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Influence of the tolerability of vinegar as an oral source of short-chain fatty acids on appetite control and food intake

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Background Vinegar is promoted as a natural appetite suppressant, based on previous reports that vinegar ingestion significantly increases subsequent satiety. However there are concerns about the appropriateness and safety of this advice and it is unclear if poor product palatability may explain previously published effects on appetite.Objective To investigate if vinegar palatability and tolerability have a role in suppressing appetite and food intake in two sequential and related acute human feeding studies.Subjects and methodsHealthy, young, normal weight unrestrained eaters were recruited to Study 1 (n=16), an acute feeding study supplying vinegar within both palatable and unpalatable drinks alongside a mixed breakfast in comparison to a non-vinegar control; and to Study 2 (n=14), a modified sham feeding study (taste only without ingestion) comparing vinegar to a non-vinegar control following a milkshake preload. Both studies were a randomised cross-over balanced design for the assessment of appetite, energy intake and glycemic response.ResultsIn Study 1 ingestion of vinegar significantly reduced quantitative and subjective measures of appetite, which were accompanied by significantly higher nausea ratings, with Unpal treatment having the greatest effect. Significant correlations between palatability ratings and appetite measures were found. In Study 2, orosensory stimulation with vinegar did not influence subsequent subjective or quantitative measures of appetite compared to control.Conclusions These studies indicate that vinegar ingestion enhances satiety while orosensory stimulation alone does not, and that these effects are largely due to poor tolerability following ingestion invoking feelings of nausea. On this basis the promotion of vinegar as a natural appetite suppressant does not seem appropriate.International Journal of Obesity accepted article preview online, 27 August 2013. doi:10.1038/ijo.2013.157.
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ORIGINAL ARTICLE
Influence of the tolerability of vinegar as an oral source
of short-chain fatty acids on appetite control and food intake
J Darzi
1
, GS Frost
2
, R Montaser
1
,JYap
1
and MD Robertson
1
BACKGROUND: Vinegar is promoted as a natural appetite suppressant, based on previous reports that vinegar ingestion
significantly increases subsequent satiety. However there are concerns about the appropriateness and safety of this advice, and
it is unclear if poor product palatability may explain previously published effects on appetite.
OBJECTIVE: To investigate if vinegar palatability and tolerability have a role in suppressing appetite and food intake in two
sequential and related acute human feeding studies.
SUBJECTS AND METHODS: Healthy, young, normal weight unrestrained eaters were recruited to Study 1 (n ¼ 16), an acute feeding
study supplying vinegar within both palatable and unpalatable drinks alongside a mixed breakfast in comparison to a non-vinegar
control; and to Study 2 (n ¼ 14), a modified sham feeding study (taste only without ingestion) comparing vinegar to a non-vinegar
control following a milkshake preload. Both studies were a randomized crossover balanced design for the assessment of appetite,
energy intake and glycaemic response.
RESULTS: In Study 1, ingestion of vinegar significantly reduced quantitative and subjective measures of appetite, which were
accompanied by significantly higher nausea ratings, with unpalatable treatment having the greatest effect. Significant correlations
between palatability ratings and appetite measures were found. In Study 2, orosensory stimulation with vinegar did not influence
subsequent subjective or quantitative measures of appetite compared with control.
CONCLUSIONS: These studies indicate that vinegar ingestion enhances satiety whereas orosensory stimulation alone does not, and
that these effects are largely due to poor tolerability following ingestion invoking feelings of nausea. On this basis the promotion of
vinegar as a natural appetite suppressant does not seem appropriate.
International Journal of Obesity advance online publication, 15 October 2013; doi:10.1038/ijo.2013.157
Keywords: satiety; acetate; acetic acid; cephalic; palatability; modified sham feeding
INTRODUCTION
The provision of vinegar as a source of oral acetate, the two
carbon short-chain fatty acid, has been reported to significantly
increase subsequent satiety in acute conditions
1–3
and to
significantly lower body mass index in chronic conditions
4
(reviewed by Darzi et al.
5
).
Vinegar is therefore being promoted as a natural appetite
suppressant in the popular press, resulting in the perception that
vinegar is a healthy addition to the diet to aid weight loss,
6
and
giving rise to the marketing of weight loss capsules that contain
apple cider vinegar. However, this raises concerns about the
appropriateness and safety of this advice, as ingestion of vinegar
products have been reported to be linked with oesophageal
injury,
7,8
biochemical disturbances,
9
dental erosion
10
and acute
pancreatitis
11
and symptoms such as acid reflux, burping/
flatulence and changes in bowel habit.
12
It could further be
argued that the scientific evidence currently available is not
sufficient to warrant such health claims.
It is unclear if previously reported effects of vinegar ingestion
on satiety arose from a physiological effect of short-chain fatty
acid ingestion, possibly mediated via activation of the free fatty
acid receptors FFA2 (previously GPR43) and FFA3 (previously
GPR41),
13–16
or if poor product tolerability may explain the effects.
In appetite investigations, palatability, tolerability and acceptability
pose large confounding influences. A strong linear relationship
between rated palatability and differences in food intake following
such manipulation (for example by adding citric acid to soup
17
or
cumin to a yogurt drink
18
) has been demonstrated.
19
This provides
a rationale that the palatability of oral acetate may explain effects
on appetite and satiety.
The validity of results from previous studies investigating acute
effects of vinegar ingestion on subsequent satiety are also uncertain
as quantitative effects on appetite were not investigated, and
subjective effects on appetite were investigated with the use of a
single-rating bipolar scale,
1,2
or point scale
3
rather than a variety of
appetite-related visual analogue scale (VAS) questionnaires. VAS are
considered the most appropriate questionnaire to subjectively
assess appetite and their use has been previously validated.
20
Vinegar ingestion has also been shown to blunt postprandial
glycaemia and insulinaemia both in healthy individuals
2,21–25
and
in individuals with insulin resistance and type 2 diabetes
mellitus.
26
Product tolerability may also explain these findings.
A higher cephalic-phase insulin release is reported to occur following
exposure to foods rated as highly palatable in comparison with foods
with lower palatability ratings,
27,28
although this is not a consistent
finding.
29
Furthermore, sham feeding with unappetizing foods has
1
Nutritional Sciences, University of Surrey, Guildford, UK and
2
Nutrition and Dietetics Research Group, Division of Diabetes, Endocrinology and Metabolism, Faculty of Medicine,
Imperial College London, London, UK. Correspondence: Dr J Darzi, Diabetes and Nutritional Sciences Division, School of Medicine, King’s College London, 4th Floor
Franklin-Wilkins Building, 150 Stamford Street, London, UK.
E-mail julia.darzi@kcl.ac.uk
Received 15 March 2013; revised 6 August 2013; accepted 8 August 2013; accepted article preview online 27 August 2013
International Journal of Obesity (2013), 17
&
2013 Macmillan Publishers Limited All rights reserved 0307-0565/13
www.nature.com/ijo
been shown to significantly delay gastric emptying
30
and reduce
cephalic-phase vagal stimulation
31
in comparison with more
appetizing foods, which would in turn suggest a role for product
tolerability in metabolic effects.
We therefore carried out two related human investigations with
the aim of determining if vinegar influences appetite when
validated methodology is used (appetite VAS ratings, energy intake
(EI) at subsequent ad libitum meal and 24 h intake), and further to
investigate if the palatability and tolerability of vinegar-containing
products have a role in influencing appetite. Effects on postprandial
glycaemia (Studies 1 and 2) and insulinaemia (Study 2 only) were
also investigated. In Study 1, we investigated the acute effects of
vinegar ingestion provided when the palatability had been
manipulated but the ingested dose of acetate (25 mmol) was
identical; in Study 2, we investigated acute effects of orosensory
stimulation with vinegar, without ingestion of the acetate, using the
modified sham feeding (MSF) technique, on appetite and metabolic
response, allowing the separation between the physiological effects
of ingestion/absorption and those of taste.
SUBJECTS AND METHODS
This paper reports the results from two studies:
In Study 1, acute postprandial effects on appetite and blood glucose in
response to a standard breakfast preload served alongside either an
unpalatable (Unpal) or more palatable (Pal) vinegar-containing drink or
control (CON) drink were investigated.
In Study 2, acute postprandial effects on appetite and plasma glucose and
insulin in response to a standard milkshake preload followed by an MSF
phase with either a vinegar-containing (VIN) or CON drink were investigated.
Both studies were conducted at the University of Surrey Clinical
Investigation Unit (CIU) and were approved by the University of Surrey
Ethics Committee and conducted in accordance with the guidelines laid
down in the Declaration of Helsinki. All subjects provided written, informed
consent prior to commencing the studies. Figure 1 gives an overview of
the study day protocols.
Subjects
Sixteen healthy subjects (3 male, 13 female) aged 21–33 years (Study 1)
and fourteen healthy subjects (6 male, 8 female) aged 20–42 years
(Study 2) were recruited from the student population at the University of
Surrey (Table 1). Inclusion criteria were a body mass index 19–27 kg m
2
,
age o45 years, fasting blood glucose p6.0 mmol/l, weight stable for at
least 3 months and not following a weight-reducing diet, a score o3.5 on
the Dutch Eating Behaviour Questionnaire restraint scale,
32
absence of
gastrointestinal, endocrine or cardiovascular disorders, no history
of depression, eating disorders or substance abuse, not pregnant or
lactating, not taking regular medication (except birth control medication),
non-smoker and reported habitual alcohol intake p20 units. All recruited
subjects completed the studies.
Experimental design
Both studies were a randomized crossover design. Subjects attended study
mornings at the CIU separated by at least 2 days (for washout) and were
assigned to the experimental condition (Pal, Unpal or CON in Study 1; VIN
or CON in Study 2) in a counterbalanced randomly assigned order (using
http://www.randomizer.org/). For both studies, subjects completed 24 h
food diaries and refrained from unaccustomed exercise and alcohol
consumption during the 24 h proceeding each study morning. A standard,
commercially prepared low-fibre meal (o5 g fibre) was consumed for the
evening meal before the test day. On each study morning, subjects arrived
following an overnight fast of at least 12 h. Due to the nature of the studies
it was not possible to blind participants or investigators to the
experimental conditions.
Study 1 protocol (influence of vinegar palatability following
ingestion)
Subjects attended study mornings at the CIU on three occasions. Upon
arrival, two initial fasting capillary whole blood samples were taken 30 and
5 min before the test preload. Two initial VAS to subjectively assess
appetite and nausea were completed following each blood sample.
Subjects were then served a standard breakfast of jam sandwiches (8 g
Olivio spread and 16 g Tesco strawberry jam per 38 g slice Kingsmill
Everyday Soft Bread) cut into quarters alongside the test drink they were
randomized to on that occasion. On the first study morning, subjects were
provided seven quarters of a jam sandwich (2543 kJ, 12.3 g protein, 95.4 g
carbohydrate, 21.7 g fat), equivalent to three and a half slices bread, and
were instructed to consume a minimum of four full quarters (1454 kJ, 6.9 g
protein, 54.5 g carbohydrate, 12.4 g fat), equivalent to two slices bread. On
subsequent study mornings, subjects were provided the same number of
quarters ingested on the first study occasion. This procedure has been
previously reported
33
and used in our group.
34
Subjects were instructed to
consume the breakfast and drinks within 15 min. The test drinks all had a
total mass of 350 g divided between two glasses, supplied 24 kJ and
25 mmol acetic acid, and were prepared as follows:
CON drink: 75 g sugar-free squash þ 275 g water divided across two
drinks
Unpal drink: 25 g vinegar þ 25 g sugar-free squash þ 100 g water in one
drink that was consumed first, followed by 50 g sugar-free squash
þ 100 g water in a second drink
Pal drink: 25 g vinegar þ 75 g sugar-free squash þ 250 g water divided
across two drinks
The vinegar used was Tesco White Wine Vinegar, which contains 6%
acetic acid. The first drink for the Unpal treatment was less palatable than
the Pal treatment, as the vinegar was more concentrated and the drink less
-30 0 30 60 90 120 150 180
Blood samples
Appetite VAS
Breakfast
preload
Ad libitum
test meal
Start MSF End MSF
-30 0 30 60 90 120 150 180
Blood samples
Appetite VAS
Milkshake
preload
Ad libitum
test meal
611
-5
-5
a
b
Figure 1. Schematic representation of study day protocol for (a) Study 1, and (b) Study 2. Timings for blood samples are depicted by filled
circles (K), and for VAS questionnaires are depicted by unfilled circles (J ).
Vinegar and satiety
J Darzi et al
2
International Journal of Obesity (2013) 1 7 & 2013 Macmillan Publishers Limited
sweet, due to less squash being added. After breakfast subjects completed
VAS rating questionnaires asking ‘How pleasant was the taste of the drink?’
and ‘How palatable was the breakfast?’. Blood samples were collected at
15, 30, 45, 60, 90, 120 and 180 min postprandially and VAS to assess
appetite and nausea were completed after blood samples at 30, 60, 90, 120
and 180 min postprandially. At 180 min, subjects were served an ad libitum
test meal.
Study 2 protocol (orosensory effects of vinegar)
Subjects attended study mornings at the CIU on two occasions. Upon
arrival, two initial fasting capillary whole blood samples were taken 30 and
5 min before the test preload. Two baseline VAS to subjectively assess
appetite and nausea were completed following each blood sample.
Subjects were then provided Nurishment milkshake (420 g, 1804 kJ, 21.0 g
protein, 60.0 g CHO and 12.6 g fat) at time ¼ 0 min that they were asked to
consume within 5 min. At time ¼ 6 min, an MSF phase was commenced
comprising either:
CON drink: 180 g tap water
VIN drink: 30 g Tesco White Wine Vinegar (containing 6% acetic
acid) þ 150 g water
The VIN drink contained added vinegar at a level of 16.7 g vinegar per
100 g total volume (equivalent to 167 mmol/l acetic acid), which is the
same conc entration as the Unpal drink used in Study 1. T he MSF drinks
were divided equally between 10 small taster cups. Subjects were
asked to sip from on e cup at a time and to hold the drink in their mouth
for 25 s without swallowin g. They then expectorated the drink into a
pre-weighed receptacle and 5 s later were asked to sip from the next cup.
This sequence continued for all 10 c ups, which took ap proximately 5 min.
The pre-weighed receptacle was then re-weig hed in order to determine
the recovery following the MSF sequence. Subjects completed VAS
asking ‘How pleasant was the tast e of the sham fed drink?’ and ‘How
palatable was the milkshake?’. Blood samples were collected at 15, 30, 45,
60, 90, 120 and 180 min postprandially and VAS to assess appetite and
naus ea were completed after blood samples at 30, 60, 90, 120 and
180 min postprandially. Subjects were then served an ad libitum test
meal.
Qualitative and quantitative appetite assessment
Appetite sensations were subjectively assessed using 100 mm VAS for
fullness, hunger, prospective food consumption and desire to eat sweet/
savoury/salty/fatty as previously described.
20,35
A question regarding
nausea was also included. Additional questions unrelated to appetite (for
example calmness, tiredness and anxiety) were asked to mask the purpose
of the study. Subjects were not informed that the studies were
investigating effects on appetite. Appetite was assessed quantitatively by
providing an ad libitum test meal at 180 min comprising a homogenous
pasta dish served in a quantity exceeding usual portion sizes as previously
used by our group.
34,36
The dish supplied 9750 kJ, 81.5 g protein, 339.1 g
carbohydrate, 70.0 g fat and 15.9 g fibre. Subjects were served in confined
individual booths free from distractions and instructed to eat until they
were ‘comfortably full’. Subjects were then free to leave and completed a
diet diary for the remainder of the day for determination of 24 h EI. Dietary
analysis was performed using WinDiets Professional Version 2005 (Robert
Gordan University, Aberdeen, UK).
Blood sample processing and analysis
In Study 1, whole blood capillary samples were immediately analysed for
blood glucose concentrations using the HemoCue 201 Plus (HemoCue,
Sheffield, UK). The first drop of capilla ry blood drawn fol lowi ng
fingerprick was wiped away and the next drop was loaded onto a
HemoCue microcuvette for analysis. In Study 2, capillary blood samples
were collected into fluoride mic rove tte tubes (Starstedt, Beaumont,
Leicester, UK) and centrifuged at 1750 g for 10 min. Plasma glucos e
concentrations were analysed on the day of collec tion using the YSI 2300
Stat Plus Glucose Analyzer (YSI Incorporated , Yellow Springs, OH, USA),
which had an intra- and inter-as say CV of o2% and 1.2%, respectively.
The remaining plasma was stored at 20 1C until analysed for insulin
concentrations using an immunochemiluminometric ELISA k it (Invitron,
Monmouth, UK), which had an intra- and inter-assay CV of 5.8 and 12.5%,
respectively. Samples from the same subjects were analysed on the same
plate.
Calculations and statistical analysis
The primary outcome for both studies was EI of the ad libitum test meal
served 3 h postprandially. Assuming a s.d. for EI of 494 kJ from data
previously reported by our group,
34
a post priori power calculation
determined that there was an 80% probability of detecting a 370 kJ
difference in EI with 16 volunteers for Study 1 (three-way crossover) and of
detecting a 401 kJ difference in EI with 14 volunteers for Study 2 (two-way
crossover) at a significance level of 0.05. All statistical analyses were
conducted using SPSS for Windows 16.0. Data was tested for normality
using the Kolmogorov–Smirnov test. Differences between treatments for
palatability VAS scores, 3 h ad libitum EI and 24 h EI were assessed by one-
way repeated measures ANOVA with post hoc Holm–Bonferroni test if
normally distributed, and by Friedman’s ANOVA with post hoc Wilcoxon
signed-rank test if not normally distributed in Study 1 and by paired
samples t-test if normally distributed, and by Wilcoxon signed-rank test if
not normally distributed in Study 2. Postprandial subjective VAS ratings
and glycemic and insulinemic response were assessed by two-way (vinegar
treatment time) repeated measures ANOVA in both studies. The area
under curve (AUC) for postprandial plasma metabolites and subjective
appetite and nausea ratings were calculated by the trapezoidal rule. Data
from Study 1 was pooled from all study days to examine the relationship of
palatability VAS ratings and nausea AUC with subjective appetite AUC, 3 h
ad libitum EI and 24 h EI by correlation analysis (two-tailed Pearson’s
product moment (parametric) and Spearman’s rho (non-parametric) as
appropriate). Differences were considered to be significant at a level of
Pp0.05. Post hoc differences in Study 1 were considered significant at a
level of Pp0.0167 ( ¼ 0.05/3), Pp0.025 ( ¼ 0.05/2) and Pp0.05 ( ¼ 0.05/1)
for the lowest, second lowest and highest P value respectively, with
sequential rejection, as specified by Holm
37
for parametric data, and at a
level of Pp0.0167 ( ¼ 0.05/3) for the Wilcoxon signed-rank test for non-
parametric data. All data are displayed as mean
±
s.d.
RESULTS
Study 1: Influence of ingested vinegar palatability
Pleasantness and palatability ratings. Vinegar treatment signifi-
cantly decreased the rated pleasantness of taste of the test drinks
(Figure 2a) and palatability of breakfast (Table 2). Mean ratings
increased in the order Unpal, Pal and CON, with post hoc analysis
finding significant differences between all comparisons.
Postprandial nausea ratings. Postprandial nausea ratings were
significantly influenced by vinegar treatment (Table 2, Figure 2b).
Post hoc analysis found nausea ratings were significantly higher
following both Pal and Unpal treatment in comparison with CON,
and were higher following Unpal treatment than Pal, although this
difference was not significant.
Qualitative appetite assessment. Vinegar treatment significantly
influenced postprandial VAS appetite ratings for fullness, hunger
and prospective food consumption, and the desire to eat
Table 1. Subject baseline characteristics for Study 1 and Study 2
Study 1
(N ¼ 16, 3 male)
Study 2
(N ¼ 14, 6 male)
Mean s.d. Mean s.d.
Age (years) 22.2 3.0 27.5 5.4
DEBQ restraint score 1.9 0.7 2.2 0.7
BMI (kg m
2
) 22.1 2.4 22.7 3.2
Waist circumference (cm) 74.6 8.6 81.4 9.4
Body fat (%) 23.6 6.3 21.7 8.9
Systolic BP (mm Hg) 122 13 108 11
Diastolic BP (mm Hg) 74 9.6 68 6
Fasting blood glucose (mmol l
1
) 4.5 0.4 4.7 0.4
Abbreviations: BMI, body mass index; BP, blood pressure; DEBQ, Dutch
eating behaviour questionnaire.
Vinegar and satiety
J Darzi et al
3
& 2013 Macmillan Publishers Limited International Journal of Obesity (2013) 1 7
something sweet was influenced with a trend approaching
significance when analysed by two-way (treatment*time) repeated
measures ANOVA (Table 2). No significant effects for the desire to
eat something savoury, salty and fatty were found. Post hoc
analysis found fullness was significantly higher for both Pal and
Unpal treatment compared with CON.
Quantitative appetite assessment . Vinegar treatment significantly
reduced 3 h ad libitum EI and 24 h EI. Mean intake increased in the
order Unpal, Pal and CON. Differences between Unpal and CON
approached significance and were significant for 3 h ad libitum EI
and 24 h EI, respectively (Table 2). Analysis of ad libitum EI was
carried out on 15 subjects following removal of an outlier with an
intake value 43 s.d. over the mean intake during Unpal treatment.
Data from two subjects was excluded due to incomplete 24 h
intake dietary records, therefore analyses on 24 h intake were
carried out on the remaining 14 subjects.
Postprandial glucose response. Vinegar treatment significantly
reduced postprandial glycaemia, with vinegar ingestion resulting
in a lower and later glucose peak than CON (Table 2), which was to
a significant level between Pal treatment and CON.
Correlation of appetite parameters with nausea and palatability
ratings. Appetite VAS ratings AUC were significantly and
positively correlated with pleasantness of drink taste ratings and
breakfast palatability ratings, whereas correlations with nausea
VAS ratings AUC were weak, negative and non-significant, except
for prospective consumption (Table 3). Ad libitum EI was
significantly and positively correlated with drink pleasantness
taste ratings and breakfast palatability ratings, and was signifi-
cantly and negatively correlated with nausea ratings AUC. Twenty-
four hour EI was significantly correlated with drink pleasantness
ratings. Selected correlations are displayed in Figure 3.
Study 2: Orosensory effects of vinegar
Pleasantness and palatability ratings. The VIN drink was rated as
significantly less pleasant than CON, whereas palatability ratings
for the milkshake did not differ between treatments (Table 2).
Postprandial nausea ratings. Postprandial nausea ratings did not
differ between treatments (Table 2).
Qualitative appetite assessment. None of the postprandial
appetite ratings differed between treatments (Table 2).
0
20
40
60
80
100
CON Pal Unpal
VAS Score (mm)
0
2000
4000
6000
8000
10000
CON Pal Unpal
AUC (mm*min)
P <0.0001
P <0.0001
P =0.055
P <0.007
P <0.024
Figure 2. Vinegar treatment in Study 1 significantly influenced
(a) rated pleasantness of test drinks and (b) postprandial nausea
ratings AUC.
Table 2. Summary of main findings from Studies 1 and 2 for palatability ratings, AUC (0–180 min) for subjective appetite ratings and postprandial
glycaemia, EI at the ad libitum test meal, 24 h EI and recovery of the MSF drink (Study 2 only)
Study 1 (N ¼ 16) Study 2 (N ¼ 14)
CON Pal Unpal P-value
a,b,c
CON VIN P-value
d,e,f
Pleasantness rating drink (mm) 77.8
±
17.5
g
21.8
±
15.7
h
10.0
±
9.0
i
o0.001
a
73.0
±
18.7
g
22.4
±
22.5
h
o0.001
d
Palatability rating breakfast (mm) 70.7
±
13.0
g
58.5
±
16.4
h
46.0
±
20.1
i
o0.0001
a
60.5
±
25.1 56.6
±
26.4 0.455
d
Nausea AUC (min mm
1
) 1709
±
1302
g
3518
±
2754
h
4985
±
3497
h
0.001
b
1765
±
2508 2904
±
3335 0.105
e
Glycaemia AUC (min mmol l
1
) 1020
±
85
g
957
±
82
h
987
±
68 0.023
b
1005
±
67 1002
±
71 0.517
e
Fullness AUC (min mm
1
) 6668
±
2261
g
8664
±
2551
h
8965
±
2006
h
o0.0001
b
7625
±
3521 8061
±
2782 0.665
e
Hunger AUC (min mm
1
) 8407
±
3375 7535
±
2784 6743
±
3097 0.045
b
9013
±
3452 7158
±
2733 0.081
e
Prospective consumption AUC (min mm
1
) 9662
±
3269 8578
±
2369 7494
±
3298 0.036
b
9089
±
3275 8124
±
2813 0.130
e
Desire to eat fatty AUC (min mm
1
) 5788
±
4651 5231
±
3701 4520
±
3260 0.168
b
6384
±
3443 6074
±
3248 0.757
e
Desire to eat salty AUC (min mm
1
) 5471
±
4175 4590
±
2870 4698
±
3183 0.404
b
7680
±
3966 6754
±
3439 0.312
e
Desire to eat sweet AUC (min mm
1
) 6852
±
3752 6719
±
3261
g
5202
±
2761
h
0.058
b
6639
±
3958 5674
±
3387 0.197
e
Desire to eat savoury AUC (min mm
1
) 9220
±
3591 8371
±
3945 7657
±
3747 0.225
b
8765
±
4239 7879
±
3290 0.294
e
3h EI ad libitum test meal (kJ) 3430
±
1010
g
3034
±
851 2797
±
888
h
0.022
c
3636
±
1909 3392
±
1119 0.153
d
24 h EI (kJ) 9515
±
2560
g
8565
±
2710 7475
±
2092
h
0.021
a
9304
±
2866 9576
±
2079 0.510
f
% recovery of MSF drink (%) 97
±
5
g
107
±
4
h
0.001
f
Abbreviations: ANOVA, analysis of variance; AUC, area under the curve; CON, control; EI, energy intake; MSF, modified sham feeding; PAL, palatable; Unpal,
unpalatable; VIN, vineger containing. Values are shown as mean
±
s.d. Different superscripts within rows for each study denote significant differences between
treatments (approaching significance for CON vs Unpal 3 h ad libitum intake in Study 1). Significance in Study 1 assessed by
a
one-way repeated measures
ANOVA analysis with post hoc Holm–Bonferroni,
b
treatment*time two-way repeated measures ANOVA analysis with post hoc Holm-Bonferroni and
c
Friedmans
ANOVA with post hoc Wilcoxon. Significance in Study 2 assessed by
d
paired samples t-test,
e
treatment*time two-way repeated measures ANOVA analysis and
f
Wilcoxon signed-Rank test.
Vinegar and satiety
J Darzi et al
4
International Journal of Obesity (2013) 1 7 & 2013 Macmillan Publishers Limited
Quantitative appetite assessment. Mean intake of the ad libitum
test meal provided 3 h postprandially and 24 h EI did not differ
between treatments (Table 2).
Postprandial glucose and insulin response. No influence of VIN
treatment on postprandial glycaemia (Table 2) or insulinaemia
(data not shown) was found.
Recovery of MSF drink following sham feeding. Recovery of the
VIN drink when expectorated following sham feeding was
significantly higher than CON recovery (Table 2), suggestive that
vinegar stimulated saliva production.
DISCUSSION
Our findings from the present studies suggest that vinegar
ingestion influences appetite when investigated using validated
methodology, and also influences postprandial glycaemia. The
tolerability of VIN products appears to have a role in observed
effects on appetite and glycaemia, possibly arising from induced
nausea following ingestion.
In Study 1, it was found that vinegar ingestion (supplying
25 mmol acetic acid) significantly influenced quantitative and
subjective appetite measures and glycaemia, suggesting that
vinegar treatment is associated with a significantly reduced
appetite, in agreement with previous studies,
1–3
which used
similar dosages of acetic acid (28 mmol). Vinegar treatment was
also associated with a reduced glycaemic response, in common
with previous studies.
2,21–23
By contrast, in Study 2 orosensory
stimulation with a drink containing vinegar (of the same
concentration as the Unpal drink in Study 1) did not influence
appetite when assessed subjectively or quantitatively, nor did it
influence glycaemic and insulinaemic responses.
Vinegar ingestion invoked significant increases in rated nausea
in Study 1, which increased with decreasing product palatability,
suggesting poor tolerability, with Unpal being the least well
tolerated. Palatability and nausea appeared to have an influence
on appetite, with appetite tending to decrease and nausea
tending to increase in the order CON, Pal and Unpal. This provides
support for the hypothesis that the palatability and tolerability of
vinegar had an influence on subsequent appetite. However, in
Study 2, the mere taste of vinegar in the absence of ingestion did
not induce nausea and did not influence the rated palatability of
the milkshake, although the VIN drink in Study 2 was rated as
significantly less pleasant than CON and stimulated enhanced
salivary production. This suggests the influence of the palatability
of the VIN drink is short-lived when only tasted and not ingested.
The results from Study 1 and Study 2 together imply that it is the
interaction between ingestion and palatability that is important,
and the orosensory properties alone of vinegar-containing
products are not sufficient to influence appetite and the metabolic
response. This is suggestive of a role for the poor tolerability rather
than palatability of vinegar giving rise to feelings of nausea
following ingestion, thereby reducing subsequent appetite and
glycaemia.
Medium to strong significant correlations were found between
palatability VAS ratings and all appetite VAS (positive for hunger,
Table 3. Correlations of ratings for pleasantness of taste of the test drinks, palatability of breakfast and nausea AUC with subjective and quantitative
appetite measures in Study 1
a,b,c,d,e
Pleasant rating
a
Palatable rating
b
Nausea AUC
b
R P- value R P-value R P-value
VAS AUC
c
Fullness 0.528 o0.001*** 0.447 0.001*** 0.155 0.293
Hunger 0.313 0.030* 0.540 o0.001*** 0.247 0.090
Prospective consumption 0.394 0.006** 0.640 o0.001*** 0.387 0.007**
Desire to eat savoury 0.316 0.029* 0.613 o0.001*** 0.138 0.350
Desire to eat sweet 0.239 0.102 0.618 o0.001*** 0.148 0.317
Desire to eat fatty 0.194 0.187 0.391 0.006** 0.052 0.723
Desire to eat salty 0.223 0.127 0.402 0.005** 0.093 0.529
Nausea 0.408 0.004** 0.557 o0.001***
Energy intake
Ad libitum test meal EI
d
0.449 0.002** 0.452 0.002** 0.313 0.037**
24 h EI
e
0.428 0.005** 0.262 0.093 0.279 0.073
Abbreviations: AUC, area under the curve; EI, energy intake; VAS, visual analogue scale. Significant correlations *Po0.05, **Po0.01 and ***Po0.001.
a
Correlation analysis carried out by Spearman Rho correlation.
b
Correlation analysis carried out by Pearsons product moment correlation.
c
Analyses for the
AUC VAS were carried out on the entire dataset (n ¼ 3 16 ¼ 48).
d
Analyses for ad libitum test meal EI were carried out after outlier was removed
(n ¼ 3 15 ¼ 45).
e
Analyses for 24 h EI was carried out after missing data from two subjects were removed (n ¼ 3 14 ¼ 42).
0
4000
8000
12000
16000
0 20406080100
Fullness AUC (mm.min)
Breakfast palatability rating (mm)
0
2000
4000
6000
020406080100
Ad libitum EI (kJ)
Breakfast palatability rating (mm)
R= -0.447
R= 0.452
Figure 3. In Study 1, VAS ratings for the palatability of the breakfast
were significantly correlated to the (a) fullness VAS ratings AUC and
(b) EI at the ad libitum test buffet meal.
Vinegar and satiety
J Darzi et al
5
& 2013 Macmillan Publishers Limited International Journal of Obesity (2013) 1 7
prospective consumption and desire to eat sweet/fatty/salty, and
negative for fullness), ad libitum test meal and 24 h EI in Study 1.
Although correlations do not imply causality, these findings
support our hypothesis that the palatability or tolerability of the
vinegar-containing test products had a role in decreasing
appetite/increasing satiety.
The influence of palatability on appetite has been investigated
by a number of researchers. Yeomans (2007) re-analysed data
from 11 different studies that measured ad libitum intake of an
unpalatable food in comparison with a control food; for example
cumin banana colada vs control banana colada
18
and stale vs
fresh popcorn.
38
A strong, linear relationship was found between
differences in palatability ratings and ad libitum intakes of those
foods (R ¼ 0.85, Po0.0001),
19
thereby supplying evidence of a role
for palatability in satiation. These findings fit in with the findings
from the present study of a more transient and short-term
influence of palatability on appetite regulation. Effects of
palatability on subsequent satiety have not been extensively
investigated. De Graaf and colleagues (1999) reported that food
palatability influenced satiation (intra-meal satiety), but not
subsequent satiety. A dose–response reduction in ad libitum
intake of the soup was found with decreasing palatability;
however, there were no effects on subsequent satiety, hunger
ratings or ad libitum test meal intake regardless of intermeal
duration.
17
Unfortunately, effects on nausea were not assessed, so
it is difficult to directly relate the postprandial findings from that
study to the present study.
There is also evidence that food palatability and/or tolerability
may influence the metabolic response, which may explain the
observed effects of vinegar ingestion on postprandial glycaemia in
Study 1. However, findings are not equivocal. In comparison with a
‘palatable test meal’, ingestion of a ‘non-palatable meal’ (the same
meal blended and freeze-dried into a desiccated biscuit) resulted
in significantly lower postprandial glycaemia
39
and insulinaemia.
40
It is, however, possible that the meal form and texture may have
influenced the metabolic effects rather than the product
palatability. A role for palatability in cephalic-phase metabolic
responses has also been tested. Bellisle and colleagues
27,28
reported a significantly lower cephalic-phase insulin release
amplitude with ingestion of a ‘low palatability meal’ in
comparison to a ‘high palatability meal’, although these early
studies did have low participant numbers. However, Teff and
Engelman
29
found no difference between cephalic-phase insulin
release amplitude following MSF with ‘palatable’ and ‘unpalatable’
foods. This suggests that ingestion of the unpalatable product is
necessary to induce differential effects on cephalic-phase
responses, which offers similarities to findings reported in the
present paper, where vinegar ingestion invoked effects on
appetite and glycaemia (Study 1) whereas merely tasting
vinegar did not (Study 2).
Gastric motility may also be influenced by food palatability
and taste, which in turn may influence appetite and the
metabolic response. The rate of gastric emptying has been
shown to be significantly delayed whe n an oral liquid test meal i s
preceded by a MSF bitter tasting meal replacement bar in
comparison with a non-bitter control.
30
As would be expected,
the influence of t aste a ppears to occur d uring the cephalic phase
of digestion as demons trated by intragastric infusion of a bitter
solution having no influence on the gastric emptying rate in
compariso n to water.
41
These findings supply a rationale for the
observ ed effects in Study 1 in the present paper, but not for
Study 2. The gastric emptying rate is reported to be dela yed
following ingestion of both acetate provided as vinegar
23,42
and
propionate adde d to b read
24,43
and a pasta meal
44
wit h the
exception of one study that found no effect on the gastric
emptying rate following an acute challenge with vinegar.
1
Delayed gastric emptying has been linked to nausea and early
satiety in patients suffering from gastroparesis.
45,46
Thus, delayed
gas tric emptying may also provide an explanation for short- chain
fatty acid inges tion invoking feelings of nausea, in addition to
the unp leasant taste.
An alternate possible explanation is that the vinegar may be
‘tasted’ further down the GIT when ingested. There is evidence
that taste molecules are expressed in the GIT
47,48
and that taste-
signalling proteins are expressed on enteroendocrine L cells in the
small intestine, the same cells that express the appetite regulatory
gut peptides glucagon-like peptide 1 (GLP-1) and peptide YY
(PYY).
47,49
This suggests taste sensing in the GIT may have a role in
modulating appetite and may provide an explanation for
observed effects in the present studies, with vinegar ingestion
influencing appetite and glycaemia (Study 1), but orosensory
stimulation not (Study 2). This provides further rationale for a role
for an interaction between ingestion and tolerability in influencing
appetite, in part due to induced nausea.
A limitation of the present studies is that effects on gut hormones
were not assessed, effects on satiation were not investigated and
the gastric emptying rate was not measured. Furthermore, in Study
2, it may have been of benefit to use a solid mixed meal rather than
a liquid milkshake preload to allow closer comparison with Study 1.
The use of a liquid preload may provide some explanation for the
shorter-lived influence of vinegar treatment on appetite compared
with Study 1. We chose to use a milkshake in Study 2, as it can be
consumed much quicker than a solid meal, thus allowing the MSF
phase of the protocol to commence at the earlier phase of digestion
and absorption of the preload.
In conclusion, results from these studies indicate that vinegar
ingestion reduces appetite when investigated using validated
appetite assessment methods and suppresses postprandial
glycaemia. These effects appear to be largely due to poor product
tolerability following ingestion invoking feelings of nausea,
whereas orosensory stimulation alone did not induce any effects.
On this basis, the promotion of vinegar as a natural appetite
suppressant does not seem appropriate, particularly in view of the
potential health risks.
7–11
Further work is warranted to investigate
effects of chronic supplementation with apple cider vinegar
capsules in overweight and obese subjects on appetite control,
body weight and adverse symptoms, to investigate if marketing
these capsules as a weight loss aid is appropriate and safe.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
ACKNOWLEDGEMENTS
We are grateful to the volunteers who participated in the study and also to Chloe Cooke,
Leanne Johnson, Vicky Martins and Jennifer Pickard for their assistance in conducting the
studies. JD was supported by an educational fellowship from Premier Foods.
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& 2013 Macmillan Publishers Limited International Journal of Obesity (2013) 1 7
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... In China, vinegar-soaked raisins are believed to be beneficial to obesity prevention. Meta-analysis research confirmed that dietary vinegar consumption could effectively improve postprandial blood glucose and insulin responses [11], reduce appetite [12], and enhance satiety [13]. However, the combined effect of dried fruits and vinegar on glycemic responses and satiety has not yet been studied. ...
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This study investigated 2 possible approaches to dietary control of acute postprandial responses to a rice-based meal under equicarbohydrate conditions: (1) a dried apple (DA) preload and (2) co-ingestion of vinegar-soaked DA. We hypothesized that both approaches would counteract hyperglycemia with no negative effect on satiety, possibly explained by an inhibitory effect on digestive enzyme activity and/or the effect of the sugar component of the DA. Fifteen healthy female subjects consumed (1) rice, (2) co-ingestion of DA and rice (DA + R), (3) DA preload and rice (PDA + R), (4) rice with sugar solution (same sugar profile as in DA) preloaded (PSS + R), or (5) co-ingestion of rice with vinegar-soaked DA (VDA + R) in a randomized crossover trial. Acute postprandial glycemic response tests and subjective satiety tests were conducted for each test meal. Compared with rice reference, the PA + R and PSS + R achieved 31.4% and 36.3% reduction of the incremental area under the curve0-120, 24.3% and 27.0% decreases in the average glucose peak, along with 21.6% and 27.0% decreases in glycemic excursion in 240 minutes, whereas the VDA + R resulted 42.4%, 27.0%, and 29.7% reductions in the incremental area under the curve0-120, peak, and glycemic excursion, respectively. The DA-containing meals had no effect or a favorable effect on satiety. The in vitro assay found larger resistant starch and smaller rapid digestible starch fractions in DA + R and VDA + R meals compared to those of the rice reference (P < .001). The result of this study supported the research hypothesis, and the DA-containing meals could be considered as a potential dietary approach for glycemic management.
Article
Research suggests that the active ingredient in vinegar, acetic acid, may reduce appetite, thereby reducing energy consumption. This article aims to assess the effect of vinegar or acetic acid on appetite measures and subsequent food intake in humans. This was conducted as a systematic literature review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All participants were considered, regardless of age or health status. A search using MedLine (Ovid), PubMed, CINAHL Plus, Web of Science, and Cochrane Library between January and April 2021 resulted in 12 studies. Outcomes included appetite, measured using an appetite rating scale or visual analog scale; satiation, measured as food intake of intervention meal; and satiety, measured as the amount of food intake after vinegar or acetic acid consumption. Some short-term interventions indicate that vinegar containing at least 24.6 mmol acetic acid, when consumed alongside a meal containing solid foods, acutely suppresses appetite up to 120 min postprandially as well as ad libitum food intake 3 and 24 h after vinegar consumption. However, longer exposure vinegar interventions suggest that vinegar does not affect overall energy intake. Further research is needed to determine whether oral vinegar consumption may lead to long-term appetite reduction, decrease energy intake, and aid in weight loss.
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Short-chain fatty acids (SCFAs) are the major products of the microbial fermentation of indigestible carbohydrates. SCFAs are known to improve host metabolism but their underlying mechanism of action remains elusive. In this study, sixteen growing pigs were infused with saline or sodium propionate solution (25 mL, 2 mol/L), respectively through a cecal fistula twice a day during a 28 days experimental period. The results showed that the cecal infusion of the SCFA propionate decreased serum and liver triglyceride levels, and increased serum PYY secretion in growing pigs. Hepatic metabolomics identified 12 metabolites that were significantly altered by propionate. These included decreased levels of lipid metabolism related stearic acid and glycerol-2-phosphate; increased levels of TCA cycle components including malic acid, fructose-6-phosphate, and succinic acid; and decreased levels of the amino acid metabolism products aspartic acid and serine. Hepatic transcriptomics demonstrated that propionate inhibited fatty acid synthesis and promoted lipid metabolic process. Pathway enrichment analysis showed that propionate accelerated gluconeogenesis and decreased glycolysis. Taken together, these data support a role of the SCFA propionate on host lipid and glucose metabolism.
Article
Some studies have reported that vinegar ingestion at mealtime attenuates postprandial glycemia in healthy adults and individuals with type 2 diabetes. Emerging data suggest that chronic vinegar ingestion impacts fat...
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Erosive tooth wear was diagnosed in the dentition of a 15-year-old girl with a Moroccan background. After an anamnesis, extensive analysis of possible risk factors and a study of the pattern of erosion, it was concluded that the erosive tooth wear was induced by daily consumption of a glass of apple cider vinegar Further investigation revealed that in North-African culture, women have used apple cider vinegar to achieve weight loss for generations. Bodybuilders are also known to make use of this method of weight reduction.
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There is evidence linking oral propionate to a reduction in food intake, which could confer functional food properties in the fight against obesity. However, propionate is typically volatile with a pungent smell and taste and so incorporating into foods naturally, at levels acceptable to the consumer is a novel approach. Twenty healthy, young, normal weight unrestrained eaters underwent an acute feeding study using a palatable sourdough and an identical control bread of a similar palatability, in a randomized cross-over balanced design for the assessment of appetite and energy intake. No difference in energy intake of an ad libitum test meal, 180 min after the bread-based breakfast or in energy and macronutrient intake over the entire 24 h period was found between breads. Visual analogue scale ratings for appetite were not influenced by bread type, except the desire to eat something sweet. Elevated plasma insulin concentrations were observed following the propionate-rich sourdough breakfast (P=0.033 no effects of treatment on postprandial glycaemia were found. These findings suggest propionate-rich sourdough bread does not influence appetite and food intake unlike larger doses of the food preservative N-propionate.
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The development of the Dutch Eating Behaviour Questionnaire (DEBQ) with scales for restrained, emotional, and external eating is described. Factor analyses have shown that all items on restrained and external eating each have high loadings on one factor, but items on emotional eating have two dimensions, one dealing with eating in response to diffuse emotions, and the other with eating in response to clearly labelled emotions. The pattern of corrected item-total correlation coefficients and of the factors was very similar for various subsamples, which indicates a high degree of stability of dimensions on the eating behavior scales. The norms and Cronbach's alpha coefficients of the scales and also the Pearson's correlation coefficients to assess interrelationships between scales indicate that the scales have a high internal consistency and factorial validity. However, their external validity has yet to be investigated.
Chapter
This chapter discusses the current understanding of the role of palatability in appetite control in humans. It focuses on the phenomenology of palatability effects, theoretical interpretations of palatability effects, and the relationship between palatability and homeostatic controls of eating. It also focuses specifically on obesity, and explores whether individual differences in response to palatability might explain phenotypical variation in susceptibility to weight gain, and how increased understanding of the role of palatability in appetite control might inform the future treatment and prevention of obesity. Over-consumption of palatable foods is one of the factors contributing to the current worldwide increase in the incidence of obesity. Palatability effects reflect stimulation of central reward systems by the sensory qualities of foods, and that these effects interact with satiety mechanisms to determine meal size. Appetite stimulation is a direct function of perceived palatability, with incremental increases in intake, as foods become more liked. Most food likes are acquired responses. Enhanced responsivity to palatability may underlie the failure to respond to obesity treatment, and that future treatments are likely to benefit by the inclusion of strategies or specific drug treatments that ameliorate the role of palatability in subsequent overeating.
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The possible effects of organic acids or an organic salt on the rate of gastric emptying was studied to identify the cause for reduced postmeal responses of blood glucose and insulin to foods containing such components, eg, sourdough bread. Paracetamol was included in bread products with added lactic acid or sodium propionate and used as a marker for the rate of gastric emptying in healthy subjects. In parallel, postprandial glycemia, insulinemia, and satiety were evaluated. The influence of lactic acid, propionic acid, and sodium propionate was also studied in rats after they were tube-fed with glucose solutions. The bread products with lactic acid or sodium propionate both lowered blood glucose and insulin responses. The bread with sodium propionate also prolonged satiety. The reason for the lowered metabolic responses with sodium propionate was probably a lowered gastric emptying rate, as judged from reduced blood paracetamol concentrations; there was no such effect observed with bread with added lactic acid. A similar amount of lactic acid in solution tube-fed to rats did not affect the disappearance of glucose from the stomach. In contrast with the finding in humans, sodium propionate had no effect on the rate of gastric emptying in rats whereas an equimolar solution of propionic acid reduced gastric emptying rate in rats. Possibly, less of this acid was produced in the gastric contents after a bolus load of a sodium propionate solution (in rats) than in an eating situation. Also, the pH and/or the osmolarity may be important, and when provided in excessive amounts, lactic acid reduced the gastric emptying rate in rats. A hydrochloric acid solution of similar pH was much less effective in this respect.
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Short-chain fatty acids (SCFAs), including acetate, propionate and butyrate, are the most commonly found anions found in the monogastric mammalian large intestine, and are known to have a variety of physiological and pathophysiological effects on the gastrointestinal tract. We investigated the protein and mRNA expression levels of GPR41, a possible G protein coupled receptor for SCFA, using Western blot analysis and reverse transcriptase-polymerase chain reaction. We found that GPR41 protein and mRNA are expressed in human colonic mucosa. Immunohistochemistry for GPR41 showed that mucosal GPR41 protein is localized in cytoplasm of enterocytes and enteroendocrine cells. Moreover, GPR41-immunoreactive endocrine cells contained peptide YY but not serotonin or GPR43. The cellular population of GPR41 (0.01 ± 0.01 cells/crypt) was much smaller than that of GPR43 (0.33 ± 0.01 cells/crypt) in the human colon. However, the potency order of SCFA-induced phasic contraction of colonic smooth muscle that we previously reported is consistent with GPR41 (propionate >= butyrate > acetate) but not GPR43 (propionate = butyrate = acetate). Therefore, the present study suggests that GPR41 expressed in human colonic mucosa may function as a sensor for luminal SCFAs.
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The development of the Dutch Eating Behaviour Questionnaire (DEBQ) with scales for restrained, emotional, and external eating is described. Factor analyses have shown that all items on restrained and external eating each have high loadings on one factor, but items on emotional eating have two dimensions, one dealing with eating in response to diffuse emotions, and the other with eating in response to clearly labelled emotions. The pattern of corrected item-total correlation coefficients and of the factors was very similar for various subsamples, which indicates a high degree of stability of dimensions on the eating behavior scales. The norms and Cronbach's alpha coefficients of the scales and also the Pearson's correlation coefficients to assess interrelationships between scales indicate that the scales have a high internal consistency and factorial validity. However, their external validity has yet to be investigated.
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Patient-reported symptom scales are needed to evaluate treatments for gastroparesis. The Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) was developed to assess daily symptoms of gastroparesis. This study evaluated the validity and responsiveness of the GCSI-DD in patients with gastroparesis. Symptomatic patients were started with a new treatment for gastroparesis. Patients completed the GCSI-DD each evening during a baseline week and for 8 weeks of treatment. Responders were defined based on patient and clinician global rating of change. Minimal important differences (MID) were estimated based on baseline to 4 week changes in symptoms scores for small improvements. Key Of 69 patients participating, 46 had idiopathic, 19 diabetic, and four postfundoplication gastroparesis. Excellent test-retest reliability was seen for GCSI-DD scores, and there were significant correlations between GCSI-DD scores and clinician ratings of symptom severity. Responders to treatment reported improvements in nausea [effect size (ES) = 0.42, P < 0.001], postprandial fullness, ES = 0.83, P < 0.001), bloating (ES = 0.34, P < 0.001), early satiety (ES = 0.53, P < 0.001), but lower responses for upper abdominal pain (ES = 0.29), and vomiting (ES = 0.22; P = 0.119). MIDs were 0.55 for nausea, 0.97 for excessive fullness, 0.63 for bloating, 0.77 for postprandial fullness, and 0.30 for abdominal pain. A composite score of four symptoms (Composite-1; nausea, bloating, excessive fullness, postprandial fullness) had ES of 0.61 and MID of 0.73. Composite-2 score (nausea, early satiety, bloating, abdominal pain) had a lower ES of 0.47. Symptoms of early satiety, nausea, postprandial fullness, and bloating were responsive to treatment for gastroparesis. A composite of these symptoms also demonstrates validity and responsiveness to treatment for gastroparesis, and may represent an acceptable endpoint for evaluating the effectiveness of medical treatments in clinical trials for gastroparesis.
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This paper presents a simple and widely ap- plicable multiple test procedure of the sequentially rejective type, i.e. hypotheses are rejected one at a tine until no further rejections can be done. It is shown that the test has a prescribed level of significance protection against error of the first kind for any combination of true hypotheses. The power properties of the test and a number of possible applications are also discussed.