The aim of this meta-analysis was to evaluate the effects of low-ratio n-6/n-3 PUFA on blood lipid levels.
We searched the PubMed, Embase, and Cochrane Library databases for randomized controlled trials of n-6/n-3 PUFA interventions up to March 2019. The change values were calculated as weighted mean differences (WMDs) by using a random-effect model. Subgroup analysis and meta-regression were used to explore the source of heterogeneity.
A total of 30 randomized controlled trials with 1368 participants were identified. Compared with control, low-ratio n-6/n-3 PUFA significantly reduced triglyceride (TG) concentration (WMD: − 0.079 mmol/L, 95% confidence interval (CI): − 0.148 mmol/L to − 0.009 mmol/L, p = 0.026) and increased high-density lipoprotein cholesterol (HDL-C) concentration (WMD: 0.033 mmol/L, 95% CI: 0.007 to 0.058 mmol/L, p = 0.012). Subgroup analysis revealed that the effects of low-ratio n-6/n-3 PUFA on blood lipid levels were better for a longer time. The effects of α-linolenic acid on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations were more obvious among participants. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) had more significant effects on TG and HDL-C concentrations. No significant publication bias was observed for TG and HDL-C, as suggested by the results of Begg’s test and Egger’s test.
Low-ratio n-6/n-3 PUFA significantly reduced TG concentration and increased HDL-C concentration. The beneficial effects of low-ratio n-6/n-3 PUFA on TG, TC, HDL-C, and LDL-C concentrations were enhanced with time. However, n-3 PUFA derived from plants significantly reduced TC and LDL-C concentrations, and n-3 PUFA derived from EPA and DHA significantly reduced TG concentration and increased HDL-C concentration.
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Spiteller G (2010) Is atherosclerosis a multifactorial disease or is it induced by a sequence of lipid peroxidation reactions? Ann N Y Acad Sci 1043:355–366. https://doi.org/10.1196/annals.1333.042
Finley JW, Shahidi F (2001) The chemistry, processing, and health benefits of highly unsaturated fatty acids: an overview. ACS Sym Ser 788:2–11. https://doi.org/10.1021/bk-2001-0788.ch001
Balk EM, Lichtenstein AH, Chung M et al (2006) Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis 189:19–30. https://doi.org/10.1016/j.atherosclerosis.2006.02.012
Millward DJ (2012) Identifying recommended dietary allowances for protein and amino acids: a critique of the 2007 WHO/FAO/UNU report. Br J Nutr 108:S3–S21. https://doi.org/10.1017/S0007114512002450
Griffin MD, Sanders TA, Davies IG et al (2006) Effects of altering the ratio of dietary n-6 to n-3 fatty acids on insulin sensitivity, lipoprotein size, and postprandial lipemia in men and postmenopausal women aged 45-70y: the OPTILIP Study. Am J Clin Nutr 84:1290–1298. https://doi.org/10.1556/AAlim.35.2006.4.13
Kuhnt K, Fuhrmann C, Kohler M et al (2014) Dietary echium oil increases long-chain n-3 PUFAs, including docosapentaenoic acid, in blood fractions and alters biochemical markers for cardiovascular disease independently of age, sex, and metabolic syndrome. J Nutr 144:447–460. https://doi.org/10.3945/jn.113.180802
Jacobo-Cejudo MG, Valdes-Ramos R, Guadarrama-Lopez AL et al. (2017) Effect of n-3 polyunsaturated fatty acid supplementation on metabolic and inflammatory biomarkers in type 2 diabetes mellitus patients. Nutrients, 9. DOI: https://doi.org/10.3390/nu9060573
Samimi M, Jamilian M, Asemi Z et al (2015) Effects of omega-3 fatty acid supplementation on insulin metabolism and lipid profiles in gestational diabetes: randomized, double-blind, placebo-controlled trial. Clin Nutr 34:388–393. https://doi.org/10.1016/j.clnu.2014.06.005
Kooshki A, Taleban FA, Tabibi H et al (2011) Effects of omega-3 fatty acids on serum lipids, lipoprotein (a), and hematologic factors in hemodialysis patients. Ren Fail 33:892–898. https://doi.org/10.3109/0886022x.2011.605536
Brady LM, Lovegrove SS, Lesauvage SVM et al (2004) Increased n-6 polyunsaturated fatty acids do not attenuate the effects of long-chain n-3 polyunsaturated fatty acids on insulin sensitivity or triacylglycerol reduction in Indian Asians. Am J Clin Nutr 79:983–991. https://doi.org/10.1556/AAlim.33.2004.2.12
Minihane AM, Brady LM, Lovegrove SS et al (2005) Lack of effect of dietary n-6:n-3 PUFA ratio on plasma lipids and markers of insulin responses in Indian Asians living in the UK. Eur J Nutr 44:26–32. https://doi.org/10.1007/s00394-004-0488-9
Dawczynski C, Martin L, Wagner A et al (2010) n-3 LC-PUFA-enriched dairy products are able to reduce cardiovascular risk factors: a double-blind, cross-over study. Clin Nutr (Edinburgh, Scotland) 29:592–599. https://doi.org/10.1016/j.clnu.2010.02.008
Clandinin MT, Foxwell A, Goh YK et al (1997) Omega-3 fatty acid intake results in a relationship between the fatty acid composition of LDL cholesterol ester and LDL cholesterol content in humans. Biochim Biophys Acta 1346:247–252. https://doi.org/10.1016/S0005-2760(97)00040-4
Finnegan YE, Minihane AM, Leigh Firbank EC et al (2003) Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects. Am J Clin Nutr 77:783–795. https://doi.org/10.1093/ajcn/77.4.783
Hallund J, Madsen BO, Bugel SH et al (2010) The effect of farmed trout on cardiovascular risk markers in healthy men. Br J Nutr 104:1528–1536. https://doi.org/10.1017/S0007114510002527
Wang F, Wang Y, Zhu Y et al (2017) Treatment for 6 months with fish oil-derived n-3 polyunsaturated fatty acids has neutral effects on glycemic control but improves dyslipidemia in type 2 diabetic patients with abdominal obesity: a randomized, double-blind, placebo-controlled trial. Eur J Nutr 56:2415–2422. https://doi.org/10.1007/s00394-016-1352-4
Lee TC, Ivester P, Hester AG et al (2014) The impact of polyunsaturated fatty acid-based dietary supplements on disease biomarkers in a metabolic syndrome/diabetes population. Lipids Health Dis 13:196. https://doi.org/10.1186/1476-511X-13-196
McManus RM, Jumpson J, Finegood DT et al (1996) A comparison of the effects of n-3 fatty acids from linseed oil and fish oil in well-controlled type II diabetes. Diabetes Care 19:463–467. https://doi.org/10.2337/diacare.19.5.463
Cassani RSL, Fassini PG, Silvah JH et al (2015) Impact of weight loss diet associated with flaxseed on inflammatory markers in men with cardiovascular risk factors a clinical study. Nutr J 14:5. https://doi.org/10.1186/1475-2891-14-5
Tapsell LC, Gillen LJ, Patch C et al (2004) Including walnuts in a low-fat modified-fat diet improves HDL cholesterol-to-total cholesterol ratios in patients with type 2 diabetes. Diabetes Care 27:2777–2783. https://doi.org/10.2337/diacare.27.12.2777
Zhao G, Etherton TD, Martin KR et al (2004) Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women. J Nutr 134:2991–2997. https://doi.org/10.1093/jn/134.11.2991
Kontogianni MD, Vlassopoulos A, Gatzieva A et al (2013) Flaxseed oil does not affect inflammatory markers and lipid profile compared to olive oil, in young, healthy, normal weight adults. Metabolism 62:686–693. https://doi.org/10.1016/j.metabol.2012.11.007
Kawakami Y, Yamanaka-Okumura H, Naniwa-Kuroki Y et al (2015) Flaxseed oil intake reduces serum small dense low-density lipoprotein concentrations in Japanese men: a randomized, double blind, crossover study. Nutr J 14:39. https://doi.org/10.1186/s12937-015-0023-2
Dittrich M, Jahreis G, Bothor K et al (2015) Benefits of foods supplemented with vegetable oils rich in alpha-linolenic, stearidonic or docosahexaenoic acid in hypertriglyceridemic subjects: a double-blind, randomized, controlled trail. Eur J Nutr 54:881–893. https://doi.org/10.1007/s00394-014-0764-2
Tahvonen RL, Schwab US, Linderborg KM et al (2005) Black currant seed oil and fish oil supplements differ in their effects on fatty acid profiles of plasma lipids, and concentrations of serum total and lipoprotein lipids, plasma glucose and insulin. J Nutr Biochem 16:353–359. https://doi.org/10.1016/j.jnutbio.2005.01.004
Sodergren E, Gustafsson IB, Basu S et al (2001) A diet containing rapeseed oil-based fats does not increase lipid peroxidation in humans when compared to a diet rich in saturated fatty acids. Eur J Clin Nutr 55:922–931. https://doi.org/10.1038/sj.ejcn.1601246
Arjmandi BH, Khan DA, Juma S et al (1998) Whole flaxseed consumption lowers serum LDL-cholesterol and lipoprotein(a) concentrations in postmenopausal women. Nutr Res 18:1203–1214. https://doi.org/10.1016/S0271-5317(98)00100-6
Kaul N, Kreml R, Austria JA et al (2008) A comparison of fish oil, flaxseed oil and hempseed oil supplementation on selected parameters of cardiovascular health in healthy volunteers. J Am Coll Nutr 27:51–58. https://doi.org/10.1080/07315724.2008.10719674
Ma Y, Ba JM, Katz DL (2010) Effects of walnut consumption on endothelial function in type 2 diabetic subjects: a randomized controlled crossover trial. Diabetes Care 33:227–232. https://doi.org/10.2337/dc09-1156
Woods MN, Wanke CA, Ling PR et al (2009) Effect of a dietary intervention and n-3 fatty acid supplementation on measures of serum lipid and insulin sensitivity in persons with HIV. Am J Clin Nutr 90:1566–1578. https://doi.org/10.3945/ajcn.2009.28137
Rallidis LS, Paschos G, Liakos GK et al (2003) Dietary alpha-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients. Atherosclerosis 167:237–242. https://doi.org/10.1016/S0021-9150(02)00427-6
Egert S, Kannenberg F, Somoza V et al (2009) Dietary α-linolenic acid, EPA, and DHA have differential effects on LDL fatty acid composition but similar effects on serum lipid profiles in normolipidemic humans. J Nutr 139:861–868. https://doi.org/10.3945/jn.108.103861
Chan EJ, Cho L (2009) What can we expect from omega-3 fatty acids? Cleve Clin J Med 76:245–251. https://doi.org/10.3949/ccjm.76a.08042
Rosa G, Alves Avelino AP, de Oliveira M, Maria G et al (2015) Additive effect of linseed oil supplementation on the lipid profiles of older adults. Clin Interv Aging 10:1679–1685. https://doi.org/10.2147/CIA.S75538
Khajehdehi P (2000) Lipid-lowering effect of polyunsaturated fatty acids in hemodialysis patients. J Ren Nutr 10:191–195. https://doi.org/10.1053/jren.2000.16326
McVeigh GE, Brennan GM, Johnston GD et al (1993) Dietary fish oil augments nitric oxide production or release in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 36:33–38. https://doi.org/10.1007/BF00399090
Woodman RJ, Mori TA, Burke V et al (2002) Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am J Clin Nutr 76:1007–1015. https://doi.org/10.1093/ajcn/76.5.1007
Harper CR, Edwards MC, Jacobson TA (2006) Flaxseed oil supplementation does not affect plasma lipoprotein concentration or particle size in human subjects. J Nutr 136:2844–2848. https://doi.org/10.1093/jn/136.11.2844
O’Mahoney LL, Jamie M, Price OJ et al (2018) Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials. Cardiovasc Diabetol 17:98–111. https://doi.org/10.1186/s12933-018-0740-x
I would like to extend my sincere gratitude to my supervisors, Tongcheng Xu and Hanxue Hou, for their instructive advice and useful suggestions on my thesis. I am also deeply indebted to all the other teachers and students for their help to me.
This work is supported by the National Key R&D Program of China (2018YFD0401104); by the Key R & D project of Shandong Province (2018YYSP011); by the Taishan Scholar Project (Feng-Hong Huang); and by the Key R & D project of Shandong Province (2019GHZ031). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Conflict of interest
The authors declare that they have no conflict of interest.
No animal and human experiments were involved in this study.
We the undersigned declare that this manuscript entitled “The effect of low-ratio n-6/n-3 PUFA on blood lipid: a meta-analysis” is original, has not been published before, and is not currently being considered for publication elsewhere.
We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us.
The authors are the following: Na Li, Min Jia, Qianchun Deng, Zhen Wang, Fenghong Huang, Hanxue Hou, Tongcheng Xu.
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Li, N., Jia, M., Deng, Q. et al. Effect of low-ratio n-6/n-3 PUFA on blood lipid level: a meta-analysis. Hormones (2020). https://doi.org/10.1007/s42000-020-00248-0
- N-6/n-3 PUFA
- Blood lipid
- Randomized controlled trial