Background
Methods
Results
Included studies
Design
Participants
Interventions
Reference | Dose | Control | Duration | |
---|---|---|---|---|
Omega 3 fish oils | Cussons A J; Watts GF; Mori TA; Stuckey BGA. 2009 [34] | 4000 mg per day EPA 675 mg; DHA 1400 mg (Ocean nutrition® by Halifax, Nova Scotia, Canada) | Placebo Olive oil 4000 mg (Cardinal Health Australia, Vic Australia) | 8 weeks |
Mohammadi E; Rafraf M; Farzadi L; Asghari-Jafarabadi M; Sabour S. 2012 [43] | 4000 mg omega 3 (EPA 720 mg; DHA 480 mg) (Good Health Company, USA) | Placebo liquid paraffin 2000 mg in four capsules (Zihravi Pharma, Iran) | 8 weeks | |
Vargas LM; Almario RU; Buchan W; Kim, K; Karakas SE. 2011 [50] | 3500 mg (EPA: 2450 mg; DHA: 1210 mg) (Nordic Naturals Watsonville, California) | Placebo (soybean oil 3500 mg) (Nordic Naturals, Watsonville California) | 6 weeks | |
Chromium | Lucidi SR; Thyer AC; Easton CA; Holden AEC; Schenken RS; Brzyski RG. 2009 [42] | Chromium picolinate 200mcg per day (manufacturer not reported) | Placebo (type or manufacturer was not reported) | 16 weeks |
Selenium | Hosseinzadeh F; Hosseinzadeh-Attar M; Yekaninejad J; Saeed M; Rashidi B. 2016 [39] | Selenium 200mcg per day (Nature Made Pharmaceutical Company, California USA) | Placebo (type not specified) (Roshd Pharmaceutical Incubation Centre, Tehran University, Iran) | 12 weeks |
Razavi M; Jamilian M; Kashan Z; Fakhrieh HZ; Mohseni M; Ghandi Y; Bagherian T; Asemi Z 2015 [47] | Selenium 200mcg plus Metformin 1500 mg per day (Nature Made Pharmaceutical Company, California USA) | Placebo (cellulose) plus Metformin 1500 mg per day(Barij Essence Pharmaceutical Company, Iran) | 8 weeks | |
Vitamin D | Ardibilli HR; Gargari BG; Farzadi L. 2012 [31] | Vitamin D. Three oral treatments of 50,000 IU per 20 days (D-vitin® by Zahravi Pharma Company, Iran) | Placebo, One tablet every 20 days (Zihravi Pharma Company, Iran) | 2 months |
Raja-Khan N; Shah J; Stetter CM; Lott MEJ; Kunselman AR; Dodson WC; Legro RS. [45] | Vitamin D 12000 IU per day(Cholecalciferol in soy lecithin) (Maximum D3® by BTR Group, USA) | Placebo per day (soy lecithin without cholecalciferol) (BTR Group, USA) | 12 weeks | |
Vitamin D plus Calcium | Rashidi R; Haghollahi F; Shariat M; Zayerii F. 2009 [46] | Calcium 1000 mg + vitamin D 400mcg per day (Cal D tablets by Tehran Derou, Iran) | Metformin 500 mg, three times per day (Minoo Darou, Iran) | 12 weeks |
Tehrani, HG; Mostajeran F; Shahsavari S. 2014 [49] | Calcium 1000 mg (Osvah Pharmaceuticals) Vitamin D 50,000 IU per fortnight (Zahravi Pharmaceutical company) | Metformin (Sobhan darou pharmaceutical company) | 16 weeks | |
Vitamin B complex | Kilicdag EB; Bagis T; Tarim E; Aslan E; Erkanli S; Simsek E; Haydardedeoglu B; and Kuscu E. 2005 [52] | B1: 500 mg; B6: 500 mg; B12: 2000mcg + Metformin 1700 mg/day, (Apikobal® by Santa Farma Turkey) (Glugophage® by Merke, Turkey) | Metformin 1700 mg/day (Glucophage® by Merke Turkey) | 12 weeks |
Inositol (vitamin B8) | Artini PG; Di Berardino OM; Papini F; Genazzani AD; Simi G; Ruggiero M; Cela V. 2013 [30] | Inositol 2 g and folic acid 200 mg plus folic acid 200mcg (Inofert® by Ital Pharmaco, Milano, Italy) | Folic acid 400mcg daily (Inofert® by Ital Pharmaco, Milano, Italy) | 12 weeks |
Costantino D: Minozzi G; Minozzi F; Guaraldi C. 2009 [33] | Inositol 4 g + folic acid 400mcg (Inofolic®) | Folic acid 400mcg (Fertifol®) | 12–16 weeks | |
Dona G; Sabbadin C; Fiore C; Bragadin M; Giorgino FL; Ragazzi E; Clari G; Bordin L; Armanini D. 2012 [35] | Inositol 1200 mg/day as powder, pre-dosed presented in sachets dissolved in water (manufacturer not reported) | Placebo (matched powder type or manufacturer not reported) | 12 weeks | |
Gerli M; Mignosa; Di Renzo GC. 2003 [36] | Inositol 200 mg (Gestosan®LO.LI. Pharma, Rome, Italy) | Placebo matched to Gestosan®. (Type or manufacturer not reported) | 20 weeks | |
Gerli E; Papaleo A; Ferrari GC; Di Renzo GC. 2007 [37] | Inositol 4 g plus folic acid 400mcg (Inofolic®LO.LI. Pharma, Rome, Italy) | Folic acid 400mcg (manufacturer not specified) | 20 weeks | |
Iuorno MJ; Jakubowicz DJ; Baillargeon JP; Dillon P; Gunn RD; Allan G; Nestler JE 2002 [40] | Inositol (chiro) 600 mg (INS-1® by Insmed pharmaceuticals, Richmond, Virginia, USA) | Placebo (type or manufacturer not reported) | 6–8 weeks | |
Jamilian M; Farhat P; Foroozanfard F; Ebrahimi FA; Aghadavod E; Bahmani F; Badehnoosh B; Jamilian H; Asemi Z [54] | Inositol 4 g + folic acid 400mcg (LO.LI. Rome, Italy) | Metformin (Tehran Darou Pharma. Tehran, Iran) | 12 weeks | |
Nestler JE; JakubowczDJ; Reamer P; Gunn R; Allan G. 1999 [44] | Inositol 1200 mg labelled according to subject number (INS-1® by Insmed pharmaceuticals, Virginia, USA) | Placebo Labelled and packaged at the same time as inositol. Type not reported (Insmed pharmaceuticals USA) | 6–8 weeks | |
Camellia sinensis
| Chan CW; Marcel Koo MWL; Ng EHY; Tang OS; Yeung WSB, Ho P-C. 2006 [32] |
Camellia sinensis tea infused in boiled water for 30 mins, freeze dried and encapsulated. Epigallocatechin (EGCG) standardised to 373.92 mg ± 20.57, equivalent to 1.5 cups of tea. | Placebo capsules Identical in appearance. Type or manufacturer not specified. | 12 weeks |
Cimicifuga racemosa
| Shahin AY; Mohammed SA. 2014 [48] | 120 mg Cimicifuga extract plus clomiphene 150 mg on menstrual cycle days 3–7, trigger injection (10,000 IU, intramuscular Human Chorionic Gonadotropin) and progesterone supplementation (50mcg per day for two days following trigger injection) (Klimadynon® Bionorica, Neumarkt, Germany) (Pregnyl, Organon, Holland, The Netherlands) | Clomiphene, 150 mg per day administered on menstrual cycle days three to seven, a trigger injection (HCG) and progesterone support (50mcg per day for two days following trigger injection). (Pregnyl, Organon, Holland, The Netherlands) | Three alternate menstrual cycles |
Cinnamomum sp.
| Wang JG; Anderson RA; Graham GM; Chu MC 2007 [51] |
Cinnamomum sp. 1000 mg per day (Integrity Nutriceuticals, Sarasota, Florida USA) | Placebo (Type or manufacturer were not reported) | 8 weeks |
Kort DH; Lobo RA. 2014 [41] |
Cinnamomum sp. 1500 mg per day (Cinnulin PF Integrity Nutraceuticals International, USA) | Placebo (identical) (Integrity Nutraceuticals International) | 6 months | |
Mentha spicata
| Grant, P. 2009 [38] | Tea bags standardised content of dried Mentha spicata leaves. Uniform instructions for preparation provided to participants | Chamomile tea uniform preparation instructions provided. | 30 days |
Outcomes
Risk of bias for included studies
Effects of interventions
Nutritional supplements for PCOS
Treatment n*(number of effects)/N | Control n* (number of effects)/N | Number of RCTs Heterogeneity (I2, p value) | Treatment effect MD or RR | 95% CI |
p value | |
---|---|---|---|---|---|---|
Hyperandrogenism | ||||||
Free testosterone nmol/l | 55 | 51 | 0%, p = 0.94 | MD −0.02 | −0.10 to 0.06 | 0.62 |
Total testosterone
**
nmol/l | 103 | 89 | 32%, p = 0.0009 | MD 0.99 | −1.54 to −0.44 | < 0.001 |
Androstenidione nmol/l | 73 | 59 | 0%, p = 1.0 | MD 3.59 | −4.62 to −2.55 | < 0.001 |
Sex hormone binding globulin (SHBG) nmol/l | 55 | 67 | 0%, 0.50 | MD 40.67 | 25.83 to 55.50 | < 0.001 |
Modified Ferriman Gallwey score | 30 | 30 | 1 [54] | MD 0.90 | −1.18 to 2.98 | 0.40 |
Reproduction | ||||||
Number of days to ovulation (number of days) | 181 | 194 | 0%, p = 0.90 | MD 17.7 | −31.4 to −4.1 | 0.01 |
Ratio of luteal week to total trial luteal weeks: total trial weeks | 166/697 | 140/1000 | 0%, p = 0.90 | RR 1.7 | 1.39 to 2.08 | < 0.001 |
Number of ovulations | 25/32 | 8/32 | 0%, p = 0.95 | RR 3.13 | 1.68 to 5.83 | 0.001 |
Number of women who did not ovulate | 16/181 | 34/194 | 0%, p = 0.95 | RR 0.5 | 0.29 to 0.86 | 0.01 |
Pregnancy | 18/71 | 6/63 | 0%, p = 0.95 | RR 2.78 | 1.19 to 6.5 | 0.02 |
Live births | 8/25 | 3/25 | 1 [36] | RR 2.67 | 0.80 to 8.90 | 0.11 |
FSH mIU/l | 25 | 25 | 1 [36] | MD 1.4 | −1.63 to −1.17 | 0.001 |
LH mIU/l | 25 | 25 | 1 [36] | MD 3.5 | −4.9 to −2.1 | 0.001 |
FSH:LH ratio | 25 | 25 | 1 [36] | MD 0.4 | −0.68 to −0.12 | 0.006 |
Anthropometric | ||||||
BMI
***
| 48 | 38 | MD −0.30 | −1.10 to 0.50 | 0.46 | |
57 | 57 | I2 31%, p = 0.24 | MD 0.40 | −0.07 to −0.86 | 0.86 | |
Waist to hip ratio | 32 | 32 | 0%, p = 0.32 | MD −0.02 | −0.03 to −0.01 | 0.01 |
Metabolic hormones | ||||||
Fasting glucose mmol/l | 73 | 59 | 0%, P = 0.52 | MD 1.17 | −1.72 to – 0.63 | < 0.001 |
Fasting insulin μU/ml | 73 | 59 | 18%, p = 0.30 | MD 2.7 | −3.9 to −1.5 | < 0.001 |
HOMA-IR
****
| 25 | 25 | 1 [36] | MD −1.30 | −1.60 to −1.00 | < 0.001 |
18 | 8 | 1 [37] | MD −0.60 | −0.89 to – 0.30 | < 0.001 | |
Risk factors | ||||||
Cholesterol mmol/l | 32 | 32 | 27%, p = 0.24 | MD 0.56 | −1.07 to −0.04 | 0.04 |
Triglycerides mg/dL | 32 | 32 | 8%, p = 0.30 | MD 31.6 | −61.1 to −2.0 | 0.04 |
HDLmg/dL | 22 | 22 | 1 [22] | MD 0 | −4.73 to 4.73 | 1.0 |
LDL mg/dL | 22 | 22 | 1 [22] | MD −2.0 | −13.7 to 9.7 | 0.74 |
CRP | 30 | 30 | 1 | MD −2.2 | −3.57 to −0.83 | < 0.01 |