From: Role of D-mannose in urinary tract infections – a narrative review
Reference | Study Design | Subjects and groups | Supplementation | Main Findings (including safety) |
---|---|---|---|---|
De Leo 2017 [75] Article in Italian | Multicenter, Randomized, controlled trial | 40 to 50 year old women suffering from recurrent episodes of cystitis; n = 150 | 1 Kistinox® Forte sachet per day including cranberry (Vaccinium macrocarpon), Noxamicina® (propolis extract) and 500 mg D-mannose during the first 10 days of the month, for 3 months (n = 100). No treatment in the control group (n = 50) | Product efficient and well-tolerated in treatment of acute UTI and reducing rUTI No AEs |
Efros 2010 [76] | Prospective, dose-escalation study | 18 to 75 years old women with history of recurrent UTIs (no acute infection) n = 28 (planned) n = 23 (actual) − 6 per dose group | 12 weeks daily dose of 15 ml, 30 ml, 45 ml, 60 ml, 75 ml or 90 ml of UTI-STAT with Proantinox 3875 mg Proantinox (cranberry concentrate [4:1], ascorbic acid, D-mannose, fructo-oligosaccharides, and bromelain) per 30 ml D-mannose dose not indicated | Safe and well tolerated. Efficient in reducing rUTI incidence and increasing quality of life. AES: 9 reported (nausea, heartburn, headache, dyspepsia (4), diarrhea, back pain) Max tolerated dose set for 60 ml/day. |
Genovese 2018 [77] | A randomized three-arm parallel group intervention trial | Adult Caucasian females with acute uncomplicated cystitis history of recurrent UTIs n = 72 | 12 weeks with follow-up at 24 weeks. group A: D-mannose 420 mg + berberine, arbutin and birch (n = 24) group B: D-mannose 420 mg + berberine, arbutin, birch and forskolin (n = 24) group C: D-mannose 500 mg + proanthocyanidins (n = 24) | Plant-based supplements reduce the risk for UTI but no specific benefits for D-mannose alone No AEs |
Manno 2019 [78] | Prospective comparative study | Women with acute cystitis and history of recurrent cystitis n = 40 | 12 weeks including follow-up time Acute: Fosfomycin Tromethamine (3 g) single dose (UROFOS®) for all participants Long-term: 2 sachets for 2 weeks and one sachet for two additional weeks as follows: group A: UROIAL containing S&R PACs (250 mg) with type-A proanthocyanidins (72 mg), D-mannose (1000 mg), chondroitin sulfate (200 mg), vitamin C (120 mg) and hyaluronic acid (100 mg) (n = 20) group B: no treatment (n = 20) | Complete remission in 37 participants after fosfomycin. Lower UTI episodes and symptoms in treatment group after 4 week’s intervention and follow-up time. No AES mentioned |
Marchiori 2017 [79] | Observational, retrospective study | Pre- and postmenopausal women who had survived breast cancer and had recurrent cystitis n = 60 (50 had reached menopause) | Long-term: Group 1 - antibiotic therapy associated with NDM (n = 40) given 12 h after emptying bladder for 60 days followed by dose 24 h after emptying bladder for 4 months, Group 2 - antibiotics alone (n = 20) NDM dose: D-mannose 500 mg, N-acetylcysteine 100 mg and Morinda citrifolia fruit extract 200 mg (NDM) Antibiotic options depending on microbial sensitivity: fosfomycin - 3 g per day for two days every 15 days for three cycles, nitrofurantoin - 1cps 100 mg tid for 6 days and ciprofloxacin - 1000 RM or prulifloxacin - 600 mg 1 cps/day for 6 days | Greater efficacy in NDM combined with antibiotic in reducing UTIs and urinary discomfort compared to antibiotics only No AEs related to IP usage specified |
Palleschi 2017 [80] | Prospective, randomized study | ~ 65.4 years old male [42] and female [38] patients eligible for urodynamic examination. n = 80 | Acute preventive Group A: antibiotic Prulifloxacine 400 mg/day for 5 days (n = 40), Group B: D-mannose 500 mg, N-acetylcysteine 100 mg and Morinda citrifolia fruit extract 300 mg, twice a day for 7 days (n = 40) | D-mannose and NAC therapy resulted similar results to the antibiotic therapy in preventing UTIs in patients submitted to urodynamic examination. Considered as usable alternative treatment No AEs |
Panchev 2012 [81] Article in Bulgarian | Multicenter, comparative, observational study | Female patients with acute uncomplicated urinary bladder infections (Age not reported) n = 158 | Acute: Group 1: Product containing D-mannose 1000 mg, standardized dry birch leaf extract 50 mg, standardized dry cranberry extract 50 mg according to manufacturer’s instructions (n = 86) Group 2: Ciprofloxacin 500 mg twice daily for 3 days (n = 72) | Better effectiveness related to symptoms and clinical outcomes with the product compared to antibiotic was reported No AEs |
Rădulescu 2020 [82] | a pilot, randomized study | non-pregnant, healthy women with uncomplicated lower UTI Age range 18–60 years n = 93 | First phase/Acute: 1) Antibiotic (TMP-SMX) (n = 45) or 2) Antibiotic + D-mannose (1000 mg) + cranberry (400 mg) (Uro-Care with CranActin®)(n = 48) for 7 days Second phase/ prophylaxis: For cured participants either 1) D-mannose + cranberry (n = 47) or 2) placebo (n = 46) for 21 days | Higher cure rate after acute phase in the combined group especially in the resistant strains. No significant differences between the active and the placebo in the second phase of the study No AEs related to IP usage specified |
Russo 2020 [83] | A prospective, randomized, no-placebo, controlled study | ~ 67.2 years old postmenopausal women undergoing surgery for cystocele n = 40 | Active: cranberry, D-mannose, Boswellia, Curcuma and Noxamicine VR (Kistinox ActVR) twice a day for 2 weeks starting from surgery (n = 20) Control: only surgery (n = 20) | Symptom relief was reported in the active group compared to control. No differences in UTI incidences No AEs |
Salinas-Casado 2018 [84] Article in Spanish | A multicenter, double-blind, randomized, experimental study | ~ 48 years old women with non-complicated UTI n = 95 | Long-term: Group 1: 2 g of D-mannose, 140 mg of PAC and 7.98 mg of ursolic acid together with vitamins A, C and E, and the Zinc trace element (Manosar®) (n = 44) once a day for 24 weeks Group 2: 240 mg proanthocyanidins (n = 51) as a single dose/day | Product was reported to be more efficient for preventing rUTI than single dose of PAC AEs: 21.4% in Group 1 and 21.6% in Group 2 (diarrhea, headache, vaginal discomfort, nausea rash) |
Salinas-Casado 2020 [85] Article in Spanish | A multicenter, randomized and double-blind experimental study | ~ 49.5 years old women with a history of recurrent UTIs n = 184 | Group1: 2 g of D-mannose, 140 mg of PAC and 7.98 mg of ursolic acid together with vitamins A, C and E, and the Zinc trace element (Manosar®) (n = 90) once a day for 24 weeks Group 2: 240 mg proanthocyanidins (n = 94) as a single dose | Product was reported to be more efficient for preventing rUTI than single dose of PAC AEs: 16.8% of participants experienced AEs (12 in Group 1 and 19 in Group 2) (diarrhea, headache, vaginal discomfort, nausea rash) |