Table 5.

Reviews and experimental studies investigating the effects of traditional, complimentary and integrative medicine on polycystic ovary syndrome outcomes

Intervention	N study design	N studies; N participants	Main findingsa	References
Vitamins
B-group vitamins (B1, B6, and B12)	1 RCT	1; 60	Counteracted Hcy-increasing effect of metformin ↔ HOMA-IR	Kilicdag et al. 2005 [198]
Folate (vitamin B9)	2 RCT	2; 150	↓ Hcy [199, 200], HOMA-β [199], HOMA-IR [200], FINS [200], TC:HDL-C ratio [200], CRP [199], MDA [199] ↑ TAC [199], GSH [199]	Bahmani et al. 2014 [199] Asemi et al. 2014 [200]
Inositols (vitamin B8)	1 SR/MA	9 RCT; 496	↓ HOMA-IR; ↓ FINS ↔ androstenedione, T, SHBG	Unfer et al. 2017 [191]
Vitamin D	2 SR/MA	23 RCT; 1367	↓ TC [201], LDL [201], TAG [201], HOMA-IR [203], FGL [203], FINS [203], VLDL-C [203] ↑ QUICKI [203] ↔ HDL-C [201]	Guo et al. 2020 [201] Gao et al. 2021 [203]
Vitamin E	1 RCT	1; 86	↓ FGL, HOMA-IR, SHBG, T (only when combined with coenzyme Q10)	Izadi et al. 2019 [205]
Vitamin K	1 RCT	1; 79	↓ WC, FBM, FINS, HOMA-IR, HOMA-β, TAG, FAI, DHT ↑ skeletal muscle mass, SHBG, QUICKI	Tarkesh et al. 2020 [206]
Vitamin-like supplements
Soy isoflavones	1 pilot pre-post prospective	1; 12	↓TC, LDL-C, LDL-C:HDL-C ratio, TAG	Romualdi et al. 2018 [208]
Carnitine (L-Carnitine)	1 RCT	1; 60	↓ MDA, MDA:TAC ratio ↑ TAC	Jamilian et al. 2017 [211]
Alpha-lipoic acid	2 pre-post prospective	2; 52	↓ BMI [214], IR [213], LDL-C [213], TAG [213], ovarian cysts [214] ↑ progesterone [214]	Masharani et al. 2010 [213] Cianci et al. 2015 [214]
Minerals
Vitamin D and calcium	1 SR/MA	6 RCT; 480	↓ FINS, HOMA-IR, FGL, T, TAG, VLDL-C, TC, LDL-C, hirsutism ↑ QUICKI, menstrual regularity	Shojaeian et al. 2019 [219]
Zinc	1 SR	5 RCT; 285	↓ HOMA-IR, HOMA-β, FINS, MDA, CRP, T, FSH, TC, LDL-C, TAG, VLDL-C, DHEAS ↑ TAC, QUICKI	Nasiadek et al. 2020 [220]
Selenium	1 SR	5 RCT; NR	↓ IR, CRP and MDA in some RCTs ↔ (or inconsistent findings) BMI, BW, FGL, blood lipids, androgens, acne, hirsutism	Hajizadeh-Sharafabad et al. 2019 [221]
Magnesium	1 SR	3 RCT; 156	Serum magnesium concentrations were associated with IR but supplementation had inconsistent effects	Hamilton et al. 2019 [222]
Chromium Picolinate	2 SR/MA	11 RCT; 702	↓ BMI [223], FINS [223], IR [224], T [223] ↑ T [224] ↔ BMI [224], FG [223]	Fazelian et al. [223] Tang et al. [224]
Other supplements
Omega-3 fatty acids	1 SR/MA	9 RCT; 591	↓ HOMA-IR, TC, LDL-C and TAG. ↔ FINS, FGL, BMI, androgens	Yang et al. 2018 [225]
N-acetyl-cysteine	1 SR/MA	8 RCTS; 910	↑ rates of pregnancy and live births	Thakker et al. 2015 [226]
Coenzyme Q10	1 RCT	1; 60	↓FGL, FINS, HOMA-IR, HOMA-β, , TC, LDL-C ↑ QUICKI	Samimi et al. 2017 [227]
Probiotics	2 SR/MA	19 RCT; 1261	↓ FINS [228], TG [228], VLDL-C [228], FAI [229] ↑QUICKI [228], SHBG [229] ↔ BW [228], FGL [228], HOMA-IR [228], TC [228], LDL-C [228], HDL-C [228], CRP [228], DHEA [228], T [229]	Liao et al. 2018 [228] Shamasbi et al. 2020 [229]
Quercetin	1 SR	3 RCT; 246	Some improvement in adiponectin-mediated IR ↔ BW, WHR	Pourteymour et al. 2020 [232]
Resveratrol	1 SR/MA	3 RCT; 131	↓ T ↑ high-quality oocytes and embryos ↔ BMI, blood lipids, FGL, pregnancy rate	Shojaei-Zarghani et al. 2021 [233]
Melatonin	1 SR/MA	2 RCT and 1 cell culture; 640	↑ pregnancy rates in assisted reproductive technology	Hu et al. 2020 [172]
Herbal medicine
Cinnamon	1 SR/MA	5 RCT; 448	↓HOMA-IR, TC, LDL, FGL, FINS ↑ HDL ↔ BW	Heydarpour et al. 2020 [260]
Curcumin	2 RCT	2; 118	↓ FGL [238], DHEA [238] ↔ FGL [239], FINS [238], blood lipids [239], IR [239]	Heshmati et al. 2021 [238] Sohaei et al. 2019 [239]
Sage	1 RCT	1; 70	↓ BW, BMI, WC, FGL, FINS, HOMA-IR, QUICKI ↔ WHR	Amini et al. 2020 [241]
Fennel and dry cupping	1 RCT	1; 55	↓ BMI, cycle length	Mokaberinejad et.al. 2019 [243]
Licorice	1 pre-post prospective 1 quasi-experimental	2; 41	↓ T [245] Reduce prevalence of side effects related to the diuretic activity of spironolactone [246]	Armanini et al. 2004 [245] Armanini et al. 2007 [246]
Spearmint, ginger, citrus and cinnamon	1 RCT	1; 60	↓ HOMA-IR, FINS, FGL	Ainehchi et al. 2019 [251]
Chinese herbal medicine	1 SR/MA	4 RCT; 414	↑ pregnancy rate when taken with clomiphene (versus clomiphene alone) ↔ pregnancy rate when taken alone (versus clomiphene alone) Insufficient evidence for subfertility	Zhou et al. 2016 [235]
Other TCIM
Acupuncture	2 SR/MA	31 RCT; 2846b	↓ BMI [255], LH [254], T [254] ↑ menstrual regularity [254] ↔ FGL [255], FINS [255], live birth [254], pregnancy rate [254], ovulation [254]	Wu et al. 2020 [254] Qu et al. 2016 [255]
Yoga	2 SR [120, 257] 1 SR/MA [258] 1 RCT [259]	21; 1059 a	↓ WC [259], HC [259], HOMA-IR [120], FGL [258], FINS [258], T [120], LH [120], DHEA [120], androstenedione [120], adiponectin [120], clinical hyperandrogenism [259] ↑ menstrual regularity [258], menstrual frequency [257] ↓ stress and anxiety [257]	Shele et al. 2020 [120] Thakur et al. 2021 [257] Anita et al. 2021 [258] Mohseni M et al. 2021 [259]

Abbreviations: ↑ significant increase (P ≤ 0.05), ↓ significant decrease (P ≤ 0.05), ↔ no significant change, BMI Body mass index, BW Body weight, DHEAS Dehydroepiandrosterone-sulfate, DHT Dihydrotestosterone, FGL Fasting glucose level, FINS Fasting insulin level, FBM Fat body mass, FSH Follicle stimulating hormone, FT Free testosterone, GSH Glutathione, HC Hip circumference, Hcy Homocysteine, HOMA-IR Homeostatic assessment of insulin resistance, HDL-C High density lipoprotein cholesterol, IR Insulin resistance, QUICKI Quantitative insulin sensitivity check index, QoL Quality of life, MDA Malondialdehyde, MA Meta-analysis, NR Not reported, OCP Oral Contraceptive Pill, RCT Randomised controlled trial, SHBG Sex hormone binding globulin, SR Systematic review, T Testosterone, TAC Total antioxidant capacity, TC Total cholesterol, TAG Triglycerides, TCIM Traditional, complimentary and integrative medicine, VLDL-C Very low density lipoprotein cholesterol, WC Waist circumference, WHR Wait hip ratio

^aSummarises commonly used measures in PCOS research and does not report on all measured outcomes. For prospective pre-post studies significant changes from baseline are reported. For RCTs significant changes between intervention(s) and control and reported

^bNot all participants are included in the findings reported here (e.g. where findings from subgroup analysis are reported)