Green kiwifruit for the relief of constipation in patients with functional constipation and IBS-C – meta-analysis of three international trials

Richard Gearry, Shin Fukudo, Barbara Kuhn-Sherlock, Juliet Ansell,

Lynley Drummond, Giovanni Barbara

Disclosures

• I have received the following from Zespri International

– Research funding

– Advisory board membership

– Support to attend conferences

Background

• Constipation affects ~17% of global population

• Conventional treatments may be poorly tolerated

• There is a strong demand for natural food interventions to address GI symptoms

• Studies support the use of Zespri® Green Kiwifruit (Actinidia deliciosa var. Hayward) to improve bowel function

Kiwifruit and IBS-C / FCWhat do we know so far?

Authors Country Participants Study Design N Findings

Rush et al NZ >60 yearsConstipated

Randomised, crossover, no control

38 stool frequency ease of passing BM bulkier, softer stool

Chang et al Taiwan Adult IBS -constipated

Randomised study with capsule control

41 stool frequency colonic transit time

Chan et al Hong Kong

Constipatedadults

Prospective observational study, no control

53 stool frequency bowel habit satisfaction laxative use

Hiele(unpublished)

Belgium Adult IBS -constipated

Prospective observational study, no control

38 stool frequency ease of passing BM abdominal bloating

Rush et al, APJCN, 2002, Chang et al, APJCN, 2010, Chan et al, WJG, 2007

Potential mechanisms of action of kiwifruit

Bayer, Gearry, Drummond, Critical Reviews in Food Science and Nutrition, 2017

More evidence required

Strong evidence

Permeability (actinidin)

Mucous production (actinidin)

Inflammation (kissper)

Pro-inflammatory cytokines

NO production

Protein digestion (actinidin)

Gastric emptying (actinidin)

Transit time

Water retention (fibre)

Faecal bulk (fibre)

Lactobacilli, Bifidobacteria (fibre)

SCFA (fibre)

Hypotheses

• That consumption of two Zespri green kiwifruit* daily improves bowel motion frequency in constipated individuals by >1.5 complete spontaneous bowel motions (CSBM) per week

• That consumption of two Zespri green kiwifruit* daily improves gastrointestinal discomfort in constipated individuals

• That two Zespri green kiwifruit* are well tolerated by constipated individuals and healthy controls

*Actinidia deliciosa var Hayward

Three independent studies (same methodology)

• Christchurch, New Zealand (Gearry)

• Bologna, Italy (Barbara)

• Sendai, Japan (Fukudo)

InterventionsTwo Zespri Green Kiwifruit 7.5g psyllium

Study design• Randomised single-blinded cross-over design

• Powered to show an increase of 1.5 CSBM per week 90% power, 5% significance

2-week lead in period

4-week kiwifruit

intervention

4-week psyllium

intervention

4-week washout period

2-week follow-up period

4-week kiwifruit

intervention4-week psyllium

intervention

Inclusion / exclusion criteria.

Inclusion

• 18-65 years of age• BMI 18-35• Functional constipation (20)• IBS-C (20)• Healthy (20)

Exclusion• GI alarm symptoms• Significant chronic medical

conditions• Fasting glucose >7.2mmol/L• Drugs affecting GI motility• Pregnant / breastfeeding women• Known kiwifruit or latex allergy• Not prepared to stop other

laxatives

Schedule of assessments.

GSRS

POMS

IBS- SSI

Rome III

Lead –in 2 weeks

Intervention 14 weeks

Washout 4 weeks

Follow-up2 weeks

Intervention 24 weeks

0Week 62 10 14 16

BASELINE

Daily Diary

IBS - QoL

Food Diary

Stool Sample

Blood Sample(Vitamin C)

SmartPills (Italy/NZ)Radiopaque markers (Japan) (sub-cohort)

START OF STUDY

Results

Participants (ITT)

Healthy controls (HC) 61

Functional constipation (FC) 57

Constipation-predominant IBS (IBS-C) 60

Total 178

Primary outcome – CSBM / week (ITT)*P<0.05, **P< 0.01; ***P<0.001

Change in CSBM frequency

0

2

4

6

8

10

12

Pre Wk1 Wk2 Wk3 Wk4

Nu

mb

er /

wee

kFC+IBS-C CSBM

Psyllium

Kiwifruit

*** *** *** ***

*** *** *** ***

**P< 0.01; ***P<0.001

Meta-analysis of the effect of kiwifruit on CSBM/week

Effect of kiwifruit on GSRS total score**P< 0.01; ***P<0.001

Change in stool consistency (Bristol)

2.0

2.5

3.0

3.5

4.0

4.5

5.0

Pre Wk1 Wk2 Wk3 Wk4

Sco

re

FC+IBS-C BSFS

Psyllium

Kiwifruit

** *** ** ***

**P< 0.01; ***P<0.001

Meta-analysis of the effect of kiwifruit on GSRS score

Adverse events

• No adverse events were observed

Conclusions

• Two Zespri green kiwifruit / day are safe & effective in people with IBS-C or FC for:

– relief of constipation

– improvement in gastrointestinal discomfort

– improvement in overall gastrointestinal symptoms

• Results suggest non-inferiority with psyllium

Acknowledgements• Giovanni Barbara / Bologna research team

• Shin Fukudo / Sendai research team

• Plant and Food Research

• Lynley Drummond

• Juliet Ansell / Zespri international