EC Nutrition

Systematic Review Volume 18 Issue 5 - 2023

Fish Oil Supplementation and Circulating Lipoprotein (a) Levels: A Grade-Assessed Systematic Review and Dose-Response Meta-Analysis of 20 Randomized Controlled Trials

Shahrooz Bentyaghoub1, Niki Bahrampour2, Mohsen Mohammadi-Sartang1, Nastaran Rafiepour3, Sepideh Rajabi Nezhad4, Faranak Taghipour1, Hamed Sadeghi-Dehsahraei5, Cain C. T. Clark6, Mohammad Ahmadi7*, Mohsen Ranjbar8, MohammadAli Izadi9

1Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
2Department of Nutrition, Science and Research Branch, Islamic Azad University (SRBIAU), Tehran, Iran
3Islamic Azad University, Rasht Branch, Rash, Iran
4Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
5Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
6Research Institute for Health and Wellbeing, Coventry University, Coventry, CV1 5FB, U.K
7Department of Clinical Sciences, School of Veterinary Medicine, Islamic Azad University of Shahrekord, Shahrekord, Iran
8School of Nursing and Midwifery, Shiraz University of Medical Sciences, Shiraz, Iran
9Department of Sport Sciences, Faculty of educational sciences and Psychology, Shiraz University, Shiraz, Iran
*Corresponding Author: Mohammad Ahmadi, Department of Clinical Sciences, School of Veterinary Medicine, Islamic Azad University of Shahrekord, Shahrekord, Iran.
Received: March 14, 2023; Published: April 06, 2023



Objectives: Although fish oil plays an important role in the prevention of cardiovascular diseases, the results of clinical trial studies regarding its effect on lipoprotein (a) [Lp(a)] concentrations factor are inconsistent. Therefore, we performed a meta-analysis of available randomized controlled trials (RCTs) to elucidate the efficacy of fish oil on plasma Lp(a) concentrations.

Methods: Net changes in Lp(a) were used to calculate the effect size, which was reported as a weighted mean difference (WMD) and 95% confidence intervals (CIs). The inclusion criteria were adult participants and an intervention duration of ≥ 2 weeks. In the primary search, 340 articles were found, of which 37 were assessed in full text and 20 trials (1356 participants) were included in the meta-analysis.

Results: The meta-analysis indicated a significant reduction in plasma Lp(a) levels (WMD: -1.96 mg/L, 95% CI: -3.63 to -0.30; P = 0.021) following fish oil supplementation. In the sub-group analysis, a significant reduction was observed only at doses < 3 g/day (WMD: -7.35 mg/L, 95% CI: -13.80, -0.89, p = 0.026), and with treatment duration ≥ 12 weeks (WMD: -2.56 mg/L, 95% CI: -4.67, -0.45, p = 0.017). A dose-response analysis revealed that < 3 g/day of fish oil largely decreased Lp(a) levels (P-nonlinearity = 0.006).

Conclusion: The current evidence from RCTs showed that fish oil supplementation may significantly reduce Lp(a) levels at doses lower than 3 g/day when the supplementation lasts over 12 weeks. Further well-constructed randomized clinical trials are needed.

Keywords: Fish Oil; Omega-3 Fatty Acid; Lipoprotein (a)

  1. Kostner G., et al. “Can serum Lp (a) concentrations be lowered by drugs and/or diet”. Treatment of Hyperlipoproteinemia (1984): 151-156.
  2. Dahlen GH., et al. “Association of levels of lipoprotein Lp (a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography”. Circulation4 (1986): 758-765.
  3. Boffa MB., et al. “Lipoprotein (a) as a risk factor for atherosclerosis and thrombosis: mechanistic insights from animal models”. Clinical Biochemistry5 (2004): 333-343.
  4. Nielsen LB., et al. “Increased Degradation of Lipoprotein (a) in Atherosclerotic Compared with Nonlesioned Aortic Intima–Inner Media of Rabbits In Vivo Evidence That Lipoprotein (a) May Contribute to Foam Cell Formation”. Arteriosclerosis, Thrombosis, and Vascular Biology4 (1998): 641-649.
  5. Collaboration ERF. “Lipoprotein (a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality”. JAMA: The Journal of the American Medical Association4 (2009): 412.
  6. Bennet A., et al. “Lipoprotein (a) levels and risk of future coronary heart disease: large-scale prospective data”. Archives of Internal Medicine6 (2008): 598-608.
  7. Lippi G., et al. “Screening and therapeutic management of lipoprotein (a) excess: review of the epidemiological evidence, guidelines and recommendations”. Clinica Chimica Acta11 (2011): 797-801.
  8. Hoefler G., et al. “Lipoprotein Lp (a). A risk factor for myocardial infarction”. Arteriosclerosis, Thrombosis, and Vascular Biology4 (1988): 398-401.
  9. Vongpromek R., et al. “Lipoprotein (a) levels are associated with aortic valve calcification in asymptomatic patients with familial hypercholesterolaemia”. Journal of Internal Medicine2 (2015): 166-173.
  10. Marcovina SM., et al. “Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein (a) and Cardiovascular Disease: recent advances and future directions”. Clinical Chemistry11 (2003): 1785-1796.
  11. Clarke R., et al. “Genetic variants associated with Lp (a) lipoprotein level and coronary disease”. New England Journal of Medicine26 (2009): 2518-2528.
  12. Berglund L and R Ramakrishnan. “Lipoprotein (a) an elusive cardiovascular risk factor”. Arteriosclerosis, Thrombosis, and Vascular Biology12 (2004): 2219-2226.
  13. Hobbs HH and AL White. “Lipoprotein (a): intrigues and insights”. Current Opinion in Lipidology3 (1999): 225-236.
  14. Nielsen LB. “Atherogenecity of lipoprotein (a) and oxidized low density lipoprotein: insight from in vivo studies of arterial wall influx, degradation and efflux”. Atherosclerosis2 (1999): 229-243.
  15. Kang C., et al. “Lp (a) Particles Mold Fibrin-Binding Properties of Apo (a) in Size-Dependent Manner A Study with Different-Length Recombinant Apo (a), Native Lp (a), and Monoclonal Antibody”. Arteriosclerosis, Thrombosis, and Vascular Biology7 (2002): 1232-1238.
  16. Allen S., et al. “Expression of adhesion molecules by Lp (a): a potential novel mechanism for its atherogenicity”. The FASEB Journal15 (1998): 1765-1776.
  17. Goldstein LB., et al. “Guidelines for the primary prevention of stroke a guideline for healthcare professionals from the American Heart Association/American Stroke Association”. Stroke2 (2011): 517-584.
  18. Marcovina SM., et al. “Fish Intake, Independent of Apo (a) Size, Accounts for Lower Plasma Lipoprotein (a) Levels in Bantu Fishermen of Tanzania the Lugalawa Study”. Arteriosclerosis, Thrombosis, and Vascular Biology5 (1999): 1250-1256.
  19. Nelson GJ and RG Ackman. “Absorption and transport of fat in mammals with emphasis on n−3 polyunsaturated fatty acids”. Lipids11 (1988): 1005-1014.
  20. Herrmann W and GM Kostner. “Comparison of effects of N-3 to N-6 fatty acids on serum level of lipoprotein (a) in patients with coronary artery disease”. The American Journal of Cardiology7 (1995): 459-462.
  21. Beil FU., et al. “Dietary fish oil lowers lipoprotein (a) in primary hypertriglyceridemia”. Atherosclerosis1 (1991): 95-97.
  22. Eritsland J., et al. “Serum Lp (a) lipoprotein levels in patients with coronary artery disease and the influence of long-term n-3 fatty acid supplementation”. Scandinavian Journal of Clinical and Laboratory Investigation4 (1995): 295-300.
  23. Moher D., et al. “Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement”. Systematic Reviews1 (2015): 1.
  24. Higgins JP., et al. “The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials”. BMJ (2011): 343.
  25. Guyatt G., et al. “GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables”. Journal of Clinical Epidemiology4 (2011): 383-394.
  26. Balshem H., et al. “GRADE guidelines: 3. Rating the quality of evidence”. Journal of Clinical Epidemiology4 (2011): 401-406.
  27. Higgins J and S Green. “Cochrane handbook for systematic reviews of interventions”. Wiley Online Library 5 (2008).
  28. Hozo SP., et al. “Estimating the mean and variance from the median, range, and the size of a sample”. BMC Medical Research Methodology1 (2005): 1.
  29. Sahebkar A. “Are Curcuminoids Effective C‐Reactive Protein‐Lowering Agents in Clinical Practice? Evidence from a Meta‐Analysis”. Phytotherapy Research5 (2014): 633-642.
  30. Duval S and R Tweedie. “Trim and fill: a simple funnel‐plot–based method of testing and adjusting for publication bias in meta‐analysis”. Biometrics2 (2000): 455-463.
  31. Borenstein M., et al. “Comprehensive meta-analysis version 2”. Englewood, NJ: Biostat (2005): 104.
  32. Conquer JA., et al. “Effect of supplementation with dietary seal oil on selected cardiovascular risk factors and hemostatic variables in healthy male subjects”. Thrombosis Research3 (1999): 239-250.
  33. Derosa G., et al. “Effects of long chain ω-3 fatty acids on metalloproteinases and their inhibitors in combined dyslipidemia patients”. Expert Opinion on Pharmacotherapy8 (2009): 1239-1247.
  34. Prisco D., et al. “No changes in PAI-1 levels after four-month n-3 PUFA ethyl ester supplementation in healthy subjects”. Thrombosis Research3 (1994): 237-244.
  35. Faghihi T., et al. “Role of Omega-3 fatty acids in preventing metabolic disturbances in patients on olanzapine plus either sodium valproate or lithium: a randomized double-blind placebo- controlled trial”. DARU Journal of Pharmaceutical Sciences1 (2012): 1.
  36. Schmidt EB., et al. “The effect of n-3 fatty acids on lipids and lipoproteins in patients treated with chronic haemodialysis: a randomized placebo-controlled intervention study”. Nephrology Dialysis Transplantation9 (2008): 2918-2924.
  37. Engström K., et al. “Effects of Scandinavian caviar paste enriched with a stable fish oil on plasma phospholipid fatty acids and lipid peroxidation”. European Journal of Clinical Nutrition9 (2003): 1052-1059.
  38. Christensen JH., et al. “The effect of n-3 fatty acids on plasma lipids and lipoproteins and blood pressure in patients with CRF”. American Journal of Kidney Diseases1 (2004): 77-83.
  39. Kooshki A., et al. “Effects of omega-3 fatty acids on serum lipids, lipoprotein (a), and hematologic factors in hemodialysis patients”. Renal Failure9 (2011): 892-898.
  40. Qin Y., et al. “Fish oil supplements lower serum lipids and glucose in correlation with a reduction in plasma fibroblast growth factor 21 and prostaglandin E2 in nonalcoholic fatty liver disease associated with hyperlipidemia: a randomized clinical trial”. PloS One7 (2015): e0133496.
  41. Bowden RG., et al. “Fish oil supplementation lowers C-reactive protein levels independent of triglyceride reduction in patients with end-stage renal disease”. Nutrition in Clinical Practice4 (2009): 508-512.
  42. Beavers KM., et al. “Effect of over-the-counter fish-oil administration on plasma Lp (a) levels in an end-stage renal disease population”. Journal of Renal Nutrition6 (2009): 443-449.
  43. Dahlén GH. “Lp (a) lipoprotein in cardiovascular disease”. Atherosclerosis2 (1994): 111-126.
  44. Gries A., et al. “Influence of dietary fish oils on plasma Lp (a) levels”. In Thrombosis Research (1990).
  45. Schmidt EB., et al. “The effect of n-3 polyunsaturated fatty acids on Lp (a)”. Clinica Chimica Acta3 (1991): 271-277.
  46. Malle E., et al. “Effects of dietary fish oil supplementation on platelet aggregability and platelet membrane fluidity in normolipemic subjects with and without high plasma Lp (a) concentrations”. Atherosclerosis2-3 (1991): 193-201.
  47. Colussi GL., et al. “ω-3 polyunsaturated fatty acids decrease plasma lipoprotein (a) levels in hypertensive subjects”. Clinical Nutrition5 (2004): 1246-1247.
  48. Haglund O., et al. “Effects of fish oil on some parameters of fibrinolysis and lipoprotein (a) in healthy subjects”. The American Journal of Cardiology2 (1994): 189-192.
  49. Missala I., et al. “A systematic literature review of the association of lipoprotein (a) and autoimmune diseases and atherosclerosis”. International Journal of Rheumatology (2012).
  50. Maeda S., et al. “Transient changes of serum lipoprotein (a) as an acute phase protein”. Atherosclerosis2-3 (1989): 145-150.
  51. Schultz O., et al. “Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a) levels in human subjects with rheumatoid diseases”. PloS One12 (2010): e14328.
  52. Simopoulos AP. “Omega-3 fatty acids in inflammation and autoimmune diseases”. Journal of the American College of Nutrition6 (2002): 495-505.
  53. Ellulu MS., et al. “Role of fish oil in human health and possible mechanism to reduce the inflammation”. Inflammopharmacology2-3 (2015): 79-89.
  54. Koppe C., et al. “Reduction of arteriosclerotic nanoplaque formation and size by n-3 fatty acids in patients after valvular defect operation”. Forschende Komplementärmedizin/Research in Complementary Medicine4 (2009): 237-245.
  55. Deck C and K Radack. “Effects of modest doses of omega-3 fatty acids on lipids and lipoproteins in hypertriglyceridemic subjects: a randomized controlled trial”. Archives of Internal Medicine8 (1989): 1857-1862.
  56. Schectman G., et al. “Effect of fish oil concentrate on lipoprotein composition in NIDDM”. Diabetes11 (1988): 1567-1573.
  57. Axelrod L. “Omega-3 fatty acids in diabetes mellitus: Gift from the sea?” Diabetes5 (1989): 539-543.
  58. Marcley Vergili-nelsen J. “Benefits of fish oil supplementation for hemodialysis patients”. Journal of the American Dietetic Association9 (2003): 1174-1177.

Mohammad Ahmadi., et al. "Fish Oil Supplementation and Circulating Lipoprotein (a) Levels: A Grade-Assessed Systematic Review and Dose-Response Meta-Analysis of 20 Randomized Controlled Trials". EC Nutrition 18.5 (2023): 74-91.

ECronicon Journal

Our Services

Quick Links

Information

Creative Commons LicenseOpen Access by ECronicon is licensed under a Creative Commons Attribution 4.0 International License
Based on a work at www.ecronicon.net