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Meta-analysis of the effects of flaxseed interventions on blood lipids
Open accessAbstract
Background Several clinical trials have investigated the effects of flaxseed and flaxseed-derived products (flaxseed oil or lignans) on blood lipids; however, the findings have been inconsistent.Objective We aimed to identify and quantify the effectiveness of flaxseed and its derivatives on blood lipid profiles.Design A comprehensive literature search was performed on the basis of English reports of randomized controlled trials of flaxseed or its derivatives on lipid profiles in adults, which were published from January 1990 to October 2008. Attempts also were made to access unpublished data. Study quality was assessed by using the Jadad score, and a meta-analysis was conducted.Results Twenty-eight studies were included. Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L (95% CI: -0.20, 0.00 mmol/L) and 0.08 mmol/L (95% CI: -0.16, 0.00 mmol/L), respectively; significant reductions were observed with whole flaxseed (-0.21 and -0.16 mmol/L, respectively) and lignan (-0.28 and -0.16 mmol/L, respectively) supplements but not with flaxseed oil. The cholesterol-lowering effects were more apparent in females (particularly postmenopausal women), individuals with high initial cholesterol concentrations, and studies with higher Jadad scores. No significant changes were found in the concentrations of HDL cholesterol and triglycerides.Conclusions Flaxseed significantly reduced circulating total and LDL-cholesterol concentrations, but the changes were dependent on the type of intervention, sex, and initial lipid profiles of the subjects. Further studies are needed to determine the efficiency of flaxseed on lipid profiles in men and premenopausal women and to explore its potential benefits on other cardiometabolic risk factors and prevention of cardiovascular disease.
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“Another possible explanation was that the effects of flaxseed oil may have been masked by the use of MUFA- or n-6 PUFA–enriched oils as the control regimen in these included studies [63].”
From Comparisons of the effects of different flaxseed products consumption on lipid profiles, inflammatory cytokines and anthropometric indices in patients with dyslipidemia related diseases: systematic review and a dose-response meta-analysis of randomized controlled trials (2021) · cites this paper as [63]
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“These findings were completely consistent with that meta-analysis [13, 63].”
From Comparisons of the effects of different flaxseed products consumption on lipid profiles, inflammatory cytokines and anthropometric indices in patients with dyslipidemia related diseases: systematic review and a dose-response meta-analysis of randomized controlled trials (2021) · cites this paper as [63]
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“A meta-analyses found that flaxseed intervention improved lipid profiles and reduced CVD risk [6].”
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“A meta-analysis showed that flaxseed interventions reduced total and LDL-cholesterol when whole flaxseed or lignan was used but not when flaxseed oil was administered (41) .”
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“Flaxseed (linseed, Linum usitatissimum), an edible oilrich seed/grain and 1 of the oldest arable crops, was recently acknowledged as a functional food (8).”
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“…trials on whole grains have shown that high intake of whole grains and some cereals were inversely associated with risk of type 2 diabetes (de Munter et al., 2007), cardiovascular disease (Mellen et al., 2008), BMI (Gaesser, 2007), and beneficially influenced blood lipids (Pan et al., 2009).”
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“metabolism [5, 6].”
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“Human trials have shown antihypertensive [8, 9] and cholesterol-lowering effects [10, 11] of dietary flaxseed.”
BackgroundLorzadeh, E., Ramezani‐Jolfaie, N., Mohammadi, M. R., Khoshbakht, Y., & Salehi‐Abargouei, A. (2019) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2019.04.016 · Cited by 43
Mahdavi, A., Bagherniya, M., Mirenayat, M. S., Atkin, S. L., & Sahebkar, A. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-64872-5_13 · Cited by 44
Li, Y., Wang, F., Li, J., Ivey, K. L., Wilkinson, J. E., Wang, D. D., Li, R., Liu, G., Eliassen, A. H., Chan, A. T., et al. (2022) · BMC Microbiology · doi:10.1186/s12866-022-02495-0 · Cited by 41
Langyan, S., Yadava, P., Khan, F. N., Sharma, S., Singh, R., Bana, R. S., Singh, N., Kaur, V., Kalia, S., & Kumar, A. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2023.2280768 · Cited by 40
“These studies showed a reduction in both LDL cholesterol [0.08 mmol/L (95% CI: −0.16, 0.00 mmol/L)] and total cholesterol [0.10 mmol/L (95% CI: −0.20, 0.00 mmol/L)], whereas the linseed oil didn’t show any significant effect on either LDL cholesterol or total cholesterol (Pan et al. 2009).”
InfluentialHealth Effects of Various Edible Vegetable Oils: An Umbrella Review
Voon, P. T., Ng, C. M., Ng, Y. T., Wong, Y. J., Yap, S.-Y., Leong, S. L., Yong, X. S., & Lee, S. W. H. (2024) · Advances in Nutrition · doi:10.1016/j.advnut.2024.100276 · Cited by 45
Yang, C., Xia, H., Wan, M., Lu, Y., Xu, D., Yang, X., Yang, L., & Sun, G. (2021) · Nutrition & Metabolism · doi:10.1186/s12986-021-00619-3 · Cited by 40
Food combinations for cholesterol lowering
Harland, J. I. (2012) · Nutrition Research Reviews · doi:10.1017/s0954422412000170 · Cited by 37
Varghese, S. S., Eekhoudt, C. R., & Jassal, D. S. (2021) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-021-04152-y · Cited by 39
“The main bioactive components found in FLX include alpha-linolenic acid (ALA), and the lignan secoisolariciresinol diglucoside (SDG) responsible for the potent anti-inflammatory and anti-oxidative effects of FLX [62].”
BackgroundInfluentialRistić-Medić, D., Peruničić-Peković, G., Rašić-Milutinović, Z., Takić, M. M., Popović, T., Arsić, A., & Glibetić, M. (2014) · The Scientific World JOURNAL · doi:10.1155/2014/563576 · Cited by 36
“This reduction in fasting serum triglyceride during our intervention was in contrast with the conclusion that the plant-derived n-3 fatty acid is not equivalent to marine-based fatty acid in terms of lowering triglyceride levels [52].”
ResultBoucher, B. A., Cotterchio, M., Curca, I. A., Kreiger, N., Harris, S. A., Kirsh, V. A., & Goodwin, P. J. (2012) · Nutrition and Cancer · doi:10.1080/01635581.2012.687426 · Cited by 36
“Soy foods (isoflavone sources) Any soy foodc 151 (56; 50–62) Any tofu, soybeans, soy milk, soy nuts 105 (39; 33–45) Tofu or bean curd (1/4 cup)d 59 (22; 17–27) 42 (71) 15 (25) 2 (3) Soy or tamari sauce (1 tbsp)d 56 (21; 16–26) 48 (86) 6 (11) 2 (4) Soybeans (1/4 cup)d 54 (20; 15–25) 47 (87) 7 (13) Soy milk (1 glass)d 5…”
Recent perspectives on the role of nutraceuticals as cholesterol-lowering agents
Ward, N. C., Sahebkar, A., Banach, M., & Watts, G. F. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000455 · Cited by 36
Di, Y., Jones, J., Mansell, K. D., Whiting, S. J., Fowler, S. A., Thorpe, L., Billinsky, J. L., Viveky, N., Cheng, P. C., Almousa, A. A., et al. (2017) · Journal of the American College of Nutrition · doi:10.1080/07315724.2017.1342213 · Cited by 34
“Flaxseed supplementation is known to favorably modulate blood lipid levels [15, 16, 42].”
BackgroundPonnampalam, E. N., Lewandowski, P. A., Fahri, F. T., Burnett, V. F., Dunshea, F. R., Plozza, T. E., & Jacobs, J. L. (2015) · Lipids · doi:10.1007/s11745-015-4070-4 · Cited by 34
“Others have reported that flaxseed supplementation reduced circulating low-density lipoprotein (LDL) cholesterol [31].”
BackgroundSimilarities and differences in the nutritional composition of nuts and seeds in Serbia
Dodevska, M. S., Kukić‐Marković, J., Sofrenić, I. V., Tešević, V., Janković, M. M., Djordjevic, B. I., & Ivanović, N. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.1003125 · Cited by 37
“Results of the meta-analysis, which included 28 randomized studies (RCTs), showed that dietary intervention with flaxseed, but not flaxseed oil, decreases total and LDL cholesterol, while another meta-analysis of 11 RCTs also showed a more significant effect of flaxseed compared to flaxseed oil on lowering of systolic…”
BackgroundHaldar, S., Wong, L. H., Tay, S. L., Jacoby, J. J., He, P., Osman, F., Ponnalagu, S., Jiang, Y. R., Lian, H. P. R., & Henry, C. J. (2020) · The Journal of Nutrition · doi:10.1093/jn/nxaa274 · Cited by 31
“Intervention trials with flaxseed oils, rich in ALA, have shown variable effects in reducing LDL-cholesterol concentrations (41), with this meta-analysis suggesting that flaxseed oil may be more effective in those with higher initial total or LDL-cholesterol concentrations, and more recent studies also supported the b…”
BackgroundHasaniani, N., Rahimlou, M., Ahmadi, A. R., Mehdizadeh, A., & Alizadeh, M. (2019) · Clinical Nutrition Research · doi:10.7762/cnr.2019.8.4.284 · Cited by 32
“Dietary soluble fibers have shown cholesterollowering effects [11,31].”
BackgroundClavel, T., & Mapesa, J. O. (2013) · Springer eBooks · doi:10.1007/978-3-642-22144-6_94 · Cited by 30
Dew, T. P., & Williamson, G. (2013) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0b013e3182896ae5 · Cited by 31
Flaxseed in Pediatric Hyperlipidemia
Wong, H., Chahal, N., Manlhiot, C., Niedra, E., & McCrindle, B. W. (2013) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2013.1442 · Cited by 30
Struja, T., Richard, A., Linseisen, J., Eichholzer, M., & Rohrmann, S. (2013) · European Journal of Nutrition · doi:10.1007/s00394-013-0639-y · Cited by 30
“These effects are contradictory to two extensive meta-analyses of randomized controlled trials [48, 66], which reported no effects of”
BackgroundResultInfluentialThe Effect of Diet on Cardiovascular Disease and Lipid and Lipoprotein Levels
Feingold, K. R. (2021) · Europe PMC (PubMed Central) · Cited by 30
George, E. S., Daly, R. M., Tey, S. L., Brown, R. C., Wong, T. H. T., & Tan, S. (2022) · Advances in Nutrition · doi:10.1093/advances/nmac028 · Cited by 33
Food and plant bioactives for reducing cardiometabolic disease: How does the evidence stack up?
Cicero, A. F. G., & Colletti, A. (2017) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2017.04.001 · Cited by 29
Masjedi, M. S., Pour, P. M., Shokoohinia, Y., & Asgary, S. (2021) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2021.100931 · Cited by 29
Dietary flaxseed: Cardiometabolic benefits and its role in promoting healthy aging
Kunutsor, S. K., Jassal, D. S., Ravandi, A., & Lehoczki, A. (2025) · GeroScience · doi:10.1007/s11357-025-01512-0 · Cited by 35
“In 2009, Pan and colleagues [49] pooled the results of 28 RCTs published between 1990 and 2008 to quantify the effectiveness of flaxseed and its derivatives on blood lipid profiles.”
Sun, J., Tang, Y., Yu, X., Xu, Y., Liu, P., Xiao, L., Liu, L., Deng, Q., & Yao, P. (2016) · Journal of Functional Foods · doi:10.1016/j.jff.2016.04.032 · Cited by 26
Wolters, M., Dejanovic, G. M., Asllanaj, E., Günther, K., Pohlabeln, H., Bramer, W. M., Ahrens, J., Nagrani, R., Pigeot, I., Franco, O. H., et al. (2020) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000001566 · Cited by 26
Self-citation
Metadata
- Authors
- Pan, A., Yu, D., Demark-Wahnefried, W., Franco, O. H., & Lin, X.
- Affiliations
- Unilever (United Kingdom) (GB)
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 90
- Issue
- 2
- Pages
- 288-297
- ISSN
- 0002-9165 (ISSN-L)
- PMC
- PMC3361740
- OpenAlex
- W2117685492
- Cited by
- 264
- References
- 59
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 12 · 2023: 13 · 2022: 15 · 2021: 27 · 2020: 29 · 2019: 16 · 2018: 11 · 2017: 18 · 2016: 11 · 2015: 23 · 2014: 22 · 2013: 18 · 2012: 9
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA085740)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Natural Products and Biological Research
- Keywords
- flaxseed, linseed oil, lignans, serum lipids, LDL cholesterol, total cholesterol, HDL cholesterol, triglycerides, cholesterol-lowering effect, sex differences, postmenopausal women, cardiovascular disease prevention, dietary supplements
- MeSH terms
- Anticholesteremic Agents, Cardiovascular Diseases, Cholesterol, Female, Humans, Hypercholesterolemia, Linseed Oil, Cholesterol, HDL, Cholesterol, LDL, Male, Seeds, Triglycerides, Randomized Controlled Trials as Topic, Treatment Outcome, Lignans, Flax, Lipid Metabolism
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