Mastic gum has no effect on Helicobacter pylori load in vivo

James R. Bebb1,2, Nathalie Bailey-Flitter1, Dlawer Ala’Aldeen2,3 and John C. Atherton1,2,*

1 Division of Gastroenterology, 2 Institute of Infection, Immunity and Inflammation, and 3 Department of Microbiology, University Hospital, Nottingham, NG7 2UH, UK

Received 11 April 2003; returned 19 May 2003; revised 9 June 2003; accepted 12 June 2003


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 Conflicts of interest
 References
 
Objective: To determine whether mastic gum suppresses or eradicates Helicobacter pylori infection in humans.

Patients and methods: Nine patients with H. pylori infection, and without gastroduodenal ulceration, were recruited from day-case endoscopy lists and treated with mastic 1 g four times daily for 14 days. [13C]Urea breath tests (UBTs) were carried out immediately before, on day 15 and 5 weeks after treatment with mastic.

Results: Mastic had no effect on H. pylori status in any of the eight completed patients; all remained H. pylori positive by UBT with no change in {delta} scores [pre-treatment mean ± S.E.M. 19.1 ± 3.7, day 15 (post-treatment) 18.7 ± 3.8, P = 0.8, paired t-test].

Conclusion: Despite reported anti-H. pylori action in vitro, this preliminary study shows that mastic has no effect on H. pylori in humans.

Keywords: peptic ulcers, natural treatments, dyspepsia


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 Conflicts of interest
 References
 
Helicobacter pylori infection is the main cause of peptic ulceration and gastric MALT (mucosa-associated lymphoid tissue) lymphoma and is a major risk factor for development of gastric adenocarcinoma.1 Mastic gum is a resinous exudate obtained from the stem and the main leaves of Pistacia lentiscus. It is widely used in Middle Eastern and Mediterranean countries as a chewing gum and food additive. We previously reported that mastic is bactericidal against H. pylori in vitro,2 and this has been independently confirmed.3 Since then, mastic has been marketed heavily in the UK, other European countries and the USA as a natural treatment for H. pylori infection and peptic ulceration. It is widely available in capsular form in health food shops and over the internet. We now report that mastic has no clinically significant in vivo action against H. pylori in humans.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 Conflicts of interest
 References
 
To examine whether mastic gum was effective against H. pylori in vivo, we carried out a simple screening study in human volunteer subjects using [13C]urea breath tests (UBTs). Even single doses of antibiotics reduce H. pylori load in the stomach sufficiently to render a UBT tempor-arily negative. Based on published UBT data,4 we calculated that we required eight completed subjects to detect a modest reduction in bacterial load with mastic (reduction in UBT value of 2) at P < 0.05 (two-sided) with 90% power. Thus we recruited nine H. pylori positive patients (by Clotest rapid urease test, Ballard Medical Products, Draper, UT, USA) from our routine day-case endoscopy lists. No patient had current or previous gastroduodenal ulceration, or had taken antibiotics, bismuth compounds or proton pump inhibitors for 6 weeks before the trial. The study was approved by the University Hospital Nottingham Ethics Committee. Patients were treated with mastic capsules 1 g four times daily for 14 days. A [13C]UBT (INFAI, York, UK) was carried out before, on day 15 and 5 weeks after treatment with mastic.


    Results and discussion
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 Abstract
 Introduction
 Materials and methods
 Results and discussion
 Conflicts of interest
 References
 
Eight of the nine patients completed the trial protocol (one withdrew after 5 days of treatment due to nausea and bloating). All eight patients remained H. pylori positive by UBT immediately after finishing mastic treatment, with unchanged UBT values (Figure 1; pre-treatment mean ± S.E.M. 19.1 ± 3.7, post-treatment 18.7 ± 3.8, P = 0.8, paired t-test). Eight patients attended for UBT 5 weeks after treatment finished; all remained H. pylori positive, again with unchanged UBT values (Figure 1, 18.2 ± 3.6, P = 0.5 versus pre-treatment levels). Other than the patient who withdrew, two patients reported mild adverse symptoms: one complained of fatigue and the second of constipation and bloating.



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Figure 1. {delta} Urea breath test values for each of the eight completed volunteer patients before, immediately after and 5 weeks after 2 week treatment with mastic 1 g four times daily. H. pylori negative patients have {delta} UBT values of less than 3.5. Treatment with mastic had no effect on UBT values implying no significant effect on H. pylori load. In comparison, even single doses of antibiotics reduce bacterial load sufficiently to render urea breath tests temporarily negative.

 
This preliminary study shows that high dose mastic gum has no clinically significant effect against H. pylori in vivo. Two studies from Iraq have suggested that mastic may be effective for ulcer treatment, but one was uncontrolled5 and the other seriously flawed: blinding was inadequate and analysis was not intention-to-treat.6 A recent report in this journal7 showed that mastic monotherapy had no antimicrobial activity against H. pylori in a mouse model. Treatment of H. pylori-associated peptic ulcers should be with anti-acid secretory drugs and H. pylori eradication; this heals ulcers and prevents relapse.8


    Acknowledgements
 
Dr Bebb is funded by a Clinical Training Fellowship and Professor Atherton by a Senior Clinical Fellowship from the Medical Research Council (UK).


    Conflicts of interest
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 Abstract
 Introduction
 Materials and methods
 Results and discussion
 Conflicts of interest
 References
 
Professor Ala’Aldeen has spoken at a conference funded by the growers of mastic on the Greek island of Chios. Professor Atherton has participated in clinical trials funded by Eisai, manufacturers of the proton pump inhibitor rabeprazole.


    Footnotes
 
* Corresponding author. Tel: +44-115-924-9924, ext. 41966; Fax: +44-115-942-2232; E-mail: john.atherton{at}nottingham.ac.uk Back


    References
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 Abstract
 Introduction
 Materials and methods
 Results and discussion
 Conflicts of interest
 References
 
1 . Blaser, M. J. & Berg, D. E. (2001). Helicobacter genetic diversity and risk of human disease. Journal of Clinical Investigation 107, 767–73.[Free Full Text]

2 . Huwez, F. U., Thirlwell, D., Cockayne, A. et al. (1998). Mastic gum kills Helicobacter pylori. New England Journal of Medicine 339, 1946.[Free Full Text]

3 . Marone, P., Bono, L., Leone, E. et al. (2001). Bactericidal activity of Pistacia lentiscus mastic gum against Helicobacter pylori. Journal of Chemotherapy 13, 611–4.[ISI][Medline]

4 . Mana, F., Franken, P. R., Ham, H. R. et al. (2000). 13C urea breath test with non-dispersive isotope-selective infrared spectrometry: reproducibility and importance of the fasting status. Helicobacter 5, 104–8.[CrossRef][ISI][Medline]

5 . Huwez, F. U. & Al-Habbal, M. J. (1986). Mastic in the treatment of benign gastric ulcers. Gastroenterologia Japonica 21, 273–4.[Medline]

6 . Al-Habbal, M. J., Al-Habbal, Z. & Huwez, F. U. (1984). A double-blind controlled clinical trial of mastic and placebo in the treatment of duodenal ulcer. Clinical and Experimental Pharmacology and Physiology 11, 541–4.[ISI][Medline]

7 . Loughlin, M. F., Ala’Aldeen, D. A. A. & Jenks, P. J. (2003). Monotherapy with mastic does not eradicate Helicobacter pylori infection from mice. Journal of Antimicrobial Chemotherapy 51, 367–71.[Abstract/Free Full Text]

8 . Maltertheiner, P., Megraud, F., O’Morain, C. et al. (2002). Current concepts in the management of Helicobacter pylori infection—the Maastricht 2000 Consensus report. Alimentary Pharmacology and Therapeutics 16, 167–80.[Medline]