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Cranberry and PACs for medically diagnosed cystitis

Cranberry and PACs for medically diagnosed cystitis

Cystitis is the most common type of urinary tract infection affecting over 50% of women. Cranberry, with 36mg PACs, has been clinically researched for recurrent cystitis in children and adults.  

Clinical insight

Cystitis is the most common type of urinary tract infection (UTI) with more than 50% of women experiencing at least one UTI over their life time, of which one third will suffer a recurrence, and if left untreated can lead be serious.1 Antibiotics are often first line treatment for initial cases of cystitis and as prophylaxis for recurrent infections; however, there is a worldwide increase of antibiotic-resistant strains involved in UTIs, which presents a significant health problem.2  The herb cranberry (Vaccinium macrocarpon) has been shown effective in recurrent cystitis and may be a viable option for many seeking relief.

Cystitis and UTIs explained

Cystitis is inflammation of the urinary bladder accompanied by a persistent urge to urinate and a burning sensation on urination. Haematuria and lower abdominal cramp-like pain characterise more severe attacks. It commonly affects women, the immunosuppressed, the elderly, and patients with catheters.3,4

UTIs can be classified as complicated or uncomplicated. Complicated infections are associated with functional or structural abnormality or underlying pathology. Uncomplicated infections occur sporadically in otherwise healthy individuals. 3,4

Recurrent UTIs are defined as more than two infections in six months, or three infections over twelve months, with a complete resolution for a minimum of two weeks. Recurrence may be a result of relapse from incomplete treatment through the persistence of the same bacterial strain, or re-infection from a new source. 3,4

The most common bacteria responsible for recurrent cystitis is the uropathogen Escherichia coli (E.coli), which accounts for up to 85% of cases. The remainder are caused by streptococci and staphylococci species, and very rarely by Candida albicans.5,6,7

Cystitis - typical presentations and risk factors

Typical presentations of cystitis involve symptoms of urinary pain, burning, urgency and frequency; however, symptoms may be more subtle (especially in children), such as fever, irritability, poor feeding and vomiting.  Most recurrences result from reinfection, usually within 3 months of an initial episode.8

Risk factors for cystitis include being sexually active, diabetic, pregnant or post-menopausal, and can also be due to use of indwelling/intermittent catheterisation.9-11

Recurrent cystitis is most common in women. It is initiated by a UTI that ascends from the periurethral area to the vagina, then to the distal urethra and bladder. Reservoirs of uropathogens can be retained in urothelial cells providing an opportunity for reinfection.3,12

Women, who are pregnant or post-menopausal women, are particularly prone to non-symptomatic cystitis. In pregnancy, the increasing weight of the unborn baby puts pressure on the urinary tract (UT) and can block normal drainage of urine from the bladder, which can cause infection. Recurrent cystitis is particularly prominent from weeks 6-24 of pregnancy.  

Recurrent cystitis in post-menopausal women is thought to be due to reduced oestrogen levels, which can:

  1. change the microflora in the vaginal/urethral area reducing healthy Lactobacillus spp. and promoting E coli dominance
  2. contribute to UT tissue weakening, increasing susceptibility to infection13,14

The role of cranberry and PACs in recurrent cystitis

Cranberry appears to significantly reduce the recurrence of symptomatic cystitis. It works at the level of prevention. It inhibits the adhesion of bacteria, predominantly E.coli, to uroepithelial cells, preventing the invasion of the mucosal surface and the establishment of a biofilm.7,15,16 This action is primarily attributed to the constituent in cranberry called proanthocyanidins (PACs), particularly those with an “A-type” interflavan bond (PAC-A).7,17

Studies found that cranberry with 36 mg per day of PACs helped reduce the incidence of recurrent cystitis through this process.15 

Research in adults 

A double-blind, multicentric placebo controlled study investigated the effect of cranberry extract standardised to three doses (18mg, 36mg and 72mg) of PACs on the adhesion of uropathogenic P. fimbriated E. coli in 32 sexually active women. 15

At 6 hours after taking the cranberry supplement, the 36mg and 72mg showed significant differences in anti-adhesion activity, compared to 18mg. At 24 hours there was a residual anti-adhesion effect in both the 36mg and 72mg doses, with the 72mg having a more pronounced effect.

 

The in vivo model of the same study also confirmed that E.coli strains had reduced virulence after cranberry consumption. Note above, the reduced numbers of brightly lit cellular E.coli in the 36mg and 72mg panels, compared to the placebo and 18mg panels..15

The overall study results showed 36mg of cranberry PAC per day is effective to achieve a bacterial anti-adhesion effect. Maximum anti-adhesion activity was seen at 6 hours with residual effects at 24 hours. The 72mg offered a dose-dependent effect for day and night protection. 15

Cranberry has also been shown to be effective in children.

A randomised double-blind clinical trial studied 192 patients between the ages of 1 month and 13 years. It compared the effectiveness of cranberry (standardised to 36mg PACs) to the antibiotic trimethoprim (TMP) over 22 months.19

In patients with recurrent UTIs, the mean time to infection was 271 days after taking trimethoprim. It was 312 days after taking the cranberry. The recurrence rate of UTIs in the cranberry group of 28.4% (versus 43.2% in the TMP group) after 12 months.  All outcomes demonstrated the noninferiority of cranberry versus trimethoprim in the prevention of recurrent urinary tract infections.19

The 36 mg PAC containing cranberry has been shown to be well tolerated and prevent recurrent cystitis in children and adults, including the elderly. It is also suitable in pregnancy and can be taken concomitantly with antibiotic treatment. 15,19-23

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