Role of Omega-3 Fatty Acids in Improving Metabolic Dysfunctions in Polycystic Ovary Syndrome
Abstract
:1. Introduction
2. PCOS—Diagnosis, Pathophysiology and Management
2.1. Diagnosis
2.2. Pathophysiology of PCOS
2.2.1. Neuroendocrine Disruptions in POCS
2.2.2. Insulin Resistance and Hyperinsulinemia in PCOS
2.3. Outline of the Management of PCOS
3. Dietary Patterns for Preventing/Treating Metabolic Complications of PCOS
3.1. Mediterranean Diet
3.2. DASH Diet
3.3. Low-Glycemic Index Diet
4. Role of n-3 PUFAs in Preventing/Treating Metabolic Complications in PCOS
4.1. Sources, Biological Functions, and Side Effects of n-3 PUFAs
4.2. Efficacy of n-3 PUFAs in Improving Metabolic Markers in PCOS
Study | Sample Size | Duration | Study Design | Intervention | Key Findings |
---|---|---|---|---|---|
[67] | 25 | 8 weeks | Randomized cross-over study | EPA + DHA (3.3 g/day) vs. olive oil | Reduced hepatic fat content, serum triglycerides, and systolic and diastolic blood pressure compared to control |
[68] | 22 | 6 weeks | Randomized cross-over study | EPA + DHA (2.4 g/day) vs. olive oil | Reduced plasma bioavailable testosterone compared to control |
[69] | 64 | 8 weeks | Randomized controlled study | EPA + DHA (1.2 g/day) vs. placebo | Increased plasma adiponectin, decreased insulin, glucose, HOMA-IR, total and LDL-cholesterol compared to control; no change in hs-CRP |
[70] | 61 | 8 weeks | Randomized controlled study | EPA + DHA (1.2 g/day) vs. Placebo | Decreased glucose, insulin, and HOMA-IR; no change in anthropometry |
[71] | 68 | 12 weeks | Randomized controlled study | ALA (400 mg) + Vitamin E (400 IU) vs. Placebo | Reduced LPA expression in blood mononuclear cells, reduced serum total and LDL cholesterol, triglycerides, and VLDL cholesterol; increased serum total antioxidant capacity |
[72] | 40 | 12 weeks | Randomized controlled study | Fish oil (1 g/day) vs. placebo | Up-regulation of PPARG and down-regulation of IL1A and CXCL8 (IL-8) in peripheral blood mononuclear cells |
[73] | 60 | 12 weeks | Randomized controlled study | Fish Oil (2 g/day) + Vitamin D 50,000 IU bi-weekly or Placebo | Decrease in hs-CRP and malondialdehyde, increase in total antioxidant capacity |
[74] | 60 | 12 weeks | Randomized controlled study | Flaxseed oil (2 g/day) or placebo | Decrease in insulin, HOMA-IR, serum triglycerides, VLDL cholesterol and hs-CRP |
[75] | 60 | 12 weeks | Randomized controlled study | Flaxseed oil (1 g/day containing 400 mg ALA) + Vitamin E (400 IU) or placebo | Decreases in carotid intima-media thickness and hs-CRP levels |
[76] | 51 | 6 weeks | Randomized controlled study | Fish oil (EPA + DHA 3.5 g/day) or flaxseed oil (ALA 3.5 g/day) or placebo of soybean oil | Reduced triglycerides by both fish oil and flax seed oil |
[77] | 84 | 8 weeks | Randomized controlled study | Fish oil (EPA + DHA 900 mg) or placebo | Reduced LH and increased adiponectin by fish oil |
[78] | 88 | 6 months | Randomized controlled study | Fish oil (EPA + DHA 600 mg/day) vs. placebo | Decreased waist circumference, serum LDL-C, triglycerides, total cholesterol, and menstrual cycle interval; increased HDL-C by fish oil |
[79] | 45 | 6 months | Randomized controlled study | n-3 PUFA (1.5 g/day) vs. placebo | Decreased BMI, serum insulin, HOMA-IR, hirsutism score, serum testosterone, and LH; increased SHBG by fish oil |
4.3. Potential Mechanisms by Which n-3 PUFAs Improve Metabolic Markers in PCOS
4.3.1. Reducing Serum Triglycerides
4.3.2. Reducing Androgen Production
4.3.3. Anti-Inflammatory Effects of n-3 PUFA
4.3.4. n-3 PUFAs and Gut Dysbiosis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Lizneva, D.; Suturina, L.; Walker, W.; Brakta, S.; Gavrilova-Jordan, L.; Azziz, R. Criteria, Prevalence, and Phenotypes of Polycystic Ovary Syndrome. Fertil. Steril. 2016, 106, 6–15. [Google Scholar] [CrossRef]
- Teede, H.J.; Tay, C.T.; Laven, J.J.E.; Dokras, A.; Moran, L.J.; Piltonen, T.T.; Costello, M.F.; Boivin, J.; Redman, L.M.; Boyle, J.A.; et al. Recommendations From the 2023 International Evidence-Based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. J. Clin. Endocrinol. Metab. 2023, 108, 2447–2469. [Google Scholar] [CrossRef] [PubMed]
- Dong, J.; Rees, D.A. Polycystic Ovary Syndrome: Pathophysiology and Therapeutic Opportunities. BMJ Med. 2023, 2, e000548. [Google Scholar] [CrossRef]
- Rocha, A.L.; Oliveira, F.R.; Azevedo, R.C.; Silva, V.A.; Peres, T.M.; Candido, A.L.; Gomes, K.B.; Reis, F.M. Recent Advances in the Understanding and Management of Polycystic Ovary Syndrome. F1000Res 2019, 8, 565. [Google Scholar] [CrossRef]
- Sheikh, J.; Khalil, H.; Shaikh, S.; Hebbar, M.; Zia, N.; Wicks, S.; Jayaprakash, S.; Narendran, A.; Subramanian, A.; Malhotra, K.; et al. Emotional and Psychosexual Well-Being Is Influenced by Ethnicity and Birthplace in Women and Individuals with Polycystic Ovary Syndrome in the UK and India. BJOG 2023, 130, 978–986. [Google Scholar] [CrossRef] [PubMed]
- Hazlehurst, J.M.; Singh, P.; Bhogal, G.; Broughton, S.; Tahrani, A.A. How to Manage Weight Loss in Women with Obesity and PCOS Seeking Fertility? Clin. Endocrinol. 2022, 97, 208–216. [Google Scholar] [CrossRef]
- Scannell, N.; Mantzioris, E.; Rao, V.; Pandey, C.; Ee, C.; Mousa, A.; Moran, L.; Villani, A. Type and Frequency in Use of Nutraceutical and Micronutrient Supplementation for the Management of Polycystic Ovary Syndrome: A Systematic Scoping Review. Biomedicines 2023, 11, 3349. [Google Scholar] [CrossRef]
- Ortega, I.; Duleba, A.J. Ovarian Actions of Resveratrol. Ann. N. Y Acad. Sci. 2015, 1348, 86–96. [Google Scholar] [CrossRef] [PubMed]
- Ochiai, A.; Kuroda, K. Preconception Resveratrol Intake against Infertility: Friend or Foe? Reprod. Med. Biol. 2020, 19, 107–113. [Google Scholar] [CrossRef]
- Kalupahana, N.S.; Goonapienuwala, B.L.; Moustaid-Moussa, N. Omega-3 Fatty Acids and Adipose Tissue: Inflammation and Browning. Annu. Rev. Nutr. 2020, 40, 25–49. [Google Scholar] [CrossRef]
- Albracht-Schulte, K.; Kalupahana, N.S.; Ramalingam, L.; Wang, S.; Rahman, S.M.; Robert-McComb, J.; Moustaid-Moussa, N. Omega-3 Fatty Acids in Obesity and Metabolic Syndrome: A Mechanistic Update. J. Nutr. Biochem. 2018, 58, 1–16. [Google Scholar] [CrossRef] [PubMed]
- Kalupahana, N.S.; Claycombe, K.J.; Moustaid-Moussa, N. (N-3) Fatty Acids Alleviate Adipose Tissue Inflammation and Insulin Resistance: Mechanistic Insights. Adv. Nutr. 2011, 2, 304–316. [Google Scholar] [CrossRef] [PubMed]
- Yang, K.; Zeng, L.; Bao, T.; Ge, J. Effectiveness of Omega-3 Fatty Acid for Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. Reprod. Biol. Endocrinol. 2018, 16, 27. [Google Scholar] [CrossRef] [PubMed]
- Azziz, R.; Carmina, E.; Chen, Z.; Dunaif, A.; Laven, J.S.E.; Legro, R.S.; Lizneva, D.; Natterson-Horowtiz, B.; Teede, H.J.; Yildiz, B.O. Polycystic Ovary Syndrome. Nat. Rev. Dis. Primers 2016, 2, 1–18. [Google Scholar] [CrossRef]
- Chen, X.; Xiao, Z.; Cai, Y.; Huang, L.; Chen, C. Hypothalamic Mechanisms of Obesity-Associated Disturbance of Hypothalamic–Pituitary–Ovarian Axis. Trends Endocrinol. Metab. 2022, 33, 206–217. [Google Scholar] [CrossRef]
- Yildiz, B.O.; Azziz, R. The Adrenal and Polycystic Ovary Syndrome. Rev. Endocr. Metab. Disord. 2007, 8, 331–342. [Google Scholar] [CrossRef]
- Shaaban, Z.; Khoradmehr, A.; Amiri-Yekta, A.; Nowzari, F.; Jafarzadeh Shirazi, M.R.; Tamadon, A. Pathophysiologic Mechanisms of Insulin Secretion and Signaling-Related Genes in Etiology of Polycystic Ovary Syndrome. Genet. Res. 2021, 2021, e4. [Google Scholar] [CrossRef]
- Alesi, S.; Ee, C.; Moran, L.J.; Rao, V.; Mousa, A. Nutritional Supplements and Complementary Therapies in Polycystic Ovary Syndrome. Adv. Nutr. 2022, 13, 1243–1266. [Google Scholar] [CrossRef]
- Jurczewska, J.; Ostrowska, J.; Chełchowska, M.; Panczyk, M.; Rudnicka, E.; Kucharski, M.; Smolarczyk, R.; Szostak-Węgierek, D. Abdominal Obesity in Women with Polycystic Ovary Syndrome and Its Relationship with Diet, Physical Activity and Insulin Resistance: A Pilot Study. Nutrients 2023, 15, 3652. [Google Scholar] [CrossRef]
- Fonseka, S.; Subhani, B.; Wijeyaratne, C.N.; Gawarammana, I.B.; Kalupahana, N.S.; Ratnatunga, N.; Rosairo, S.; Vithane, K.P. Association between Visceral Adiposity Index, Hirsutism and Cardiometabolic Risk Factors in Women with Polycystic Ovarian Syndrome: A Cross-Sectional Study. Ceylon Med. J. 2019, 64, 111–117. [Google Scholar] [CrossRef]
- Kalupahana, N.S.; Moustaid-Moussa, N.; Claycombe, K.J. Immunity as a Link between Obesity and Insulin Resistance. Mol. Asp. Med. 2012, 33, 26–34. [Google Scholar] [CrossRef] [PubMed]
- Perry, R.J.; Samuel, V.T.; Petersen, K.F.; Shulman, G.I. The Role of Hepatic Lipids in Hepatic Insulin Resistance and Type 2 Diabetes. Nature 2014, 510, 84–91. [Google Scholar] [CrossRef]
- Dumesic, D.A.; Phan, J.D.; Leung, K.L.; Grogan, T.R.; Ding, X.; Li, X.; Hoyos, L.R.; Abbott, D.H.; Chazenbalk, G.D. Adipose Insulin Resistance in Normal-Weight Women with Polycystic Ovary Syndrome. J. Clin. Endocrinol. Metab. 2019, 104, 2171–2183. [Google Scholar] [CrossRef] [PubMed]
- Dunaif, A.; Xia, J.; Book, C.B.; Schenker, E.; Tang, Z. Excessive Insulin Receptor Serine Phosphorylation in Cultured Fibroblasts and in Skeletal Muscle: A Potential Mechanism for Insulin Resistance in the Polycystic Ovary Syndrome. J. Clin. Investig. 1995, 96, 801–810. [Google Scholar] [CrossRef] [PubMed]
- Sanchez-Garrido, M.A.; Tena-Sempere, M. Metabolic Dysfunction in Polycystic Ovary Syndrome: Pathogenic Role of Androgen Excess and Potential Therapeutic Strategies. Mol. Metab. 2020, 35, 100937. [Google Scholar] [CrossRef]
- Victor, V.M.; Rovira-Llopis, S.; Bañuls, C.; Diaz-Morales, N.; De Marañon, A.M.; Rios-Navarro, C.; Alvarez, A.; Gomez, M.; Rocha, M.; Hernández-Mijares, A. Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase. PLoS ONE 2016, 11, e0151960. [Google Scholar] [CrossRef]
- Boulman, N.; Levy, Y.; Leiba, R.; Shachar, S.; Linn, R.; Zinder, O.; Blumenfeld, Z. Increased C-Reactive Protein Levels in the Polycystic Ovary Syndrome: A Marker of Cardiovascular Disease. J. Clin. Endocrinol. Metab. 2004, 89, 2160–2165. [Google Scholar] [CrossRef]
- Siemers, K.M.; Klein, A.K.; Baack, M.L. Mitochondrial Dysfunction in PCOS: Insights into Reproductive Organ Pathophysiology. Int. J. Mol. Sci. 2023, 24, 13123. [Google Scholar] [CrossRef]
- Kim, S.H.; Reaven, G.M. Insulin Resistance and Hyperinsulinemia. Diabetes Care 2008, 31, 1433–1438. [Google Scholar] [CrossRef]
- Barbieri, R.L.; Hornstein, M.D. Hyperinsulinemia and Ovarian Hyperandrogenism. Cause and Effect. Endocrinol. Metab. Clin. N. Am. 1988, 17, 685–703. [Google Scholar] [CrossRef]
- Biernacka-Bartnik, A.; Kocełak, P.; Owczarek, A.J.; Chorȩza, P.; Puzianowska-Kuźnicka, M.; Markuszewski, L.; Madej, P.; Chudek, J.; Olszanecka-Glinianowicz, M. Prediction of Insulin Resistance and Impaired Fasting Glucose Based on Sex Hormone-Binding Globulin (SHBG) Levels in Polycystic Ovary Syndrome. Int. J. Endocrinol. 2022, 2022, 1–6. [Google Scholar] [CrossRef]
- Qu, X.; Donnelly, R. Sex Hormone-Binding Globulin (Shbg) as an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome. Int. J. Mol. Sci. 2020, 21, 8191. [Google Scholar] [CrossRef] [PubMed]
- Lim, S.S.; Hutchison, S.K.; Van Ryswyk, E.; Norman, R.J.; Teede, H.J.; Moran, L.J. Lifestyle Changes in Women with Polycystic Ovary Syndrome. Cochrane Database Syst. Rev. 2019, 2019, CD007506. [Google Scholar] [CrossRef]
- Kim, C.H.; Chon, S.J.; Lee, S.H. Effects of Lifestyle Modification in Polycystic Ovary Syndrome Compared to Metformin Only or Metformin Addition: A Systematic Review and Meta-Analysis. Sci. Rep. 2020, 10, 7802. [Google Scholar] [CrossRef] [PubMed]
- Abdolahian, S.; Tehrani, F.R.; Amiri, M.; Ghodsi, D.; Yarandi, R.B.; Jafari, M.; Majd, H.A.; Nahidi, F. Effect of Lifestyle Modifications on Anthropometric, Clinical, and Biochemical Parameters in Adolescent Girls with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. BMC Endocr. Disord. 2020, 20, 71. [Google Scholar] [CrossRef]
- Karimzadeh, M.A.; Javedani, M. An Assessment of Lifestyle Modification versus Medical Treatment with Clomiphene Citrate, Metformin, and Clomiphene Citrate-Metformin in Patients with Polycystic Ovary Syndrome. Fertil. Steril. 2010, 94, 216–220. [Google Scholar] [CrossRef]
- Fonseka, S.; Wijeyaratne, C.N.; Gawarammana, I.B.; Kalupahana, N.S.; Rosairo, S.; Ratnatunga, N.; Kumarasiri, R. Effectiveness of Low-Dose Ethinylestradiol/Cyproterone Acetate and Ethinylestradiol/Desogestrel with and without Metformin on Hirsutism in Polycystic Ovary Syndrome: A Randomized, Double-Blind, Triple-Dummy Study. J. Clin. Aesthetic Dermatol. 2020, 13, 18. [Google Scholar]
- Shang, Y.; Zhou, H.; He, R.; Lu, W. Dietary Modification for Reproductive Health in Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. Front. Endocrinol. 2021, 12, 735954. [Google Scholar] [CrossRef] [PubMed]
- Yannakoulia, M.; Scarmeas, N. Diets. N. Engl. J. Med. 2024, 390, 2098–2106. [Google Scholar] [CrossRef]
- Che, X.; Chen, Z.; Liu, M.; Mo, Z. Dietary Interventions: A Promising Treatment for Polycystic Ovary Syndrome. Ann. Nutr. Metab. 2021, 77, 313–323. [Google Scholar] [CrossRef]
- Barrea, L.; Arnone, A.; Annunziata, G.; Muscogiuri, G.; Laudisio, D.; Salzano, C.; Pugliese, G.; Colao, A.; Savastano, S. Adherence to the Mediterranean Diet, Dietary Patterns and Body Composition in Women with Polycystic Ovary Syndrome (PCOS). Nutrients 2019, 11, 2278. [Google Scholar] [CrossRef] [PubMed]
- Kazemi, M.; Jarrett, B.Y.; Vanden Brink, H.; Lin, A.W.; Hoeger, K.M.; Spandorfer, S.D.; Lujan, M.E. Obesity, Insulin Resistance, and Hyperandrogenism Mediate the Link between Poor Diet Quality and Ovarian Dysmorphology in Reproductive-Aged Women. Nutrients 2020, 12, 1953. [Google Scholar] [CrossRef]
- Dinu, M.; Pagliai, G.; Casini, A.; Sofi, F. Mediterranean Diet and Multiple Health Outcomes: An Umbrella Review of Meta-Analyses of Observational Studies and Randomised Trials. Eur. J. Clin. Nutr. 2018, 72, 30–43. [Google Scholar] [CrossRef] [PubMed]
- Juhász, A.E.; Stubnya, M.P.; Teutsch, B.; Gede, N.; Hegyi, P.; Nyirády, P.; Bánhidy, F.; Ács, N.; Juhász, R. Ranking the Dietary Interventions by Their Effectiveness in the Management of Polycystic Ovary Syndrome: A Systematic Review and Network Meta-Analysis. Reprod. Health 2024, 21, 28. [Google Scholar] [CrossRef] [PubMed]
- Shang, Y.; Zhou, H.; Hu, M.; Feng, H. Effect of Diet on Insulin Resistance in Polycystic Ovary Syndrome. J. Clin. Endocrinol. Metab. 2020, 105, 3346–3360. [Google Scholar] [CrossRef]
- Asemi, Z.; Samimi, M.; Tabassi, Z.; Shakeri, H.; Sabihi, S.S.; Esmaillzadeh, A. Effects of DASH Diet on Lipid Profiles and Biomarkers of Oxidative Stress in Overweight and Obese Women with Polycystic Ovary Syndrome: A Randomized Clinical Trial. Nutrition 2014, 30, 1287–1293. [Google Scholar] [CrossRef]
- Asemi, Z.; Esmaillzadeh, A. DASH Diet, Insulin Resistance, and Serum Hs-CRP in Polycystic Ovary Syndrome: A Randomized Controlled Clinical Trial. Horm. Metab. Res. 2015, 47, 232–238. [Google Scholar] [CrossRef]
- Vlachos, D.; Malisova, S.; Lindberg, F.A.; Karaniki, G. Glycemic Index (GI) or Glycemic Load (GL) and Dietary Interventions for Optimizing Postprandial Hyperglycemia in Patients with T2 Diabetes: A Review. Nutrients 2020, 12, 1561. [Google Scholar] [CrossRef]
- Chiavaroli, L.; Lee, D.; Ahmed, A.; Cheung, A.; Khan, T.A.; Blanco, S.; Mejia; Mirrahimi, A.; Jenkins, D.J.A.; Livesey, G.; et al. Effect of Low Glycaemic Index or Load Dietary Patterns on Glycaemic Control and Cardiometabolic Risk Factors in Diabetes: Systematic Review and Meta-Analysis of Randomised Controlled Trials. BMJ 2021, 374, n1651. [Google Scholar] [CrossRef]
- Szczuko, M.; Zapalowska-Chwyć, M.; Drozd, R. A Low Glycemic Index Decreases Inflammation by Increasing the Concentration of Uric Acid and the Activity of Glutathione Peroxidase (GPX3) in Patients with Polycystic Ovary Syndrome (PCOS). Molecules 2019, 24, 1508. [Google Scholar] [CrossRef]
- Marsh, K.A.; Steinbeck, K.S.; Atkinson, F.S.; Petocz, P.; Brand-Miller, J.C. Effect of a Low Glycemic Index Compared with a Conventional Healthy Diet on Polycystic Ovary Syndrome. Am. J. Clin. Nutr. 2010, 92, 83–92. [Google Scholar] [CrossRef] [PubMed]
- Sordia-Hernandez, L.H.; Rodriguez, P.A.; Rodriguez, D.S.; Guzman, S.T.; Zenteno, E.S.S.; Gonzalez, G.G.; Patino, R.I. Effect of a Low Glycemic Diet in Patients with Polycystic Ovary Syndrome and Anovulation -A Randomized Controlled Trial. Clin. Exp. Obs. Gynecol. 2016, 43, 555–559. [Google Scholar] [CrossRef]
- Kazemi, M.; Hadi, A.; Pierson, R.A.; Lujan, M.E.; Zello, G.A.; Chilibeck, P.D. Effects of Dietary Glycemic Index and Glycemic Load on Cardiometabolic and Reproductive Profiles in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Adv. Nutr. 2021, 12, 161–178. [Google Scholar] [CrossRef]
- Iervolino, M.; Lepore, E.; Forte, G.; Laganà, A.S.; Buzzaccarini, G.; Unfer, V. Natural Molecules in the Management of Polycystic Ovary Syndrome (Pcos): An Analytical Review. Nutrients 2021, 13, 1677. [Google Scholar] [CrossRef]
- Schmitz, G.; Ecker, J. The Opposing Effects of N-3 and n-6 Fatty Acids. Prog. Lipid Res. 2008, 47, 147–155. [Google Scholar] [CrossRef] [PubMed]
- NIH Omega-3 Fatty Acids—Health Professional Fact Sheet. Available online: https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/ (accessed on 28 August 2024).
- Rimm, E.B.; Appel, L.J.; Chiuve, S.E.; Djoussé, L.; Engler, M.B.; Kris-Etherton, P.M.; Mozaffarian, D.; Siscovick, D.S.; Lichtenstein, A.H. Seafood Long-Chain n-3 Polyunsaturated Fatty Acids and Cardiovascular Disease: A Science Advisory From the American Heart Association. Circulation 2018, 138, e35–e47. [Google Scholar] [CrossRef]
- Scientific Opinion on the Tolerable Upper Intake Level of Eicosapentaenoic Acid (EPA), Docosahexaenoic Acid (DHA) and Docosapentaenoic Acid (DPA). EFSA J. 2012, 10, 2815. [CrossRef]
- Arterburn, L.M.; Hall, E.B.; Oken, H. Distribution, Interconversion, and Dose Response of n-3 Fatty Acids in Humans. Am. J. Clin. Nutr. 2006, 83, 1467S–1476S. [Google Scholar] [CrossRef]
- Brenna, J.T.; Salem, N.; Sinclair, A.J.; Cunnane, S.C. α-Linolenic Acid Supplementation and Conversion to n-3 Long-Chain Polyunsaturated Fatty Acids in Humans. Prostaglandins Leukot. Essent. Fat. Acids 2009, 80, 85–91. [Google Scholar] [CrossRef] [PubMed]
- Swanson, D.; Block, R.; Mousa, S.A. Omega-3 Fatty Acids EPA and DHA: Health Benefits throughout Life. Adv. Nutr. 2012, 3, 1–7. [Google Scholar] [CrossRef] [PubMed]
- Lu, L.; Li, X.; Lv, L.; Xu, Y.; Wu, B.; Huang, C. Dietary and Serum N-3 PUFA and Polycystic Ovary Syndrome: A Matched Case-Control Study. Br. J. Nutr. 2022, 128, 114–123. [Google Scholar] [CrossRef] [PubMed]
- Lu, L.; Li, X.; Lv, L.; Xu, Y.; Wu, B.; Huang, C. Associations between Omega-3 Fatty Acids and Insulin Resistance and Body Composition in Women with Polycystic Ovary Syndrome. Front. Nutr. 2022, 9, 1016943. [Google Scholar] [CrossRef] [PubMed]
- Zhou, J.; Zuo, W.; Tan, Y.; Wang, X.; Zhu, M.; Zhang, H. Effects of N-3 Polyunsaturated Fatty Acid on Metabolic Status in Women with Polycystic Ovary Syndrome: A Meta-Analysis of Randomized Controlled Trials. J. Ovarian Res. 2023, 16, 54. [Google Scholar] [CrossRef] [PubMed]
- Moslehi, N.; Zeraattalab-Motlagh, S.; Rahimi Sakak, F.; Shab-Bidar, S.; Tehrani, F.R.; Mirmiran, P. Effects of Nutrition on Metabolic and Endocrine Outcomes in Women with Polycystic Ovary Syndrome: An Umbrella Review of Meta-Analyses of Randomized Controlled Trials. Nutr. Rev. 2023, 81, 555–577. [Google Scholar] [CrossRef]
- Xia, Y.; Wang, Y.; Cui, M.; Su, D. Efficacy of Omega-3 Fatty Acid Supplementation on Cardiovascular Risk Factors in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. Ann. Palliat. Med. 2021, 10, 6425–6437. [Google Scholar] [CrossRef]
- Cussons, A.J.; Watts, G.F.; Mori, T.A.; Stuckey, B.G.A. Omega-3 Fatty Acid Supplementation Decreases Liver Fat Content in Polycystic Ovary Syndrome: A Randomized Controlled Trial Employing Proton Magnetic Resonance Spectroscopy. J. Clin. Endocrinol. Metab. 2009, 94, 3842–3848. [Google Scholar] [CrossRef]
- Phelan, N.; O’Connor, A.; Tun, T.K.; Correia, N.; Boran, G.; Roche, H.M.; Gibney, J. Hormonal and Metabolic Effects of Polyunsaturated Fatty Acids in Young Women with Polycystic Ovary Syndrome: Results from a Cross-Sectional Analysis and a Randomized, Placebo-Controlled, Crossover Trial. Am. J. Clin. Nutr. 2011, 93, 652–662. [Google Scholar] [CrossRef]
- Mohammadi, E.; Rafraf, M.; Farzadi, L.; Asghari-Jafarabadi, M.; Sabour, S. Effects of Omega-3 Fatty Acids Supplementation on Serum Adiponectin Levels and Some Metabolic Risk Factors in Women with Polycystic Ovary Syndrome. Asia Pac. J. Clin. Nutr. 2012, 21, 511–518. [Google Scholar] [PubMed]
- Rafraf, M.; Mohammadi, E.; Asghari-Jafarabadi, M.; Farzadi, L. Omega-3 Fatty Acids Improve Glucose Metabolism without Effects on Obesity Values and Serum Visfatin Levels in Women with Polycystic Ovary Syndrome. J. Am. Coll. Nutr. 2012, 31, 361–368. [Google Scholar] [CrossRef]
- Rahmani, E.; Samimi, M.; Ebrahimi, F.A.; Foroozanfard, F.; Ahmadi, S.; Rahimi, M.; Jamilian, M.; Aghadavod, E.; Bahmani, F.; Taghizadeh, M.; et al. The Effects of Omega-3 Fatty Acids and Vitamin E Co-Supplementation on Gene Expression of Lipoprotein(a) and Oxidized Low-Density Lipoprotein, Lipid Profiles and Biomarkers of Oxidative Stress in Patients with Polycystic Ovary Syndrome. Mol. Cell Endocrinol. 2017, 439, 247–255. [Google Scholar] [CrossRef]
- Rahmani, E.; Jamilian, M.; Dadpour, B.; Nezami, Z.; Vahedpoor, Z.; Mahmoodi, S.; Aghadavod, E.; Taghizadeh, M.; Beiki Hassan, A.; Asemi, Z. The Effects of Fish Oil on Gene Expression in Patients with Polycystic Ovary Syndrome. Eur. J. Clin. Investig. 2018, 48, e12893. [Google Scholar] [CrossRef]
- Jamilian, M.; Samimi, M.; Mirhosseini, N.; Afshar Ebrahimi, F.; Aghadavod, E.; Talaee, R.; Jafarnejad, S.; Hashemi Dizaji, S.; Asemi, Z. The Influences of Vitamin D and Omega-3 Co-Supplementation on Clinical, Metabolic and Genetic Parameters in Women with Polycystic Ovary Syndrome. J. Affect. Disord. 2018, 238, 32–38. [Google Scholar] [CrossRef]
- Mirmasoumi, G.; Fazilati, M.; Foroozanfard, F.; Vahedpoor, Z.; Mahmoodi, S.; Taghizadeh, M.; Esfeh, N.K.; Mohseni, M.; Karbassizadeh, H.; Asemi, Z. The Effects of Flaxseed Oil Omega-3 Fatty Acids Supplementation on Metabolic Status of Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Exp. Clin. Endocrinol. Diabetes 2018, 126, 222–228. [Google Scholar] [CrossRef]
- Talari, H.R.; Poladchang, S.; Hamidian, Y.; Samimi, M.; Gilasi, H.R.; Ebrahimi, F.A.; Asemi, Z. The Effects of Omega-3 and Vitamin E Co-Supplementation on Carotid Intimamedia Thickness and Inflammatory Factors in Patients with Polycystic Ovary Syndrome. Oman Med. J. 2018, 33, 473–479. [Google Scholar] [CrossRef]
- Vargas, M.L.; Almario, R.U.; Buchan, W.; Kim, K.; Karakas, S.E. Metabolic and Endocrine Effects of Long-Chain versus Essential Omega-3 Polyunsaturated Fatty Acids in Polycystic Ovary Syndrome. Metabolism 2011, 60, 1711–1718. [Google Scholar] [CrossRef]
- Nadjarzadeh, A.; Dehghani-Firouzabadi, R.; Daneshbodi, H.; Lotfi, M.H.; Vaziri, N.; Mozaffari-Khosravi, H. Effect of Omega-3 Supplementation on Visfatin, Adiponectin, and Anthropometric Indices in Women with Polycystic Ovarian Syndrome. J. Reprod. Infertil. 2015, 16, 212–220. [Google Scholar]
- Khani, B.; Mardanian, F.; Fesharaki, S.J. Omega-3 Supplementation Effects on Polycystic Ovary Syndrome Symptoms and Metabolic Syndrome. J. Res. Med. Sci. 2017, 2, 64. [Google Scholar] [CrossRef]
- Oner, G.; Muderris, I.I. Efficacy of Omega-3 in the Treatment of Polycystic Ovary Syndrome. J. Obs. Gynaecol. 2013, 33, 289–291. [Google Scholar] [CrossRef]
- Bornfeldt, K.E. Triglyceride Lowering by Omega-3 Fatty Acids: A Mechanism Mediated by N-Acyl Taurines. J. Clin. Investig. 2021, 131, e147558. [Google Scholar] [CrossRef] [PubMed]
- Bhatt, D.L.; Steg, P.G.; Miller, M.; Brinton, E.A.; Jacobson, T.A.; Ketchum, S.B.; Doyle, R.T.; Juliano, R.A.; Jiao, L.; Granowitz, C.; et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N. Engl. J. Med. 2019, 380, 11–22. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Walsh, L.P.; Stocco, D.M. The Role of Arachidonic Acid on LH-Stimulated Steroidogenesis and Steroidogenic Acute Regulatory Protein Accumulation in MA-10 Mouse Leydig Tumor Cells. Endocrine 1999, 10, 7–12. [Google Scholar] [CrossRef]
- Wang, X.J.; Walsh, L.P.; Reinhart, A.J.; Stocco, D.M. The Role of Arachidonic Acid in Steroidogenesis and Steroidogenic Acute Regulatory (StAR) Gene and Protein Expression. J. Biol. Chem. 2000, 275, 20204–20209. [Google Scholar] [CrossRef]
- Mourente, G.; Tocher, D.R. In Vivo Metabolism of [1-14C]Linolenic Acid (18:3(n − 3)) and [1-14C]Eicosapentaenoic Acid (20:5(n − 3)) in a Marine Fish: Time-Course of the Desaturation/Elongation Pathway. Biochim. Et. Biophys. Acta (BBA)/Lipids Lipid Metab. 1994, 1212, 109–118. [Google Scholar] [CrossRef]
- Rett, B.S.; Whelan, J. Increasing Dietary Linoleic Acid Does Not Increase Tissue Arachidonic Acid Content in Adults Consuming Western-Type Diets: A Systematic Review. Nutr. Metab. 2011, 8, 36. [Google Scholar] [CrossRef] [PubMed]
- Yuan, J.; Wen, X.; Jia, M. Efficacy of Omega-3 Polyunsaturated Fatty Acids on Hormones, Oxidative Stress, and Inflammatory Parameters among Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. Ann. Palliat. Med. 2021, 10, 8991–9001. [Google Scholar] [CrossRef] [PubMed]
- Morshedzadeh, N.; Saedisomeolia, A.; Djalali, M.; Eshraghian, M.R.; Hantoushzadeh, S.; Mahmoudi, M. Resolvin D1 Impacts on Insulin Resistance in Women with Polycystic Ovary Syndrome and Healthy Women. Diabetes Metab. Syndr. Clin. Res. Rev. 2019, 13, 660–664. [Google Scholar] [CrossRef] [PubMed]
- Serhan, C.N.; Levy, B.D. Resolvins in Inflammation: Emergence of the pro-Resolving Superfamily of Mediators. J. Clin. Investig. 2018, 128, 2657–2669. [Google Scholar] [CrossRef]
- Regidor, P.A.; Mueller, A.; Sailer, M.; Santos, F.G.; Rizo, J.M.; Egea, F.M. Chronic Inflammation in Pcos: The Potential Benefits of Specialized pro-Resolving Lipid Mediators (Spms) in the Improvement of the Resolutive Response. Int. J. Mol. Sci. 2021, 22, 384. [Google Scholar] [CrossRef]
- Tosatti, J.A.G.; Alves, M.T.; Cândido, A.L.; Reis, F.M.; Araújo, V.E.; Gomes, K.B. Influence of N-3 Fatty Acid Supplementation on Inflammatory and Oxidative Stress Markers in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. Br. J. Nutr. 2021, 125, 657–668. [Google Scholar] [CrossRef]
- Wu, J.H.Y.; Cahill, L.E.; Mozaffarian, D. Effect of Fish Oil on Circulating Adiponectin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Clin. Endocrinol. Metab. 2013, 98, 2451–2459. [Google Scholar] [CrossRef]
- Oh, D.Y.; Talukdar, S.; Bae, E.J.; Imamura, T.; Morinaga, H.; Fan, W.Q.; Li, P.; Lu, W.J.; Watkins, S.M.; Olefsky, J.M. GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-Inflammatory and Insulin-Sensitizing Effects. Cell 2010, 142, 687–698. [Google Scholar] [CrossRef] [PubMed]
- Zhang, H.; Zheng, L.; Li, C.; Jing, J.; Li, Z.; Sun, S.; Xue, T.; Zhang, K.; Xue, M.; Cao, C.; et al. Effects of Gut Microbiota on Omega-3-Mediated Ovary and Metabolic Benefits in Polycystic Ovary Syndrome Mice. J. Ovarian Res. 2023, 16, 138. [Google Scholar] [CrossRef] [PubMed]
- Wang, T.; Sha, L.; Li, Y.; Zhu, L.; Wang, Z.; Li, K.; Lu, H.; Bao, T.; Guo, L.; Zhang, X.; et al. Dietary α-Linolenic Acid-Rich Flaxseed Oil Exerts Beneficial Effects on Polycystic Ovary Syndrome Through Sex Steroid Hormones—Microbiota—Inflammation Axis in Rats. Front. Endocrinol. 2020, 11, 284. [Google Scholar] [CrossRef] [PubMed]
Treatment | Description |
---|---|
Combined oral contraceptive pills | For managing hirsutism and irregular menstrual cycles in women and adolescents with PCOS. |
Metformin | Suggested to improve metabolic outcomes in persons with PCOS and a BMI > 25 kg/m2. May be explored for cycle control in teenagers and individuals with a BMI < 25 kg/m2 despite weak data. Should be part of lifestyle changes with low-dose administration to reduce adverse effects. |
Combination therapy | Combining COCP with metformin offers little additional benefit over either medication alone, except in high metabolic risk groups. |
Inositol | For improving metabolic profile. |
Anti-obesity drugs | For managing greater weight in PCOS patients, lifestyle therapies and medications such as orlistat, semaglutide, liraglutide, and GLP-1 receptor agonists may be combined. |
Anti-androgens | May be used to treat hirsutism in cases where COCP and cosmetic therapy are ineffective, when used with effective contraception. |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Albardan, L.; Platat, C.; Kalupahana, N.S. Role of Omega-3 Fatty Acids in Improving Metabolic Dysfunctions in Polycystic Ovary Syndrome. Nutrients 2024, 16, 2961. https://doi.org/10.3390/nu16172961
Albardan L, Platat C, Kalupahana NS. Role of Omega-3 Fatty Acids in Improving Metabolic Dysfunctions in Polycystic Ovary Syndrome. Nutrients. 2024; 16(17):2961. https://doi.org/10.3390/nu16172961
Chicago/Turabian StyleAlbardan, Laila, Carine Platat, and Nishan Sudheera Kalupahana. 2024. "Role of Omega-3 Fatty Acids in Improving Metabolic Dysfunctions in Polycystic Ovary Syndrome" Nutrients 16, no. 17: 2961. https://doi.org/10.3390/nu16172961