α-Linolenic acid and risk of cardiovascular disease: a systematic review and meta-analysis
Open accessAbstract
Background Prior studies of α-linolenic acid (ALA), a plant-derived omega-3 (n-3) fatty acid, and cardiovascular disease (CVD) risk have generated inconsistent results.Objective We conducted a meta-analysis to summarize the evidence regarding the relation of ALA and CVD risk.Design We searched multiple electronic databases through January 2012 for studies that reported the association between ALA (assessed as dietary intake or as a biomarker in blood or adipose tissue) and CVD risk in prospective and retrospective studies. We pooled the multivariate-adjusted RRs comparing the top with the bottom tertile of ALA using random-effects meta-analysis, which allowed for between-study heterogeneity.Results Twenty-seven original studies were identified, including 251,049 individuals and 15,327 CVD events. The overall pooled RR was 0.86 (95% CI: 0.77, 0.97; I² = 71.3%). The association was significant in 13 comparisons that used dietary ALA as the exposure (pooled RR: 0.90; 95% CI: 0.81, 0.99; I² = 49.0%), with similar but nonsignificant trends in 17 comparisons in which ALA biomarkers were used as the exposure (pooled RR: 0.80; 95% CI: 0.63, 1.03; I² = 79.8%). An evaluation of mean participant age, study design (prospective compared with retrospective), exposure assessment (self-reported diet compared with biomarker), and outcome [fatal coronary heart disease (CHD), nonfatal CHD, total CHD, or stroke] showed that none were statistically significant sources of heterogeneity.Conclusions In observational studies, higher ALA exposure is associated with a moderately lower risk of CVD. The results were generally consistent for dietary and biomarker studies but were not statistically significant for biomarker studies. However, the high unexplained heterogeneity highlights the need for additional well-designed observational studies and large randomized clinical trials to evaluate the effects of ALA on CVD.
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Whole flaxseed rather than flaxseed oil seems effective in weight and BMI reduction, which is attributed to the fact that flaxseed can control energy intake and increase satiety by containing 28% fibers.
“Whole flaxseed rather than flaxseed-oil seems effective in weight and BMI reduction which is attributed to the fact that the flaxseed can control the energy intake and increase satiety by containing 28% fibers [88].”
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 [88]
The Introduction discusses plant sources of α-linolenic acid, and the Discussion addresses its association with cardiovascular outcomes. Searches for flaxseed, weight and BMI reduction, satiety, and 28% fiber found no passage in our copy addressing the claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredMost studies have evaluated combined intakes or biomarker levels of long-chain ω-3 PUFAs.
“Most studies10,11 have evaluated combined intakes or biomarker levels of long-chain ω-3 PUFAs.”
From ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies (2016) · cites this paper as [11]
Most prior research has focused on seafood-derived long-chain ω-3 PUFAs, and the potential CHD effects of plant-derived ALA are far less understood.
“most prior research11 has focused on seafood-derived long-chain ω-3 PUFAs, and potential CHD effects of plant-derived α-linolenic acid (ALA; 18:3ω-3) are far less understood.”
From ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies (2016) · cites this paper as [11]
A meta-analysis of prior reports of dietary and biomarker ALA and CHD risk revealed inconsistency, perhaps due to methodologic and analytic differences.
“However, a meta-analysis11 of prior reports of dietary and biomarker ALA and CHD risk revealed inconsistency, perhaps owing to methodologic and analytic differences in these investigations.”
From ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies (2016) · cites this paper as [11]
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- Authors
- Pan, A., Chen, M., Chowdhury, R., Wu, J. H., Sun, Q., Campos, H., Mozaffarian, D., & Hu, F. B.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 96
- Issue
- 6
- Pages
- 1262-1273
- ISSN
- 0002-9165 (ISSN-L)
- PMC
- PMC3497923
- OpenAlex
- W2112093807
- Cited by
- 329
- References
- 63
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 13 · 2023: 15 · 2022: 28 · 2021: 31 · 2020: 35 · 2019: 20 · 2018: 25 · 2017: 22 · 2016: 31 · 2015: 25 · 2014: 30 · 2013: 20 · 2012: 1
- FWCI
- 2.97
- 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
- British Heart Foundation (RG/08/014/24067)
- National Institutes of Health
- National Heart, Lung, and Blood Institute (K99HL098459, HL-034594, R00HL098459, HL-088521, R01HL034594, R01HL088521)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Nursing › Nutrition and Dietetics › Nuts composition and effects
- Keywords
- alpha-linolenic acid, omega-3 fatty acids, cardiovascular risk, dietary intake, coronary artery disease, stroke, observational studies, heterogeneity
- MeSH terms
- Cardiovascular Diseases, Diet, Humans, Risk, Reproducibility of Results, Biomarkers, alpha-Linolenic Acid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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