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The effects of omega-3 fatty acids supplementation on metabolic status in pregnant women: a systematic review and meta-analysis of randomized controlled trials

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Abstract

Background and objective

Data regarding the effects of omega-3 polyunsaturated fatty acids (PUFA) supplementation on metabolic status of pregnant women are limited. This systematic review and meta-analysis were done based on randomized controlled trials (RCTs) dealing with the effects of omega-3 PUFA supplementation on glycemic control, lipoproteins, inflammation and oxidative stress in pregnant women.

Methods

Following databases were searched for eligible studies published from inception to until 2019: MEDLINE, EMBASE, Web of Science, PubMed, Scopus, Cochrane Library, and Google scholar. Studies that evaluated the effect of omega-3 PUFA supplementation on parameters of glycemic control, lipoproteins, inflammation and oxidative stress in pregnant women were found by using the key MeSH. A study quality assessment was performed using the Cochrane Collaboration risk of bias tool and heterogeneity between studies was statistically computed using Cochrane’s Q test and I-square (I2). Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size.

Results

No significant effects of omega-3 PUFA supplementation on FPG, insulin, insulin resistance, total cholesterol, triglycerides, LDL-cholesterol, total cholesterol/HDL-cholesterol, interleukin 6 (IL-6), IL-8, and malondialdehyde were found. However, omega-3 PUFA significantly increased serum concentrations of HDL-cholesterol (WMD: 3.10; 95% CI: 0.18, 6.03) and reduced C-reactive protein (WMD: -1.85; 95% CI: -2.61, -1.09).

Conclusion

Based on the results of this meta-analysis omega-3 PUFA supplementation during pregnancy has a significant beneficial effect on HDL-cholesterol, and C-reactive protein.

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Availability of data and material

The primary data for this study is available from the authors on direct request.

Abbreviations

HOMA IR:

homeostasis model assessment of insulin resistance

TG:

triglyceride

TC:

total cholesterol

HDL-C:

HDL cholesterol

LDL-C:

LDL cholesterol

CRP:

C-Reactive Protein

MDA:

malondialdehyde

IL:

interleukin

References

  1. Herrera E, Desoye G. Maternal and fetal lipid metabolism under normal and gestational diabetic conditions. Horm Mol Biol Clin Investig. 2016;26:109–27.

    CAS  PubMed  Google Scholar 

  2. Kalagiri RR, Carder T, Choudhury S, Vora N, Ballard AR, Govande V, et al. Inflammation in Complicated Pregnancy and Its Outcome. Am J Perinatol. 2016;33:1337–56.

    PubMed  Google Scholar 

  3. Wu F, Tian FJ, Lin Y, Xu WM. Oxidative stress: placenta function and dysfunction. Am J Reprod Immunol. 2016;76:258–71.

    PubMed  Google Scholar 

  4. Hoch D, Gauster M, Hauguel-de Mouzon S, Desoye G. Diabesity-associated oxidative and inflammatory stress signalling in the early human placenta. Mol Aspects Med. 2019;66:21–30.

    CAS  PubMed  Google Scholar 

  5. Segovia SA, Vickers MH, Gray C, Reynolds CM. Maternal obesity, inflammation, and developmental programming. BioMed research international. 2014;2014:418975.

    PubMed  PubMed Central  Google Scholar 

  6. Milman N, Paszkowski T, Cetin I, Castelo-Branco C. Supplementation during pregnancy: beliefs and science. Gynecol Endocrinol. 2016;32:509–16.

    CAS  PubMed  Google Scholar 

  7. Hovdenak N, Haram K. Influence of mineral and vitamin supplements on pregnancy outcome. Eur J Obstet Gynecol Reprod Biol. 2012;164:127–32.

    CAS  PubMed  Google Scholar 

  8. Goel A, Pothineni NV, Singhal M, Paydak H, Saldeen T, Mehta JL. Fish, fish oils and cardioprotection: promise or fish tale? Int J Mol Sci. 2018;19.

  9. Lowensohn RI, Stadler DD, Naze C. Current concepts of maternal nutrition. Obstet Gynecol Surv. 2016;71:413–26.

    PubMed  PubMed Central  Google Scholar 

  10. Wadhwani N, Patil V, Joshi S. Maternal long chain polyunsaturated fatty acid status and pregnancy complications. Prostaglandins, leukotrienes, and essential fatty acids. 2018;136:143–52.

  11. Middleton P, Gomersall JC, Gould JF, Shepherd E, Olsen SF, Makrides M. Omega-3 fatty acid addition during pregnancy. Cochrane Database Syst Rev. 2018;11:Cd003402.

    PubMed  Google Scholar 

  12. Zhong N, Wang J. The efficacy of omega-3 fatty acid for gestational diabetes: a meta-analysis of randomized controlled trials. Gynecol Endocrinol. 2019;35:4–9.

    CAS  PubMed  Google Scholar 

  13. AbuMweis S, Jew S, Tayyem R, Agraib L. Eicosapentaenoic acid and docosahexaenoic acid containing supplements modulate risk factors for cardiovascular disease: a meta-analysis of randomised placebo-control human clinical trials. J Hum Nutr Diet. 2018;31:67–84.

    CAS  PubMed  Google Scholar 

  14. Zhang YY, Liu W, Zhao TY, Tian HM. Efficacy of omega-3 polyunsaturated fatty acids supplementation in managing overweight and obesity: a meta-analysis of randomized clinical trials. J Nutr Health Aging. 2017;21:187–92.

    CAS  PubMed  Google Scholar 

  15. Haghiac M, Yang XH, Presley L, Smith S, Dettelback S, Minium J, et al. Dietary omega-3 fatty acid supplementation reduces inflammation in obese pregnant women: a randomized double-blind controlled clinical trial. PloS one. 2015;10:e0137309.

  16. Jamilian M, Samimi M, Kolahdooz F, Khalaji F, Razavi M, Asemi Z. Omega-3 fatty acid supplementation affects pregnancy outcomes in gestational diabetes: a randomized, double-blind, placebo-controlled trial. J Matern Fetal Neonat Med. 2016;29:669–75.

    CAS  Google Scholar 

  17. Barden AE, Dunstan JA, Beilin LJ, Prescott SL, Mori TA. n -- 3 fatty acid supplementation during pregnancy in women with allergic disease: effects on blood pressure, and maternal and fetal lipids. Clin Sci (Lond). 2006;111:289–94.

    CAS  Google Scholar 

  18. Franke C, Demmelmair H, Decsi T, Campoy C, Cruz M, Molina-Font JA, et al. Influence of fish oil or folate supplementation on the time course of plasma redox markers during pregnancy. Br J Nutr. 2010;103:1648–56.

    CAS  PubMed  Google Scholar 

  19. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.

    PubMed  PubMed Central  Google Scholar 

  20. Mansournia MA, Higgins JP, Sterne JA, Hernan MA. Biases in Randomized Trials: A Conversation Between Trialists and Epidemiologists. Epidemiology. 2017;28:54–9.

    PubMed  PubMed Central  Google Scholar 

  21. Overvad K, Diamant B, Holm L, Holmer G, Mortensen SA, Stender S. Coenzyme Q10 in health and disease. Eur J Clin Nutr. 1999;53:764–70.

    CAS  PubMed  Google Scholar 

  22. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    PubMed  PubMed Central  Google Scholar 

  23. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj. 1997;315:629–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Helland IB, Saugstad OD, Saarem K, Van Houwelingen AC, Nylander G, Drevon CA. Supplementation of n-3 fatty acids during pregnancy and lactation reduces maternal plasma lipid levels and provides DHA to the infants. J Matern Fetal Neonatal Med. 2006;19:397–406.

    CAS  PubMed  Google Scholar 

  25. Samimi M, Jamilian M, Asemi Z, Esmaillzadeh A. Effects of omega-3 fatty acid supplementation on insulin metabolism and lipid profiles in gestational diabetes: randomized, double-blind, placebo-controlled trial. Clin Nutr. 2015;34:388–93.

  26. Faraji I, Ostadrahimi A, Farshbaf-Khalili A, Aslani H. The impact of supplementation with fish oil on lipid profile of pregnant mothers: a randomized controlled trial. Changes. 2016;2:5.

  27. Jamilian M, Samimi M, Ebrahimi FA, Hashemi T, Taghizadeh M, Razavi M, et al. The effects of vitamin D and omega-3 fatty acid co-supplementation on glycemic control and lipid concentrations in patients with gestational diabetes. J Clin Lipidol. 2017;11:459–68.

    PubMed  Google Scholar 

  28. Razavi M, Jamilian M, Samimi M, Afshar Ebrahimi F, Taghizadeh M, Bekhradi R, et al. The effects of vitamin D and omega-3 fatty acids co-supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in patients with gestational diabetes. Nutr Metab. 2017;14:80.

    Google Scholar 

  29. Jamilian M, Samimi M, Mirhosseini N, Afshar Ebrahimi F, Aghadavod E, Taghizadeh M, et al. A Randomized double-blinded, placebo-controlled trial investigating the effect of fish oil supplementation on gene expression related to insulin action, blood lipids, and inflammation in gestational diabetes mellitus-fish oil supplementation and gestational diabetes. Nutrients. 2018;10.

  30. Kajarabille N, Peña M, Díaz-Castro J, Hurtado JA, Peña-Quintana L, Iznaola C, et al. Omega-3 LCPUFA supplementation improves neonatal and maternal bone turnover: a randomized controlled trial. J Funct Foods. 2018;46:167–74.

  31. Mozurkewich EL, Berman DR, Vahratian A, Clinton CM, Romero VC, Chilimigras JL, et al. Effect of prenatal EPA and DHA on maternal and umbilical cord blood cytokines. BMC Pregnancy Childbirth. 2018;18:261.

    PubMed  PubMed Central  Google Scholar 

  32. Vahedi L, Ostadrahimi A, Edalati-Fard F, Aslani H, Farshbaf-Khalili A. Is fish oil supplementation effective on maternal serum FBS, oral glucose tolerance test, hemoglobin and hematocrit in low risk pregnant women? A triple-blind randomized controlled trial. J Complement Integr Med. 2018;15.

  33. Pellonpera O, Mokkala K. Efficacy of fish oil and/or probiotic intervention on the incidence of gestational diabetes mellitus in an at-risk group of overweight and obese women: a randomized, placebo-controlled. Double-Blind Clin Trial. 2019;42:1009–17.

    CAS  Google Scholar 

  34. Herrera E, Ortega-Senovilla H. Lipid metabolism during pregnancy and its implications for fetal growth. Curr Pharm Biotechnol. 2014;15:24–31.

    CAS  PubMed  Google Scholar 

  35. Gao H, Geng T, Huang T, Zhao Q. Fish oil supplementation and insulin sensitivity: a systematic review and meta-analysis. Lipids Health Dis. 2017;16:131.

    PubMed  PubMed Central  Google Scholar 

  36. Choi HD, Chae SM. Comparison of efficacy and safety of combination therapy with statins and omega-3 fatty acids versus statin monotherapy in patients with dyslipidemia: a systematic review and meta-analysis. Medicine. 2018;97:e13593.

  37. Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2018;11:Cd003177.

    PubMed  Google Scholar 

  38. Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH. The pathophysiology of gestational diabetes mellitus. Int J Mol Sci. 2018;19.

  39. Marchlewicz EH, Dolinoy DC, Tang L, Milewski S, Jones TR, Goodrich JM, et al. Lipid metabolism is associated with developmental epigenetic programming. Sci Rep. 2016;6:34857.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Wild R, Weedin EA, Wilson D. Dyslipidemia in pregnancy. Cardiol Clin. 2015;33:209–15.

    PubMed  Google Scholar 

  41. Palinski W, Nicolaides E, Liguori A, Napoli C. Influence of maternal dysmetabolic conditions during pregnancy on cardiovascular disease. J Cardiovasc Transl Res. 2009;2:277–85.

    PubMed  PubMed Central  Google Scholar 

  42. Mendelson MM, Lyass A, O’Donnell CJ, D’Agostino RB, Sr., Levy D. Association of maternal prepregnancy dyslipidemia with adult offspring dyslipidemia in excess of anthropometric, lifestyle, and genetic factors in the Framingham heart study. JAMA Cardiol. 2016;1:26–35.

    PubMed  PubMed Central  Google Scholar 

  43. Adkins Y, Kelley DS. Mechanisms underlying the cardioprotective effects of omega-3 polyunsaturated fatty acids. J Nutr Biochem. 2010;21:781–92.

    CAS  PubMed  Google Scholar 

  44. Lalia AZ, Lanza IR. Insulin-sensitizing effects of omega-3 fatty acids: lost in translation? Nutrients. 2016;8.

  45. Pinel A, Morio-Liondore B, Capel F. n-3 Polyunsaturated fatty acids modulate metabolism of insulin-sensitive tissues: implication for the prevention of type 2 diabetes. J Physiol Biochem. 2014;70:647–58.

    CAS  PubMed  Google Scholar 

  46. Cicero AFG, Colletti A, Bajraktari G, Descamps O, Djuric DM, Ezhov M, et al. Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel. Nutr Rev. 2017;75:731–67.

    PubMed  Google Scholar 

  47. Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, et al. Effects of n-3 fatty acid supplements in diabetes mellitus. N Engl J Med. 2018;379:1540–50.

  48. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11–22.

  49. Reiner Z, Laufs U, Cosentino F, Landmesser U. The year in cardiology 2018: prevention. Eur Heart J. 2019;40:336–44.

    CAS  PubMed  Google Scholar 

  50. O'Mahoney LL, Matu J, Price OJ, Birch KM, Ajjan RA, Farrar D, et al. Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials. Cardiovascular diabetology. 2018;17:98.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. He L, Li MS, Lin M, Zhao TY, Gao P. Effect of fish oil supplement in maintenance hemodialysis patients: a systematic review and meta-analysis of published randomized controlled trials. Eur J Clin Pharmacol. 2016;72:129–39.

    CAS  PubMed  Google Scholar 

  52. Sepidarkish M, Akbari-Fakhrabadi M, Daneshzad E, Yavari M, Rezaeinejad M, Morvaridzadeh M, et al. Effect of omega-3 fatty acid plus vitamin E Co-Supplementation on oxidative stress parameters: a systematic review and meta-analysis. Clinical nutrition (Edinburgh, Scotland). 2019.

  53. Ren GY, Chen CY, Chen GC, Chen WG, Pan A, Pan CW, et al. Effect of flaxseed intervention on inflammatory marker c-reactive protein: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2016;8:136.

  54. Hu C, Yang M, Zhu X, Gao P, Yang S, Han Y, et al. Effects of omega-3 fatty acids on markers of inflammation in patients with chronic kidney disease: a controversial issue. Ther Apher Dial. 2018;22:124–32.

  55. Polettini J, Dutta EH, Behnia F, Saade GR, Torloni MR, Menon R. Aging of intrauterine tissues in spontaneous preterm birth and preterm premature rupture of the membranes: a systematic review of the literature. Placenta. 2015;36:969–73.

  56. Dutta EH, Behnia F, Boldogh I, Saade GR, Taylor BD, Kacerovsky M, et al. Oxidative stress damage-associated molecular signaling pathways differentiate spontaneous preterm birth and preterm premature rupture of the membranes. Mol Hum Reprod. 2016;22:143–57.

    CAS  PubMed  Google Scholar 

  57. Girardi G. Can statins prevent pregnancy complications? J Reprod Immunol. 2014;101–102:161–7.

    PubMed  Google Scholar 

  58. Groom KM, David AL. The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction. Am J Obstet Gynecol. 2018;218:829-s40.

    Google Scholar 

  59. Calder PC. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans. 2017;45:1105–15.

    CAS  PubMed  Google Scholar 

  60. Bannenberg G, Serhan CN. Specialized pro-resolving lipid mediators in the inflammatory response: an update. Biochim Biophys Acta. 2010;1801:1260–73.

  61. Jones ML, Mark PJ, Waddell BJ. Maternal dietary omega-3 fatty acids and placental function. Reproduction. 2014;147:R143-52.

    PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran

    Elaheh Amirani & Zatollah Asemi

  2. Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran

    Omid Asbaghi

  3. Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Alireza Milajerdi

  4. Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran

    Alireza Milajerdi

  5. Department of Internal Medicine, School of Medicine, University Hospital Centre Zagreb, University of Zagreb, Zagreb, Croatia

    Željko Reiner

  6. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Ali Mansournia

  7. Department of Biochemistry and Nutrition, Research Center for Evidence-Based Health Management, Maragheh University of Medical Sciences, Maragheh, Iran

    Jamal Hallajzadeh

  8. Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran

    Bahram Moazzami & Shahla Chaichian

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  1. Elaheh Amirani
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Contributions

JH and SC contributed in conception, design, statistical analysis and drafting of the manuscript. EA, ZA, OA, AM, MAM, ZR and BM contributed in conception, data collection and manuscript drafting. The final version was confirmed by all authors for submission.

Corresponding authors

Correspondence to Jamal Hallajzadeh or Shahla Chaichian.

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Amirani, E., Asemi, Z., Asbaghi, O. et al. The effects of omega-3 fatty acids supplementation on metabolic status in pregnant women: a systematic review and meta-analysis of randomized controlled trials. J Diabetes Metab Disord 19, 1685–1699 (2020). https://doi.org/10.1007/s40200-020-00558-5

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