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Cited by 148Fatty Acid Research and HealthAquaculture Nutrition and GrowthNutritional Studies and Diet

A Meta-Analysis Shows That Docosahexaenoic Acid from Algal Oil Reduces Serum Triglycerides and Increases HDL-Cholesterol and LDL-Cholesterol in Persons without Coronary Heart Disease3

Open access
Bernstein, Adam M., Ding, Eric L., Willett, Walter C., Rimm, Eric B.·2012·The Journal of Nutrition
DOI 10.3945/jn.111.148973
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Abstract

Certain algae contain the (n-3) fatty acid DHA, yet the relation between algal oil supplementation and cardiovascular disease risk factors has not been systematically examined. Our objective was to examine the relation between algal oil supplementation and cardiovascular disease risk factors. We conducted a systematic review of randomized controlled trials published between 1996 and 2011 examining the relation between algal oil supplementation and cardiovascular disease risk factors and performed a meta-analysis of the association between algal oil DHA supplementation and changes in the concentrations of TG, LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C). We identified 11 randomized controlled trials with 485 healthy participants that evaluated the relation between algal oil DHA supplementation and TG, LDL-C, and HDL-C. The median dose of algal DHA was 1.68 g/d. The pooled estimate for the change in TG concentration was -0.20 mmol/L (95% CI: -0.27 to -0.14), 0.23 mmol/L (95% CI: 0.16-0.30) for LDL-C, and 0.07 mmol/L (95% CI: 0.05-0.10) for HDL-C. DHA supplementation from algal oil, a marine source of (n-3) fatty acids not extracted from fish, may reduce serum TG and increase HDL-C and LDL-C in persons without coronary heart disease.

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Crossref · 10.3945/jn.111.148973

Cites

55 of 55 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 36 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Algal oil DHA supplementation increased HDL-C by a pooled estimate of 0.07 mmol/L (95% CI: 0.05 to 0.10).

    “0.07 mmol/L (95% CI: 0.05-0.10)for HDL-C”
    • Also stated in: § Results · plain
      “for HDL-C it was 0.07 mmol/L (95% CI: 0.05-0.10)(Fig. 3 and Supplemental Table 5)”
    Quote in the paperSubstantial claim
  • Findingown data

    Limiting the analysis to the seven studies that reported using the Friedewald equation, the effect estimate for change in LDL-C was 0.29 mmol/L (95% CI: 0.20 to 0.38).

    “Limiting the study to the seven studies that reported using the Friedewald equation (18,19,22,23,28,29,34), the effect estimate of change in LDL-C was 0.29 (95% CI: 0.20-0.38)mmol/L LDL-C.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Trim-and-fill correction analysis with serum TG showed that the main results remained significant and robust.

    “Trim-and-fill correction analysis with serum TG showed the main results remained significant and robust.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Algal oil DHA supplementation increased LDL-C by a pooled estimate of 0.23 mmol/L (95% CI: 0.16 to 0.30).

    “0.23 mmol/L (95% CI: 0.16-0.30)for LDL-C”
    • Also stated in: § Results · plain
      “for LDL-C it was 0.23 mmol/ L (95% CI: 0.16-0.30)(Fig. 2 and Supplemental Table 4)”
    Quote in the paperSubstantial claim
  • Findingown data

    All algal oil supplements in the analyzed studies contained either no EPA or a negligible amount of EPA.

    “All algal oil supplements used in the analyzed studies contained either no EPA (18,22,23,29,33,35,36) or a negligible amount of EPA (19,26,28,34) (e.g., 1/20 the amount of DHA/d or ,0.005 g/d).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 18
  • May combine two claims. 28

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    All but one included study reported that the algal oil contained a mixture of SFA and PUFA in addition to DHA, with an overall mean DHA fatty acid content of 41% by weight.

    “All but one of the studies reported that the algal oil contained a mixture of SFA and PUFA in addition to DHA, although the overall mean DHA fatty acid content was 41% by weight (Supplemental Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Of three Begg rank correlation tests and three Egger tests, five were not significant and only the Egger test with serum TG was significant (P = 0.01), suggesting an overall small potential for publication bias or small-study effects.

    “Of the three Begg rank correlation tests and three Egger tests, five were not significant and only the Egger test with serum TG was significant (P value 0.01), suggesting an overall small potential for publication bias or small-study effects.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    All studies but one had doses of algal oil DHA less than 3 g/d.

    “All studies but one had doses of algal oil DHA ,3 g/d.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    This is the first systematic review and meta-analysis of algae-derived DHA supplementation and serum lipids.

    “To our knowledge, this is the first systematic review and metaanalysis of algae-derived DHA supplementation and serum lipids.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Two studies showing a decrease in LDL-C included vegetarian participants, although the confidence intervals were wide, and a third vegetarian study observed a significant rise in LDL-C similar to other studies.

    “The two studies that showed a decrease in LDL-C included vegetarian participants (18,35), although the CI were wide, and a third study with vegetarian participants (34) observed a significant rise in LDL-C, similar to other studies.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [18] Conquer, 1996, Supplementation with an algae source of docosahexaenoic acid increases (n-3) fatty acid status and alters selected risk factors for heart disease in vegetarian subjects., J Nutr. source

      Not checked in the free run.

    • cites [35] Wu, 2006, Effects of docosahexaenoic acid supplementation on blood lipids, estrogen metabolism, and in vivo oxidative stress in postmenopausal vegetarian women., Eur J Clin Nutr. source

      Not checked in the free run.

    • cites [34] Geppert, 2006, Microalgal docosahexaenoic acid decreases plasma triacylglycerol in normolipidaemic vegetarians: a randomised trial., Br J Nutr. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    One study reported using standard methods for estimating LDL-C, and one did not report its method.

    “One study reported using “standard” methods for estimating LDL-C (36) and one did not report its method (26).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [36] Neff, 2011, Algal docosahexaenoic acid affects plasma lipoprotein particle size distribution in overweight and obese adults., J Nutr. source

      Not checked in the free run.

    • cites [26] Theobald, 2004, LDL cholesterol-raising effect of low-dose docosahexaenoic acid in middle-aged men and women., Am J Clin Nutr. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    The one study that showed a higher increase in HDL-C compared with other studies had young participants, was of longer duration than most studies, and was single-blinded.

    “The one study that showed a higher increase in HDL-C compared to other studies had young study participants, was of longer duration than most studies, and was single-blinded (33).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Agren, 1996, Fish diet, fish oil and docosahexaenoic acid rich oil lower fasting and postprandial plasma lipid levels., Eur J Clin Nutr.

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    All but one of the placebo arms in the trials contained corn, soy, or olive oil, each rich in palmitic, oleic, and linoleic acids; soy oil also has a small amount of alpha-linolenic acid.

    “All but one of the placebo arms in the trials we examined contained corn, soy, or olive oil, each of which is rich in palmitic, oleic, and linoleic acids.Soy oil also has a small amount of a-linolenic acid.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    One study using direct methods for estimating LDL-C showed a decrease in LDL-C, whereas another study using direct methods showed no effect.

    “One study that reported using direct methods for estimating LDL-C, rather than the Freidewald equation, showed a decrease in LDL-C (35), whereas another that used the direct method showed no effect (33).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [35] Wu, 2006, Effects of docosahexaenoic acid supplementation on blood lipids, estrogen metabolism, and in vivo oxidative stress in postmenopausal vegetarian women., Eur J Clin Nutr. source

      Not checked in the free run.

    • cites [33] Agren, 1996, Fish diet, fish oil and docosahexaenoic acid rich oil lower fasting and postprandial plasma lipid levels., Eur J Clin Nutr.

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The greatest decrease in TG and greatest increase in LDL-C appeared in the two studies that included participants with elevated serum lipid concentrations at baseline.

    “The greatest decrease in TG and greatest increase in LDL-C appeared in the two studies that included participants with elevated serum lipid concentrations at baseline (23,29).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [23] Kelley, 2007, Docosahexaenoic acid supplementation improves fasting and postprandial lipid profiles in hypertriglyceridemic men., Am J Clin Nutr. source

      Not checked in the free run.

    • cites [29] Davidson, 1997, Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial., J Am Coll Nutr. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Most algal oil supplements contained palmitic and oleic acid, though in different amounts than the placebos.

    “Most of the algal oil supplements contained palmitic and oleic acid, though in different amounts than the placebos.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The median dose of algal DHA in the serum lipid analysis was 1.68 g/d.

    “The median dose of algal DHA was 1.68 g/d.”
    • Also stated in: § Results · plain
      “The median dose of algal DHA in the analysis of serum lipids was 1.68 g/d.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The three funnel plots were symmetrical, suggesting that effect estimates were not associated with SE or study size.

    “The three funnel plots were symmetrical, suggesting that effect estimates were not associated with SE or study size.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In meta-regression, no significant dose response was observed between algal DHA and TG, LDL-C, or HDL-C; a 1-g/day increase in algal DHA was associated with a 0.06 mmol/L decrease in TG (95% CI: -0.19, 0.07), a 0.04 mmol/L reduction in LDL-C (95% CI: -0.28, 0.19), and a 0.02 mmol/L reduction in HDL-C (95% CI: -0.07, 0.04).

    “In the meta-regression, we did not observe a significant dose response between algal DHA and TG, LDL-C, or HDL-C concentration: a 1-g increase per day in the dose of algal DHA was associated with a 0.06-mmol/L decrease in TG (95% CI: 20.19, 0.07), a 0.04-mmol/L reduction in LDL-C (95% CI: 20.28, 0.19), and a 0.02-mmol/L reduction in HDL-C (95% CI: 20.07, 0.04).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The meta-analysis included 11 randomized controlled trials with 485 participants, published from 1996 to 2011.

    “We identified 11 randomized controlled trials with 485 healthy participants that evaluated the relation between algal oil DHA supplementation and TG, LDL-C, and HDL-C.”
    • Also stated in: § Results · plain
      “We identified 11 randomized controlled trials, including a total of 485 participants, dating from 1996 to 2011 (18,19,22,23,26, 28,29,33-36) (Supplemental Table 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The increase in HDL-C with algal oil was similar to that with fish oil (0.01 mmol/L; 95% CI: 0.00 to 0.02), while the increase in LDL-C was higher (0.06 mmol/L; 95% CI: 0.03 to 0.09).

    “The increase in HDL-C was also similar to that with fish oil (0.01 mmol/L; 95% CI: 0.00-0.02); the increase in LDL-C was higher (0.06 mmol/L; 95% CI: 0.03-0.09)(42).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [42] Eslick, 2009, Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta-analysis., Int J Cardiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Purified ethyl ester DHA supplementation has been shown to lower TG and mildly elevate LDL-C and HDL-C.

    “Purified ethyl ester DHA supplementation has been shown to lower TG and mildly elevate LDL-C and HDL-C (51,52).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [51] Grimsgaard, 1997, Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids., Am J Clin Nutr. source

      Not checked in the free run.

    • cites [52] Mori, 2000, Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men., Am J Clin Nutr. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    DHA supplementation from algal oil may reduce serum TG and increase HDL-C and LDL-C in persons without coronary heart disease.

    “DHA supplementation from algal oil, a marine source of (n-3) fatty acids not extracted from fish, may reduce serum TG and increase HDL-C and LDL-C in persons without coronary heart disease.”
    • Also stated in: § Discussion · hedged
      “In conclusion, DHA supplementation from algal oil, a marine source of (n-3) fatty acids not extracted from fish, may reduce serum TG and increase LDL-C and HDL-C in persons without CHD.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Aquaculture provides an alternative source of fish for consumption but has been associated with damage to and pollution of sensitive ecologic areas.

    “Aquaculture, or fish farming, provides an alternative or perhaps additional source of fish for consumption, yet the practice has been associated with damage to and pollution of sensitive ecologic areas (8)(9)(10).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [8] Jenkins, 2009, Are dietary recommendations for the use of fish oils sustainable?, CMAJ. source

      Not checked in the free run.

    • cites [9] Naylor, 2000, Effect of aquaculture on world fish supplies., Nature. source

      Not checked in the free run.

    • cites [10] Reijnders, 2003, Quantification of the environmental impact of different dietary protein choices., Am J Clin Nutr. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The DHA content of the supplements could explain the findings; however, it is also likely that the saturated fat content of the algal oil contributed to participant lipid concentrations different from those expected from purified DHA.

    “The DHA content of the supplements could explain our findings; however, it is also likely that the saturated fat content of the algal oil contributed to study participant lipid concentrations different than that those expected from purified DHA.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Reduced hepatic VLDL synthesis leads to reduced secretion and smaller VLDL particles, which are more readily converted to LDL than large VLDL particles and compete with LDL for uptake by LDL receptors, both actions leading to higher serum LDL-C.

    “Reduced synthesis in turn leads to reduced secretion and smaller VLDL particles, which are more readily converted to LDL than are large VLDL particles and which also compete with LDL for uptake by LDL receptors (52).Both of these actions lead to higher serum LDL-C.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Mori, 2000, Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men., Am J Clin Nutr. source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    The included studies were of good quality, with 9 of 11 scoring 4 of 5.

    “Studies were of good quality (9 of 11 scored 4 of 5).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Consumption of wild marine fish is severely limited because most ocean fish populations are exploited and cannot sustain current catch levels.

    “Consumption of wild marine fish is severely limited, however, because most ocean fish populations are exploited and unable to yield sustainable catches at current levels (6)(7)(8).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [6] FAO of the United Nations. The state of the world's fisheries and aquaculture; 2008 [cited 2010 Jul 6]. Available from: http://www.fao.org/fishery/sofia/en.

      Not checked in the free run.

    • cites [7] Gussow, 1995, Mediterranean diets: are they environmentally responsible?, Am J Clin Nutr. source

      Not checked in the free run.

    • cites [8] Jenkins, 2009, Are dietary recommendations for the use of fish oils sustainable?, CMAJ. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Because particle size, in addition to lipoprotein cholesterol content, may help predict atherogenic risk, the net effect of algal DHA supplementation on serum lipoproteins and lipids may be beneficial despite the increase in LDL-C.

    “because particle size, in addition to lipoprotein cholesterol content, may help predict atherogenic risk, the net effect of algal DHA supplementation on serum lipoproteins and lipids may be beneficial despite the increase in LDL-C (55).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [55] Berneis, 2002, Metabolic origins and clinical significance of LDL heterogeneity., J Lipid Res. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The systematic review and meta-analysis followed PRISMA guidelines.

    “We observed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for this systematic review and meta-analysis (17).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Moher, 2009, Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement., Ann Intern Med. source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductnone given

    Study designs were of good quality, and with an average duration of 6 weeks there was adequate time to see changes in measured outcomes.

    “Study designs were of good quality and with an average duration of 6 wk, there was adequate time to see changes in measured outcomes.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The search covered all randomized controlled trials of algae-derived EPA or DHA and serum lipoproteins or cardiovascular disease, with no language restrictions.

    “We searched for all randomized controlled trials that examined the association between algae-derived EPA or algae-derived DHA and serum lipoproteins or cardiovascular disease.”
    • Also stated in: § Search strategy. · plain
      “There were no language restrictions in our search.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The 8% increase in LDL-C and 5% increase in HDL-C observed with algal oil is similar to that observed with 4 g/d purified DHA, which was also associated with a transition to larger, possibly less-atherogenic LDL particles.

    “The 8% increase in LDL-C and 5% increase in HDL-C we observed with algal oil is similar to that observed with 4 g/d of purified DHA, the latter which was also associated with a transition to larger, possibly less-atherogenic LDL particles (52).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Mori, 2000, Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men., Am J Clin Nutr. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The analysis was only able to assess the relation between algal oil supplementation and serum lipids.

    “We were also only able to assess the relation between algal oil supplementation and serum lipids.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Algae have recently been cultivated to preferentially produce DHA, and their oil has been extracted to make supplements.

    “Recently, algae have been cultivated to preferentially produce DHA and their oil has been extracted to make supplements (13,14).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [13] Gebauer, 2006, n-3 Fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits., Am J Clin Nutr. source

      Not checked in the free run.

    • cites [14] Sijtsma, 2004, Biotechnological production and applications of the omega-3 polyunsaturated fatty acid docosahexaenoic acid., Appl Microbiol Biotechnol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Because one recognized benefit of fish oil supplementation is antiarrhythmic with a reduction in sudden death, the ability to compare algal oil supplementation to fish oil supplementation is limited.

    “Because one of the recognized benefits of fish oil supplementation is antiarrhythmic with a reduction in sudden death, our ability to compare algal oil supplementation to fish oil supplementation is limited.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Most included studies lasted 6 weeks and either did not independently assess algal oil concentration or did not report such an assessment (6 of 11).

    “Most studies were 6 wk in duration and either did not independently assess algal oil concentration or did not report such an assessment (6 of 11 studies).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Study quality was assessed with a validated quality scoring system.

    “The quality of each study, defined as the confidence that its design, conduct, analysis, and presentation limited bias in its results, was assessed by a validated quality scoring system (39).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Moher, 1998, Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?, Lancet. source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductnone given

    The chief limitations are that the studies were few and small, all were funded or gifted by industry, and most did not independently verify the algal oil supplements.

    “The chief limitations are that the studies were few and small, all were funded or gifted by industry, and most did not independently verify the algal oil supplements.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In the wild, fish accumulate EPA and DHA by consuming marine algae.

    “In the wild, fish accumulate EPA and DHA by consumption of marine algae (11,12).”
    • Also stated in: § Discussion · plain
      “Fish naturally accumulate EPA and DHA by consumption of marine algae (11,12), which are a diverse group of uni-and multi-cellular photosynthetic organisms.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [11] Metz, 2001, Production of polyunsaturated fatty acids by polyketide synthases in both prokaryotes and eukaryotes., Science. source

      Not checked in the free run.

    • cites [12] Simopoulos, 1991, Omega-3 fatty acids in health and disease and in growth and development., Am J Clin Nutr. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    All included studies used fasting blood samples for lipid measurements, and the majority used the Friedewald equation to estimate LDL-C.

    “All studies used fasting blood samples for lipid measurements and the majority used the Freidewald equation to estimate LDL-C.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    The different methods of estimating LDL-C may have been a source of between-study heterogeneity, and this possibility should be explored further.

    “However, in our analysis, the different methods may have been a source of between-study heterogeneity and this possibility should be explored further.”
    Quote in the paperNot a substantial claim
37 of 37

  • The authors state this as an assumption.

    The fixed-effects model assumes that the true treatment effect is identical across studies and that any differences among study results arise by chance.

    “The fixed-effects model assumes that the true effect of treatment is the same in each study and that differences between study results are due to chance (40).”
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Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • ω3 PUFA increased LDL-C level significantly with a dose greater than 2 g/d.

    “ω3 PUFA increased LDL‐C level significantly with a dose greater than 2 g/d, consistent with previous findings. 7 , 9 , 12 , 13”

    From Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials (2023) · cites this paper as [12]

    The Results (page unavailable) report a significant pooled LDL-C increase with algal DHA supplementation. They do not establish an increase specifically at doses greater than 2 g/d; the median dose was 1.68 g/d, and the meta-regression found no significant dose response. The paper studies algal DHA rather than ω3 PUFA generally. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • ω3 PUFAs reduce serum triglyceride concentration by approximately 15% to 30% but do not affect or may even increase LDL-C levels.

    “ω3 PUFAs could reduce serum triglyceride concentration by approximately 15% to 30% 6 , 7 , 8 , 9 but could not affect or even increase LDL‐C levels. 9 , 10 , 11 , 12 , 13”

    From Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials (2023) · cites this paper as [12]

    The Results (page not specified) report a 15% triglyceride decrease and an 8% LDL-C increase with algal DHA; they also note an individual study with no LDL-C effect. The cited meta-analysis studied algal DHA rather than ω3 PUFAs generally, and its pooled result does not establish the claimed reduction of up to 30%. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Previous systematic reviews and meta-analyses have been unable to reveal a significant dose-response relationship between omega-3 PUFA intake and lipid changes.

    “Previous systematic reviews and meta‐analyses have been unable to reveal a significant dose–response relationship. 12 , 14”

    From Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials (2023) · cites this paper as [12]

    The Results report no significant dose-response relationship between algal DHA dose and TG, LDL-C, or HDL-C concentrations. That supports the claim for this meta-analysis, but the paper examined algal DHA specifically, not omega-3 PUFA intake broadly. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Previous dose-response models using pooled meta-regression were conducted based on the assumption that a linear causal relationship existed, without taking into account correlations at different dose levels.

    “Previous dose–response models using pooled meta‐regression method were conducted based on the assumption that a linear causal relationship existed, 9 , 12 , 13 , 16 without taking into account the correlations at different dose levels.”

    From Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials (2023) · cites this paper as [12]

    The Statistical analysis section describes fixed-effects meta-regressions using mean algal DHA dose to estimate a dose–response relation, and the Results express estimates per 1-g increase. The paper does not state that it assumed a causal relationship or that it failed to account for correlations between dose levels; the Discussion instead cautions that between-study confounding may affect the dose–response analysis. Page numbers are unavailable in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Past meta-analyses examined the dose-response relationship using pooled linear meta-regression without accounting for correlations among effects at different dose levels.

    “These past meta‐analyses examined the dose–response relationship using pooled linear meta‐regression 9 , 12 , 13 , 16 without taking into account the correlations among effects at different dose levels. 17”

    From Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials (2023) · cites this paper as [12]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Citation 61 has no bibliography entry

    Minor

    The cost comparison cites references 60 and 61, but the bibliography ends at reference 60. No entry is provided for citation 61.

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Cites

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Authors
Bernstein, A. M., Ding, E. L., Willett, W. C., & Rimm, E. B.
Affiliations
  • Cleveland Clinic (US)
  • Harvard University (US)
  • Brigham and Women's Hospital (US)
Corresponding author
Bernstein, Adam M.
ORCID
Venue
The Journal of Nutrition
Publisher
Elsevier BV
Published
2012-01
Volume
142
Issue
1
Pages
99-104
ISSN
0022-3166 (ISSN-L)
DOI
10.3945/jn.111.148973
OpenAlex
W2115191862
Cited by
148
References
55
Citations by year
2026: 4 · 2025: 8 · 2024: 10 · 2023: 10 · 2022: 5 · 2021: 12 · 2020: 13 · 2019: 7 · 2018: 4 · 2017: 10 · 2016: 12 · 2015: 13 · 2014: 16 · 2013: 15 · 2012: 9
FWCI
1.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Nutrition (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
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
docosahexaenoic acid, algal oil, omega-3 fatty acids, serum triglycerides, HDL cholesterol, LDL cholesterol, cardiovascular risk factors, dietary supplementation, coronary artery disease
MeSH terms
Coronary Disease, Docosahexaenoic Acids, Humans, Cholesterol, HDL, Cholesterol, LDL, Plant Oils, Triglycerides

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-01.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-01.

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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