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Dietary intake and biomarkers of alpha linolenic acid and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of cohort studies

BMJ 2021; 375 doi: (Published 14 October 2021) Cite this as: BMJ 2021;375:n2213

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Current evidence on dietary intakes of fatty acids and mortality

  1. Sina Naghshi, masters student1 2,
  2. Dagfinn Aune, associate professor3 4 5 6,
  3. Joseph Beyene, professor of biostatistics7 8,
  4. Sara Mobarak, assistant professor of infectious disease9,
  5. Masoomeh Asadi, masters of operation room10,
  6. Omid Sadeghi, professor of nutrition11 12
  1. 1Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
  2. 2Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
  3. 3Department of Nutrition, Bjørknes University College, Oslo, Norway
  4. 4Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
  5. 5Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway
  6. 6Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  7. 7Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
  8. 8Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada
  9. 9Abadan University of Medical Sciences, Abadan, Iran
  10. 10Department of Operating Room Nursing, Abadan University of Medical Sciences, Abadan, Iran
  11. 11Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
  12. 12Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
  1. Correspondence to: O Sadeghi omidsadeghi69{at}
  • Accepted 7 September 2021


Objective To examine the associations between dietary intake and tissue biomarkers of alpha linolenic acid (ALA) and risk of mortality from all causes, cardiovascular disease (CVD), and cancer.

Design Systematic review and meta-analysis of prospective cohort studies.

Data sources PubMed, Scopus, ISI Web of Science, and Google Scholar to 30 April 2021.

Study selection Prospective cohort studies that reported the risk estimates for death from all causes, CVD, and cancer.

Data synthesis Summary relative risks and 95% confidence intervals were calculated for the highest versus lowest categories of ALA intake using random effects and fixed effects models. Linear and non-linear dose-response analyses were conducted to assess the dose-response associations between ALA intake and mortality.

Results 41 articles from prospective cohort studies were included in this systematic review and meta-analysis, totalling 1 197 564 participants. During follow-up ranging from two to 32 years, 198 113 deaths from all causes, 62 773 from CVD, and 65 954 from cancer were recorded. High intake of ALA compared with low intake was significantly associated with a lower risk of deaths from all causes (pooled relative risk 0.90, 95% confidence interval 0.83 to 0.97, I2=77.8%, 15 studies), CVD (0.92, 0.86 to 0.99, I2=48.2%, n=16), and coronary heart disease (CHD) (0.89, 0.81 to 0.97, I2=5.6%, n=9), and a slightly higher risk of cancer mortality (1.06, 1.02 to 1.11, I2=3.8%, n=10). In the dose-response analysis, a 1 g/day increase in ALA intake (equivalent to one tablespoon of canola oil or 0.5 ounces of walnut) was associated with a 5% lower risk of all cause (0.95, 0.91 to 0.99, I2=76.2%, n=12) and CVD mortality (0.95, 0.91 to 0.98, I2=30.7%, n=14). The pooled relative risks for the highest compared with lowest tissue levels of ALA indicated a significant inverse association with all cause mortality (0.95, 0.90 to 0.99, I2=8.2%, n=26). Also, based on the dose-response analysis, each 1 standard deviation increment in blood concentrations of ALA was associated with a lower risk of CHD mortality (0.92, 0.86 to 0.98, I2=37.1%, n=14).

Conclusions The findings show that dietary ALA intake is associated with a reduced risk of mortality from all causes, CVD, and CHD, and a slightly higher risk of cancer mortality, whereas higher blood levels of ALA are associated with a reduced risk of all cause and CHD mortality only.

Systematic review registration PROSPERO CRD42021229487.


  • Contributors: OS and MA ( are joint corresponding authors and were equally involved in the study. OS and SN searched the literature and extracted data. SN and DA analysed the data. OS and SN drafted the manuscript, which was critically revised for important intellectual content by all authors. JB drafted the manuscript and analysed the data. SM and MA obtained funding and edited the manuscript. OS supervised the study. All authors have read and approved the final manuscript. OS is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding: This study was funded by the Abadan University of Medical Sciences, Abadan, Iran (grant No 871). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: support from the Abadan University of Medical Sciences, Abadan, Iran, for the submitted work; no financial relationships with any organisation that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • The corresponding authors (OS and MA) affirm that the manuscript is an honest, accurate, and transparent account of the study being reported. No important aspects of the study have been omitted and any discrepancies from the study as planned have been disclosed.

  • Dissemination to participants and related patient and public communities: We plan to disseminate these findings to participants in our annual newsletter.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

Data availability statement

No additional data available.

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