CMAJ: Canadian Medical Association Journal

Probiotic Capsules and Xylitol Chewing Gum to Manage Symptoms of Pharyngitis: A Randomized Controlled Factorial Trial

There are 800 consultations per 10000 patients annually in the United States for pharyngotonsillitis. (1) Although most cases are viral, a substantial proportion are caused by pathogenic streptococci. (2-4) Despite the risk of antibiotic resistance from the prescribing of antibiotics in primary care, most patients who present with pharyngitis still receive these drugs. (5-9) The risk of antibiotic resistance increases with the use of broader-spectrum antibiotics, an approach that has been advocated because of the waning effectiveness of penicillin V. (10,11)

Both patients and health professionals are concerned about complications of infections, (12) but symptom control is actually patients' main concern; (13) therefore, finding alternatives to immediate antibiotics to help control symptoms is a priority. A major economic argument for using antibiotics is the assumption that individuals who are ill and the parents of children with illness will take more time off work. (14) However, if simple treatments could limit the effects of both bacterial and viral infections and help patients to manage symptoms, enabling a quicker return to work, the societal arguments to use antibiotics would be weaker.

Xylitol is a birch sugar that causes local "bacterial interference" by inhibiting bacterial growth and adherence to the pharyngeal wall, (15-18) which should reduce the inflammation and the severity of symptoms caused by bacterial infections. Although sorbitol has no such effect, chewing gum could plau sibly help both bacterial and viral throat infections by generating more saliva. Probiotics are benign, nonpathogenic bacteria that may act through both local "interference" and the immune system--thus affecting both viral and bacterial infections--including local activation of immunoglobulin A and T cells. (19,20) Cochrane reviews have suggested that probiotics can prevent recurrence of upper respiratory tract infections (21) (although the quality of the evidence is limited) and that xylitol can also reduce recurrence. (22)

It is plausible that both probiotics and xylitol could limit the severity of pharyngeal infections and help with symptom control, but there is no direct evidence to support this supposition. Our aim was to estimate the efficacy of probiotics and xylitol chewing gum in the symptomatic management of pharyngitis.


Design and setting

This parallel-group, individually randomized controlled trial had an equal allocation ratio. We invited practices around the study centre in Southampton, England, to participate. There were no exclusion criteria for practices.

Participant recruitment and eligibility

We used a variety of recruitment mechanisms. We sent letters to individuals who had previously consulted with pharyngitis, inviting them to participate should a new episode develop. Participants were also identified opportunistically when presenting to their general practitioner. Participants were assessed by either the physician or a practice nurse to determine eligibility for the study.

We included previously well people, aged 3 years or older, with an acute illness ([less than or equal to] 21 d), with sore throat as the main symptom and abnormal results on throat examination.

We excluded individuals with a history of peritonsillar abscess, rheumatic fever or glomerulonephritis; those reporting allergy to any constituents of the gum; and those with serious chronic disorders mandating antibiotics (e.g., cystic fibrosis). We also excluded individuals with suspected pregnancy or immune deficiency.


We used a 3 x 2 factorial design, based on a xylitol factor and a probiotic factor.

The xylitol factor had 3 alternatives: xylitol gum (Wrigley Orbit gum with 15% xylitol), sorbitol gum (Wrigley Extra gum with no xylitol [i.e., no active ingredient]) or advice not to chew gum. Patients in the 2 gum groups were advised to chew 5 sticks per day for 3 months, based on a similar regimen in prior studies, (16-18,22) and were provided with supplies of chewing gum. We included the nonchewing group to ensure that chewing itself was not important.

Each patient in these 3 groups was then randomly assigned to receive probiotic capsules or placebo capsules (all capsules supplied by Cultech), to be taken daily, with milk, for 3 months. Each active probiotic capsule contained a mixture of lactobacilli and bifidobacteria species (Lactobacillus acidophilus CUL60 [NCIMB 30157], Lactobacillus acidophilus CUL21 [NCIMB 30156], Bifidobacterium bifidum CUL20 [NCIMB 30153], Bifidobacterium animalis ssp. lactis CUL34 [NCIMB 30172]), which provided, in combination, 24 x [10.sup.9] colony-forming units.

All study participants had access to usual care. Prescription of medication or referral was at the physicians' discretion, according to their usual practices (i.e., not standardized).


Randomization was carried out by nurses, who gave an intervention pack to each eligible patient, according to a predefined sequential order. The contents of each pack were previously determined by a University of Southampton statistician (independent of the main study team), who used computer-generated random numbers to determine 3 kinds of material and advice for each pack: no offer of chewing gum, advice to use xylitol-based chewing gum or advice to use sorbitol-based chewing gum. The patients in each group were also randomly assigned to receive either probiotic capsules or placebo probiotic capsules, as described above. Participants were blinded as to whether they were receiving probiotics; they could not be blinded as to whether they chewed gum or not, but were blinded to the hypothesis that xylitol could help.

We used sequential packs for 2 reasons. The complex factorial design made group differentiation more difficult to guarantee, so use of the packs facilitated immediate access to the correct structured materials and advice sheets for each group, ensuring robust group differentiation and greater logistic simplicity for recruiters. …

Log in to your account to read this article – and millions more.