) and numbers of reflux
periods (12.7
2.1; 7.1
2.3, p Z 0.026) (Fig. 2D) were noted after high carbohydrate diet 2 h than low carbohydrate. After
testing meal, more numbers of longer than 5 min after high carbohydrate diet than low carbohydrate (1.3
0.5; 0.3
0.3,
p Z 0.02) (Fig.2E) was noted. Longest reflux time was found after high than low carbohydrate diet (5.8
1.5; 2.8
0.9 min,
p Z 0.015) (Fig.2F). *p < 0.05.

p Z 0.02) (Fig. 2E) and more acid reflux symptoms
(heartburn sensation and acid regurgitation) were noted.
The longest reflux time was found in those patients after
taking high carbohydrate diet (5.8
1.5; 2.8
0.9 min,
p Z 0.015) (Fig. 2F). In different stages of GERD, there
were more symptoms reported in GERD Grade B compared
to Grade A and NERD. Furthermore, in this study had
demonstrated that patients had more reflux symptoms in
five NERD patients (1.0
0.2; 0.2
0.2, p Z 0.034), three
GERD Grade A patients (2.3
0.4; 0.7
0.4, p Z 0.036)
and four GERD Grade B patients (3.3
0.5; 1.3
0.3,
p Z 0.016) (Fig. 3) after high carbohydrate diet.
Discussion
In this study, a high carbohydrate diet could increase both acid
reflux duration, reflux periods, and as well as induced more
reflux symptoms in GERD patients. Yancy et al. first reported
that five obesity individuals experienced resolution of GERD
symptoms after self-initiation of a low-carbohydrate diet.
Based on their observations, they had suggested that carbo-
hydrate restriction may have attributed to the resolution of
reflux symptoms.17 Subsequently, Colomb et al. reported that
increasing the caloric content of balanced meals increased
GERD.23 These findings were supported by a study conducted
by Fox et al. which revealed that esophageal acid exposure
was greater during the high-calorie diet than the low-calorie
diet, however the frequency of reflux symptoms was not
affected by calorie density.24 In our study, the outcome of the
tests was similar compared to the previous studies.17,23,24 In a
recently published study by Wu et al., high intake of protein,
carbohydrate, calories from protein and eggs correlates with
a reduced risk for reflux esophagitis. However, this was a
retrospective study, and limited to some confounding fac-
tors.25 It was suggested that a high carbohydrate diet could
produce more calories and thus more food content would stay
over the fundus and decreased gastric emptying. Ultimately,
it could induce more mixed liquidegas reflux, increased
duration of acid reflux exposure and symptoms of GERD.
We had used same volume but different carbohydrate
and calories to study the effect of carbohydrate density.
We noted that from our previous study that higher volume
of liquid meal would generate more acid reflux symp-
toms.13There were difference of carbohydrate and calories
of the two test meals, but at the same time other compo-
nents (protein, lipid) remained the same. Based on the
different calories produced from different carbohydrate,
we noted that calories were more important to induce the
postprandial reflux. Nonetheless, obese patients with GERD
may experience a resolution of symptoms utilizing a very
low-carbohydrate diet. Austin et al. reported that a very
low-carbohydrate diet in obese individuals with GERD
significantly reduced distal esophageal acid exposure and
improved symptoms.16 However, the present study has
some limitations. In this study, analysis of the esophageal
pH data of 120 min after different test meals, was not a
routine examination for 24 pH monitoring tests. We only
Carbohydrate on reflux disease
Figure 3 Symptoms between high carbohydrate and low carbohydrate diet. More acid reflux symptoms were noted after high
carbohydrate in different GERD stage, NERD (high carbohydrate: low carbohydrate: 1.0
0.2; 0.2
0.2, p Z 0.034), GERD Gr A
(2.3
0.4; 0.7
0.4, p Z 0.036) and GERD Gr B (3.3
0.5; 1.3
0.3, p Z 0.016) *p < 0.05.
analyzed two-hours pH monitoring data as gastric emptying
was less than 2e3 h in normal subject and usually liquid
diet had emptied into the duodenum within 2 h. This con-
dition was demonstrated in our previous study, as we had
established that high carbohydrates could delay gastric
emptying.21 Thus, this condition had result more food stasis
in stomach after high carbohydrate and more reflux epi-
sodes and more symptoms were reported. It was well
known that ambulatory esophageal pH monitoring for pH
detection and impedance-pH monitoring was the gold
standard for detecting all reflux episodes and could provide
more bolus transit information. However, in our study,
there was no adequate wash-over time between two test
meals. Moreover, pH monitor data were analyzed during a
short duration (120 min) after different test meals. Thus,
we did not find a real effect of carbohydrate density on
GERD during 24 h. In addition, the symptom was not
recorded by well-designed questionnaire. Other than that,
polysaccharide as a sole carbohydrate source might affect
the outcome as analyzing different carbohydrate compo-
nent (monosaccharide, disaccharide and oligosaccharide)
on GERD were necessary and might give different results. In
conclusion, high carbohydrate diet could increase the acid
reflux time, acid periods in the lower esophagus and cause
more reflux symptoms in GERD patients. On the contrary,
low carbohydrate diet had a reversed effect. At present,
there are limited studies on short term and long-term ef-
fect on the low carbohydrate diet in relation to GERD, more
studies are needed in the future to explore the potential of
low carbohydrate diet in the management of GERD.
Conflicts of interest
The authors declare that they have no competing interests.
977
Acknowledgments
This study was funded by a research grant (CMRPG8A1071)
awarded by Chang Gung Memorial Hospital, Taiwan, R.O.C.
The authors wish to thank Miss Yi-Hua Lin, Division of
Hepatogastroenterology, Kaohsiung Chang Gung Memorial
Hospital for her assistance with data collection. We
appreciate the Biostatistics Center, Kaohsiung Chang Gung
Memorial Hospital for the statistical analysis.
Appendix A. Supplementary data
Supplementary data related to this article can be found at
https://doi.org/10.1016/j.jfma.2017.11.001.
References
1. Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. The Mon-
treal definition and classification of gastroesophageal reflux
disease: a global evidence-based consensus. Am J Gastro-
enterol 2006;101:1900e20.
2. Moayyedi P, Talley NJ. Gastro-oesophageal reflux disease.
Lancet 2006;367:2086e100.
3. El-Serag HB, Ergun GA, Pandolfino J, Fitzgerald S, Tran T,
Kramer JR. Obesity increases oesophageal acid exposure. Gut
2007;56:749e55.
4. Dent J, El-Serag HB, Wallander MA, Johansson S. Epidemiology
of gastro-oesophageal reflux disease: a systematic review. Gut
2005;54:710e7.
5. Lien HC, Chang CS, Yeh HZ, Ko CW, Chang HY, Cheng KF, et al.
Increasing prevalence of erosive esophagitis among taiwanese
aged 40 years and above: a comparison between two time
periods. J Clin Gastroenterol 2009;43:926e32.
978
6. Tseng PH, Lee YC, Chiu HM, Huang SP, Liao WC, Chen CC, et al.
Prevalence and clinical characteristics of Barrett’s esophagus
in a Chinese general population. J Clin Gastroenterol 2008;42:
1074e9.
7. Dodds WJ, Dent J, Hogan WJ, Helm JF, Hauser R, Patel GK,
et al. Mechanisms of gastroesophageal reflux in patients with
reflux esophagitis. N Engl J Med 1982;307:1547e52.
8. Dent J, Dodds WJ, Friedman RH, Sekiguchi T, Hogan WJ,
Arndorfer RC, et al. Mechanisms of gastroesophageal reflux in
recumbent asymptomatic subjects. J Clin Invest 1980;65:
256e67.
9. Holloway RH, Hongo M, Berger K, McCallum RW. Gastric
distention: a mechanism for postprandial gastroesophageal
reflux. Gastroenterology 1985;89:779e84.
10. Iwakiri K, Kobayashi M, Kotoyori M, Yamada H, Sugiura T,
Nakagawa Y. Relationship between postprandial esophageal
acid exposure and meal volume and fat content. Dig Dis Sci
1996;41:926e30.
11. Nebel OT, Fornes MF, Castell DO. Symptomatic gastroesopha-
geal reflux: incidence and precipitating factors. Am J Dig Dis
1976;21:953e6.
12. El-Serag HB, Satia JA, Rabeneck L. Dietary intake and the risk
of gastro-esophageal reflux disease: a cross sectional study in
volunteers. Gut 2005;54:11e7.
13. Wu KL, Rayner CK, Chuah SK, Chiu YC, Chiu KW, Hu TH, et al.
Effect of liquid meals with different volumes on gastroesoph-
ageal reflux disease. J Gatrol Hepatol 2014;29:469e73.
14. Salvia G, De Vizia B, Manguso F, Iula VD, Terrin G, Spadaro R,
et al. Effect of intragastric volume and osmolality on mecha-
nisms of gastroesophageal reflux in children with gastro-
esophageal reflux disease. Am J Gastroenterol 2001;96:
1725e32.
15. Emerenziani S, Zhang X, Blondeau K, Silny J, Tack J,
Janssens J, et al. Gastric fullness, physical activity, and prox-
imal extent of gastroesophageal reflux. Am J Gastroenterol
2005;100:1251e6.
K.-L. Wu et al.
16. Austin GL, Thiny MT, Westman EC, Yancy Jr WS, Shaheen NJ. A
very low-carbohydrate diet improves gastroesophageal reflux
and its symptoms. Dig Dis Sci 2006;51:1307e12.
17. Yancy Jr WS, Provenzale D, Westman EC. Improvement of
gastroesophageal reflux disease after initiation of a low-
carbohydrate diet: five brief case reports. Altern Ther
Health Med 2001;7:116e9.
18. Lundell LR, Dent J, Bennett JR, Blum AL, Armstrong D,
Galmiche JP, et al. Endoscopic assessment of oesophagitis:
clinical and functional correlates and further validation of the
Los Angeles classification. Gut 1999;45:172e80.
19. Modlin IM, Hunt RH, Malfertheiner P, Moayyedi P, Quigley EM,
Tytgat GN, et al. Non-erosive reflux diseaseedefining the en-
tity and delineating the management. Digestion 2008;78:1e5.
20. Lee SW, Lee TY, Lien HC, Yang SS, Yeh HZ, Chang CS. Charac-
teristics of symptom presentation and risk factors in patients
with erosive esophagitis and nonerosive reflux disease. Med
Princ Pract 2014;23(5):460e4.
21. Wu KL, Rayner CK, Chuah SK, Changchien CS, Lu SN, Chiu YC,
et al. Effects of ginger on gastric emptying and motility in
healthy humans. Eur J Gastroenterol Hepatol 2008;20:436e40.
22. Dickman R, Parthasarathy S, Malagon IB, Jones P, Han B,
Powers J, et al. Comparisons of the distribution of oesophageal
acid exposure throughout the sleep period among the different
gastro-oesophageal reflux disease groups. Aliment Pharmacol
Ther 2007;26:41e8.
23. Colombo P, Mangano M, Bianchi PA, Penagini R. Effect of cal-
ories and fat on postprandial gastro-oesophageal reflux. Scand
J Gastroenterol 2002;37:3e5.
24. Fox M, Barr C, Nolan S, Lomer M, Anggiansah A, Wong T. The
effects of dietary fat and calorie density on esophageal acid
exposure and reflux symptoms. Clin Gastroenterol Hepatol
2007;5:439e44.
25. Wu P, Zhao XH, Ai ZS, Sun HH, Chen Y, Jiang YX, et al. Dietary
intake and risk for reflux esophagitis: a case-control study.
Gastroenterol Res Pract 2013:691026.