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. 2021 Aug 25;13(9):2938. doi: 10.3390/nu13092938

Table 2.

Effect of supplementation on clinical and laboratory features in human subjects.

Supplement Dosage Hormonal Changes Changes in Lipid Profile Changes in Oxidative Stress Markers Genes Affected
Folate [22] 5 mg/d for 8 weeks ↓ Plasma Hcy, MDA, serum hs-CRP;
↑ plasma TAC and total GSH levels
Omega-3 fatty acids and vitamin E [25] Co-supplementation
for 12 weeks
↓ Serum TGA, VLDL, LDL- and total-/HDL cholesterol in PCOS subjects ↑ Plasma TAC levels, ↓ malondialdehyde levels Gene expression of Lp(a) and Ox-LDL
Flaxseed oil omega-3 fatty acids [24] Supplementation
for 12 weeks
↑ mFG scores Beneficial effects on insulin metabolism, serum triglycerides, VLDL-cholesterol and hs-CRP levels
Fish oil omega-3 fatty acid [25] Supplementation for 12 weeks Beneficial effects on mental health parameters, total testosterone, hirsutism Effective on insulin markers ↓ Inflammatory markers and oxidative stress
Vitamin E [26] 100 mg/d No significant differences of ovulation rate, clinical pregnancy rate and ongoing pregnancy rate ↓ Oxidative stress
Alpha lipoic acid [27] 600 mg twice daily for 16 weeks No improvement in serum oxidative stress markers
Carnitine and chromium co-supplementation [28] 1000 mg/d carnitine plus 200 mg/d chromium as chromium picolinate for 12 weeks ↓ Total testosterone and hirsutism ↓ Malondialdehyde (MDA) levels and higher total antioxidant capacity (TAC) ↑ Gene expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a)
Melatonin supplementation [45] 5 mg melatonin supplements ↓ Hirsutism, serum total testosterone ↓ Malondialdehyde (MDA) levels,
↑ plasma total antioxidant capacity (TAC) levels and total glutathione (GSH)
↓ Gene expression of IL-1, (TNF-α)
Curcumin supplementation [46] 1500 mg/d Curcumin for 12 weeks ↑ Serum activity of GPx ↑ SIRT1 gene expression
Selenium supplementation [30] 200 μg selenium per day for 8 weeks ↑ Pregnancy rate,
↓ Alopecia and acne,
↓ Serum (DHEAS), hirsutism (modified Ferriman–Gallwey scores)
Probiotic and selenium co- supplementation [32] 8 × 109 CFU/d probiotic
200 μg/d
↓Total testosterone, hirsutism ↓ MDA levels,
↑ TAC and GSH levels
Selenium supplementation [29] 200 mcg/d for 8 weeks ↓ Serum triglycerides and VLDL-C concentrations ↓ Serum insulin levels, homeostasis model of assessment-insulin resistance (HOMA-IR), (HOMA-B);
↑quantitative insulin sensitivity check index (QUICKI)
Soy isoflavones [34] 50 mg/d soy isoflavones for 12 weeks ↓ Circulating serum levels of insulin and HOMA-IR,
↑quantitative insulin sensitivity check index,
↓ free androgen index and serum triglycerides,
↑ plasma total glutathione,↓malondialdehyde
↓ Free androgen index and serum triglycerides ↓ Circulating serum levels of insulin and HOMA-IR,
↑ Quantitative insulin sensitivity check index,
↑ Plasma total glutathione
↓Malondialdehyde levels
Synbiotic supplementation [35] Synbiotic supplements containing Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum ↑ (SHBG), plasma NO,
↓ modified Ferriman–Gallwey (mFG) scores and serum hs-CRP
Dietary soy [36] 0.8 g protein kg−1 body weight (35% animal proteins, 35% soy protein and 30% vegetable proteins) ↓ Total testosterone,
↓ triglycerides
↓Triglycerides, body mass index (BMI), fasting plasma glucose, insulin and insulin resistance; ↑ quantitative insulin sensitivity check index ↓ MDA, ↑ NO and GSH
Probiotic supplementation [47] Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum (2 × 109 CFU/g each) for 12 weeks ↑ Serum SHBG and plasma TAC;
↓ serum total testosterone, mFG scores, serum hs-CRP and plasma MDA
↑ Plasma TAC,
↓ plasma MDA
Vitamin D-K-calcium co-supplementation [38] 200 IU vitamin D, 90 μg vitamin K plus, 500 mg calcium supplements for 8 weeks ↓ Serum-free testosterone,
↓ luteinizing hormone
↑ Plasma TAC,
↓ plasma MDA
Vitamin D [48] 4000 IU vitamin D or 1000 IU of vitamin D for 12 weeks ↓ Total testosterone, free androgen index (FAI), hirsutism;
↑ mean change in SHBG
↑ Total antioxidant capacity (TAC)
Vitamin D [49] 50,000 IU Vitamin D ↓ FPG, insulin, HOMA-IR, estimated B cell function;
↑ quantitative insulin sensitivity check index
↓ Plasma malondialdehyde (MDA) levels
Vitamin D and [40] 1000 IU vitamin D3 plus 1000 mg Vitamin E ↓ Triglycerides, very low-density lipoprotein (VLDL) cholesterol levels ↑ Serum 25(OH) D and plasma GSH,
↓ MDA
Vitamin D and omega-3 co-supplementation [41] 50,000 IU vitamin D every 2 weeks plus 2000 mg/d omega-3 fatty acid from fish oil ↓ Serum total testosterone levels; ↑ Beck depression inventory, general health questionnaire scores and depression anxiety and stress scale scores ↓ Serum hs-CRP and MDA,
↑ TAC compared with the placebo
↓ Gene expression of (IL-1) and (VEGF)
Vitamin D and probiotic co-supplementation [42] 50,000 IU vitamin D and 8 × 109 CFU/d probiotic every 2 weeks ↓ Total testosterone ↓ MDA,
↑ TAC and GSH
MitoQ10 and Vitamin D3 [43] ↓ Estradiol, progesterone, FSH, LH, LH/FSH ↓ MDA and SOD ↓ mRNAs of 3β-HSD, Cyp19a1, Cyp11a1, StAR, Keap1, HO-1 and Nrf2

Abbreviations: FSH: follicle-stimulating hormone, LH: luteinizing hormone, MDA: malondialdehyde, SOD: superoxide dismutase, TAC: total antioxidant capacity, GSH: glutathione, (hs-CRP): high-sensitivity C-reactive protein, (25(OH) D): 25-hydroxyvitamin D, HOMA-IR: homeostasis model of assessment-IR, VLDL: very low-density lipoprotein, SHBG: sex hormone binding globulin, FAI: free androgen index, FPG: fasting plasma glucose, mFG: modified Ferriman–Gallway, TGA: triglycerides, NO: nitric oxide, Hcy: homocysteine. ↓ depressed, ↑ elevated.