Gastrointestinal toleracne and utlization of agave inulin by healthy adults 2014

Gastrointestinal tolerance and utilization of agave
inulin by healthy adults†‡
Hannah D. Holscher,a
Jamie L. Doligale,a
Laura L. Bauer,a
Vishnupriya Gourineni,b
Christine L. Pelkman,b
George C. Fahey, Jr.a
and Kelly S. Swanson*a
Little clinical research exists on agave inulin as a fiber source. Due to differences in botanical origin and
chemical structure compared to other inulin-type fibers, research is needed to assess gastrointestinal
(GI) tolerance following consumption. This study aimed to evaluate GI tolerance and utilization of 5.0
and 7.5 g per day of agave inulin in healthy adults (n ¼ 29) using a randomized, double-blind, placebo-
controlled crossover trial consisting of three 21 day periods with 1 week washouts among periods. GI
tolerance was assessed via daily and weekly questionnaires, three fecal samples were collected on days
16–20 of each period, and breath hydrogen testing was completed on the final day of each treatment
period. Survey data were compared using a generalized linear mixed model. All other outcomes were
analyzed using a mixed linear model with a repeated measures procedure. Composite GI intolerance
scores for 5.0 and 7.5 g treatments were both greater (P < 0.05) than control, however, scores were low,
with means of 0.4, 1.9, and 2.3 on a 0–12 point composite scale for 0, 5.0, and 7.5 g treatments,
respectively. There were slight increases (P < 0.05) in bloating, flatulence, and rumbling frequency with
5.0 and 7.5 g agave inulin. Abdominal pain and rumbling intensity were marginally greater (P < 0.05) with
7.5 g. Bloating and flatulence intensity increased (P < 0.05) with 5.0 g and 7.5 g. Agave inulin did not
affect diarrhea (P > 0.05). Number of bowel movements per day increased, stools were softer, and
stool dry matter percentage was lower with 7.5 g (P < 0.05). Breath hydrogen concentrations increased
(P < 0.001) from 5–8 hour postprandial when participants consumed agave inulin compared to control.
These data demonstrate that doses up to 7.5 g per day of agave inulin led to minimal GI upset, do not
increase diarrhea, and improve laxation in healthy young adults.
Introduction
Dietary ber intake is associated with a number of benecial
health effects, including reduced risk of obesity, cardiovascular
disease, type 2 diabetes, and colon cancer.1–4
Furthermore,
certain types of ber aid laxation and alleviate constipation.5,6
Additionally, many fermentable bers have prebiotic effects
whereby the growth or activity of benecial bacteria in the
gastrointestinal (GI) tract is selectively stimulated, providing
benets to the host.7
The current recommended dietary refer-
ence intake level of ber is 14 g per 1000 kcal or 38 g per day for
men and 25 g per day for women; however, nearly 90% of
Americans fail to consume an adequate amount of ber, with
the average daily intake ranging from 12–18 g per day.8,9
Due to
these low intakes and associated disease risk, the 2010 Dietary
Guidelines for Americans recognized ber as a shortfall
nutrient and encouraged efforts to increase intake.10
One way to increase ber intake is through food supple-
mentation. Food manufacturers supplement different types of
functional bers, including inulin, to a range of foods.11
Inulin
is present in a number of plants, including chicory root, Jer-
usalem artichoke, garlic, onions, leeks, asparagus, and
bananas.12
As inulin has a net caloric value of approximately 2
kcal gÀ1
and a bland neutral avor, the food industry can utilize
inulin as a fat and sugar replacer and low calorie bulking agent
in foods such as candies, breakfast cereals, and breads.13
Although inulin is commonly commercialized from chicory root
and Jerusalem artichoke, there is growing interest in utilizing
other sources of inulin, including agave inulin, which was
investigated in the present study.
Little clinical research exists on agave inulin. Animal studies
have demonstrated that rodents fed 10–15% of their diet as
agave inulin had lower body weights (4–50%), fat mass
percentages (16–18%), blood triglycerides (5–35%), blood
cholesterol (13–31%) and blood glucose concentrations (2–16%)
compared to animals fed other inulin-type bers (ITFs), which
is likely due to differing botanical origins and chemical
a
University of Illinois, Department of Animal Sciences and Division of Nutritional
Sciences, 1207 West Gregory Drive, Urbana, IL 61801, USA. E-mail: ksswanso@
illinois.edu; Fax: +1 217-333-7861; Tel: +1 217-333-4189
b
Ingredion Incorporated, 10 Finderne Ave, Bridgewater, NJ 08807, USA
† Supported in part by Ingredion, Inc., Bridgewater, NJ, USA.
‡ Electronic supplementary information (ESI) available. See DOI:
10.1039/c3fo60666j
Cite this: DOI: 10.1039/c3fo60666j
Received 7th December 2013
Accepted 8th March 2014
DOI: 10.1039/c3fo60666j
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structures.14–16
Agave inulin is composed of branched and linear
fructose chains, typically with a terminal glucose unit, con-
nected with b-2,1 and b-2,6 linkages, and an average degree of
polymerization (DP) between 25 and 34, while chicory inulin is a
linear molecule with b-2,1 linkages.17–19
The b-linkages in ITFs
are resistant to hydrolytic digestion by human salivary and
intestinal enzymes and, thus, mostly escape digestion in the
proximal GI tract and instead are readily fermented by bacteria
in the distal GI tract.20
Due to the high fermentability of ITFs,
they oen are associated with undesirable GI symptoms such as
bloating and atulence.21
As both the branching and DP of
agave inulin differs from other ITFs, clinical investigation in
warranted to assess acceptable intake levels.
The objectives of the present study were to determine toler-
ance and utilization of agave inulin at two dosage levels in
healthy adults. As 5 g is recognized on food labels as an excel-
lent source of ber, it was selected as our low dose. The higher
dose was set at 7.5 g for two reasons—rst, to ensure an
adequate level of intake to affect the gut microbiota (a
secondary objective of the study to be addressed in a subse-
quent publication) and secondly, to avoid the GI intolerance
that can occur with inulin supplementation at higher levels of
intake.12,22
A 21 day treatment period was utilized so that GI
adaption also could be investigated. To meet our study objec-
tives, daily and weekly subjective scoring of GI tolerance
(abdominal pain, bloating, burping, atulence, nausea, reux,
and rumblings), stool characteristics (fecal score and
frequency), ease of stool passage, and dry matter percentage
were assessed. Breath gas production and composition
following agave inulin intake also were measured to determine
its fermentation prole.
Materials and methods
Participants
Thirty men and women were recruited via an email list server
from the College of Agricultural, Consumer and Environmental
Sciences at the University of Illinois. Our study sample size was
calculated based on published GI tolerance trials in the litera-
ture, which ranged in size from 8–30 participants. Participants
were screened to ensure general health and to collect demo-
graphic information. Of the 30 participants enrolled in the
study, nineteen were self-described as Caucasian, nine as
Latino, and two as Asian. All participants were free of antibiotic
use for at least 4 months prior to study initiation. The inclusion
criteria included: (1) be between 20 and 40 years of age; (2) have
a body mass index <29.5 kg mÀ2
; (3) be free of any known
metabolic or GI diseases, with no history of metabolic or GI
diseases; (4) avoid medications that affect GI function; (5) be
free of antibiotic use for at least 2 months prior to study initi-
ation; (6) limit alcohol consumption to 2 servings per day; (7)
avoid taking pre- or probiotics throughout the study; (8)
consume a moderate ber diet; (9) continue to consume the
same dose of vitamin and/or mineral supplements throughout
the study, if applicable; (10) maintain their current level of
physical activity and exercise; (11) agree to keep a detailed die-
tary, GI symptom, and stool characteristic journal during
baseline and treatment periods; (12) meet with study personnel
weekly to review journals and complete weekly questionnaires;
and (13) voluntarily sign a written informed consent form prior
to study participation. Female participants were excluded if they
were pregnant, lactating, or had a menstrual cycle <27 days or
>29 days in length.
Experimental design and treatments
Study protocols and informed consent forms were approved by
the University of Illinois Institutional Review Board prior to
recruitment. All participants provided written informed consent
prior to study initiation. This randomized, double-blind,
placebo-controlled crossover trial consisting of three 21 day
periods with a 7 day washout among periods was conducted
from January 2013 to May 2013. The number of males and
females per treatment group and the six treatment sequences
were balanced by number and sex to minimize potential carry-
over effects. Prior to the rst treatment period, all participants
completed a 7 day baseline period. Each 21 day treatment
period consisted of a 15 day adaptation phase, a 5 day fecal
collection phase (days 16–20), and 1 day of breath gas testing
(day 21). On day 21 of each period, participants completed an 8
hour breath gas test following consumption of their respective
treatment for that period. Twenty-nine participants completed
three treatments (0, 5, and 7.5 g per day of ber). Chocolate
chews (Bruce's Candy Kitchen, Cannon Beach, OR) were
formulated with 0, 5.7 and 8.6 g of agave inulin (BioAgave®
Agave inulin ber, Ingredion Incorporated, Bridgewater, NJ) to
deliver 0, 5.0 and 7.5 g of ber (AOAC 2009.01) in three chews.
Dietary records
Participants were required to maintain daily dietary records
during the 7 day baseline period and each 21 day treatment
period. Participants did not keep records during the 7 day
washouts. Prior to study initiation, all participants were
instructed on how to properly maintain an accurate dietary
diary by a registered dietitian. Participants met with a member
of the research team weekly to review records for completeness
and accuracy. The amount and type of all foods and liquids
consumed in each 24 h period were recorded. Participants also
were instructed to indicate the time that each chocolate chew
was consumed daily. Dietary records were analyzed using
Nutritionist Pro (Version 5.2, 2012, Axxya Systems, Stafford, TX).
Gastrointestinal tolerance, stool records, and fecal
composition
During baseline and treatment periods, participants recorded the
date, time, consistency, and ease of passage of each bowel move-
ment. Daily stool records used the Bristol Stool Scale and a 5-point
scale rating ease of passage.23,24
Ease of passage was scaled 1 to
5 : 1 ¼ very easy; 2 ¼ easy; 3 ¼ neither easy nor difficult; 4 ¼
difficult; 5 ¼ very difficult. Also in the daily records, participants
scored seven GI symptoms: abdominal pain, bloating, burping,
atulence, nausea, reux, and rumblings. The GI tolerance
domains investigated and the scale utilized were based on previ-
ously published research.21,25,26
The daily GI symptoms assessed
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the intensity of each symptom using a 4 point scale: 0 ¼ absent, 1
¼ mild, 2 ¼ moderate, 3 ¼ severe. During weekly meetings with
research staff, participants completed weekly GI symptom ques-
tionnaires that consisted of questions about the presence and
frequency of six symptoms: nausea, GI rumblings, abdominal
pain, bloating, atulence, and diarrhea. This questionnaire has
been utilized previously.27
Participants were asked if they experi-
enced any of the GI symptoms indicated about during the past 7
days (no or yes). If yes, they were asked to rate the frequency as “no
more than usual”, “somewhat more than usual”, or “much more
than usual”. A composite GI symptom score was calculated based
on the sum of ratings for the six symptoms. A score of “0” was
given for each symptom not experienced. Symptoms reported as
being experienced “no more than usual”, “somewhat more than
usual” or “much more than usual” were scored as 0, 1, or 2,
respectively, for a total possible score of 0–12.
During days 16 to 20 of each treatment period, participants
were instructed to bring three fresh fecal specimen samples to
the laboratory within 15 minutes of defecation. Participants
were able to bring only one sample per day. Samples were
collected using Commode Specimen Collection Systems (Sage
Products, Crystal Lake, IL). Fresh samples were homogenized
upon arrival and aliquoted for dry matter determination. Fecal
dry matter (105
C) was measured according to the Association
of Official Analytical Chemists28
using a Precision Thelco Oven
(Precision Scientic Co, Chicago, IL).
Breath gas production and composition
End-alveolar CO2, H2, and CH4 concentrations were measured
hourly for 8 hours on the last day of each treatment period.29,30
The
day prior to breath gas testing, participants were instructed to
consume a low-ber diet and complete an overnight (10–12 hours)
fast, during which they were allowed to consume only water. On
testing days, participants collected a baseline breath gas sample (0
hour), consumed their respective treatment, and then collected 1
breath gas sample every 60 minutes for 8 hours. Participants were
provided the same low-ber breakfast (bagel, cream cheese, and
coffee) and lunch (sandwich, chips, cookie, and water) during each
of the 3 breath gas collection days (e.g., the 21st
day of each
treatment period). Participants were instructed not to sleep, exer-
cise, or smoke during the collection period. Concentrations of CO2,
H2, and CH4 in breath samples were analyzed by gas chromatog-
raphy utilizing a solid-state gas detector (Microlyzer Gas Analyzer,
model SC:Quintron Instruments, Milwaukee, WI).29,30
Briey,
breath H2 values were corrected for atmospheric contamination of
alveolar air by normalizing the concentrations of observed CO2 to
5.25% (5.33 kPa or 40 mm Hg, which is the partial pressure of CO2
in alveolar air). Samples with a CO2 concentration less than 1.5%
were considered poor samples and data points were excluded from
analysis. Changes in H2 concentrations were calculated by sub-
tracting the lowest H2 concentration among the baseline (0 hour),
1 hour, or 2 hour samples from the subsequent values.
Calculations and statistical analyses
Non-continuous survey data were compared using the GLIM-
MIX produce of SAS (version 9.3, 2013, SAS Institute, Inc. Cary,
NC). The xed effects of treatment, week, and treatment–week
interaction were tested. Period, week, and subject were
considered random effects. Breath H2 and CH4 and fecal dry
matter data were analyzed using the Mixed Models repeated
measures procedure of SAS. The xed effects of treatment, time,
and treatment by time were tested. Period and subject were
considered random effects. Data were tested for normality using
the UNIVARIATE procedure of SAS. Differences among treat-
ments were determined using a Fisher-protected least signi-
cant difference with a Tukey adjustment to control for
experiment-wise error. A probability of P 0.05 was accepted as
statistically signicant and a probability of P 0.10 was
considered a trend. Reported pooled standard errors of the
mean were determined according to the Mixed Models proce-
dure of SAS.
Results
Of the 30 participants enrolled in the study, 29 completed all
three treatments. One subject was removed from the study due
to consumption of a medication restricted by the study. The
descriptions of the 29 study participants are presented in Table
1. Dietary intake and body weight data for each treatment
period are presented in Table 2. Dietary intake and body weight
were not different among periods (P 0.05). Treatment period
did not have a signicant effect on any variable (P 0.05),
indicating that there were no carry-over effects among
treatments.
Daily symptom ratings
The main effects of treatment on subjective daily GI intolerance
symptoms are presented in Table 3. The intensity of atulence
and bloating were greater (P 0.05) when participants
consumed either 5.0 or 7.5 g of supplemental agave inulin
compared to control (0 g). Intensity of abdominal pain and
rumblings were greater (P 0.05) when participants consumed
7.5 g, but not 5.0 g, supplemental agave inulin compared to 0 g.
Burping, nausea, and reux intensity did not differ among
treatments (P 0.05). Of all the daily symptoms, atulence was
the most intense GI symptom experienced by participants
consuming agave inulin; however, the mean atulence intensity
scores were mild (1.08 for 5.0 g and 1.24 for the 7.5 g treatment
group).
Table 1 Baseline characteristics of study participants
Item Mean Æ SD Range
Age (year) 27.1 Æ 4.1 20–36
Body weight (kg) 70.4 Æ 11.3 52–92
Female (kg) 63.0 Æ 7.9 52–82
Male (kg) 78.3 Æ 9.4 71–92
BMI (kg mÀ2
) 24.4 Æ 2.3 20–29
Systolic blood pressure (mmHg) 127.5 Æ 13.3 97–147
Diastolic blood pressure (mmHg) 74.9 Æ 7.2 61–97
Menstrual cycle length (day)a
28.0 Æ 0.3 28–29
a
Female participants.
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The treatment–week interaction was different (P 0.05) for
atulence and nausea. ESI Table 1‡ provides data on the
comparisons of each of the symptoms by week. Participants had
the greatest frequency of nausea during week 2 of the 7.5 g
treatment; however, nausea frequency was not different (P
0.05) from control by week 3 of treatment. Frequency of atu-
lence was greatest during all three weeks of 7.5 g agave inulin
consumption, with no change over time. Participants
consuming 5.0 g of agave inulin tended (P ¼ 0.058) to have more
atulence during week 2 as compared to week 1; however,
frequency returned to week 1 levels by the end of the period.
Frequency of atulence was greater (P 0.001) in agave inulin
groups as compared to control (0 g) each week of the period.
Weekly symptom ratings
The subjective weekly GI intolerance symptoms are shown in
Table 4. Participants experienced more bloating (P 0.05) when
5.0 and 7.5 g agave inulin compared to the control (0 g). Flat-
ulence and rumblings was greater (P 0.05) when participants
consumed 7.5 g, but not 5.0 g, supplemental agave inulin
compared to 0 g. The frequency of bloating, atulence, and
rumblings also was greater (P 0.05) when participants
consumed agave inulin compared to control (Table 3).
There were no signicant differences in tolerance symptoms
when the treatment–week interaction was assessed. These data
can be found in ESI Table 2.‡ The symptoms that were the most
frequently observed in the agave inulin groups compared to the
control were bloating, atulence, and rumblings (Table 3 and
ESI Table 3‡). Most of the participants that experienced these
symptoms reported that they occurred “somewhat more than
usual” as opposed to “no more than usual” or “much more than
usual.” The mean frequencies for all weekly GI tolerance
symptoms were low. Flatulence was the most frequently expe-
rienced symptom with scores of 0.78 and 1.02 for 5.0 and 7.5 g
treatments, respectively. The frequency of diarrhea did not
differ among groups (P 0.05). The number and proportion of
participants experiencing each GI symptom can be found in ESI
Table 3.‡
Composite GI symptom scores for weeks 1, 2, and 3 of each
treatment are in Fig. 1. The main effect of treatment revealed
that both 5.0 and 7.5 g agave inulin increased the frequency of
GI intolerance symptoms (P 0.05). There were no differences
over time; however, a numeric decrease was observed during the
last week of each ber treatment.
Stool characteristics
The number of bowel movements per day increased and stools
were soer (P 0.05) with 7.5 g agave inulin compared to control
(Table 5). Ease of stool passage did not differ due to treatment.
Stool dry matter percentage was lower (P ¼ 0.03) when
Table 2 Energy and macronutrient intake and body weight of study participants at baseline and after each 3 week treatment period
Itemb
Treatmenta
(g agave inulin per day)
SEM P value0 5.0 7.5
Energy consumed (kcal per day) 2001.1 1958.7 2025.7 100.7 0.392
Protein (g per day) 82.7 82.9 86.9 3.8 0.306
Fat (g per day) 74.6 72.9 75.1 4.5 0.909
Carbohydrate (g per day) 243.5 241.0 245.8 13.9 0.215
Total dietary ber (g per day)c
18.2 17.6 18.0 1.3 0.545
Protein (% of energy) 16.9 17.4 17.5 0.6 0.589
Fat (% of energy) 33.1 33.3 33.2 0.9 0.620
Carbohydrates (% of energy) 48.8 49.0 48.4 1.0 0.599
Body weight (kg) 70.1 70.5 70.1 2.1 0.210
a
Values are least squares means with pooled SEM, n ¼ 29. b
Values are calculated from dietary records using Nutritionist Pro soware. c
Total
dietary ber values reect dietary ber consumed in the normal diet of the participants only; supplemental ber values are not included.
Table 3 Subjective daily and weekly gastrointestinal intolerance
symptoms during 3 week treatment periods
Item
Treatmentc
Dailyd
Abdominal pain 0.1b
0.2ab
0.2a
0.1 0.023
Bloating 0.2b
0.4a
0.4a
0.1 0.001
Burping 0.1 0.2 0.2 0.1 0.093
Flatulence 0.6b
1.1a
1.2a
0.1 0.001
Nausea 0.0 0.1 0.1 0.0 0.056
Reux 0.0 0.1 0.0 0.0 0.420
Rumblings 0.2b
0.3ab
0.4a
0.1 0.009
Weeklye
Abdominal pain 0.1 0.2 0.3 0.1 0.074
Bloating 0.1b
0.4a
0.5a
0.1 0.001
Flatulence 0.1b
0.8a
1.0a
0.1 0.001
Nausea 0.0 0.2 0.2 0.1 0.069
Rumblings 0.1b
0.4a
0.4a
0.1 0.003
Diarrhea 0.0 0.0 0.1 0.0 0.245
ab
Mean values in a row with unlike superscript letters differ (P 0.05).
c
Values are least squares means with pooled SEM, n ¼ 29. d
Daily
gastrointestinal symptoms were scored using the following scale: 0 ¼
absent, 1 ¼ mild, 2 ¼ moderate, 3 ¼ severe. e
Adults were asked if
they experienced any of the gastrointestinal symptoms listed above
during the past 7 days (yes or no). If yes, frequency of gastrointestinal
symptoms was scored using the following scale: 0 ¼ no more than
usual, 1 ¼ somewhat more than usual, or 2 ¼ much more than usual.
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participants consumed 7.5 g agave inulin. Mean fecal dry matter
percentages were 24.8 Æ 0.9%, 26.0 Æ 0.9%, and 26.3 Æ 0.9% for
7.5, 5.0, and 0 g treatments, respectively.
Breath hydrogen
The changes in breath H2 concentration over time are shown in
Fig. 2. When participants consumed agave inulin, breath H2
concentration tended (P 0.08) to increase at 4 hours and
increased (P 0.05) at 5, 6, 7, and 8 hours postprandial compared
to control. There were no differences between 5.0 and 7.5 g agave
inulin at any time point during the 8 hours of testing. The total
area under the curve during the eight hours of testing were greater
(P 0.05) in the 5.0 g (172 + 21 ppm AUC) and 7.5 g (201 Æ 21 ppm
total AUC) treatments compared to control (36 + 21 ppm total
AUC). There were no differences (P 0.05) in breath CH4
concentration regardless of treatment (means of 8.5, 8.5, and 6.9
ppm for 0, 5.0, and 7.5 g agave inulin, respectively).
Discussion
Overall, compliance was excellent throughout the trial. All partic-
ipants with the exception of one (withdrawn aer period 1 due to
initiation of a medication known to impact GI function) completed
all three treatment periods. As this was a cross-over design
whereby participants acted as their own control, all data points for
the withdrawn participant were excluded from analysis. All dietary,
GI tolerance, and stool records were collected from the 29 partic-
ipants that completed the trial. Study records indicated that the
subjects consumed nearly 100% of treatments (3 chocolate chews
per day), maintained a moderate-ber diet (average ber intake,
17.9 g per day) within the range of that consumed by the majority
of Americans, had similar caloric and macronutrient intake
proles across the three periods, and had no signicant changes in
body weight throughout the study. The lack of a signicant effect
of period indicates that a one-week washout period and a 21 day
adaption period was adequate to assess study outcomes related to
ber supplementation.
Table 4 Number of participants that did not experience GI intolerance
symptom ratings while consuming 0, 5.0, or 7.5 g agave inulin per day
Itema
Number of subjects (%)
P valueb
Treatment (g agave inulin per day)
0 5.0 7.5
Nausea
Week 1 28 (96.6) 25 (86.2) 24 (82.8) 0.063
Week 2 27 (93.1) 23 (79.3) 24 (82.8)
Week 3 28 (96.6) 25 (86.2) 24 (82.8)
Bloatingc
Week 1 23 (79.3) 17 (58.6) 13 (44.8) 0.001
Week 2 21 (72.4) 17 (58.6) 13 (44.8)
Week 3 21 (72.4) 16 (55.2) 13 (44.8)
GI rumblingd
Week 1 19 (65.5) 14 (48.3) 11 (37.9) 0.018
Week 2 17 (58.6) 13 (44.8) 12 (41.4)
Week 3 18 (62.1) 14 (48.3) 13 (44.8)
Gas/Flatulencee
Week 1 4 (13.8) 3 (10.3) 1 (3.4) 0.019
Week 2 7 (24.1) 2 (6.9) 3 (10.3)
Week 3 5 (17.2) 3 (10.3) 2 (6.9)
Abdominal pain
Week 1 27 (93.1) 24 (82.8) 20 (69.0) 0.198
Week 2 24 (82.8) 24 (82.8) 25 (86.2)
Week 3 26 (89.7) 24 (82.8) 22 (75.9)
Diarrhea
Week 1 28 (96.6) 28 (96.6) 28 (96.6) 0.139
Week 2 28 (96.6) 27 (93.1) 27 (93.1)
Week 3 28 (96.6) 28 (96.6) 23 (79.3)
a
Adults were asked if they experienced any of the gastrointestinal
symptoms listed above during the past 7 days (yes or no). Values
listed denote number and percentage of adults who responded no to
each domain. b
P values shown are the main effect of treatment from
the nal generalized linear model. c de
For means pooled for diet: (c)
0 5.0 = 7.5; (d) 0 = 5.0, 5.0 = 7.5, 0 7.5; (e) 0 = 5.0, 5.0 = 7.5, 0 7.5.
Fig. 1 Composite GI symptom scores for weeks 1, 2, and 3 of each
treatment. Values are least squares means with pooled SEM, n ¼ 29.
a,b
Mean values with unlike superscript letters differ (P 0.05). There
was no interaction of treatment and time (P ¼ 0.82).
Table 5 Subjective daily stool characteristics during 3 week treatment
periods
Item
Treatmentc
Number of bowel
movements per day
1.2b
1.3ab
1.4a
0.1 0.032
Ease of stool passaged
2.4 2.8 2.3 0.2 0.079
Stool consistencye
3.4b
3.5ab
3.6a
0.1 0.043
ab
Mean values in a row with unlike superscript letters differ (P 0.05).
c
Values are least squares means with pooled SEM, n ¼ 29. d
Ease of
stool passage was scored using the following scale: 1 ¼ very easy; 2 ¼
easy; 3 ¼ neither easy nor difficult; 4 ¼ difficult; 5 ¼ very difficult.
e
Stool consistency was scored using the Bristol stool scale: 1 ¼
separate hard lumps, like nuts; 2 ¼ sausage-shaped but lumpy; 3 ¼
like a sausage but with cracks on surface; 4 ¼ Like a sausage or
snake, smooth and so; 5 ¼ so blobs with clear-cut edges; 6 ¼ uffy
pieces with ragged edges, mushy; 7 ¼ watery, no solid pieces, entirely
liquid.
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Our study demonstrated that consumption of agave inulin at
5.0 and 7.5 g per day was generally well-tolerated with only mild
frequencies and intensities of GI intolerance symptoms. The GI
intolerance symptoms were generally reported as absent to mild
and frequencies noted as “no more than usual”. The 7.5 g agave
inulin dose increased the incidence of atulence and rumblings
and the daily intensity of rumblings and abdominal pain, while
5.0 g was not different from 0 g. However, overall frequencies of
GI intolerance symptoms, as measured by composite GI scores,
were not different between the two agave inulin treatments. Both
5.0 and 7.5 g agave inulin increased the frequency of the
composite GI symptom score compared to control. However,
scores were low with the highest treatment (7.5 g) measuring 2.3
on a 12 point scale while control (0 g) was 1.9 points lower,
measuring 0.4. The most frequent and intense symptom reported
by participants was atulence, which was reported to be present
somewhat more than usual in mild to moderate levels when
agave inulin was consumed. Bloating and rumbling were the next
most frequent symptoms experienced when participants
consumed agave inulin. Both bloating and rumblings were
experienced by participants at a mild level of intensity. Agave
inulin up to 7.5 g did not affect the incidence of diarrhea. Our
ndings are consistent with previous studies in that chicory
inulin and oligofructose were generally well tolerated up to 10 g
per day with gaseous symptoms, including bloating, abdominal
pain, and rumblings, being rated between absent and mild and
atulence rated between mild and moderate.21,22,25,31,32
The tolerability of agave inulin intake also may be related to
the characteristics of the treatment vehicle as well as timing of
intake.21
The agave inulin was given in a solid rather than liquid
form, and participants were given three chocolate chews per day
and encouraged to consume one with each meal. Providing
treatments in solid form and dividing them into doses may have
helped to improve tolerance although little data is available to
support this.12,33
Many of the participants rarely or never reported
many of the GI intolerance symptoms, while some reported
several symptoms continuously, suggesting a wide range of
individual tolerance to agave inulin. These differences also may
relate to dietary differences among ethnic groups whereby indi-
viduals of Latino descent generally eat a higher ber diet
compared to Caucasians (18.0 vs. 16.1 g per day; P 0.05).9
As
31% our study participants self-reported themselves as Latinos,
this may provide a potential explanation of these variations in
ber supplementation tolerance. Improved tolerance to ber
intake also has been noted in cases of habitual intake.32,34,35
In
our experiment, we observed a numeric decrease in the tolerance
score by week three, suggesting that participants may have begun
to develop a higher tolerance to inulin. However, differences were
not statistically signicant. A longer treatment period may be
necessary to detect a difference.
Our study demonstrated that 7.5 g agave inulin improved
laxation (soer, more frequent stools) without increasing the
frequency of diarrhea. No serious symptoms were reported
following consumption of agave inulin up to 7.5 g per day.
Participants' daily stool records throughout the trial denoted a
shi toward soer stools when consuming the 7.5 g treatment
as compared to 0 g. Taken together with the slight decrease in
dry matter percentage in the 7.5 g group, one can hypothesize
that this treatment increased luminal osmotic pressure in the
colon, thereby increasing the water content of the stool. It also
should be noted that 7.5 g also had the lowest numeric ease of
stool passage score (i.e., easiest of the three treatments to pass);
however, this difference was not statistically signicant. To our
knowledge, this is the rst study to report a laxative effect of
agave inulin. Similar decreases in fecal dry matter percentage
and increased number of bowel movements with supplemen-
tation of 15 g per day of chicory inulin have been reported.36–39
Langlands et al. also reported a laxative effect with 2.5 g of
inulin plus 2.5 g oligofructose consumed three times per day
over a 2 week period.40
Dietary bers, including inulin, are indigestible by human
digestive enzymes and, instead, are fermented by bacteria in the
GI tract, primarily in the large intestine. Bacterial fermentation
results in production of short chain fatty acids and gases
including H2, CO2, N, and CH4. Hydrogen produced by this
fermentative process is removed via bacterial cross-feeding by
other bacteria, atulence, and diffusion into the blood with
subsequent excretion via the lungs.41
Perfusion into the lungs
occurs at a constant fraction (14%) of total H2 production
within the GI lumen.42
Breath H2 studies measure pulmonary
Fig. 2 Postprandial breath H response. The incidence of a positive breath hydrogen test was higher when participants consumed 5.0 and 7.5 g
per day as compared to control (0 g per day) (treatment, P 0.0001; 7.5 g per day ¼ 5.0 g per day 0 g per day). Breath H2 concentration tended
to increase at 4 hours postprandial (#P 0.08; 7.5 g per day ¼ 5.0 g per day 0 g per day). There was a significant increase in H2 concentration at
5, 6, 7, and 8 hours postprandial (***P 0.0001; 7.5 g per day ¼ 5.0 g per day 0 g per day). Values are means Æ SEM, n ¼ 29.
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excretion of H2 gas thereby indirectly assessing colonic
fermentation.43
In our experiment, we observed that the
fermentation proles of 5.0 and 7.5 g agave inulin were not
different from each other; however, both tended to be greater
than 0 g at 4 hours postprandial and were signicantly greater
5–8 hours postprandial. Our breath H2 results showed a peak
with sustained fermentation from 6–8 hours postprandial,
while chicory inulin breath H2 data suggest it reaches the same
level of fermentation 8 hours postprandial.37
Agave inulin is a
branched inulin with b-2,1 and b-2,6 linkages and DP 25–34,
whereas chicory inulin is linear with b-2,1 linkages and DP 20.
The branched structure of agave inulin may provide an expla-
nation for the faster fermentation prole.
In conclusion, our study demonstrated that agave inulin is
readily fermented in the distal GI tract and that consumption at
practical doses of 5.0 and 7.5 g per day by healthy adult humans
was generally well-tolerated with mild frequencies and inten-
sities of GI intolerance symptoms. Further, 7.5 g of agave inulin
modestly improved laxation. Future studies should investigate
the impact of agave inulin supplementation on the human
microbiome and clinical outcomes such as glucose tolerance
and blood lipids.
Acknowledgements
H.D.H., V.G., C.L.P., G.C.F., and K.S.S. designed research;
H.D.H., J.L.D., and L.L.B. conducted research; V.G. and C.L.P.
provided essential materials for research; H.D.H. analyzed data;
H.D.H., J.L.D., and K.S.S. wrote the paper; and K.S.S. had
primary responsibility for nal content. All authors read and
approved the nal manuscript. V.G. and C.L.P. work for Ingre-
dion, Inc. who provided funding for the study. H.D.H., J.L.D.,
L.L.B., G.C.F., and K.S.S. have no conicts of interest. The
author would like to acknowledge the technical support of
Amanda Ayers, Alison Beloshapka, Ping Deng, Maria Godoy,
Brooke Pfest, and Leila Shinn. We also are grateful to the study
participants for their dedication to the project.
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