Studi Zenzero/Zintona* *Xamamina Natura all estero è commercializzata con marchio Zintona.



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Kinetosis (Motion Sickness) Careddu et al., Children with 1999 history of sickness n=28 (ages 4 8 2 days Ages 3 6 years: 250 mg 1/2 hour before trip, 250 mg every 4 hours as necessary; 6 years and older: 500 mg using above formula; or 1/2 1 capsule (12.5 25mg) dimenhydrinate 1/2 hour before the trip and if necessary 1 capsule every 4 hours Zintona vs. dimenhydrinate Significantly better therapeutic effectiveness in treated group than dimenhydrinate-treated group. Physician ratings reported good results in 100% of subjects taking, and 31% of subjects taking dimenhydrinate. Ginger reduced symptoms within 30 minutes, and this difference was highly significant (p< 0.0001). None of the children taking had any adverse side effects, while 69% of cases in the dimenhydrinate group had adverse effects from the drug, and this difference was also highly significant (p< 0.0001). Zintona vs dimenhydrinate Significantly improved total sickness score (p<0.005). Ginger is as effective as dimenhydrinate for treatment of with greater tolerability and lower incidence (13.3% vs. 40%) of side effects (p<0.001). Riebenfeld and Borzone, 1999 Sea sickness in passengers on a cruise ship n=60 (ages 10 77 years; mean age 31 7 months 500 mg, 1/2 hour before embarkation, 500 mg every 4 hours over a 48-hour period, or 100 mg of dimenhydrinate, 1/2 hour before embarkation 100 mg every 4 hours over a 48-hour period Schmid et al., 1994 Sea sickness in tourists on a whalewatching safari n=1,489 (ages 16 65 3 months Zintona Group 1: 500 mg, 2 hours prior to departure, 500 mg, during trip, if needed. Group 2: 500 mg, after dinner on evening before trip, 500 mg, 2 hours prior to departure Ginger showed equal potency to 7 common pharmaceutical drugs for sea and better effectiveness than scopolamine transdermal patch (p=0.14). As neither clinically relevant nor significant differences were found between products used, personal preference should be followed as to the medication taken as prophylaxis for seasickness. cohort, MA meta-analysis, MC multi-center, n number of patients, O open, OB observational, OL open label, OR odds ratio, P prospective, PB patient-blind, PC -controlled, 1

Kinetosis (Motion Sickness) Stewart et al., 1991 Motion sickness and gastric function PC, Cm Phase 1 n=8; Phase 2 n=8; Phase 3 n=4; Phase 4 gastric function, n=8 14 hours Phase 1: 500 mg or 1,000 mg ground root or 0.6 mg scopolamine HBr or on separate test days; Phase 2 One 1,000 mg fresh root capsule or Phase 3: 940 mg ground or placbo Phase 4: Two, 250 mg or Phase 1: ground root Phase 2: fresh ( prepared by Phase 3: ground Phase 4: 250 mg of partially inhibited tachygastria but did not enhance the EGG amplitude. Did not significantly alter gastric function during sickness or possess anti sickness activity. Grøntved et al., 1988 Seasickness in naval cadets unaccustomed to sailing n=80 (median age 17 4 hours 1g vs. Ginger significantly reduced tendency to vomit and experience cold sweats (p<0.05). No side effects reported in both groups. Grøntved and Hentzer, 1986 Vertigo and nystagmus (healthy who received caloric stimulation of the vestibular system) R, DB, CO, PC 6 days n=48 1 g/day Ginger significantly reduced the induced vertigo better than (p<0.05). No statistically significant action upon the duration or maximum slow phase velocity of nystagmus. Mowrey and Clayson, 1982 Motion sickness produced by a motor driven, tilted, revolving chair R, Cm, PC, SB n=36 volunteer subjects with self-rated extreme or very high susceptibility to sickness (ages 18 20 Single dose of 2 (940 mg total) Ginger is superior to both and dimenhydrinate (p<0.05) in preventing the gastrointestinal symptoms of experimentally-induced sickness in highly susceptible individuals. 31 minutes cohort, MA meta-analysis, MC multi-center, n number of patients, O open, OB observational, OL open label, OR odds ratio, P prospective, PB patient-blind, PC -controlled, 2

Nausea During Pregnancy Vutyavanich et Hypermesis al., 2001 gravidarum (women with nausea and vomiting in early pregnancy) FischerRasmussen et al., 1990 Hyperemesis gravidarum n=70 7 days 4 days R, DB, CO n=30 pregnant women admitted to hospital before 20 weeks of gestation with symptoms 2x/day (ages 18 39 One, 250 mg Fresh, baked capsule 4x/day root ground into powder Significant median change in nausea scores with post-therapy (p=0.014). Significant reduction in nausea scores with on day 4 of only treatment (p=0.0348). Significant improvement in patients subjective response with (p<0.001). No adverse effect with on pregnancy outcomes. One, 250 mg capsule 4x/day Ginger diminished or eliminated symptoms of hyperemesis gravidarum. Statistically significant preference for. Reduced degree of nausea and number of attacks of vomiting. No side effects observed. Four, 500 mg, or 1.25 mg droperidol, or vs. vs. droperidol IV No significant reduction in incidence of postoperative nausea and vomiting. Severity of nausea and frequency of vomiting within 24 hours were not statistically different with root or the combination of root and droperidol. Postoperative Nausea Vislyaputra et Gynecological al., 1998 diagnostic, Cm 24 hours n=120 (ages 20 40 Arfeen et al., 1995 Day case n=108 (ages 18 75 3 hours One-time dose before surgery of 10 mg diazepam (orally) plus either 1 2 (500 mg ea.) powdered or Blackmores Ltd. BP 1988 custom powdered vs. Ginger in doses of 0.5 or 1.0 g given with oral diazepam premedication one hour prior to surgery was found ineffective in reducing the incidence of postoperative nausea and vomiting. Incidence of nausea and vomiting increased slightly, but insignificantly (nausea, p=0.2; vomiting, p=0.15), with increasing dose of. Phillips et al., 1993 Day case R, P, DB, PC, Cm n=120 (ages >16 24 hours Two, 500 mg, or 10 mg Martindale Pharmaceuticals powdered vs. vs. Ginger similarily reduced incidence of nausea and vomiting as. Oral administration of 1 g of reduced incidence of nausea and vomiting by 50% and appears to be as effective as, 10 mg when given by mouth one hour before anesthesia. Ginger is an effective and promising prophylactic antiemetic without toxic effects, which may be especially useful in day case surgery. Bone et al., 1990 Major surgery, Cm 24 hours n=60 (ages 16 65 0.5 g or 10 mg injection or (brand not vs. vs. Statistically fewer recorded incidences of nausea for compared with (p<0.05). Numbers of incidences of nausea in vs. groups were similar. cohort, MA meta-analysis, MC multi-center, n number of patients, O open, OB observational, OL open label, OR odds ratio, P prospective, PB patient-blind, PC -controlled, 3

Cardiovascular PC Bordia et al., 1997 aggregation in n=60 patients with coronary artery disease with history of myocardial infarcation (76 months) 3 months 4 g daily for 3 months or single dose of 10 g vs. 5 g (2 x 2.5 g) fenugreek daily for 3 months vs. vs. fenugreek vs. in dose of 4 g/day did not affect ADP and epinephrine-induced platelet aggregation. However, single dose of 10 g powdered after 4 hours produced a significant reduction in platelet aggregation (p<0.05). Janssen et al., 1996 thromboxane production R, PC, multiple CO n=18 healthy (mean age 22 3 x 2 weeks 15 g daily raw root vs. 40 g daily stem Vanilla custard with either 15 g raw root or 40 g stem Daily treatment with either 15 g root or 40 g stem mixed in custard for 14 days did not affect maximum ex vivo platelet thromboxane B2 production (p=0.616). Lumb, 1994 function, CO n=8 healthy male 24 hours Single dose of 4 (2 g total) dried powder Dried power ( prepared by No significant differences in bleeding time, platelet count, or platelet aggregation. 2 g dried unlikely to cause platelet dysfunction when used therapeutically. Verma et al., 1993 aggregation induced by fatty diet (fed 100 g butter x 7 days) R, PC n=20 healthy males (ages 30 50 Four, 625 mg 2x/day with meals, 625 mg (prepared by Ginger significantly decreased platelet aggregation (p<0.001) when taken with fatty meals. Serum cholesterol and triglyceride levels remained unchanged from. Srivastava, 1989 Thromboxane synthesis CC, Cm n=12 5 g/day Raw fresh Ginger inhibited eicosanoid biosynthesis. Ginger consumption produced 37% inhibition (p<0.1) on TxB2 production in serum. Author/Year Altman and Marcussen, 2001 Subject Osteoarthritis (OA) of the knee, MC, PG n=247 men and women with OA of the knee (ages 18 6 weeks preceeded by washout period One, 255 mg capsule 2x/day or EV. EXT 77, (each capsule contains 255 mg extract from 2,500 4,000 mg dried and 500 1,500 mg dried galanga [Alpinia galanga] rhizomes) or Ginger extract produced greater reduction in the primary efficacy variable, knee pain on standing, compared with (63% vs. 50%; p= 0.048). Ginger extract also produced a greater response in the secondary efficacy variables compared with, when analyzing mean values: reduction in knee pain after walking 50 ft (15.1 mm vs. 8.7 mm on a visual analog scale; p=0.016), reduction in the Western Ontario and McMaster Universities OA composite index (12.9 mm vs. 9.0 mm on a visual analog scale; p=0.087). The researchers concluded that this highly purified and standardized extract statistically significantly reduced symptoms of OA of the knee. The extract had a moderate effect and a good safety profile with usually mild g.i. adverse events in 59 patients (45%) in the group compared to 21 (16%) in group. An accompanying editorial noted possible lack of effective blinding ( patients were told of s pungent taste), although the trial was otherwise well designed; nevertheless, the editorial notes s beneficial effects were small and inconsistent. Bliddal et al., 2000 Osteoarthritis R, PC, DB, CO, Cm n=56 (mean age 66 10 weeks 170 mg extract 2x/day or 400 mg ibuprofen 2x/day EV. EXT 33 ( extract) vs. ibuprofen vs. Statistically significant effect demonstrated by explorative statistical methods in the first period of treatment before cross-over, but not following crossover periods. Caution should be observed in the interpretation of a cross-over study of extract. The study concluded that 400 mg/day ibuprofen found to be more efficacious on pain level and function than 170 mg (p<0.0001).the 3-week period of therapy and the single dosage level of used may have been insufficient to discover all of s effects. Other cohort, MA meta-analysis, MC multi-center, n number of patients, O open, OB observational, OL open label, OR odds ratio, P prospective, PB patient-blind, PC -controlled, 4

Other (cont.) Meyer et al., 1995 O, Cm n=11 Not reported Single dose of three, 530 mg, 30 minutes prior to 8-MOP ingestion Extracorporeal chemotherapy (photopheresis) nausea associated with oral psoralen (8-MOP) therapy Significantly reduced nausea induced by psoralen (8-MOP) therapy when taken 30 minutes prior to 8-MOP ingestion. Did not affect 8-MOP absorption or therapeutic effectiveness. cohort, MA meta-analysis, MC multi-center, n number of patients, O open, OB observational, OL open label, OR odds ratio, P prospective, PB patient-blind, PC -controlled, 5