Nutritional support and dietary interventions for women with polycystic ovary syndrome

Figures & data

Table 1 Effects of nutritional support and dietary interventions for women with PCOS

Study	Age (years) BW category (kg/m^2)	Duration and design of dietary intervention	Sample size	Description of groups	Dietary intervention	Clinical outcome measures
Dietary interventions with varying macronutrient composition and dietary patterns
Marzouk and Sayed Ahmed^Citation77	17–24 36.0±4.7/35.8±4.8	6 months RCT	60	Weight loss group	Deficit of 500 kcal/day 15–20% PRO 50–55% CHO 30% FAT	Significant reduction: BMI (−2.8 kg/m^2) WC (−7.8 cm) Hirsutism (modified FG score, −4.2)
				Control group	15–20% PRO 50–55% CHO 30% FAT
Wong et al^Citation86	15.4±1.3/16.3±2.2 36.2±5.3/33.9±4.7	6 months RCT	16	LGL diet	20% PRO 45% CHO 35% FAT low-GI sources of carbohydrates	Decreased in both groups: BMI percentile (−1.7±0.7) Body fat percentage (−1.0±0.7%) Trunk fat (−1.1 ±0.7 kg)
				LGL diet	20% PRO 55%CHO 25% FAT	The decrease in BMI percentile was greater for the LF group (−2.0±0.6) compared to LGL group (−0.4±0.1)
Barr et al^Citation95	31.5±6.9 29.0±5.9	36 weeks Nonrandomized clinical trial	21	Control phase (weeks 0–12) LGI dietary intervention phase (weeks 12–24)	Following their habitual diet Replace high-GI and medium-GI foods with LGI foods	The LGI diet resulted in: Increased insulin sensitivity Decreased NEFAs Small reduction in HDL
				Follow-up phase (weeks 24–36)	No dietary intervention or support
Mehrabani et al^Citation83	28.5±5.2/30.5±6.4 31.1±4.6/31.9±4.0	3 months RCT	49	CHCD	Deficit of 500–1000 kcal 15% PRO 55% CHO 30% FAT	Both hypocaloric diets led to equal changes in: BW (CHCD: −3.3±0.62%, MHCD: −4.1 ±0.58%) LDL-C (CHCD: −23.7± 13.8%, MHCD: 25.5± 10.5%) DHEAS (CHCD: −32.0±8.9 ng/mL, MHCD: −42.1±16.1 ng/mL) SHBG (CHCD: 10.6±4.1 nmol/L, MHCD: 8.8±2.8 nmol/L) MHCD induced concomitant reductions in: Insulin (−3.6±0.7 mIU/L) HOMA-IR (−0.8±0.2) hsCRP (−0.9±0.4 mg/L)
				MHCD	Deficit of 500–1000 kcal 40% CHO low and medium GL 30% PRO 30% FAT Limitation of high glycemic foods
Marsh et al^Citation79	31.0±0.7/29.3±0.8 34.3± 1.0/34.7±0.9	12 months or until they achieved a 7% weight loss	96	LF, LGI diet	23% PRO 50% CHO 27% FAT	LGI diet improved post-OGTT insulin sensitivity Subjects on LGI diet who were prescribed metformin therapy achieved greater improvements in insulin sensitivity compared to those on LGI diet not on metformin More women who consumed the LGI diet showed improved menstrual cyclicity (95% compared to 63%) Serum fibrinogen concentrations showed significant differences between diets (LGI: −0.2±0.1 g/L compared to CHD: 0.2±0.1 g/L)
				LF CHD	23% PRO 50% CHO 27% FAT
Sørensen et al^Citation87	27.7±5.5/28.4±5.8 30.6±7.8/30.5±8.5	6 months RCT	27	HP diet	>40% PRO <30% CHO 30% FAT Ad libitum diet	Compared to SP, HP resulted in significantly greater decreases in: BW (−4.4 kg)
				SP diet	<15% PRO >55% CHO 30% FAT Ad libitum diet	Fat mass (−4.3 kg) WC (−3.7 cm), but both diets equally decreased Glucose (HP: 5.2 mmol/L, SP: 5.4 mmol/L) Between the two groups, there were no significant differences in changes of: SHBG Total and free testosterone C-peptide
Toscani et al^Citation88	22.72±5.68 29.35±5.74	8 weeks RCT	40	HP diet	30% PRO 40% CHO 30% FAT 20–30 kcal × BW/day	Decreased significantly after both diets in both groups: BW BMI WC Body fat % Sum of trunk skinfolds No changes in lipid profile with either diet. Total testosterone decreased in both PCOS and controls, independently of diet composition
				NP diet	15% PRO 55% CHO 30% FAT 20–30 kcal × BW/day
Kasim-Karakas et al^Citation89	18–45 38.9±1.6/35.4±1.8	2 months RCT	24	PRO: deficit of 450 kcal/day (energy intake was reduced by 700 kcal) plus a 240-kcal supplement containing whey PRO Simple sugar: deficit of 450 kcal/day (energy intake was reduced by 700 kcal) plus a 240-kcal supplement containing simple sugars	1379 kcal/day 33.7% PRO 39.5% CHO 26.2% FAT	The PRO group lost more: BW (–3.3±0.8 kg vs –1.1 ±0.6 kg) Fat mass (–3.1 ±0.9 kg vs −0.5±0.6 kg) The PRO group had greater decreases in: Serum cholesterol (−33.0±8.4 mg/dL vs −2.3±6.8 mg/dL) HDL (–4.5± 1.3 mg/dL vs −0.4± 1.3 mg/dL) Apolipoprotein B (−20±5 mg/dL vs 3±5 mg/dL) There were no significant changes between the two groups in fasting glucose, insulin, HOMA, HbAlc, TGs and hs-CRP
					1352 kcal/day 16.6% PRO 56.7% CHO 25.9% FAT
Mavropoulos et al^Citation85	34.5 38.5	6 months Nonrandomized clinical trial without a control group	5	LCKD (≤20 g CHO/day)	Diet included unlimited consumption of animal foods (meat, chicken, turkey, other fowl, fish, shellfish), cheeses (up to 4 and 2 ounces per day) unlimited eggs, nonstarchy vegetables (two cups per day), and limited intake of starchy vegetables (one cup per day)	Significant reductions from baseline to 24 weeks with the LCKD in: BW (−12%) Percent-free testosterone (−22%) LH/FSH ratio (−36%) Fasting insulin (−54%)
Stamets et al^Citation42	29±4/26±4 38±4/37±5	1 month RCT	26	HP energyrestricted diet (1000-kcal deficit per day) High-carbohydrate energyrestricted diet (1000-kcal deficit per day)	30% PRO 40% CHO 30% FAT	Significant BW loss with both diets: HP (−3.7±1.9 kg) High-carbohydrate (−4.4± 1.5 kg) No differences between diets on a variety of measures (circulating androgens, measures of glucose metabolism, leptin) The effects of a hypocaloric diet per se showed significant changes and reductions in: DHEAS (161 ng/mL) Fasting insulin (5 mIU/L) 3-h OGTT AUC for insulin (−5.823 mIU/L×min) Fasting leptin (−11 ng/mL) 3-h OGTT AUC for leptin (−1.854 mIU/L×min) Total cholesterol (−22 mg/dL) LDL-C (−12 mg/dL)
					15% PRO 55% CHO 30% FAT
Moran et al^Citation41	33±0.84 37.4+1.24	16 weeks (12 weeks of energy restriction, followed by 4 weeks of weight maintenance) RCT	28	LP: 15% PRO 55% CHO 30% FAT HP: 30% PRO 40% CHO 30% FAT	Isocaloric diets energy-restricted diet (6000 kJ/day) was prescribed for 12 weeks, followed by a weight maintenance diet for the final 4 weeks with the same dietary composition in both phases plus advice for weekly exercise	Both diets resulted in decreased: BW (−7.7±0.7 kg) Total fat mass (−14.4%) Total lean mass (−3.4%) Abdominal fat (−12.5%) Total cholesterol (−8.8%) TGs (−12.5%) LDL-C (−9.8%) Fasting insulin (−20%) HOMA (−9%) The LP diet decreased HDL-C (−10%) No association between dietary composition and reproductive clinical parameters
Phy et al^Citation96	29.8±4.0 38.3±5.5	2 months Nonrandomized clinical trial without a control group	24	Ad libitum low starch/low dairy diet	Participants were instructed to eat animal PRO (meat and poultry), fish and shellfish, eggs, nonstarchy vegetables, low-sugar fruits (berries, apples, oranges, plums, etc), avocados, olives, nuts and seeds and oils (olive and coconut)	Significant reductions in: BW (−8.61 ±2.34 kg) BMI (−3.25±0.88 kg/m^2) WC (−8.4±3.1 cm) WHtR (−0.05±0.02 inches) Fasting insulin (−17.0± 13.6 mIU/L) 2-hour insulin (−82.8± 177.7 mIU/L) HOMA-IR (−1.9± 1.2) Total testosterone (−10.0± 17.0 ng/dL) Free testosterone (−1.8 pg/dL) FG scores (2.1 ±2.7 points)
Foroozanfard et al^Citation105	27.1 ±4.7 32.3±4.6	3 months RCT	53	Low-calorie DASH diet	Calorie-restricted (350–700 kcal less) 16–18% PRO 52–55% CHO 30% FAT (rich in fruits, vegetables, whole grains, LF dairy products and low in saturated fats, cholesterol, refined grains and sweets)	Adherence to the DASH diet, compared to the control diet, resulted in significant decreases in: BW (−4.3± 1.4 vs -3.2± 1.9 kg) BMI (−1.6±0.5 vs -1.2±0.7 kg/m^2) AMH (−1.1±3.1 vs +0.3±0.7 ng/mL) Insulin (−25.2±51.0 vs -1.2±28.8 pmol/L) HOMA-IR score (−0.9±2.0 vs -0.1±1.0) FAI (−0.03±0.09 vs +0.06±0.21) Malondialdehyde levels (−0.5±0.4 vs +0.2±0.3 μmol/L) Significant increases in: Quantitative insulin sensitivity check index (+0.01±0.03 vs -0.004±0.01) SHBG (+3.7±8.5 vs -1.5±7.2 nmol/L) Nitric oxide (+9.0±4.9 vs +0.6±2.3 μmol/L)
				Control diet	Calorie-restricted (350–700 kcal less) 52–55% CHO 16–18% PRO 30% FAT (different in food groups contained)
Perelman et al^Citation90	30±7 39±7	Two phases of 3-week isocaloric program RCT crossover design	6	Eucaloric diet ↑poly- and monounsaturated fat	15% PRO 40% CHO 45% FAT 7% saturated fat Ratio of poly to mono= 1.0 200 mg Cholesterol 20 g fiber No weight loss	AUC for insulin concentrations were 30% lower on the low CHO/fat-enriched diet (−194± 148 mIU/L × 8 h) LDL-C was significantly lower on the low-CHO/fat-enriched diet (−12±60 mg/dL)
				Eucaloric diet ↑CHO	15% PRO 60% CHO 25% FAT 7% saturated fat Ratio of poly to mono=1.0 200 mg Cholesterol 20 g fiber No weight loss	Fasting plasma total cholesterol, TG and HDL-C concentrations did not differ between diets
Asemi and Esmaillzadeh^Citation78	30.7±6.7/29.4±6.2 29.1±3.2/31.5±5.7	2 months RCT	48	Control diet: calorierestricted diet	Deficit of 350–700 kcal/day 18% PRO 52% CHO 30% FAT Designed based on Iranian traditional dietary pattern	Adherence to the DASH eating pattern, compared to the control diet, resulted in significant reductions in: Insulin (−1.88 μIU/mL) HOMA-IR (−0.45) Serum hs-CRP levels (−763.29) WC (−5.2 cm) HC (−5.9 cm)
				DASH diet: calorierestricted diet	Deficit of 350–700 kcal/day 18% PRO 52% CHO 30% FAT Rich in: fruits/vegetables/whole grains/LF dairy products low in: saturated fats/cholesterol/refined grains/sweets
Asemi et al^Citation106	30.7±6.7/29.4±6.2 29.1±3.2/31.5±5.7	2 months RCT	48	Control diet: calorierestricted diet	Deficit of 350–700 kcal/day 18% PRO 52% CHO 30% FAT Designed based on Iranian traditional dietary pattern	Adherence to DASH diet, compared to the control diet, resulted in a significant decrease in: BW (−4.4 kg) BMI (−1.7 kg/m^2) Serum TGs (−10.0 mg/dL) VLDL-C levels (−2.0 mg/dL) Significantly increased concentrations of: Plasma total antioxidant capacity (+98.6 mmol/L) Total glutathione (+66.4 μmol/L)
				DASH diet: calorierestricted diet	Deficit of 350–700 kcal/day 18% PRO 52% CHO 30% FAT Rich in: fruits/vegetables/whole grains/LF dairy products low in: saturated fats/cholesterol/refined grains/sweets
Goss et al^Citation76	31 ±5.8 31.8±5.7	2 months/ 2 months RCT crossover design	23/27	1800 kcal Standard diet	18% PRO 55% CHO 27% FAT	Significant reduction in body fat (reduced CHO diet: −3.7%, standard diet: −2.2%). The reduced CHO diet induced a greater decrease in: Intra-abdominal adipose tissue (−7.1%) Subcutaneous abdominal adipose tissue (−4.6%) Intermuscular adipose tissue (−11.5%) The standard diet induced a decrease in total lean mass (−1.3%)
				1800 kcal Reduced CHO diet	19% PRO 41% CHO 40% FAT
Gower et al^Citation91	31.2+5.8 31.8±5.7	Two phases of 8-week isocaloric program RCT crossover design	27	Standard eucaloric diet	18% PRO 55% CHO 27% FAT	Low CHO diet induced significant decreases in: Basal beta-c response (−1.7 x 10^Citation9/min) Fasting insulin (−15.6 pmol/L) Fasting glucose (−0.26 mmol/L) HOMA (−0.7) Total testosterone (−0.55 nM) Cholesterol (−0.53 mmol/L) LDL-C (−0.41 mmol/L) HDL-C (−0.11 mmol/L) Significant increases in: Insulin sensitivity index (+1.2) Dynamic beta-cell response to glucose (+96.110^9/min)
				Low-carbohydrate eucaloric diet	19% PRO 41% CHO 40% FAT
Turner-McGrievy et al^Citation152	27.8+4.5 39.9+6.1	6 months RCT (randomized controlled feasibility study)	18	LF and LGI vegan diet	Plant-based diet (fruits, vegetables, whole grains and legumes/beans, excluding all animal products)	LF, LGI vegan diet produced significantly greater BW losses at 3 months (−1.8 kg) Greater improvements in dietary intake at 6 months (−265 kcal/day) compared to a standard low-calorie dietary approach No significant differences in changes in any of the domains of the PCOS Health-Related Quality of Life Questionnaire (emotional health, body hair, BW, infertility, menstrual concerns)
				Low-calorie diet	1200 kcal/day for participants weighing ≤90 kg and 1500 kcal/day for participants weighing ≥90 kg
Douglas et al^Citation92	33±6 30.0±3.7	3×16-day dietary treatment RCT crossover design	11	Standard eucaloric diet	16% PRO 56% CHO 31% FAT	Fasting insulin was lower following the Low CHO diet relative to the STD diet (−3.2 mIU/L) Acute insulin response to glucose was lower following the low CHO diet relative to the MUFA diet (−97.7 mIU/L × 10 minutes) No differences in: Fasting glucose Insulin sensitivity Circulating concentrations of reproductive hormones
				Low CHO eucaloric diet	15% PRO 43% CHO 45% FAT
				High MUFA eucaloric diet	55% CHO 15% PRO 33% FAT
Moran et al^Citation81	32.1 ±5.2 34.9±7.0	8 weeks weight loss 6 months weight maintenance RCT (Phase I: all subjects followed the same intervention, Phase II: randomly assigned to a carbohydrate counting group [CC], with ≤120 g carbohydrate/day; or a fat counting [FC] group with ≤50 g carbohydrate/day)	34 completed Phase I 23 completed Phase II	Phase I	8 weeks of energy restriction in which two meals/day were replaced with commercially available meal replacements (twomeal replacements/day, 4904.4± 127 kJ) 8000 steps/day 24 weeks of weight loss maintenance during which subjects followed either a carbohydrate counting (<120 g/day; CC) or fat counting (<50 g/day; FC) protocol 8000 steps/day	Phase I: significant reductions in BW (−5.6±2.4 kg) WC (−6.1 ±2.5 cm) Body fat (−4.1 ±2.2 kg) Insulin (−2.8± 1.1 mIU/L) Total testosterone (0.3±0.7 nmol/L) FAI (−3.1 ±4.6) These changes were sustained during Phase II. Improvements in menstrual cyclicity occurred for 16 (57.1%) of 28 subjects. Moderate fat or carbohydrate restriction was equally effective in maintaining weight reduction and improving reproductive and metabolic variables
				Phase II
Alternative dietary interventions
Papakonstantinou et al^Citation132	27±6 Whole sample (n=40, 27±6) Normal weight (n=20, 24± 1.22) Overweight/obese (n=20, 30± 1.21)	24-week crossover design, RCT trial	40	Weight maintenance, isocaloric diet consumed as a three-meal pattern Weight maintenance, isocaloric diet consumed as a six-meal pattern	25% PRO 40% CHO 35% FAT	Six meals decreased significantly vs three meals: Fasting insulin (three meals:112± 10 pmol/L, six meals: 92± 10 pmol/L) Post-OGTT insulin sensitivity (Matsuda index, three meals: 3.80±0.31, six meals: 5.25±0.67) Trend toward significance (p=0.063): HOMA-IR (three meals: 2.94±0.25, six meals: 2.45±0.31)
					25% PRO 40% CHO 35% FAT
Jakubowicz et al^Citation133	25–39 23.7±0.2	3 months RCT	51	Isocaloric diet High-calorie BF	1800±25 kcal/day (42% PRO 27% CHO 31% FAT) BF (980 kcal, 54% daily energy intake) Lunch (640 kcal, 35% daily energy intake) Dinner (190 kcal, 11% daily energy intake)	The BF group has significant changes in: Fasting glucose (−8%) Insulin (−53%) HOMA-IR (−56%) HOMA-B (−35%) ISI (135%) Compared to baseline, the BF group had significantly lower: AUC glucose (−20%) AUC insulin (−49%) Androstenedione (−34%) DHEAS (−35%) Total testosterone (−47%) Free testosterone (from 3.4±0.2 to 1.7±0.1 ng/dL) Compared to baseline, the BF group had significantly higher: SHBG (from 2±0.1 to 4.1 ±0.2 μg/dL)
				Isocaloric diet High-calorie dinner	BF (190 kcal, 11% daily energy intake) Lunch (640 kcal, 35% daily energy intake) Dinner (980 kcal, 54% daily energy intake)

Abbreviations: AMH, anti-Mullerian hormone; AUC, area under the curve; BF, breakfast; BMI, body mass index; BW, body weight; CC, clomiphene citrate; CHCD, conventional hypocaloric diet; CHD, conventional healthy diet; CHO, carbohydrates; DASH, Dietary Approaches to Stop Hypertension; DHEAS, dehydroepiandrosterone sulfate; FAI, free androgen index; FAT, dietary fat content; FG, Ferriman-Gallwey; FSH, follicle-stimulating hormone; GI, glycemic index; GL, glycemic load; HbAlc, hemoglobin Alc; HC, hip circumference; HDL-C, high-density lipoprotein cholesterol; HOMA-B, homeostatic model assessment for B-cell function; HOMA-IR, homeostatic model assessment for insulin resistance; HP, high protein; hsCRP, high-sensitivity C-reactive protein; ISI, insulin sensitivity index; LCKD, low-carbohydrate ketogenic diet; LF, low fat; LGI, low glycemic index; LGL, low glycemic load; LDL-C, low-density lipoprotein cholesterol; LH, luteinizing hormone; MHCD, modified hypocaloric diet; MUFA, monounsaturated fatty acid; NEFA, non-esterified fatty acids; NP, normal protein; OGTT, oral glucose tolerance test; PCOS, polycystic ovary syndrome; PRO, protein; RCT, randomized controlled trial; SHBG, sex hormone-binding globulin; SP, standard protein; TGs, triglycerides; VLDL-C, very low-density lipoprotein cholesterol; WC, waist circumference.

Table 2 Nutrition interventions with PUFAs in women with PCOS

Study	Age (years)/body weight category (kg/m^2)	Duration and design of dietary intervention	Sample size	Description of groups	Characteristics/interventions	Main conclusions
Cussons et al^Citation117	32.7±7.7 34.8±6.8	8 weeks RCT Double-blind, randomized crossover study design	25	n-3 PUFA	4 g n-3/day (4×1 g capsules of 56% DHA and 27% EPA)	n-3 PUFA compared to placebo significantly decreased: Liver fat content TGs Systolic blood pressure Diastolic blood pressure Hepatic fat in women with hepatic steatosis
Karakas et al^Citation109	31.7±7.8 36.3±7.8	6 weeks RCT Three parallelarm, randomized, double-blind study design	51	Fish oil (n=17)	Fish oil (3.5 g n-3 PUFA, six capsules/day; each capsule contained 358 mg EPA and 242 mg DHA)	Effects of fish oil and soybean oil on plasma aromatic amino acids were similar and differed significantly from those of flaxseed oil Dietary PUFA may influence insulin secretion and resistance directly and alter plasma aromatic amino acids indirectly Dietary PUFA may directly affect aromatic amino acid metabolism and the changes in insulin secretion and resistance may be secondary
Khani et al^Citation120	31.0±5.0 29.2±6.7	6 months Double-blind Placebocontrolled	87	n-3 PUFA (n=43) Placebo (n=44)	2 g n-3 (two capsules/day) containing 180g EPA and 120 mg DHA Two olive oil capsules	n-3 PUFA compared to placebo decreased: BMI WC TG Interval between periods n-3 PUFA compared to placebo increased: HDL
Kalgaonkar et al^Citation108	36.2± 1.7 35.1 ± 1.8	6 weeks RCT Parallel, randomized controlled study design	31	Almonds	46 g of almonds (2.4 g saturated fat, 19.5 g MUFA, 7.5 g linoleic acid)	Walnuts increased the n-3/n-6 essential PUFA in the diet and plasma phospholipids Walnuts significantly decreased LDL-C (−6%) and apolipoprotein B (−11%) Walnuts significantly increased insulin response during OGTT (26%) Both walnuts and almonds significantly increased adiponectin Walnuts decreased HbAIc with significant intergroup difference from almonds Walnuts increased SHBG and almonds reduced FAI
Nasri et al^Citation113	27.5±5.7 27.1 ±4.6	12 weeks RCT	60	n-3 PUFA (n=30)	2 g n-3 from flaxseed oil containing 800 mg ALA/day	n-3 PUFA supplementation had beneficial effects on gene expression of PPAR-γ and LDLR, gene expression involved in insulin and lipid signaling pathways
		Parallel, randomized, double-blind, placebocontrolled study design		Placebo (n=30) Flaxseed oil (n=17)	Paraffin Flaxseed oil (3.5 g n-3 PUFA, six capsules/day; each capsule contained 545 mg ALA)
				Soybean oil placebo (n= 17)	Soybean oil (six capsules/day; each capsule contained 200 mg oleic acid, 429 mg LA, 57 mg ALA)
Nadjarzadeh et al^Citation112	26.92±5.46 31.69±4.84	8 weeks RCT Parallel, randomized, double-blind, placebocontrolled study design	78	n-3 (n=39)	3 g/day n-3	n-3 PUFAs significantly decreased testosterone compared to the placebo group FAI and the concentration of sex hormone-binding protein did not differ
				Placebo (n=39)	Paraffin
Oner et al^Citation115	22.6±4.75 22.4±3.1	6 months Nonrandomized clinical trial	45	n-3 PUFA	1.5 g/day n-3	Insulin levels and HOMA-IR significantly decreased during treatment Serum LH, total testosterone, free testosterone and androstenedione levels decreased significantly SHBG levels and TNF-α levels were significantly increased at 6 months
Mohammadi et al^Citation114	27.3±4.27 28.7±3.21	8 weeks RCT Parallel, doubleblind, randomized controlled study design	61	n-3 (n=30) Placebo (n=31)	4 g n-3/day (720 mg EPA and 480 mg DHA) Paraffin	Supplementation with n-3 PUFA compared to placebo: Increased adiponectin (19.5%) and HDL-C (7.4%) Glucose (−11.4%) Insulin (−8.4%) HOMA-IR (−21.8%) TC (−8.1%) LDL-C (−14.9%)
Vargas et al^Citation116	31.7±7.8 36.3±7.8	6 weeks RCT Three parallelarm, randomized, double-blind, placebocontrolled study	51	Fish oil (n=17)	Fish oil (3.5 g n-3 PUFA, six capsules/day; each capsule contained 358 mg EPA and 242 mg DHA)	Fish oil and flaxseed oil lowered TGs Soybean oil increased glucose at 30 and 60 min and AUC for glucose during OGTT and reduced testosterone Fish oil significantly increased glucose at 120 min of OGTT and significantly decreased Matsuda index)
				Flaxseed oil (n=17)	Flaxseed oil (3.5 g n-3 PUFA, six capsules/day; each capsule contained 545 mg ALA)
				Soybean oil placebo (n= 17)	Soybean oil (six capsules/day; each capsule contained 200 mg oleic acid, 429 mg LA, 57 mg ALA
Phelan et al^Citation110	18–40 years 35.07±6.10	6 weeks RCT Randomized double-blind, placebocontrolled, crossover design study	22	LC n-3 PUFA supplementation	4×1 g capsules/day 2.4 g LC n-3 PUFAs that contained 1.9 g EPA and DHA/d in a ratio of EPA to DHA of 1.49:1	LC n-3 PUFA supplementation increased plasma concentrations of n-3 PUFAs and had an antiandrogenic effect in PCOS Significant increase in plasma EPA and DHA concentrations after LC n-3 PUFA supplementation Bioavailable testosterone concentrations were significantly reduced after LC n-3 PUFA supplementation than after placebo intake
				Placebo olive oil	4×1 g olive oil capsules/day
				Walnuts	36 g of walnuts (2.9 g saturated fat, 4.5 g MUFA, 19.2 g LA and 4.3 g ALA)
				Placebo	Olive oil (4×1000 mg capsules of olive oil containing 67% oleic acid)
Kasim-Karakas et al^Citation118	34±5 34.0± 1.9	3 months control and then 3 months intervention Nonrandomized clinical trial	17	Walnuts	48 g walnuts/800 kcal energy intake (19 g LA and 3.3 g ALA)	PUFA-rich diet significantly increased fasting glucose and AUC for glucose Fasting plasma-free fatty acids decreased and ketone bodies decreased Plasma testosterone, free testosterone, SHBG, DHEAS, LH, FSH, and urinary estrogen conjugates did not change

Abbreviations: ALA, α-linolenic acid; AUC, area under the curve; BMI, body mass index; DHA, docosahexaenoic acid; DHEAS, dehydroepiandrosterone sulfate; EPA, eicosapentaenoic acid; FAI, free androgen index; FSH, follicle-stimulating hormone; HbA1c, hemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostatic model assessment for insulin resistance; LA, linoleic acid; LC, long-chain fatty acids; LDL-C, low-density lipoprotein cholesterol; LDLR, low-density lipoprotein receptor; LH, luteinizing hormone; MUFA, monounsaturated fatty acid; OGTT, oral glucose tolerance test; PCOS, polycystic ovary syndrome; PPAR-γ, peroxisome proliferator-activated receptor gamma; PUFAs, polyunsaturated fatty acids; RCT, randomized controlled trial; SHBG, sex hormone-binding globulin; TC, total cholesterol; TGs, triglycerides; TNF-a, tumor necrosis factor-alpha; WC, waist circumference.

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