Cited by 138Fatty Acid Research and HealthAquaculture Nutrition and GrowthNutritional Studies and Diet

The DOI matches its Crossref record; 128 of the 128 references it cites were found in a registry or an index; 2 of the 118 sources its claims cite were checked for support.

Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: review of recent studies and recommendations

Open access
Van Dael, Peter·2021·Nutrition Research and Practice

Abstract

Long-chain (LC) n-3 polyunsaturated fatty acids (n-3 PUFAs), in particular docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are nutrients involved in many metabolic and physiological processes, and are referred to as n-3 LCPUFA. They have been extensively studied for their effects in human nutrition and health. This paper provides an overview on metabolism, sources, dietary intake, and status of n-3 LCPUFA. A summary of the dietary recommendations for n-3 LCPUFAs for different age groups as well as specific physiological conditions is provided. Evidence for n-3 LCPUFA in cardiovascular diseases, including new studies, is reviewed. Expert recommendations generally support a beneficial effect of n-3 LCPUFA on cardiovascular health and recommend a daily intake of 500 mg as DHA and EPA, or 1-2 servings of fish per week. The role of n-3 LCPUFA on brain health, in particular neurodegenerative disorders and depression, is reviewed. The evidence for beneficial effects of n-3 LCPUFA on neurodegenerative disorders is non-conclusive despite mechanistic support and observational data. Hence, no definite n-3 LCPUFA expert recommendations are made. Data for the beneficial effect of n-3 LCPUFA on depression are generally compelling. Expert recommendations have been established: 200-300 mg/day for depression; up to 1-2 g/day for major depressive disorder. Recent studies support a beneficial role of n-3 LCPUFAs in reducing the risk for premature birth, with a daily intake of 600-800 mg of DHA during pregnancy. Finally, international experts recently reviewed the scientific evidence on DHA and arachidonic acid (ARA) in infant nutrition and concluded that the totality of data support that infant and follow-on formulas should provide both DHA and ARA at levels similar to those in breast milk. In conclusion, the available scientific data support that dietary recommendations for n-3 LCPUFA should be established for the general population and for subjects with specific physiological conditions.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes n-3 LCPUFA metabolism, sources, intake/status, and expert recommendations, focusing on cardiovascular disease, brain health, pregnancy, and infant nutrition. It concludes that dietary recommendations are supported for the general population and specific physiological conditions, while evidence for neurodegenerative disorders remains non-conclusive.

Key findings

  • Cardiovascular expert recommendations generally support benefit and recommend a daily intake of 500 mg DHA + EPA, or 1–2 servings of fish per week; EFSA set an adequate intake of 250 mg/day EPA + DHA for adults. In VITAL, the primary outcome was not statistically significant but showed an 8% reduction in major cardiovascular events, 28% lower total myocardial infarction, and 50% lower fatal myocardial infarction; REDUCE-IT reported that 4 g/day EPA reduced first major adverse cardiovascular events by 25% and cardiovascular death by 20%.
  • For brain health, evidence for neurodegenerative disorders is non-conclusive and no definite expert n-3 LCPUFA recommendations are made; depression evidence is generally compelling, with ANSES recommending 200–300 mg/day and MDD guidelines recommending 1–2 g/day net EPA. A 2019 meta-analysis of 26 studies and 2,160 participants found an overall beneficial effect on depression symptoms, with EPA-pure and EPA-major formulations at ≤ 1 g/day showing clinical benefits.
  • During pregnancy, recent studies support 600–800 mg/day DHA to reduce premature birth risk; one trial with 800 mg/day DHA reported early-preterm birth at 1.09% vs. 2.25% (P = 0.03), and another with 600 mg/day DHA reported longer gestation by 2.9 days and greater birth weight by 172 g. International experts concluded infant and follow-on formulas should provide both DHA and ARA at levels similar to breast milk.
  • Globally, less than 20% of the world’s population consume ≥ 250 mg/day of seafood-origin n-3 LCPUFA; blood EPA + DHA levels were very low (≤ 4%) in North, Central, and South America, Europe, the Middle East, Southeast Asia, and Africa, and high (> 8%) in countries adjacent to the Sea of Japan, Scandinavia, and some indigenous or non-Westernized populations.

Methods

  • Narrative review; no primary data collection. It provides an overview of n-3 LCPUFA metabolism, dietary sources, intake and status, and expert recommendations, then reviews recent evidence in CVD, brain health, pregnancy/prematurity, and infant nutrition.
  • Evidence base includes expert reports (FAO/WHO, EFSA, IOM, NHMRC, ANSES, AHA), randomized trials (e.g., VITAL, REDUCE-IT, pregnancy DHA trials), observational studies, systematic reviews, and meta-analyses.
  • Main analysis is qualitative synthesis and interpretation of cited literature; no systematic search strategy or quantitative pooling is described.

Limitations

  • Stated in the paper: EPA and DHA intake estimates are limited by food composition databases and dietary reporting errors; neurodegenerative evidence is non-conclusive; clinical trials are less conclusive than observational studies; no tolerable upper intake level for n-3 LCPUFA could be established due to insufficient data; not all reviews support a beneficial role in cardiovascular health, with heterogeneity among populations, n-3 status, and intake discrepancies.
  • Evident from the text: as a narrative review, it lacks a described systematic search, inclusion criteria, risk-of-bias assessment, or meta-analytic synthesis, so conclusions depend on the selected cited studies and expert interpretations.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.4162/nrp.2021.15.2.137

Cites

128 of 128 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Figures

Fig. 1 Metabolic pathway for n-3 LCPUFA synthesis from ALA. LCPUFA, long-chain polyunsaturated fatty acid; ALA, alpha-linolenic acid; SA, stearidonic acid; EPA, eicosapentaenoic acid; ETA, eicosatetraenoic acid; DPA, docosapentaenoic acid; DHA, docosahexaenoic acid.
Fig. 1 Metabolic pathway for n-3 LCPUFA synthesis from ALA. LCPUFA, long-chain polyunsaturated fatty acid; ALA, alpha-linolenic acid; SA, stearidonic acid; EPA, eicosapentaenoic acid; ETA, eicosatetraenoic acid; DPA, docosapentaenoic acid; DHA, docosahexaenoic acid.CC BY-NC · PubMed Central

Verification

Claims the paper makes

104 Not checked yet · 21 Own interpretation · 2 No basis given · 1 Supported

Verify all 116 references — free account

Show all 60 claims

  • It may state two separate claims as one. 47
  • Probably not a substantial claim. 35
68 of 68
  • The paper relies on this without support.

    Less than 20% of the world's human population consume ≥ 250 mg/day of seafood-origin n-3 LCPUFA.

    “Global dietary intakes of n-3 LCPUFA has been examined, and it has been estimated that less than 20% of the world's human population consume ≥ 250 mg/day of seafood-origin n-3 LCPUFA.”
  • The paper relies on this without support.

    The current mean intakes of EPA and DHA in the United States are approximately 100 mg/day.

    “This recommendation is similar to the current mean intakes of EPA and DHA in the United States (US) (approximately 100 mg/day), an intake that is much lower than that being recommended by many groups worldwide.”
  • The paper relies on this without support.

    n-3 LCPUFA are involved in many physiological and metabolic processes and play a key role in human metabolism.

    “The n-3 LCPUFA are involved in many physiological and metabolic processes and hence play a key role in human metabolism.”
  • The paper relies on this without support.

    ALA is essential in human nutrition as a precursor for n-3 LCPUFA.

    “ALA is essential in human nutrition as a precursor for n-3 LCPUFA.”
  • The paper relies on this without support.

    Fish, in particular fatty fish, is a rich source of n-3 LCPUFA (EPA and DHA).

    “Fish, in particular fatty fish, is a rich source of n-3 LCPUFA (EPA and DHA).”
  • The paper relies on this without support.

    The developing brain accumulates large amounts of DHA both pre- and postnatally, particularly during the first 2 years of life, with DHA predominantly acquired from the mother via placental transfer and breast milk.

    “The developing brain accumulates large amounts of DHA both pre- and postnatally, particularly during the first 2 years of life, with DHA predominantly acquired from the mother via placental transfer and breast milk.”
  • The paper relies on this without support.

    The conversion of ALA into EPA and DHA is decreased when the amount of LA in the diet increases (and vice versa).

    “The conversion of ALA into EPA and DHA is decreased when the amount of LA in the diet increases (and vice versa).”
  • The paper relies on this without support.

    DHA is a key/essential component of membrane structural lipids/phospholipids in the brain, nervous tissue, and retina.

    “The key role of n-3 LCPUFA has been associated specifically with DHA as it is a key component of membrane structural lipids, especially in nervous tissue and the retina.”
    “Because DHA is an essential component of cellular membrane phospholipids in the brain, researchers have hypothesized that n-3 LCPUFAs might protect cognitive function by helping to maintain neuronal function and cell membrane integrity within the brain [73].”
  • The paper relies on this without support.

    The developing brain accumulates large amounts of DHA both pre- and postnatally, particularly during the first 2 years of life.

    “The developing brain accumulates large amounts of DHA both pre- and postnatally, particularly during the first 2 years of life.”
  • The paper relies on this without support.

    Treatment with omega-3 fatty acids is generally safe and well-tolerated.

    “Regardless, treatment with omega-3 fatty acids is generally reported to be safe and well-tolerated.”
  • The paper relies on this without support.

    Major depressive disorder is of heterogeneous etiology with multiple contributory biological mechanisms.

    “MDD is of heterogeneous etiology with multiple contributory biological mechanisms.”
11 of 11

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1 of 1

Citations

Cites

Research works printed but not linked: 12

  1. Middleton, 2018, Cochrane Database Syst Rev, 11, CD003402
  2. Kinsella, 1990, Nutrition, 6, 24
  3. Food and Agriculture Organization of the United Nations, 2010, FAO Fats and Fatty Acids in Human Nutrition. Report of an Expert Consultation
  4. EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA), 2010, EFSA J, 8, 1461
  5. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), 2012, EFSA J, 10, 2815
  6. US Department of Agriculture, 2015, Scientific Report of the 2015 Dietary Guidelines Advisory Committee
  7. National Health and Medical Research Council (AU), 2017, Nutrient Reference Values for Australia and New Zealand including Recommended Dietary Intakes (version 1.2)
  8. Beaufrère, 2001, Recommended Nutritional Intakes for the French Population
  9. Abdelhamid, 2018, Cochrane Database Syst Rev, 7, CD003177
  10. Burckhardt, 2016, Cochrane Database Syst Rev, 4, CD009002
  11. Sydenham, 2012, Cochrane Database Syst Rev, 6, CD005379
  12. Appleton, 2015, Cochrane Database Syst Rev, 2015, CD004692

Cited by

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Metadata

Authors
Van Dael, P.
Affiliations
Nutrition Science & Advocacy, DSM Nutritional Products, 4303 Kaiseraugst, Switzerland.
Venue
Nutrition Research and Practice
Publisher
XMLink
Published
2021
Volume
15
Issue
2
Pages
137
ISSN
  • 1976-1457 (ISSN-L)
  • 2005-6168
OpenAlex
W3118775982
Cited by
138
References
128
Citations by year
2026: 30 · 2025: 30 · 2024: 36 · 2023: 16 · 2022: 18 · 2021: 8
FWCI
2.60
Type
journal article
Language
en
Open access
Locations
  • Nutrition Research and Practice (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Aquaculture Nutrition and Growth
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Keywords
n-3 long-chain polyunsaturated fatty acids, docosahexaenoic acid, eicosapentaenoic acid, dietary recommendations, cardiovascular disease, neurodegenerative diseases, depression, preterm birth, infant formula, arachidonic acid, fatty acid metabolism, fish consumption

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